<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03298451</url>
  </required_header>
  <id_info>
    <org_study_id>D419CC00002</org_study_id>
    <secondary_id>2016-005126-11</secondary_id>
    <nct_id>NCT03298451</nct_id>
  </id_info>
  <brief_title>Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma</brief_title>
  <acronym>HIMALAYA</acronym>
  <official_title>A Randomized, Open-label, Multi-center Phase III Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, open-label, multi-center, global, Phase III study to assess the&#xD;
      efficacy and safety of durvalumab plus tremelimumab combination therapy and durvalumab&#xD;
      monotherapy versus sorafenib in the treatment of patients with no prior systemic therapy for&#xD;
      unresectable HCC. The patients cannot be eligible for locoregional therapy&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study population includes patients 18 years of age or older with advanced HCC, Barcelona&#xD;
      Clinic Liver Cancer stage B not eligible for locoregional therapy or stage C, and Child-Pugh&#xD;
      A classification liver disease. Patients must not have received any prior systemic therapy&#xD;
      for unresectable HCC.&#xD;
&#xD;
      Patients in all treatment arms may continue receiving their originally assigned treatment, at&#xD;
      the Investigator's discretion, until progression&#xD;
&#xD;
      Patients in all arms with confirmed PD who, in the Investigator's opinion, continue to&#xD;
      receive benefit from their assigned treatment and meet the criteria for treatment in the&#xD;
      setting of PD may continue to receive their assigned treatment.&#xD;
&#xD;
      If a patient discontinues study drug(s) due to disease progression, the patient will enter&#xD;
      survival follow-up. Patients who have discontinued treatment due to toxicity or symptomatic&#xD;
      deterioration or who have commenced subsequent anticancer therapy, will have tumor&#xD;
      assessments until confirmed PD and will be followed for survival&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 11, 2017</start_date>
  <completion_date type="Anticipated">August 27, 2024</completion_date>
  <primary_completion_date type="Actual">August 27, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Survival (OS) - Treme 300 mg x1 Dose + Durva 1500 mg vs Sora 400 mg</measure>
    <time_frame>From the date of randomization until death due to any cause, assessed up to the data cut-off date (27Aug2021, to a maximum of approximately 46 months).</time_frame>
    <description>OS was defined as the time from the date of randomization until death due to any cause, regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Any participant not known to have died at the DCO date was censored based on the last recorded date on which the participant was known to be alive. If the last known date alive or if the date of death was after the DCO date, participants were censored at the DCO date. This primary outcome measure presents OS analysis of Treme 300mg x1 dose + Durva 1500 mg vs Sora 400 mg at the time of the final analysis DCO (27Aug2021).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) - Durva 1500 mg vs Sora 400 mg</measure>
    <time_frame>From the date of randomization until death due to any cause, assessed up to the data cut-off date (27Aug2021, to a maximum of approximately 46 months).</time_frame>
    <description>OS was defined as the time from the date of randomization until death due to any cause, regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Any participant not known to have died at the DCO date was censored based on the last recorded date on which the participant was known to be alive. If the last known date alive or if the date of death was after the DCO date, participants were censored at the DCO date. This secondary outcome measure presents OS analysis of Durva 1500 mg vs Sora 400 mg at the time of the final analysis DCO (27Aug2021).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) at 18, 24, and 36 Months After Randomization</measure>
    <time_frame>At 18, 24, and 36 months post-randomization. Assessed at the final analysis DCO (27Aug2021).</time_frame>
    <description>Percentage of participants who were alive at fixed time points (18, 24, and 36 months) after randomization. The estimated percentage of survival along with the 95% confidence interval were calculated using Kaplan-Meier technique on the full analysis set.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Tumor scans performed at baseline, every 8 weeks for the first 48 weeks following randomization, and every 12 weeks thereafter until RECIST 1.1-defined progression. Assessed up to DCO (27Aug2021, to a maximum of approximately 46 months)</time_frame>
    <description>PFS (per Response Evaluation Criteria in Solid Tumors, version 1.1 [RECIST 1.1] using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death by any cause in the absence of progression, regardless of whether the patient withdrew from study treatment or received another anticancer therapy prior to progression. Progression (i.e., PD) was defined as a at least 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) - this includes the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm from nadir.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time To Progression (TTP)</measure>
    <time_frame>From the date of randomization until objective tumor progression, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).</time_frame>
    <description>TTP was defined as the time from randomization until objective tumor progression in the absence of death. If participants died without tumor progression, they were censored at the time of death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>From the date of randomization until objective tumor progression, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).</time_frame>
    <description>ORR (per RECIST 1.1 as assessed by the Investigator) was defined as the number (%) of participants with at least 1 confirmed visit response of CR or PR until progression, or the last evaluable assessment in the absence of progression. Participants who go off treatment without progression, receive a subsequent therapy, and then respond will not be included as responders in the ORR. Complete response (ie., CR) was defined as disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to &lt;10 mm. Partial response (ie., PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>From the date of randomization until objective tumor progression or date of death, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).</time_frame>
    <description>Number (%) of participants with a Best Objective Response (BoR) of CR, PR, or SD. Complete response (ie., CR) was defined as disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to &lt;10 mm. Partial response (ie., PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters. Stable disease (ie., SD) was defined as neither sufficient decrease in sum of diameters to qualify for PR nor sufficient increase to qualify for progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Objective Response (DoR)</measure>
    <time_frame>From the date of first documented response until the first date of documented progression or death, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).</time_frame>
    <description>Time from the date of first documented confirmed response (complete or partial response) until the first date of documented progression or death in the absence of disease progression. Complete response (ie., CR) was defined as disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to &lt;10 mm. Partial response (ie., PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) by PD-L1</measure>
    <time_frame>From the date of randomization until death due to any cause, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).</time_frame>
    <description>Overall survival by baseline PD-L1 expression levels (positive vs. negative). PD-L1 expression level is based on the Tumor and Immune Cell Positivity (TIP) score method as: PD-L1 Positive (TIP ≥ 1%) or PD-L1 Negative (TIP &lt; 1%).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EORTC QLQ-C30 Time to Global Health Status/QoL Deterioration</measure>
    <time_frame>At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.</time_frame>
    <description>European Organisation for Research and Treatment of Cancer (EORTC) 30-item core quality of life questionnaire (QLQ-C30), which consists of 30 questions combined to produce a global health status/QoL scale. Higher scores indicate better health. A clinically meaningful deterioration is defined as a decrease in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EORTC QLQ-HCC18 Time to Symptom (Abdominal Pain) Deterioration</measure>
    <time_frame>At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.</time_frame>
    <description>EORTC 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) is an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30, which includes 8 symptom scales such as fatigue, jaundice, body image, nutrition, pain, fever, sex life and abdominal swelling. A high score for a symptom scale/item represents a high level of symptomatology/problem. A clinically meaningful deterioration is defined as an increase in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EORTC QLQ-HCC18 Time to Symptom (Shoulder Pain) Deterioration</measure>
    <time_frame>At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.</time_frame>
    <description>EORTC 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) is an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30, which includes 8 symptom scales such as fatigue, jaundice, body image, nutrition, pain, fever, sex life and abdominal swelling. A high score for a symptom scale/item represents a high level of symptomatology/problem. A clinically meaningful deterioration is defined as an increase in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EORTC QLQ-HCC18 Time to Symptom (Abdominal Swelling) Deterioration</measure>
    <time_frame>At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.</time_frame>
    <description>EORTC 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) is an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30, which includes 8 symptom scales such as fatigue, jaundice, body image, nutrition, pain, fever, sex life and abdominal swelling. A high score for a symptom scale/item represents a high level of symptomatology/problem. A clinically meaningful deterioration is defined as an increase in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of ADA for Durvalumab</measure>
    <time_frame>Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of durvalumab. Assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).</time_frame>
    <description>Number of participants with Anti-Drug Antibody (ADA) response to Durvalumab. ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA was defined as the sum of treatment-induced ADA and treatment-boosted ADA. Results are reported as number of participants with ADA responses to Durvalumab for each indicated category.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of ADA for Tremelimumab</measure>
    <time_frame>Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of tremelimumab. Assessed up to approximately 46 months after the first randomization.</time_frame>
    <description>Number of participants with Anti-Drug Antibody (ADA) response to Tremelimumab. ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA was defined as the sum of treatment-induced ADA and treatment-boosted ADA. Results are reported as number of participants with ADA responses to Tremelimumab for each indicated category.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summary of Durvalumab Concentration Over Time</measure>
    <time_frame>To evaluate the PK of Durvalumab, samples were collected pre-dose at week 4 and week 12 and post-dose at week 12. Assessed at the final analysis DCO (27Aug2021).</time_frame>
    <description>Blood sample were collected at pre-specified timepoints and Durvalumab concentrations in serum (ug/mL) were reported over time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summary of Tremelimumab Concentration Over Time</measure>
    <time_frame>To evaluate the PK of Tremelimumab, samples were collected at week 0 (post-dose), week 4, and week 12. Assessed at the final analysis DCO (27Aug2021).</time_frame>
    <description>Blood sample were collected at pre-specified timepoints and Tremelimumab concentrations in serum (ug/mL) were reported over time.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">1324</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Durvalumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Durvalumab in combination with tremelimumab (Regimen 1)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Durvalumab in combination with tremelimumab (Regimen 2)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 4</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sorafenib</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Durvalumab IV (intravenous infusion).</description>
    <arm_group_label>Arm 1</arm_group_label>
    <other_name>MEDI4736</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tremelimumab (Regimen 1)</intervention_name>
    <description>Tremelimumab IV (intravenous infusion).</description>
    <arm_group_label>Arm 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tremelimumab (Regimen 2)</intervention_name>
    <description>Tremelimumab IV (intravenous infusion).</description>
    <arm_group_label>Arm 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sorafenib</intervention_name>
    <description>Sorafenib, as per standard of care</description>
    <arm_group_label>Arm 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab (Regimen 1)</intervention_name>
    <description>Durvalumab IV (intravenous infusion).</description>
    <arm_group_label>Arm 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab (Regimen 2)</intervention_name>
    <description>Durvalumab IV (intravenous infusion).</description>
    <arm_group_label>Arm 3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          -  HCC based on histopathological confirmation&#xD;
&#xD;
          -  No prior systemic therapy for HCC&#xD;
&#xD;
          -  Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional&#xD;
             therapy) or stage C&#xD;
&#xD;
          -  Child-Pugh Score class A&#xD;
&#xD;
          -  ECOG performance status of 0 or 1 at enrollment&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  Hepatic encephalopathy within past 12 months or requirement for medication to prevent&#xD;
             or control encephalopathy&#xD;
&#xD;
          -  Clinically meaningful ascites&#xD;
&#xD;
          -  Main portal vein tumor thrombosis&#xD;
&#xD;
          -  Active or prior documented GI bleeding (eg, esophageal varices or ulcer bleeding)&#xD;
             within 12 months&#xD;
&#xD;
          -  HBV and HVC co-infection, or HBV and Hep D co-infection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33916</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28262</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>74235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77090</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Murray</city>
        <state>Utah</state>
        <zip>84107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barretos</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Curitiba</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Florianopolis</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Porto Alegre</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rio de Janeiro</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sao Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
