<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/NCT03040999</url>
  </required_header>
  <id_info>
    <org_study_id>3475-412</org_study_id>
    <secondary_id>MK-3475-412</secondary_id>
    <secondary_id>173640</secondary_id>
    <secondary_id>KEYNOTE-412</secondary_id>
    <secondary_id>2016-003934-25</secondary_id>
    <nct_id>NCT03040999</nct_id>
  </id_info>
  <brief_title>Study of Pembrolizumab (MK-3475) or Placebo With Chemoradiation in Participants With Locally Advanced Head and Neck Squamous Cell Carcinoma (MK-3475-412/KEYNOTE-412)</brief_title>
  <official_title>A Randomized Phase III Study of Pembrolizumab Given Concomitantly With Chemoradiation and as Maintenance Therapy Versus Chemoradiation Alone in Subjects With Locally Advanced Head and Neck Squamous Cell Carcinoma (KEYNOTE-412)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck Sharp &amp; Dohme LLC</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>
      The purpose of this study is to determine the efficacy and safety of pembrolizumab given&#xD;
      concomitantly with chemoradiation (CRT) and as maintenance therapy versus placebo plus CRT in&#xD;
      participants with locally advanced head and neck squamous cell carcinoma (LA HNSCC). The&#xD;
      primary hypothesis is that pembrolizumab in combination with CRT is superior to placebo in&#xD;
      combination with CRT with respect to event-free survival (EFS).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 5, 2017</start_date>
  <completion_date type="Anticipated">June 29, 2024</completion_date>
  <primary_completion_date type="Actual">May 31, 2022</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Event-free Survival (EFS)</measure>
    <time_frame>Up to approximately 62 months</time_frame>
    <description>EFS is the time from date of randomization to the date of first record of any of the following events: death due to any cause; progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR) or biopsy as indicated for locoregional progression or recurrence or distant metastasis. As well as the first record of the following types of surgery: salvage surgery for persistent or residual disease at the primary tumor site requiring surgical removal when invasive cancer is present on final pathology; neck dissection or surgery (performed for clinical or radiological disease progression per RECIST 1.1) ≤ 20 weeks from end of CRT when invasive cancer is present; or neck dissection or surgery &gt;20 weeks from end of CRT when invasive cancer is present. From product-limit (Kaplan-Meier) method for censored data.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to approximately 62 months</time_frame>
    <description>OS is the time from randomization to death due to any cause, from product-limit (Kaplan-Meier) method for censored data. The hypothesis was that pembrolizumab in combination with CRT is superior to placebo in combination with CRT; but based on the protocol, because the statistical criterion for success in the primary EFS hypothesis was not met, the OS hypothesis was not tested</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events (AEs)</measure>
    <time_frame>From time of first dose of study treatment until 90 days after last dose (up to approximately 19 months)</time_frame>
    <description>An AE is any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE is any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Discontinuing Study Drug Due to an AE</measure>
    <time_frame>From time of first dose of study treatment until the end of treatment (up to approximately 16 months)</time_frame>
    <description>An AE is any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE is any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Global Health Status/Quality of Life (GHS/QoL)</measure>
    <time_frame>Prior to the first dose of study treatment (Baseline) and up to Week 45</time_frame>
    <description>The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) contains 30 items and measures five functional dimensions (physical, role, emotional, cognitive and social), three symptom items (fatigue, nausea/vomiting, and pain), six single items (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and QoL scale. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, so that a higher score indicates a better overall GHS. A change from baseline of 10 points on the 100-point EORTC QLQ-C30 scale is considered as clinically relevant. Based on a constrained longitudinal data analysis (cLDA) model with the patient reported outcomes (PRO) scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of human papilloma virus (HPV) status and overall cancer stage.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Swallowing, Speech, and Pain Symptoms</measure>
    <time_frame>Prior to the first dose of study treatment (Baseline) and up to Week 45</time_frame>