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  <location>
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  <location>
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  <location>
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  <location>
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  <location>
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  <location>
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  <location>
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  <location>
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  <location>
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    <facility>
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  <location>
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      <address>
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    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Oviedo</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Pamplona Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Santander</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chiayi</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kaohsiung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tainan</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Taoyuan</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bangkok</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chang Mai</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Khon Kaen</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Phitsanulok</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Songkhla</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dnipro</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>IvanoFrankivsk</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kharkiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kropyvnitskyi</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kyiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lviv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Odesa</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Uzhgorod</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hanoi</city>
        <country>Vietnam</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hochiminh</city>
        <country>Vietnam</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
    <country>Canada</country>
    <country>China</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hong Kong</country>
    <country>India</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>Thailand</country>
    <country>Ukraine</country>
    <country>United States</country>
    <country>Vietnam</country>
  </location_countries>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;amp;parentIdentifier=D419CC00002&amp;amp;attachmentIdentifier=5492a658-0cae-4a53-9c5f-2c7d7dd2f180&amp;amp;fileName=419CC00002CSP_redacted.pdf&amp;amp;versionIdentifier=</url>
    <description>CSP_redacted</description>
  </link>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;amp;parentIdentifier=D419CC00002&amp;amp;attachmentIdentifier=dfa10daf-41b0-454d-ab99-f62959a00fdc&amp;amp;fileName=D419CC00002_SAP_redacted.pdf&amp;amp;versionIdentifier=</url>
    <description>SAP_redacted</description>
  </link>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;amp;parentIdentifier=D419CC00002&amp;amp;attachmentIdentifier=7f90991f-10dd-4176-8b36-c5535f3ba6d6&amp;amp;fileName=D419CC00002_CSR__synopsis_redacted.pdf&amp;amp;versionIdentifier=</url>
    <description>CSR_synopsis</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>September 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 2, 2017</study_first_posted>
  <results_first_submitted>August 26, 2022</results_first_submitted>
  <results_first_submitted_qc>June 14, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">June 18, 2023</results_first_posted>
  <last_update_submitted>June 14, 2023</last_update_submitted>
  <last_update_submitted_qc>June 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepatocellular Carcinoma Non-Resectable</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sorafenib</mesh_term>
    <mesh_term>Durvalumab</mesh_term>
    <mesh_term>Tremelimumab</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 22, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT03298451/Prot_004.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 31, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT03298451/SAP_005.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study includes 1324 participants. Participants were screened in 16 countries from Oct2017 to Jun2019. Recruitment in T75+D arm was closed during the study. Results are reported at data cut-off (DCO).</recruitment_details>
      <pre_assignment_details>Of 1,950 participants screened in the study, 1,324 were randomized across 4 arms, out of which 1,302 participants received treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Durva 1500 mg</title>
          <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
        </group>
        <group group_id="P2">
          <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
          <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
        </group>
        <group group_id="P3">
          <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
          <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
        </group>
        <group group_id="P4">
          <title>Sora 400 mg</title>
          <description>Sorafenib 400 mg twice daily (BID)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="389"/>
                <participants group_id="P2" count="393"/>
                <participants group_id="P3" count="153"/>
                <participants group_id="P4" count="389"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Treatment</title>
              <participants_list>
                <participants group_id="P1" count="386"/>
                <participants group_id="P2" count="389"/>
                <participants group_id="P3" count="153"/>
                <participants group_id="P4" count="374"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="104"/>
                <participants group_id="P2" count="125"/>
                <participants group_id="P3" count="30"/>
                <participants group_id="P4" count="82"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="285"/>
                <participants group_id="P2" count="268"/>
                <participants group_id="P3" count="123"/>
                <participants group_id="P4" count="307"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="275"/>
                <participants group_id="P2" count="260"/>
                <participants group_id="P3" count="122"/>
                <participants group_id="P4" count="280"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="20"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The full analysis set (FAS) included all participants who were randomized.</population>
      <group_list>
        <group group_id="B1">
          <title>Durva 1500 mg</title>
          <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
        </group>
        <group group_id="B2">
          <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
          <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
        </group>
        <group group_id="B3">
          <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
          <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
        </group>
        <group group_id="B4">
          <title>Sora 400 mg</title>
          <description>Sorafenib 400 mg twice daily (BID)</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="389"/>
            <count group_id="B2" value="393"/>
            <count group_id="B3" value="153"/>
            <count group_id="B4" value="389"/>
            <count group_id="B5" value="1324"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.6" spread="11.47"/>
                    <measurement group_id="B2" value="63.0" spread="11.65"/>
                    <measurement group_id="B3" value="63.4" spread="12.03"/>
                    <measurement group_id="B4" value="63.5" spread="11.12"/>
                    <measurement group_id="B5" value="63.1" spread="11.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>&lt;65</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="203"/>
                    <measurement group_id="B2" value="195"/>
                    <measurement group_id="B3" value="74"/>
                    <measurement group_id="B4" value="195"/>
                    <measurement group_id="B5" value="667"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=65-&lt;75</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="130"/>
                    <measurement group_id="B2" value="145"/>
                    <measurement group_id="B3" value="55"/>
                    <measurement group_id="B4" value="137"/>
                    <measurement group_id="B5" value="467"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=75</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56"/>
                    <measurement group_id="B2" value="53"/>
                    <measurement group_id="B3" value="24"/>
                    <measurement group_id="B4" value="57"/>
                    <measurement group_id="B5" value="190"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="66"/>
                    <measurement group_id="B2" value="66"/>
                    <measurement group_id="B3" value="32"/>
                    <measurement group_id="B4" value="52"/>
                    <measurement group_id="B5" value="216"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="323"/>
                    <measurement group_id="B2" value="327"/>
                    <measurement group_id="B3" value="121"/>
                    <measurement group_id="B4" value="337"/>
                    <measurement group_id="B5" value="1108"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="160"/>
                    <measurement group_id="B2" value="182"/>
                    <measurement group_id="B3" value="70"/>
                    <measurement group_id="B4" value="179"/>
                    <measurement group_id="B5" value="591"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="10"/>
                    <measurement group_id="B5" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="212"/>
                    <measurement group_id="B2" value="195"/>
                    <measurement group_id="B3" value="75"/>
                    <measurement group_id="B4" value="189"/>
                    <measurement group_id="B5" value="671"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="21"/>
                    <measurement group_id="B5" value="66"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="376"/>
                    <measurement group_id="B2" value="372"/>
                    <measurement group_id="B3" value="142"/>
                    <measurement group_id="B4" value="362"/>
                    <measurement group_id="B5" value="1252"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region group</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Asia (except Japan)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="167"/>
                    <measurement group_id="B2" value="156"/>
                    <measurement group_id="B3" value="60"/>
                    <measurement group_id="B4" value="156"/>
                    <measurement group_id="B5" value="539"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rest of World (includes Japan)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="222"/>
                    <measurement group_id="B2" value="237"/>
                    <measurement group_id="B3" value="93"/>
                    <measurement group_id="B4" value="233"/>
                    <measurement group_id="B5" value="785"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Survival (OS) - Treme 300 mg x1 Dose + Durva 1500 mg vs Sora 400 mg</title>
        <description>OS was defined as the time from the date of randomization until death due to any cause, regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Any participant not known to have died at the DCO date was censored based on the last recorded date on which the participant was known to be alive. If the last known date alive or if the date of death was after the DCO date, participants were censored at the DCO date. This primary outcome measure presents OS analysis of Treme 300mg x1 dose + Durva 1500 mg vs Sora 400 mg at the time of the final analysis DCO (27Aug2021).</description>
        <time_frame>From the date of randomization until death due to any cause, assessed up to the data cut-off date (27Aug2021, to a maximum of approximately 46 months).</time_frame>
        <population>The FAS included all participants who were randomized. T75+D arm was closed during study.</population>
        <group_list>
          <group group_id="O1">
            <title>Durva 1500 mg</title>
            <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
          </group>
          <group group_id="O2">
            <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
            <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O3">
            <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
            <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O4">
            <title>Sora 400 mg</title>
            <description>Sorafenib 400 mg twice daily (BID)</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) - Treme 300 mg x1 Dose + Durva 1500 mg vs Sora 400 mg</title>
          <description>OS was defined as the time from the date of randomization until death due to any cause, regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Any participant not known to have died at the DCO date was censored based on the last recorded date on which the participant was known to be alive. If the last known date alive or if the date of death was after the DCO date, participants were censored at the DCO date. This primary outcome measure presents OS analysis of Treme 300mg x1 dose + Durva 1500 mg vs Sora 400 mg at the time of the final analysis DCO (27Aug2021).</description>
          <population>The FAS included all participants who were randomized. T75+D arm was closed during study.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="389"/>
                <count group_id="O2" value="393"/>
                <count group_id="O3" value="153"/>
                <count group_id="O4" value="389"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.56" lower_limit="14.06" upper_limit="19.12"/>
                    <measurement group_id="O2" value="16.43" lower_limit="14.16" upper_limit="19.58"/>
                    <measurement group_id="O3" value="16.36" lower_limit="12.39" upper_limit="19.65"/>
                    <measurement group_id="O4" value="13.77" lower_limit="12.25" upper_limit="16.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>The analysis was performed using stratified log-rank test adjusting for treatment, etiology of liver disease (HBV versus HCV versus others), ECOG (0 versus 1), and macro-vascular invasion (yes versus no). The values of the stratification factors were obtained from IVRS.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0035</p_value>
            <p_value_desc>The adjusted alpha levels (0.0398) for the two-sided superiority test were derived based upon the exact number of OS events for each comparison using the Lan and DeMets approach that approximates the O'Brien Fleming spending function.</p_value_desc>