    <description>EORTC QLQ Head and Neck Questionnaire (H&amp;N35) consists of 7 multi-item scales (pain in the mouth, problems with swallowing, senses, speech, social eating, social contact, and sexuality), Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Change from baseline in swallowing, speech, and pain symptoms was measured. A change from baseline of 10 points on the 100-point EORTC QLQ-H&amp;N35 is considered as clinically relevant. Based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Physical Functioning</measure>
    <time_frame>Prior to the first dose of study treatment (Baseline) and up to Week 45</time_frame>
    <description>Participant responded to 5 questions from the EORTC QLQ-C30 about their physical functioning scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100, where a higher score indicates a better quality of life. A change from baseline of 10 points on the 100-point scale is considered as clinically relevant. Based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">804</enrollment>
  <condition>Head and Neck Neoplasms</condition>
  <arm_group>
    <arm_group_label>Pembrolizumab + Cisplatin + CRT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive a priming dose of pembrolizumab before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with pembrolizumab.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo + Cisplatin + CRT</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants receive placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Administered as an intravenous (IV) infusion every 3 weeks (Q3W)</description>
    <arm_group_label>Pembrolizumab + Cisplatin + CRT</arm_group_label>
    <other_name>KEYTRUDA®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Normal saline or dextrose solution administered as an IV infusion Q3W</description>
    <arm_group_label>Placebo + Cisplatin + CRT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>100 mg/m^2 administered as an IV infusion Q3W</description>
    <arm_group_label>Pembrolizumab + Cisplatin + CRT</arm_group_label>
    <arm_group_label>Placebo + Cisplatin + CRT</arm_group_label>
    <other_name>Platinol®</other_name>
    <other_name>Platinol®-AQ</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Accelerated Fractionation (AFX) Radiotherapy</intervention_name>
    <description>70 Gray (Gy) given in 35 fractions over 6 weeks</description>
    <arm_group_label>Pembrolizumab + Cisplatin + CRT</arm_group_label>
    <arm_group_label>Placebo + Cisplatin + CRT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Standard Fractionation (SFX) Radiotherapy</intervention_name>
    <description>70 Gy given in 35 fractions over 7 weeks</description>
    <arm_group_label>Pembrolizumab + Cisplatin + CRT</arm_group_label>
    <arm_group_label>Placebo + Cisplatin + CRT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Has a pathologically proven new diagnosis of oropharyngeal p16 positive, oropharyngeal&#xD;
             p16 negative, or larynx/hypopharynx/oral cavity (independent of p16) squamous cell&#xD;
             carcinoma. Participants with oral cavity tumors need to have unresectable disease.&#xD;
             Participants with multiple synchronous tumors are not eligible for the study.&#xD;
&#xD;
          -  Has provided tissue for Programmed Cell Death Receptor Ligand 1 (PD-L1) biomarker&#xD;
             analysis from a core or excisional biopsy. If an excisional or incisional biopsy has&#xD;
             been performed, participants remain eligible for the study provided the residual&#xD;
             disease meets the staging criteria required for the trial (e.g., excisional biopsy of&#xD;
             a lymph node with residual T4 primary). Prior surgical debulking, including&#xD;
             tonsillectomy, for the head and neck cancer under study is not allowed.&#xD;
&#xD;
          -  Has evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed&#xD;
             by computed tomography scan or magnetic resonance imaging, based on RECIST version 1.1&#xD;
&#xD;
          -  Is eligible for definitive CRT and not considered for primary surgery based on&#xD;
             investigator decision&#xD;
&#xD;
          -  Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed&#xD;
             within 10 days prior to receiving the first dose of study therapy&#xD;
&#xD;
          -  Female participants of childbearing potential must have a negative urine or serum&#xD;
             pregnancy test within 72 hours prior to receiving the first dose of study therapy&#xD;
&#xD;
          -  Female and male participants of reproductive potential must agree to use adequate&#xD;
             contraception throughout the study period and for up to 180 days after the last dose&#xD;
             of study therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Is currently participating or has participated in a study with an investigational&#xD;
             agent or using an investigational device within 4 weeks of the first dose of study&#xD;
             therapy&#xD;
&#xD;
          -  Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1),&#xD;
             anti-PD-L1, anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an&#xD;
             agent directed to another co-inhibitory T-cell receptor or has previously participated&#xD;
             in clinical studies with pembrolizumab&#xD;
&#xD;
          -  Has received a live vaccine within 30 days prior to the first dose of study therapy&#xD;
&#xD;
          -  Has cancer outside of the oropharynx, larynx, and hypopharynx or oral cavity, such as&#xD;
             nasopharyngeal, sinus, other para-nasal, or other unknown primary head and neck cancer&#xD;
&#xD;
          -  Has had prior systemic therapy, targeted therapy, radiotherapy treatment or radical&#xD;
             surgery for head and neck cancer under study&#xD;
&#xD;
          -  Has not recovered from major surgery prior to starting study therapy&#xD;
&#xD;
          -  Has known active Hepatitis B or C&#xD;
&#xD;
          -  Has known history of Human Immunodeficiency Virus (HIV)&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any&#xD;
             other form of immunosuppressive therapy within 7 days prior to the first dose of study&#xD;
             therapy&#xD;
&#xD;
          -  Has a history of (non-infectious) pneumonitis that required steroids or current&#xD;
             pneumonitis&#xD;
&#xD;
          -  Has an active autoimmune disease that has required systemic treatment in the past 2&#xD;
             years. Replacement therapy is not considered a form of systemic treatment.&#xD;
&#xD;
          -  Has history of a diagnosed and/or treated hematologic or primary solid tumor&#xD;
             malignancy, unless in remission for at least 5 years prior to randomization&#xD;
&#xD;
          -  Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis&#xD;
&#xD;
          -  Has had previous allogeneic tissue/solid organ transplant&#xD;
&#xD;
          -  Has active infection requiring systemic therapy&#xD;
&#xD;
          -  Has a history of severe hypersensitivity reaction to pembrolizumab, Cisplatin or&#xD;
             radiotherapy or their analogs&#xD;
&#xD;
          -  Is pregnant or breast feeding or expecting to conceive or father children throughout&#xD;
             the study period and for up to 180 days after the last dose of study therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCLA Medical Center ( Site 0273)</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Francisco ( Site 0274)</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Joseph Heritage Healthcare ( Site 0254)</name>
      <address>
        <city>Santa Rosa</city>
        <state>California</state>
        <zip>95403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Smilow Cancer Hospital at Yale New Haven ( Site 0256)</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center ( Site 0260)</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University ( Site 0264)</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mary Bird Perkins Cancer Center at St. Tammany Parish Hospital ( Site 0281)</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70809</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Massachusetts Memorial Medical Center ( Site 0285)</name>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01655</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Hospital and Health Systems ( Site 0267)</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barbara Ann Karmanos Cancer Institute ( Site 0272)</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Clinic Cancer and Hematology - Chub O'Reilly Cancer Center ( Site 0290)</name>
      <address>
        <city>Springfield</city>
        <state>Missouri</state>
        <zip>65804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincent Healthcare Frontier Cancer Center ( Site 0286)</name>
      <address>
        <city>Billings</city>
        <state>Montana</state>
        <zip>59102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada ( Site 8004)</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester - James P. Wilmot Cancer Center ( Site 0255)</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Hematology Care, Inc. ( Site 8003)</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Willamette Valley Cancer Institute and Research Center ( Site 8000)</name>
      <address>
        <city>Eugene</city>
        <state>Oregon</state>
        <zip>97401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Luke's Cancer Center - Anderson ( Site 0251)</name>
      <address>
        <city>Easton</city>
        <state>Pennsylvania</state>
        <zip>18045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Francis Hospital Cancer Center ( Site 1461)</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-Arlington North ( Site 8005)</name>
      <address>
        <city>Arlington</city>
        <state>Texas</state>
        <zip>76014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-Austin Central ( Site 8002)</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology PA ( Site 8001)</name>