            <method>Log Rank</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>The analysis was performed using a Cox proportional hazards model adjusting for treatment, etiology of liver disease (HBV versus HCV versus others), ECOG (0 versus 1), and macro-vascular invasion (yes versus no). Values of the variables used for adjustment were obtained from IVRS.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.78</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.66</ci_lower_limit>
            <ci_upper_limit>0.92</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS) - Durva 1500 mg vs Sora 400 mg</title>
        <description>OS was defined as the time from the date of randomization until death due to any cause, regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Any participant not known to have died at the DCO date was censored based on the last recorded date on which the participant was known to be alive. If the last known date alive or if the date of death was after the DCO date, participants were censored at the DCO date. This secondary outcome measure presents OS analysis of Durva 1500 mg vs Sora 400 mg at the time of the final analysis DCO (27Aug2021).</description>
        <time_frame>From the date of randomization until death due to any cause, assessed up to the data cut-off date (27Aug2021, to a maximum of approximately 46 months).</time_frame>
        <population>The FAS included all participants who were randomized. T75+D arm was closed during study.</population>
        <group_list>
          <group group_id="O1">
            <title>Durva 1500 mg</title>
            <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
          </group>
          <group group_id="O2">
            <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
            <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O3">
            <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
            <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O4">
            <title>Sora 400 mg</title>
            <description>Sorafenib 400 mg twice daily (BID)</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) - Durva 1500 mg vs Sora 400 mg</title>
          <description>OS was defined as the time from the date of randomization until death due to any cause, regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Any participant not known to have died at the DCO date was censored based on the last recorded date on which the participant was known to be alive. If the last known date alive or if the date of death was after the DCO date, participants were censored at the DCO date. This secondary outcome measure presents OS analysis of Durva 1500 mg vs Sora 400 mg at the time of the final analysis DCO (27Aug2021).</description>
          <population>The FAS included all participants who were randomized. T75+D arm was closed during study.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="389"/>
                <count group_id="O2" value="389"/>
                <count group_id="O3" value="153"/>
                <count group_id="O4" value="389"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.56" lower_limit="14.06" upper_limit="19.12"/>
                    <measurement group_id="O2" value="16.43" lower_limit="14.16" upper_limit="19.58"/>
                    <measurement group_id="O3" value="16.36" lower_limit="12.39" upper_limit="19.65"/>
                    <measurement group_id="O4" value="13.77" lower_limit="12.25" upper_limit="16.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>The analysis was performed using a Cox proportional hazards model adjusting for treatment, etiology of liver disease (HBV versus HCV versus others), ECOG (0 versus 1), and macro-vascular invasion (yes versus no). Values of the variables used for adjustment were obtained from IVRS.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Non-interiority for the comparison of arm Durva 1500 mg vs Sora 400 mg is declared if the upper limit of the two-sided alpha adjusted CI for HR is less than the NI margin of 1.08.</non_inferiority_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.86</param_value>
            <ci_percent>95.67</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.73</ci_lower_limit>
            <ci_upper_limit>1.03</ci_upper_limit>
            <estimate_desc>The 95.67% confidence interval were derived based upon the exact number of OS events for each comparison using the Lan and DeMets approach that approximates the O'Brien Fleming spending function.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>The analysis was performed using stratified log-rank test adjusting for treatment, etiology of liver disease (HBV versus HCV versus others), ECOG (0 versus 1), and macro-vascular invasion (yes versus no). The values of the stratification factors were obtained from IVRS.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Superiority was tested sequentially per protocol as non-inferiority was satisfied.</non_inferiority_desc>
            <p_value>0.0674</p_value>
            <p_value_desc>The adjusted alpha levels (0.0433) for the two-sided superiority test were derived based upon the exact number of OS events for each comparison using the Lan and DeMets approach that approximates the O'Brien Fleming spending function.</p_value_desc>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS) at 18, 24, and 36 Months After Randomization</title>
        <description>Percentage of participants who were alive at fixed time points (18, 24, and 36 months) after randomization. The estimated percentage of survival along with the 95% confidence interval were calculated using Kaplan-Meier technique on the full analysis set.</description>
        <time_frame>At 18, 24, and 36 months post-randomization. Assessed at the final analysis DCO (27Aug2021).</time_frame>
        <population>The FAS included all participants who were randomized. T75+D arm was closed during study.</population>
        <group_list>
          <group group_id="O1">
            <title>Durva 1500 mg</title>
            <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
          </group>
          <group group_id="O2">
            <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
            <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O3">
            <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
            <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O4">
            <title>Sora 400 mg</title>
            <description>Sorafenib 400 mg twice daily (BID)</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) at 18, 24, and 36 Months After Randomization</title>
          <description>Percentage of participants who were alive at fixed time points (18, 24, and 36 months) after randomization. The estimated percentage of survival along with the 95% confidence interval were calculated using Kaplan-Meier technique on the full analysis set.</description>
          <population>The FAS included all participants who were randomized. T75+D arm was closed during study.</population>
          <units>percentage of survival</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="389"/>
                <count group_id="O2" value="393"/>
                <count group_id="O3" value="153"/>
                <count group_id="O4" value="389"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Survival rate at 18 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.4" lower_limit="42.4" upper_limit="52.3"/>
                    <measurement group_id="O2" value="48.7" lower_limit="43.6" upper_limit="53.5"/>
                    <measurement group_id="O3" value="46.4" lower_limit="38.4" upper_limit="54.1"/>
                    <measurement group_id="O4" value="41.5" lower_limit="36.5" upper_limit="46.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Survival rate at 24 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.6" lower_limit="34.8" upper_limit="44.5"/>
                    <measurement group_id="O2" value="40.5" lower_limit="35.6" upper_limit="45.3"/>
                    <measurement group_id="O3" value="37.3" lower_limit="29.6" upper_limit="44.9"/>
                    <measurement group_id="O4" value="32.6" lower_limit="27.9" upper_limit="37.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Survival rate at 36 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.7" lower_limit="20.0" upper_limit="29.8"/>
                    <measurement group_id="O2" value="30.7" lower_limit="25.8" upper_limit="35.7"/>
                    <measurement group_id="O3" value="22.9" lower_limit="16.6" upper_limit="29.8"/>
                    <measurement group_id="O4" value="20.2" lower_limit="15.8" upper_limit="25.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS)</title>
        <description>PFS (per Response Evaluation Criteria in Solid Tumors, version 1.1 [RECIST 1.1] using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death by any cause in the absence of progression, regardless of whether the patient withdrew from study treatment or received another anticancer therapy prior to progression. Progression (i.e., PD) was defined as a at least 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) - this includes the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm from nadir.</description>
        <time_frame>Tumor scans performed at baseline, every 8 weeks for the first 48 weeks following randomization, and every 12 weeks thereafter until RECIST 1.1-defined progression. Assessed up to DCO (27Aug2021, to a maximum of approximately 46 months)</time_frame>
        <population>The FAS included all participants who were randomized. T75+D arm was closed during study.</population>
        <group_list>
          <group group_id="O1">
            <title>Durva 1500 mg</title>
            <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
          </group>
          <group group_id="O2">
            <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
            <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O3">
            <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
            <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O4">
            <title>Sora 400 mg</title>
            <description>Sorafenib 400 mg twice daily (BID)</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS)</title>
          <description>PFS (per Response Evaluation Criteria in Solid Tumors, version 1.1 [RECIST 1.1] using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death by any cause in the absence of progression, regardless of whether the patient withdrew from study treatment or received another anticancer therapy prior to progression. Progression (i.e., PD) was defined as a at least 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) - this includes the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm from nadir.</description>
          <population>The FAS included all participants who were randomized. T75+D arm was closed during study.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="389"/>
                <count group_id="O2" value="393"/>
                <count group_id="O3" value="153"/>
                <count group_id="O4" value="389"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.65" lower_limit="3.19" upper_limit="3.75"/>
                    <measurement group_id="O2" value="3.78" lower_limit="3.68" upper_limit="5.32"/>
                    <measurement group_id="O3" value="3.65" lower_limit="2.79" upper_limit="4.86"/>
                    <measurement group_id="O4" value="4.07" lower_limit="3.75" upper_limit="5.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time To Progression (TTP)</title>
        <description>TTP was defined as the time from randomization until objective tumor progression in the absence of death. If participants died without tumor progression, they were censored at the time of death.</description>
        <time_frame>From the date of randomization until objective tumor progression, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).</time_frame>
        <population>The FAS included all participants who were randomized. T75+D arm was closed during study.</population>
        <group_list>
          <group group_id="O1">
            <title>Durva 1500 mg</title>
            <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
          </group>
          <group group_id="O2">
            <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
            <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O3">
            <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
            <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O4">
            <title>Sora 400 mg</title>
            <description>Sorafenib 400 mg twice daily (BID)</description>
          </group>
        </group_list>
        <measure>
          <title>Time To Progression (TTP)</title>
          <description>TTP was defined as the time from randomization until objective tumor progression in the absence of death. If participants died without tumor progression, they were censored at the time of death.</description>
          <population>The FAS included all participants who were randomized. T75+D arm was closed during study.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="389"/>
                <count group_id="O2" value="393"/>
                <count group_id="O3" value="153"/>
                <count group_id="O4" value="389"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.75" lower_limit="3.68" upper_limit="5.42"/>
                    <measurement group_id="O2" value="5.42" lower_limit="3.81" upper_limit="5.62"/>
                    <measurement group_id="O3" value="3.75" lower_limit="3.55" upper_limit="5.59"/>
                    <measurement group_id="O4" value="5.55" lower_limit="5.13" upper_limit="5.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR)</title>
        <description>ORR (per RECIST 1.1 as assessed by the Investigator) was defined as the number (%) of participants with at least 1 confirmed visit response of CR or PR until progression, or the last evaluable assessment in the absence of progression. Participants who go off treatment without progression, receive a subsequent therapy, and then respond will not be included as responders in the ORR. Complete response (ie., CR) was defined as disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to &lt;10 mm. Partial response (ie., PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters.</description>
        <time_frame>From the date of randomization until objective tumor progression, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).</time_frame>
        <population>The FAS included all participants who were randomized. T75+D arm was closed during study.</population>
        <group_list>
          <group group_id="O1">
            <title>Durva 1500 mg</title>
            <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
          </group>
          <group group_id="O2">
            <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
            <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O3">
            <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
            <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O4">
            <title>Sora 400 mg</title>
            <description>Sorafenib 400 mg twice daily (BID)</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR)</title>
          <description>ORR (per RECIST 1.1 as assessed by the Investigator) was defined as the number (%) of participants with at least 1 confirmed visit response of CR or PR until progression, or the last evaluable assessment in the absence of progression. Participants who go off treatment without progression, receive a subsequent therapy, and then respond will not be included as responders in the ORR. Complete response (ie., CR) was defined as disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to &lt;10 mm. Partial response (ie., PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters.</description>
          <population>The FAS included all participants who were randomized. T75+D arm was closed during study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="389"/>
                <count group_id="O2" value="393"/>
                <count group_id="O3" value="153"/>
                <count group_id="O4" value="389"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66"/>
                    <measurement group_id="O2" value="79"/>
                    <measurement group_id="O3" value="26"/>
                    <measurement group_id="O4" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease Control Rate (DCR)</title>
        <description>Number (%) of participants with a Best Objective Response (BoR) of CR, PR, or SD. Complete response (ie., CR) was defined as disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to &lt;10 mm. Partial response (ie., PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters. Stable disease (ie., SD) was defined as neither sufficient decrease in sum of diameters to qualify for PR nor sufficient increase to qualify for progression.</description>
        <time_frame>From the date of randomization until objective tumor progression or date of death, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).</time_frame>
        <population>The FAS included all participants who were randomized. T75+D arm was closed during study.</population>
        <group_list>
          <group group_id="O1">
            <title>Durva 1500 mg</title>
            <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
          </group>
          <group group_id="O2">
            <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
            <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O3">
            <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
            <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O4">
            <title>Sora 400 mg</title>
            <description>Sorafenib 400 mg twice daily (BID)</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Control Rate (DCR)</title>
          <description>Number (%) of participants with a Best Objective Response (BoR) of CR, PR, or SD. Complete response (ie., CR) was defined as disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to &lt;10 mm. Partial response (ie., PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters. Stable disease (ie., SD) was defined as neither sufficient decrease in sum of diameters to qualify for PR nor sufficient increase to qualify for progression.</description>
          <population>The FAS included all participants who were randomized. T75+D arm was closed during study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="389"/>
                <count group_id="O2" value="393"/>
                <count group_id="O3" value="153"/>
                <count group_id="O4" value="389"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="213"/>
                    <measurement group_id="O2" value="236"/>
                    <measurement group_id="O3" value="89"/>
                    <measurement group_id="O4" value="236"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="176"/>
                    <measurement group_id="O2" value="157"/>
                    <measurement group_id="O3" value="64"/>
                    <measurement group_id="O4" value="153"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Objective Response (DoR)</title>
        <description>Time from the date of first documented confirmed response (complete or partial response) until the first date of documented progression or death in the absence of disease progression. Complete response (ie., CR) was defined as disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to &lt;10 mm. Partial response (ie., PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters.</description>
        <time_frame>From the date of first documented response until the first date of documented progression or death, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).</time_frame>
        <population>A subset of FAS subjects who achieve confirmed CR or PR as determined per RECIST 1.1 using Investigator assessment. T75+D arm was closed during study.</population>
        <group_list>
          <group group_id="O1">
            <title>Durva 1500 mg</title>
            <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
          </group>
          <group group_id="O2">
            <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
            <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O3">
            <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
            <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O4">
            <title>Sora 400 mg</title>
            <description>Sorafenib 400 mg twice daily (BID)</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Objective Response (DoR)</title>
          <description>Time from the date of first documented confirmed response (complete or partial response) until the first date of documented progression or death in the absence of disease progression. Complete response (ie., CR) was defined as disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to &lt;10 mm. Partial response (ie., PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters.</description>
          <population>A subset of FAS subjects who achieve confirmed CR or PR as determined per RECIST 1.1 using Investigator assessment. T75+D arm was closed during study.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
                <count group_id="O2" value="79"/>
                <count group_id="O3" value="26"/>
                <count group_id="O4" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Duration of response from onset of response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.82" lower_limit="7.43" upper_limit="NA">Not reached</measurement>
                    <measurement group_id="O2" value="22.34" lower_limit="8.54" upper_limit="NA">Not reached</measurement>
                    <measurement group_id="O3" value="14.75" lower_limit="7.46" upper_limit="14.75"/>
                    <measurement group_id="O4" value="18.43" lower_limit="6.51" upper_limit="25.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Time to onset of response from randomization</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.09" lower_limit="1.87" upper_limit="3.98"/>
                    <measurement group_id="O2" value="2.17" lower_limit="1.84" upper_limit="3.98"/>
                    <measurement group_id="O3" value="2.02" lower_limit="1.87" upper_limit="3.71"/>
                    <measurement group_id="O4" value="3.78" lower_limit="1.89" upper_limit="8.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS) by PD-L1</title>
        <description>Overall survival by baseline PD-L1 expression levels (positive vs. negative). PD-L1 expression level is based on the Tumor and Immune Cell Positivity (TIP) score method as: PD-L1 Positive (TIP ≥ 1%) or PD-L1 Negative (TIP &lt; 1%).</description>
        <time_frame>From the date of randomization until death due to any cause, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).</time_frame>
        <population>A subset of FAS who had non-missing baseline PD-L1 status. T75+D arm was closed during study.</population>
        <group_list>
          <group group_id="O1">
            <title>Durva 1500 mg</title>
            <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
          </group>
          <group group_id="O2">
            <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
            <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O3">
            <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
            <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O4">
            <title>Sora 400 mg</title>
            <description>Sorafenib 400 mg twice daily (BID)</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) by PD-L1</title>
          <description>Overall survival by baseline PD-L1 expression levels (positive vs. negative). PD-L1 expression level is based on the Tumor and Immune Cell Positivity (TIP) score method as: PD-L1 Positive (TIP ≥ 1%) or PD-L1 Negative (TIP &lt; 1%).</description>
          <population>A subset of FAS who had non-missing baseline PD-L1 status. T75+D arm was closed during study.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="344"/>
                <count group_id="O2" value="337"/>
                <count group_id="O3" value="144"/>
                <count group_id="O4" value="329"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>PD-L1 expression positive (TIP&gt;=1%)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="154"/>
                    <count group_id="O2" value="148"/>
                    <count group_id="O3" value="65"/>
                    <count group_id="O4" value="148"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.22" lower_limit="12.29" upper_limit="24.38"/>
                    <measurement group_id="O2" value="17.00" lower_limit="13.11" upper_limit="22.31"/>
                    <measurement group_id="O3" value="24.21" lower_limit="14.55" upper_limit="27.24"/>
                    <measurement group_id="O4" value="15.93" lower_limit="10.68" upper_limit="21.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PD-L1 expression negative (TIP&lt;1%)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="190"/>
                    <count group_id="O2" value="189"/>
                    <count group_id="O3" value="79"/>
                    <count group_id="O4" value="181"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.06" lower_limit="12.68" upper_limit="18.53"/>
                    <measurement group_id="O2" value="14.26" lower_limit="11.50" upper_limit="21.29"/>
                    <measurement group_id="O3" value="14.46" lower_limit="8.97" upper_limit="17.51"/>
                    <measurement group_id="O4" value="13.93" lower_limit="12.39" upper_limit="16.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>EORTC QLQ-C30 Time to Global Health Status/QoL Deterioration</title>
        <description>European Organisation for Research and Treatment of Cancer (EORTC) 30-item core quality of life questionnaire (QLQ-C30), which consists of 30 questions combined to produce a global health status/QoL scale. Higher scores indicate better health. A clinically meaningful deterioration is defined as a decrease in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.</description>
        <time_frame>At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.</time_frame>
        <population>A subset of the FAS who had baseline scores of &gt;=10. T75+D arm was closed during study.</population>
        <group_list>
          <group group_id="O1">
            <title>Durva 1500 mg</title>
            <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
          </group>
          <group group_id="O2">
            <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
            <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O3">
            <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
            <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O4">
            <title>Sora 400 mg</title>
            <description>Sorafenib 400 mg twice daily (BID)</description>
          </group>
        </group_list>
        <measure>
          <title>EORTC QLQ-C30 Time to Global Health Status/QoL Deterioration</title>
          <description>European Organisation for Research and Treatment of Cancer (EORTC) 30-item core quality of life questionnaire (QLQ-C30), which consists of 30 questions combined to produce a global health status/QoL scale. Higher scores indicate better health. A clinically meaningful deterioration is defined as a decrease in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.</description>
          <population>A subset of the FAS who had baseline scores of &gt;=10. T75+D arm was closed during study.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="319"/>
                <count group_id="O2" value="302"/>
                <count group_id="O3" value="132"/>
                <count group_id="O4" value="323"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.4" lower_limit="5.68" upper_limit="9.33"/>
                    <measurement group_id="O2" value="7.5" lower_limit="5.82" upper_limit="10.84"/>
                    <measurement group_id="O3" value="7.3" lower_limit="5.65" upper_limit="9.33"/>
                    <measurement group_id="O4" value="5.7" lower_limit="4.80" upper_limit="7.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>EORTC QLQ-HCC18 Time to Symptom (Abdominal Pain) Deterioration</title>
        <description>EORTC 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) is an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30, which includes 8 symptom scales such as fatigue, jaundice, body image, nutrition, pain, fever, sex life and abdominal swelling. A high score for a symptom scale/item represents a high level of symptomatology/problem. A clinically meaningful deterioration is defined as an increase in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.</description>
        <time_frame>At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.</time_frame>
        <population>A subset of the FAS who have a baseline symptom score &lt;= 90. T75+D arm was closed during study.</population>
        <group_list>
          <group group_id="O1">
            <title>Durva 1500 mg</title>
            <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
          </group>
          <group group_id="O2">
            <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
            <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O3">
            <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
            <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O4">
            <title>Sora 400 mg</title>
            <description>Sorafenib 400 mg twice daily (BID)</description>
          </group>
        </group_list>
        <measure>
          <title>EORTC QLQ-HCC18 Time to Symptom (Abdominal Pain) Deterioration</title>
          <description>EORTC 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) is an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30, which includes 8 symptom scales such as fatigue, jaundice, body image, nutrition, pain, fever, sex life and abdominal swelling. A high score for a symptom scale/item represents a high level of symptomatology/problem. A clinically meaningful deterioration is defined as an increase in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.</description>
          <population>A subset of the FAS who have a baseline symptom score &lt;= 90. T75+D arm was closed during study.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="315"/>
                <count group_id="O2" value="291"/>
                <count group_id="O3" value="127"/>
                <count group_id="O4" value="314"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.1" lower_limit="9.46" upper_limit="24.41"/>
                    <measurement group_id="O2" value="16.8" lower_limit="11.17" upper_limit="NA">Not reached</measurement>
                    <measurement group_id="O3" value="14.7" lower_limit="8.97" upper_limit="36.04"/>
                    <measurement group_id="O4" value="8.9" lower_limit="7.23" upper_limit="11.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>EORTC QLQ-HCC18 Time to Symptom (Shoulder Pain) Deterioration</title>
        <description>EORTC 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) is an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30, which includes 8 symptom scales such as fatigue, jaundice, body image, nutrition, pain, fever, sex life and abdominal swelling. A high score for a symptom scale/item represents a high level of symptomatology/problem. A clinically meaningful deterioration is defined as an increase in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.</description>