      <address>
        <city>Longview</city>
        <state>Texas</state>
        <zip>75601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia Health System ( Site 0261)</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Cancer Care Alliance/Univ of Washington Medical Center ( Site 0269)</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Oncology Associates (Summit Cancer Centers) ( Site 0257)</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liverpool Hospital ( Site 0301)</name>
      <address>
        <city>Liverpool</city>
        <state>New South Wales (Australia)</state>
        <zip>2170</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Blacktown Hospital Western Sydney Local Health District ( Site 0304)</name>
      <address>
        <city>Blacktown</city>
        <state>New South Wales</state>
        <zip>2148</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Alexandra Hospital ( Site 0305)</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <zip>4102</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Brisbane and Women s Hospital ( Site 0302)</name>
      <address>
        <city>Herston</city>
        <state>Queensland</state>
        <zip>4029</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Adelaide Hospital ( Site 0303)</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peter MacCallum Cancer Centre ( Site 0300)</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Landeskrankenhaus - Universitatsklinikum Graz ( Site 0601)</name>
      <address>
        <city>Graz</city>
        <zip>8036</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Krankenhaus der Barmherzigen Schwestern Linz ( Site 0603)</name>
      <address>
        <city>Linz</city>
        <zip>4010</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Landeskrankenhaus Salzburg ( Site 0600)</name>
      <address>
        <city>Salzburg</city>
        <zip>5020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allgemeines Krankenhaus der Stadt Wien ( Site 0602)</name>
      <address>
        <city>Vienna/Wien</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniques Universitaires Saint Luc - Bruxelles ( Site 0651)</name>
      <address>
        <city>Brussels</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Gent ( Site 0650)</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven Campus Gasthuisberg ( Site 0652)</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>C.H.U. Sart Tilman-Service d'Oncologie Medicale ( Site 0654)</name>
      <address>
        <city>Liege</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinique et Maternite Sainte-Elisabeth ( Site 0653)</name>
      <address>
        <city>Namur</city>
        <zip>5000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Santa Izabel - Santa Casa de Misericordia da Bahia ( Site 0006)</name>
      <address>
        <city>Salvador</city>
        <state>Bahia</state>
        <zip>40050-410</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Regional Integrado de Oncologia ( Site 0002)</name>
      <address>
        <city>Fortaleza</city>
        <state>Ceara</state>
        <zip>60336-045</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liga Norte Riograndense Contra o Cancer ( Site 0005)</name>
      <address>
        <city>Natal</city>
        <state>Rio Grande Do Norte</state>
        <zip>59075-740</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Nossa Senhora da Conceicao ( Site 0001)</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <zip>91350-200</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Clinicas de Porto Alegre ( Site 0011)</name>
      <address>
        <city>Porto Alegre</city>
        <state>RS</state>
        <zip>90035-903</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 0003)</name>
      <address>
        <city>Barretos</city>
        <state>Sao Paulo</state>
        <zip>14784-400</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto do Cancer de Sao Paulo - ICESP ( Site 0004)</name>
      <address>
        <city>Sao Paulo</city>
        <state>SP</state>
        <zip>01246-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital das Clinicas da FMUSP de Ribeirao Preto ( Site 0008)</name>
      <address>
        <city>Ribeirao Preto</city>
        <zip>14048-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0010)</name>
      <address>
        <city>Rio de Janeiro</city>
        <zip>20230-130</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tom Baker Cancer Centre ( Site 0063)</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4N2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cross Cancer Institute ( Site 0064)</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 1Z2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Juravinski Cancer Centre ( Site 0062)</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8V 5C2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Health Sciences Centre ( Site 0055)</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 4L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ottawa Hospital - Cancer Care ( Site 0052)</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre ( Site 0051)</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGill University Health Centre ( Site 0061)</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0057)</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>J1H 5N4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Pablo Tobon Uribe ( Site 0151)</name>