        <time_frame>At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.</time_frame>
        <population>A subset of the FAS who have a baseline symptom score &lt;= 90. T75+D arm was closed during study.</population>
        <group_list>
          <group group_id="O1">
            <title>Durva 1500 mg</title>
            <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
          </group>
          <group group_id="O2">
            <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
            <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O3">
            <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
            <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O4">
            <title>Sora 400 mg</title>
            <description>Sorafenib 400 mg twice daily (BID)</description>
          </group>
        </group_list>
        <measure>
          <title>EORTC QLQ-HCC18 Time to Symptom (Shoulder Pain) Deterioration</title>
          <description>EORTC 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) is an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30, which includes 8 symptom scales such as fatigue, jaundice, body image, nutrition, pain, fever, sex life and abdominal swelling. A high score for a symptom scale/item represents a high level of symptomatology/problem. A clinically meaningful deterioration is defined as an increase in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.</description>
          <population>A subset of the FAS who have a baseline symptom score &lt;= 90. T75+D arm was closed during study.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="308"/>
                <count group_id="O2" value="288"/>
                <count group_id="O3" value="127"/>
                <count group_id="O4" value="309"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.0" lower_limit="9.03" upper_limit="22.31"/>
                    <measurement group_id="O2" value="12.6" lower_limit="9.23" upper_limit="19.58"/>
                    <measurement group_id="O3" value="13.8" lower_limit="6.47" upper_limit="19.19"/>
                    <measurement group_id="O4" value="9.4" lower_limit="7.46" upper_limit="13.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>EORTC QLQ-HCC18 Time to Symptom (Abdominal Swelling) Deterioration</title>
        <description>EORTC 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) is an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30, which includes 8 symptom scales such as fatigue, jaundice, body image, nutrition, pain, fever, sex life and abdominal swelling. A high score for a symptom scale/item represents a high level of symptomatology/problem. A clinically meaningful deterioration is defined as an increase in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.</description>
        <time_frame>At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.</time_frame>
        <population>A subset of the FAS who have a baseline symptom score &lt;= 90. T75+D arm was closed during study.</population>
        <group_list>
          <group group_id="O1">
            <title>Durva 1500 mg</title>
            <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
          </group>
          <group group_id="O2">
            <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
            <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O3">
            <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
            <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O4">
            <title>Sora 400 mg</title>
            <description>Sorafenib 400 mg twice daily (BID)</description>
          </group>
        </group_list>
        <measure>
          <title>EORTC QLQ-HCC18 Time to Symptom (Abdominal Swelling) Deterioration</title>
          <description>EORTC 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) is an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30, which includes 8 symptom scales such as fatigue, jaundice, body image, nutrition, pain, fever, sex life and abdominal swelling. A high score for a symptom scale/item represents a high level of symptomatology/problem. A clinically meaningful deterioration is defined as an increase in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.</description>
          <population>A subset of the FAS who have a baseline symptom score &lt;= 90. T75+D arm was closed during study.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="314"/>
                <count group_id="O2" value="290"/>
                <count group_id="O3" value="125"/>
                <count group_id="O4" value="319"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.7" lower_limit="9.46" upper_limit="24.8"/>
                    <measurement group_id="O2" value="20.9" lower_limit="12.88" upper_limit="36.01"/>
                    <measurement group_id="O3" value="11.3" lower_limit="5.78" upper_limit="19.19"/>
                    <measurement group_id="O4" value="11.1" lower_limit="9.26" upper_limit="13.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Presence of ADA for Durvalumab</title>
        <description>Number of participants with Anti-Drug Antibody (ADA) response to Durvalumab. ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA was defined as the sum of treatment-induced ADA and treatment-boosted ADA. Results are reported as number of participants with ADA responses to Durvalumab for each indicated category.</description>
        <time_frame>Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of durvalumab. Assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).</time_frame>
        <population>The Durvalumab ADA evaluable set includes all participants who received at least 1 dose of Durvalumab and had non-missing baseline ADA and at least 1 non-missing post-baseline ADA results for Durvalumab. T75+D arm was closed during study.</population>
        <group_list>
          <group group_id="O1">
            <title>Durva 1500 mg</title>
            <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
          </group>
          <group group_id="O2">
            <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
            <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O3">
            <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
            <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O4">
            <title>Sora 400 mg</title>
            <description>Sorafenib 400 mg twice daily (BID)</description>
          </group>
        </group_list>
        <measure>
          <title>Presence of ADA for Durvalumab</title>
          <description>Number of participants with Anti-Drug Antibody (ADA) response to Durvalumab. ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA was defined as the sum of treatment-induced ADA and treatment-boosted ADA. Results are reported as number of participants with ADA responses to Durvalumab for each indicated category.</description>
          <population>The Durvalumab ADA evaluable set includes all participants who received at least 1 dose of Durvalumab and had non-missing baseline ADA and at least 1 non-missing post-baseline ADA results for Durvalumab. T75+D arm was closed during study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="282"/>
                <count group_id="O2" value="294"/>
                <count group_id="O3" value="108"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Treatment-emergent ADA positive (ADA Incidence)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment-induced ADA (Positive Post-baseline only)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Presence of ADA for Tremelimumab</title>
        <description>Number of participants with Anti-Drug Antibody (ADA) response to Tremelimumab. ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA was defined as the sum of treatment-induced ADA and treatment-boosted ADA. Results are reported as number of participants with ADA responses to Tremelimumab for each indicated category.</description>
        <time_frame>Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of tremelimumab. Assessed up to approximately 46 months after the first randomization.</time_frame>
        <population>The Tremelimumab ADA evaluable set includes all participants who received at least 1 dose of Tremelimumab and had non-missing baseline ADA and at least 1 non-missing post-baseline ADA results for Tremelimumab. T75+D arm was closed during study.</population>
        <group_list>
          <group group_id="O1">
            <title>Durva 1500 mg</title>
            <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
          </group>
          <group group_id="O2">
            <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
            <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O3">
            <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
            <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O4">
            <title>Sora 400 mg</title>
            <description>Sorafenib 400 mg twice daily (BID)</description>
          </group>
        </group_list>
        <measure>
          <title>Presence of ADA for Tremelimumab</title>
          <description>Number of participants with Anti-Drug Antibody (ADA) response to Tremelimumab. ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA was defined as the sum of treatment-induced ADA and treatment-boosted ADA. Results are reported as number of participants with ADA responses to Tremelimumab for each indicated category.</description>
          <population>The Tremelimumab ADA evaluable set includes all participants who received at least 1 dose of Tremelimumab and had non-missing baseline ADA and at least 1 non-missing post-baseline ADA results for Tremelimumab. T75+D arm was closed during study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="182"/>
                <count group_id="O3" value="102"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Treatment-emergent ADA positive (ADA Incidence)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="20"/>
                    <measurement group_id="O3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment-induced ADA (Positive Post-baseline only)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="20"/>
                    <measurement group_id="O3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Summary of Durvalumab Concentration Over Time</title>
        <description>Blood sample were collected at pre-specified timepoints and Durvalumab concentrations in serum (ug/mL) were reported over time.</description>
        <time_frame>To evaluate the PK of Durvalumab, samples were collected pre-dose at week 4 and week 12 and post-dose at week 12. Assessed at the final analysis DCO (27Aug2021).</time_frame>
        <population>PK analysis set includes all participants who received at least 1 dose Durvalumab per the study protocol for whom any PK post-dose data were available (ie, at least 1 non-missing post-dose PK result). T75+D arm was closed during study.</population>
        <group_list>
          <group group_id="O1">
            <title>Durva 1500 mg</title>
            <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
          </group>
          <group group_id="O2">
            <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
            <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O3">
            <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
            <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O4">
            <title>Sora 400 mg</title>
            <description>Sorafenib 400 mg twice daily (BID)</description>
          </group>
        </group_list>
        <measure>
          <title>Summary of Durvalumab Concentration Over Time</title>
          <description>Blood sample were collected at pre-specified timepoints and Durvalumab concentrations in serum (ug/mL) were reported over time.</description>
          <population>PK analysis set includes all participants who received at least 1 dose Durvalumab per the study protocol for whom any PK post-dose data were available (ie, at least 1 non-missing post-dose PK result). T75+D arm was closed during study.</population>
          <units>ug/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="357"/>
                <count group_id="O2" value="388"/>
                <count group_id="O3" value="142"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 2 (Week 4) pre-dose, Geometric mean</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="340"/>
                    <count group_id="O2" value="314"/>
                    <count group_id="O3" value="142"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.7" spread="86.7"/>
                    <measurement group_id="O2" value="59.9" spread="101.6"/>
                    <measurement group_id="O3" value="65.1" spread="68.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4 (Week 12) pre-dose, Geometric mean</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="252"/>
                    <count group_id="O2" value="253"/>
                    <count group_id="O3" value="142"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="113.9" spread="116.2"/>
                    <measurement group_id="O2" value="77.5" spread="280.1"/>
                    <measurement group_id="O3" value="92.1" spread="137.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4 (Week 12) post-dose, Geometric mean</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="255"/>
                    <count group_id="O2" value="248"/>
                    <count group_id="O3" value="142"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="556.9" spread="32.7"/>
                    <measurement group_id="O2" value="539.3" spread="38.6"/>
                    <measurement group_id="O3" value="528.4" spread="36.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Summary of Tremelimumab Concentration Over Time</title>
        <description>Blood sample were collected at pre-specified timepoints and Tremelimumab concentrations in serum (ug/mL) were reported over time.</description>
        <time_frame>To evaluate the PK of Tremelimumab, samples were collected at week 0 (post-dose), week 4, and week 12. Assessed at the final analysis DCO (27Aug2021).</time_frame>
        <population>PK analysis set includes all participants who received at least 1 dose of Tremelimumab per the study protocol for whom any PK post-dose data were available (ie, at least 1 non-missing post-dose PK result). T75+D arm was closed during study.</population>
        <group_list>
          <group group_id="O1">
            <title>Durva 1500 mg</title>
            <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
          </group>
          <group group_id="O2">
            <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
            <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O3">
            <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
            <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
          </group>
          <group group_id="O4">
            <title>Sora 400 mg</title>
            <description>Sorafenib 400 mg twice daily (BID)</description>
          </group>
        </group_list>
        <measure>
          <title>Summary of Tremelimumab Concentration Over Time</title>
          <description>Blood sample were collected at pre-specified timepoints and Tremelimumab concentrations in serum (ug/mL) were reported over time.</description>
          <population>PK analysis set includes all participants who received at least 1 dose of Tremelimumab per the study protocol for whom any PK post-dose data were available (ie, at least 1 non-missing post-dose PK result). T75+D arm was closed during study.</population>
          <units>ug/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="388"/>
                <count group_id="O3" value="142"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 (Week 0) post-dose, Geometric mean</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="379"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="78.0" spread="117.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 (Week 4), Geometric mean</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="221"/>
                    <count group_id="O3" value="132"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="10.7" spread="84.7"/>
                    <measurement group_id="O3" value="3.2" spread="67.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4 (Week 12), Geometric mean</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="113"/>
                    <count group_id="O3" value="86"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="1.3" spread="156.5"/>
                    <measurement group_id="O3" value="4.3" spread="85.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All treatment-emergent adverse events (TEAEs) were collected up to the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).</time_frame>
      <desc>TEAE was defined as any AE that started after dosing or prior to dosing and worsens following treatment exposure. AE was observed up until 90 days following discontinuation of the last dose of study drug, or until the initiation of the first subsequent therapy following discontinuation of treatment. All-cause mortality was reported for all randomized participants. Adverse events were reported for participants who received at least 1 dose of study drug regardless of the randomized assignment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Durva 1500 mg</title>
          <description>Durvalumab 1500 mg every 4 weeks (Q4W)</description>
        </group>
        <group group_id="E2">
          <title>Treme 300 mg x1 Dose + Durva 1500 mg</title>
          <description>Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W</description>
        </group>
        <group group_id="E3">
          <title>Treme 75 mg x4 Doses + Durva 1500 mg</title>
          <description>Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W</description>
        </group>
        <group group_id="E4">
          <title>Sora 400 mg</title>
          <description>Sorafenib 400 mg twice daily (BID)</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="280" subjects_at_risk="389"/>
                <counts group_id="E2" subjects_affected="262" subjects_at_risk="393"/>
                <counts group_id="E3" subjects_affected="123" subjects_at_risk="153"/>
                <counts group_id="E4" subjects_affected="293" subjects_at_risk="389"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="115" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="157" subjects_at_risk="388"/>
                <counts group_id="E3" subjects_affected="52" subjects_at_risk="152"/>
                <counts group_id="E4" subjects_affected="111" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="388"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="152"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pancytopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Coagulopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Ventricular tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Myocarditis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Atrioventricular block</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Cardio-respiratory arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Cardiomyopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Left ventricular dysfunction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Vestibular disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Adrenal insufficiency</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Glucocorticoid deficiency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia of malignancy</sub_title>
                <counts group_id="E1" events="7" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Adrenocorticotropic hormone deficiency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Diplopia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Retinal detachment</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pancreatitis acute</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="152"/>
                <counts group_id="E4" events="6" subjects_affected="6" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Anal haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Autoimmune enteropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Colitis ischaemic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Duodenal obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Duodenal ulcer haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Gastrointestinal ulcer haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Melaena</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Obstructive pancreatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Oesophageal varices haemorrhage</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="152"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="9" subjects_affected="7" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="5" subjects_affected="4" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="388"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="152"/>
                <counts group_id="E4" events="6" subjects_affected="6" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Duodenal ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Enterocolitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Enterocolitis haemorrhagic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Gastric ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Gastric ulcer haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Gastric varices haemorrhage</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Gastritis erosive</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="388"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Haematemesis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Haemoperitoneum</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Intestinal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Lower gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Mesenteric vein thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Portal hypertensive gastropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Small intestinal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="388"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="388"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="152"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Dehiscence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hernia pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Multiple organ dysfunction syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="388"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Drug-induced liver injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hepatorenal syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Immune-mediated hepatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Jaundice</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Autoimmune hepatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Bile duct stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Biliary obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Cholangitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Cholangitis acute</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Cholecystitis acute</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hepatic cirrhosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hepatic failure</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="152"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hepatic function abnormal</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hepatic haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hepatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hepatotoxicity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hyperbilirubinaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Haemophagocytic lymphohistiocytosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Contrast media allergy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Drug hypersensitivity</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Enterocolitis infectious</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hepatitis c</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Meningitis listeria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Necrotising fasciitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Peritonitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pneumocystis jirovecii pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="388"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="152"/>
                <counts group_id="E4" events="8" subjects_affected="8" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Postoperative wound infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection viral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Bacillus bacteraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Biliary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Bone abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Covid-19 pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Candida infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Clostridium difficile colitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Clostridium difficile infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Cytomegalovirus infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Diarrhoea infectious</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Erysipelas</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Escherichia sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Gastroenteritis bacterial</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hepatic infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Infectious pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Liver abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Orchitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Peritonitis bacterial</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Post procedural infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pulmonary tuberculosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Salmonella sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="388"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="388"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Streptococcal sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Suspected covid-19</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Tuberculosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Poisoning</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Radius fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Humerus fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Lumbar vertebral fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Overdose</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Post embolisation syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Procedural complication</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Radiation pneumonitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Spinal fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Tendon rupture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Blood thyroid stimulating hormone decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Liver function test increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>International normalised ratio increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Liver function test abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Cell death</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus inadequate control</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Diabetic metabolic decompensation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Gout</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Type 2 diabetes mellitus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="7" subjects_affected="4" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Diabetic ketoacidosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Malnutrition</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Metabolic acidosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Type 1 diabetes mellitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Chest wall haematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Myositis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Polymyositis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Coccydynia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Immobilisation syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pathological fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Polymyalgia rheumatica</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Oesophageal adenocarcinoma stage 0</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Prostate cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Breast cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Gastric cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Intraductal proliferative breast lesion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Meningioma malignant</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Myeloproliferative neoplasm</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pancreatic carcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of head and neck</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of skin</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Thyroid cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Tumour associated fever</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Tumour haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral haematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Haemorrhage intracranial</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hepatic encephalopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Spinal cord compression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Cerebral haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Facial paralysis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hemiparesis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Myasthenia gravis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Nervous system disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Neuritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Peripheral sensorimotor neuropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Polyneuropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Thalamic infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Completed suicide</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Psychotic disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Tubulointerstitial nephritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Ureterolithiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Autoimmune nephritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Chronic kidney disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Immune-mediated nephritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory distress syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Bronchitis chronic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Interstitial lung disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pulmonary thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="388"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Dermatitis atopic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Diabetic wound</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Drug eruption</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Stevens-johnson syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Dermatitis bullous</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Erythema multiforme</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Skin ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Bleeding varicose vein</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hypovolaemic shock</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Internal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Peripheral ischaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Phlebitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Shock haemorrhagic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Thrombophlebitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 23.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="299" subjects_at_risk="388"/>
                <counts group_id="E2" subjects_affected="334" subjects_at_risk="388"/>
                <counts group_id="E3" subjects_affected="133" subjects_at_risk="152"/>
                <counts group_id="E4" subjects_affected="333" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="29" subjects_affected="28" subjects_at_risk="388"/>
                <counts group_id="E2" events="39" subjects_affected="32" subjects_at_risk="388"/>
                <counts group_id="E3" events="15" subjects_affected="13" subjects_at_risk="152"/>
                <counts group_id="E4" events="32" subjects_affected="31" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="18" subjects_affected="15" subjects_at_risk="388"/>
                <counts group_id="E2" events="20" subjects_affected="15" subjects_at_risk="388"/>
                <counts group_id="E3" events="14" subjects_affected="10" subjects_at_risk="152"/>
                <counts group_id="E4" events="26" subjects_affected="22" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="388"/>
                <counts group_id="E2" events="31" subjects_affected="30" subjects_at_risk="388"/>
                <counts group_id="E3" events="10" subjects_affected="9" subjects_at_risk="152"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="20" subjects_affected="19" subjects_at_risk="388"/>
                <counts group_id="E2" events="47" subjects_affected="47" subjects_at_risk="388"/>
                <counts group_id="E3" events="20" subjects_affected="19" subjects_at_risk="152"/>
                <counts group_id="E4" events="16" subjects_affected="16" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="24" subjects_affected="21" subjects_at_risk="388"/>
                <counts group_id="E2" events="35" subjects_affected="29" subjects_at_risk="388"/>
                <counts group_id="E3" events="9" subjects_affected="6" subjects_at_risk="152"/>
                <counts group_id="E4" events="18" subjects_affected="18" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="48" subjects_affected="42" subjects_at_risk="388"/>
                <counts group_id="E2" events="45" subjects_affected="36" subjects_at_risk="388"/>
                <counts group_id="E3" events="13" subjects_affected="12" subjects_at_risk="152"/>
                <counts group_id="E4" events="36" subjects_affected="34" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="67" subjects_affected="57" subjects_at_risk="388"/>
                <counts group_id="E2" events="125" subjects_affected="97" subjects_at_risk="388"/>
                <counts group_id="E3" events="39" subjects_affected="28" subjects_at_risk="152"/>
                <counts group_id="E4" events="241" subjects_affected="164" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="17" subjects_affected="15" subjects_at_risk="388"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="388"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="152"/>
                <counts group_id="E4" events="20" subjects_affected="20" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="21" subjects_affected="18" subjects_at_risk="388"/>
                <counts group_id="E2" events="28" subjects_affected="24" subjects_at_risk="388"/>
                <counts group_id="E3" events="10" subjects_affected="8" subjects_at_risk="152"/>
                <counts group_id="E4" events="37" subjects_affected="34" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="36" subjects_affected="35" subjects_at_risk="388"/>
                <counts group_id="E2" events="46" subjects_affected="44" subjects_at_risk="388"/>
                <counts group_id="E3" events="26" subjects_affected="24" subjects_at_risk="152"/>
                <counts group_id="E4" events="72" subjects_affected="59" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="26" subjects_affected="24" subjects_at_risk="388"/>
                <counts group_id="E2" events="24" subjects_affected="22" subjects_at_risk="388"/>
                <counts group_id="E3" events="8" subjects_affected="8" subjects_at_risk="152"/>
                <counts group_id="E4" events="21" subjects_affected="20" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="41" subjects_affected="37" subjects_at_risk="388"/>
                <counts group_id="E2" events="53" subjects_affected="46" subjects_at_risk="388"/>
                <counts group_id="E3" events="13" subjects_affected="13" subjects_at_risk="152"/>
                <counts group_id="E4" events="61" subjects_affected="52" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="388"/>
                <counts group_id="E2" events="11" subjects_affected="9" subjects_at_risk="388"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E4" events="36" subjects_affected="29" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="63" subjects_affected="48" subjects_at_risk="388"/>
                <counts group_id="E2" events="46" subjects_affected="39" subjects_at_risk="388"/>
                <counts group_id="E3" events="22" subjects_affected="20" subjects_at_risk="152"/>
                <counts group_id="E4" events="49" subjects_affected="44" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="49" subjects_affected="37" subjects_at_risk="388"/>
                <counts group_id="E2" events="71" subjects_affected="65" subjects_at_risk="388"/>
                <counts group_id="E3" events="31" subjects_affected="25" subjects_at_risk="152"/>
                <counts group_id="E4" events="75" subjects_affected="70" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="25" subjects_affected="24" subjects_at_risk="388"/>
                <counts group_id="E2" events="34" subjects_affected="32" subjects_at_risk="388"/>
                <counts group_id="E3" events="18" subjects_affected="16" subjects_at_risk="152"/>
                <counts group_id="E4" events="21" subjects_affected="19" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="38" subjects_affected="31" subjects_at_risk="388"/>
                <counts group_id="E2" events="62" subjects_affected="48" subjects_at_risk="388"/>
                <counts group_id="E3" events="18" subjects_affected="16" subjects_at_risk="152"/>
                <counts group_id="E4" events="34" subjects_affected="32" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="49" subjects_affected="42" subjects_at_risk="388"/>
                <counts group_id="E2" events="45" subjects_affected="35" subjects_at_risk="388"/>
                <counts group_id="E3" events="9" subjects_affected="9" subjects_at_risk="152"/>
                <counts group_id="E4" events="26" subjects_affected="20" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" events="11" subjects_affected="9" subjects_at_risk="388"/>
                <counts group_id="E2" events="38" subjects_affected="28" subjects_at_risk="388"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="152"/>
                <counts group_id="E4" events="17" subjects_affected="10" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="63" subjects_affected="54" subjects_at_risk="388"/>
                <counts group_id="E2" events="53" subjects_affected="46" subjects_at_risk="388"/>
                <counts group_id="E3" events="17" subjects_affected="16" subjects_at_risk="152"/>
                <counts group_id="E4" events="33" subjects_affected="24" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="30" subjects_affected="23" subjects_at_risk="388"/>
                <counts group_id="E2" events="23" subjects_affected="19" subjects_at_risk="388"/>
                <counts group_id="E3" events="5" subjects_affected="4" subjects_at_risk="152"/>
                <counts group_id="E4" events="32" subjects_affected="29" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" events="12" subjects_affected="12" subjects_at_risk="388"/>
                <counts group_id="E2" events="18" subjects_affected="18" subjects_at_risk="388"/>
                <counts group_id="E3" events="7" subjects_affected="7" subjects_at_risk="152"/>
                <counts group_id="E4" events="24" subjects_affected="19" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="27" subjects_affected="23" subjects_at_risk="388"/>
                <counts group_id="E2" events="38" subjects_affected="32" subjects_at_risk="388"/>
                <counts group_id="E3" events="10" subjects_affected="8" subjects_at_risk="152"/>
                <counts group_id="E4" events="17" subjects_affected="15" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="12" subjects_affected="11" subjects_at_risk="388"/>
                <counts group_id="E2" events="28" subjects_affected="28" subjects_at_risk="388"/>
                <counts group_id="E3" events="8" subjects_affected="8" subjects_at_risk="152"/>
                <counts group_id="E4" events="37" subjects_affected="36" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="58" subjects_affected="53" subjects_at_risk="388"/>
                <counts group_id="E2" events="69" subjects_affected="65" subjects_at_risk="388"/>
                <counts group_id="E3" events="24" subjects_affected="24" subjects_at_risk="152"/>
                <counts group_id="E4" events="72" subjects_affected="67" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="35" subjects_affected="32" subjects_at_risk="388"/>
                <counts group_id="E2" events="35" subjects_affected="28" subjects_at_risk="388"/>
                <counts group_id="E3" events="11" subjects_affected="10" subjects_at_risk="152"/>
                <counts group_id="E4" events="13" subjects_affected="13" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="388"/>
                <counts group_id="E2" events="11" subjects_affected="10" subjects_at_risk="388"/>
                <counts group_id="E3" events="12" subjects_affected="10" subjects_at_risk="152"/>
                <counts group_id="E4" events="14" subjects_affected="12" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="46" subjects_affected="37" subjects_at_risk="388"/>
                <counts group_id="E2" events="38" subjects_affected="35" subjects_at_risk="388"/>
                <counts group_id="E3" events="12" subjects_affected="11" subjects_at_risk="152"/>
                <counts group_id="E4" events="21" subjects_affected="21" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="21" subjects_affected="21" subjects_at_risk="388"/>
                <counts group_id="E2" events="44" subjects_affected="40" subjects_at_risk="388"/>
                <counts group_id="E3" events="10" subjects_affected="10" subjects_at_risk="152"/>
                <counts group_id="E4" events="16" subjects_affected="16" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="34" subjects_affected="31" subjects_at_risk="388"/>
                <counts group_id="E2" events="31" subjects_affected="30" subjects_at_risk="388"/>
                <counts group_id="E3" events="19" subjects_affected="16" subjects_at_risk="152"/>
                <counts group_id="E4" events="22" subjects_affected="22" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="388"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="152"/>
                <counts group_id="E4" events="26" subjects_affected="26" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="14" subjects_affected="13" subjects_at_risk="388"/>
                <counts group_id="E2" events="24" subjects_affected="23" subjects_at_risk="388"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="152"/>
                <counts group_id="E4" events="15" subjects_affected="14" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="388"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="388"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E4" events="54" subjects_affected="53" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="388"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="388"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="152"/>
                <counts group_id="E4" events="197" subjects_affected="173" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="61" subjects_affected="56" subjects_at_risk="388"/>
                <counts group_id="E2" events="106" subjects_affected="89" subjects_at_risk="388"/>
                <counts group_id="E3" events="34" subjects_affected="27" subjects_at_risk="152"/>
                <counts group_id="E4" events="25" subjects_affected="24" subjects_at_risk="374"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="51" subjects_affected="39" subjects_at_risk="388"/>
                <counts group_id="E2" events="101" subjects_affected="84" subjects_at_risk="388"/>
                <counts group_id="E3" events="32" subjects_affected="27" subjects_at_risk="152"/>
                <counts group_id="E4" events="54" subjects_affected="50" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="18" subjects_affected="17" subjects_at_risk="388"/>
                <counts group_id="E2" events="26" subjects_affected="22" subjects_at_risk="388"/>
                <counts group_id="E3" events="10" subjects_affected="6" subjects_at_risk="152"/>
                <counts group_id="E4" events="79" subjects_affected="68" subjects_at_risk="374"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Investigator agrees not to independently publish the results of the Study until first occurrence of one of the following: (i) multi-centre primary Publication is published; (ii) no multi-centre primary publication is submitted within two years after conclusion, abandonment, or termination of the Study at all sites; or (iii) Sponsor confirms in writing there will be no multi-centre primary Publication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Global Clinical Lead</name_or_title>
      <organization>AstraZeneca Clinical Study Information Center</organization>
      <phone>1 8772409479</phone>
      <email>information.center@astrazeneca.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03298451
org study id: D419CC00002
secondary id: 2016-005126-11
nct id: NCT03298451
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a randomized, open-label, multi-center, global, Phase III study to assess the
      efficacy and safety of durvalumab plus tremelimumab combination therapy and durvalumab
      monotherapy versus sorafenib in the treatment of patients with no prior systemic therapy for
      unresectable HCC. The patients cannot be eligible for locoregional therapy
The study population includes patients 18 years of age or older with advanced HCC, Barcelona
      Clinic Liver Cancer stage B not eligible for locoregional therapy or stage C, and Child-Pugh
      A classification liver disease. Patients must not have received any prior systemic therapy
      for unresectable HCC.

      Patients in all treatment arms may continue receiving their originally assigned treatment, at
      the Investigator's discretion, until progression

      Patients in all arms with confirmed PD who, in the Investigator's opinion, continue to
      receive benefit from their assigned treatment and meet the criteria for treatment in the
      setting of PD may continue to receive their assigned treatment.

      If a patient discontinues study drug(s) due to disease progression, the patient will enter
      survival follow-up. Patients who have discontinued treatment due to toxicity or symptomatic
      deterioration or who have commenced subsequent anticancer therapy, will have tumor
      assessments until confirmed PD and will be followed for survival
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Survival (OS) - Treme 300 mg x1 Dose + Durva 1500 mg vs Sora 400 mg
time frame: From the date of randomization until death due to any cause, assessed up to the data cut-off date (27Aug2021, to a maximum of approximately 46 months).
description: OS was defined as the time from the date of randomization until death due to any cause, regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Any participant not known to have died at the DCO date was censored based on the last recorded date on which the participant was known to be alive. If the last known date alive or if the date of death was after the DCO date, participants were censored at the DCO date. This primary outcome measure presents OS analysis of Treme 300mg x1 dose + Durva 1500 mg vs Sora 400 mg at the time of the final analysis DCO (27Aug2021).
measure: Overall Survival (OS) - Durva 1500 mg vs Sora 400 mg
time frame: From the date of randomization until death due to any cause, assessed up to the data cut-off date (27Aug2021, to a maximum of approximately 46 months).
description: OS was defined as the time from the date of randomization until death due to any cause, regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Any participant not known to have died at the DCO date was censored based on the last recorded date on which the participant was known to be alive. If the last known date alive or if the date of death was after the DCO date, participants were censored at the DCO date. This secondary outcome measure presents OS analysis of Durva 1500 mg vs Sora 400 mg at the time of the final analysis DCO (27Aug2021).
measure: Overall Survival (OS) at 18, 24, and 36 Months After Randomization
time frame: At 18, 24, and 36 months post-randomization. Assessed at the final analysis DCO (27Aug2021).
description: Percentage of participants who were alive at fixed time points (18, 24, and 36 months) after randomization. The estimated percentage of survival along with the 95% confidence interval were calculated using Kaplan-Meier technique on the full analysis set.
measure: Progression Free Survival (PFS)
time frame: Tumor scans performed at baseline, every 8 weeks for the first 48 weeks following randomization, and every 12 weeks thereafter until RECIST 1.1-defined progression. Assessed up to DCO (27Aug2021, to a maximum of approximately 46 months)
description: PFS (per Response Evaluation Criteria in Solid Tumors, version 1.1 [RECIST 1.1] using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death by any cause in the absence of progression, regardless of whether the patient withdrew from study treatment or received another anticancer therapy prior to progression. Progression (i.e., PD) was defined as a at least 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) - this includes the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm from nadir.
measure: Time To Progression (TTP)
time frame: From the date of randomization until objective tumor progression, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
description: TTP was defined as the time from randomization until objective tumor progression in the absence of death. If participants died without tumor progression, they were censored at the time of death.
measure: Objective Response Rate (ORR)
time frame: From the date of randomization until objective tumor progression, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
description: ORR (per RECIST 1.1 as assessed by the Investigator) was defined as the number (%) of participants with at least 1 confirmed visit response of CR or PR until progression, or the last evaluable assessment in the absence of progression. Participants who go off treatment without progression, receive a subsequent therapy, and then respond will not be included as responders in the ORR. Complete response (ie., CR) was defined as disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to <10 mm. Partial response (ie., PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters.
measure: Disease Control Rate (DCR)
time frame: From the date of randomization until objective tumor progression or date of death, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
description: Number (%) of participants with a Best Objective Response (BoR) of CR, PR, or SD. Complete response (ie., CR) was defined as disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to <10 mm. Partial response (ie., PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters. Stable disease (ie., SD) was defined as neither sufficient decrease in sum of diameters to qualify for PR nor sufficient increase to qualify for progression.
measure: Duration of Objective Response (DoR)
time frame: From the date of first documented response until the first date of documented progression or death, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
description: Time from the date of first documented confirmed response (complete or partial response) until the first date of documented progression or death in the absence of disease progression. Complete response (ie., CR) was defined as disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to <10 mm. Partial response (ie., PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters.
measure: Overall Survival (OS) by PD-L1
time frame: From the date of randomization until death due to any cause, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
description: Overall survival by baseline PD-L1 expression levels (positive vs. negative). PD-L1 expression level is based on the Tumor and Immune Cell Positivity (TIP) score method as: PD-L1 Positive (TIP ≥ 1%) or PD-L1 Negative (TIP < 1%).
measure: EORTC QLQ-C30 Time to Global Health Status/QoL Deterioration
time frame: At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.
description: European Organisation for Research and Treatment of Cancer (EORTC) 30-item core quality of life questionnaire (QLQ-C30), which consists of 30 questions combined to produce a global health status/QoL scale. Higher scores indicate better health. A clinically meaningful deterioration is defined as a decrease in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.
measure: EORTC QLQ-HCC18 Time to Symptom (Abdominal Pain) Deterioration
time frame: At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.
description: EORTC 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) is an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30, which includes 8 symptom scales such as fatigue, jaundice, body image, nutrition, pain, fever, sex life and abdominal swelling. A high score for a symptom scale/item represents a high level of symptomatology/problem. A clinically meaningful deterioration is defined as an increase in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.
measure: EORTC QLQ-HCC18 Time to Symptom (Shoulder Pain) Deterioration
time frame: At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.
description: EORTC 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) is an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30, which includes 8 symptom scales such as fatigue, jaundice, body image, nutrition, pain, fever, sex life and abdominal swelling. A high score for a symptom scale/item represents a high level of symptomatology/problem. A clinically meaningful deterioration is defined as an increase in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.
measure: EORTC QLQ-HCC18 Time to Symptom (Abdominal Swelling) Deterioration
time frame: At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.
description: EORTC 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) is an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30, which includes 8 symptom scales such as fatigue, jaundice, body image, nutrition, pain, fever, sex life and abdominal swelling. A high score for a symptom scale/item represents a high level of symptomatology/problem. A clinically meaningful deterioration is defined as an increase in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.
measure: Presence of ADA for Durvalumab
time frame: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of durvalumab. Assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
description: Number of participants with Anti-Drug Antibody (ADA) response to Durvalumab. ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA was defined as the sum of treatment-induced ADA and treatment-boosted ADA. Results are reported as number of participants with ADA responses to Durvalumab for each indicated category.
measure: Presence of ADA for Tremelimumab
time frame: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of tremelimumab. Assessed up to approximately 46 months after the first randomization.
description: Number of participants with Anti-Drug Antibody (ADA) response to Tremelimumab. ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA was defined as the sum of treatment-induced ADA and treatment-boosted ADA. Results are reported as number of participants with ADA responses to Tremelimumab for each indicated category.
measure: Summary of Durvalumab Concentration Over Time
time frame: To evaluate the PK of Durvalumab, samples were collected pre-dose at week 4 and week 12 and post-dose at week 12. Assessed at the final analysis DCO (27Aug2021).
description: Blood sample were collected at pre-specified timepoints and Durvalumab concentrations in serum (ug/mL) were reported over time.
measure: Summary of Tremelimumab Concentration Over Time
time frame: To evaluate the PK of Tremelimumab, samples were collected at week 0 (post-dose), week 4, and week 12. Assessed at the final analysis DCO (27Aug2021).
description: Blood sample were collected at pre-specified timepoints and Tremelimumab concentrations in serum (ug/mL) were reported over time.
arm group label: Arm 1
arm group type: Experimental
description: Durvalumab
arm group label: Arm 2
arm group type: Experimental
description: Durvalumab in combination with tremelimumab (Regimen 1)
arm group label: Arm 3
arm group type: Experimental
description: Durvalumab in combination with tremelimumab (Regimen 2)
arm group label: Arm 4
arm group type: Active Comparator
description: Sorafenib
intervention type: Drug
intervention name: Durvalumab
description: Durvalumab IV (intravenous infusion).
arm group label: Arm 1
other name: MEDI4736
intervention type: Drug
intervention name: Tremelimumab (Regimen 1)
description: Tremelimumab IV (intravenous infusion).
arm group label: Arm 2
intervention type: Drug
intervention name: Tremelimumab (Regimen 2)
description: Tremelimumab IV (intravenous infusion).
arm group label: Arm 3
intervention type: Drug
intervention name: Sorafenib
description: Sorafenib, as per standard of care
arm group label: Arm 4
intervention type: Drug
intervention name: Durvalumab (Regimen 1)
description: Durvalumab IV (intravenous infusion).
arm group label: Arm 2
intervention type: Drug
intervention name: Durvalumab (Regimen 2)
description: Durvalumab IV (intravenous infusion).
arm group label: Arm 3
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
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country: Brazil
country: Canada
country: China
country: France
country: Germany
country: Hong Kong
country: India
country: Italy
country: Japan
country: Korea, Republic of
country: Russian Federation
country: Spain
country: Taiwan
country: Thailand
country: Ukraine
country: United States
country: Vietnam
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description: CSP_redacted
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description: SAP_redacted
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description: CSR_synopsis
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Sorafenib
mesh term: Durvalumab
mesh term: Tremelimumab
mesh term: Antibodies, Monoclonal
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 