      <address>
        <city>Medellin</city>
        <state>Antioquia</state>
        <zip>050034</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacion Valle del Lili ( Site 0150)</name>
      <address>
        <city>Cali</city>
        <state>Valle Del Cauca</state>
        <zip>760032</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Medico Imbanaco de Cali S.A ( Site 0156)</name>
      <address>
        <city>Cali</city>
        <state>Valle Del Cauca</state>
        <zip>760042</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Investigacion Clinica del Country ( Site 0155)</name>
      <address>
        <city>Bogota</city>
        <zip>110221</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FN Brno. ( Site 0703)</name>
      <address>
        <city>Brno</city>
        <zip>625 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni Nemocnice Hradec Kralove ( Site 0705)</name>
      <address>
        <city>Hradec Kralove</city>
        <zip>500 05</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Olomouc ( Site 0701)</name>
      <address>
        <city>Olomouc</city>
        <zip>775 20</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Ostrava ( Site 0702)</name>
      <address>
        <city>Ostrava</city>
        <zip>708 52</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nemocnice Na Bulovce ( Site 0700)</name>
      <address>
        <city>Praha 8</city>
        <zip>180 81</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>2. LF UK a FN Motol ( Site 0704)</name>
      <address>
        <city>Praha</city>
        <zip>150 06</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Jean Bernard Laboratoire Mahe Meziani ( Site 0760)</name>
      <address>
        <city>Le Mans</city>
        <zip>72000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinique Francois Chenieux ( Site 0757)</name>
      <address>
        <city>Limoges</city>
        <zip>87039</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Claudius Regaud ( Site 0754)</name>
      <address>
        <city>Toulouse Cedex 09</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut De Cancerologie De Lorraine ( Site 0758)</name>
      <address>
        <city>Vandoeuvre les Nancy</city>
        <zip>54500</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy ( Site 0759)</name>
      <address>
        <city>Villejuif</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Erlangen ( Site 0801)</name>
      <address>
        <city>Erlangen</city>
        <zip>91054</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SRH Waldklinikum Gera GmbH ( Site 0802)</name>
      <address>
        <city>Gera</city>
        <zip>07548</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitares Cancer Center Hamburg - UCCH ( Site 0811)</name>
      <address>
        <city>Hamburg</city>
        <zip>20246</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Hochschule Hannover ( Site 0807)</name>
      <address>
        <city>Hannover</city>
        <zip>30325</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Schleswig-Holstein-Campus Luebeck ( Site 0803)</name>
      <address>
        <city>Luebeck</city>
        <zip>23538</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum der Universitaet Munchen ( Site 0810)</name>
      <address>
        <city>Munchen</city>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinik Ulm ( Site 0804)</name>
      <address>
        <city>Ulm</city>
        <zip>89075</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rambam MC ( Site 0903)</name>
      <address>
        <city>Haifa</city>
        <zip>3109601</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hadassah Ein Karem Jerusalem ( Site 0902)</name>
      <address>
        <city>Jerusalem</city>
        <zip>9112001</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rabin Medical Center ( Site 0904)</name>
      <address>
        <city>Petah Tikva</city>
        <zip>4941492</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sheba MC ( Site 0901)</name>
      <address>
        <city>Ramat Gan</city>
        <zip>5265601</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tel Aviv Sourasky Medical Center ( Site 0900)</name>
      <address>
        <city>Tel Aviv</city>
        <zip>6423906</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 0954)</name>
      <address>
        <city>Modena</city>
        <state>MO</state>
        <zip>41124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Careggi ( Site 0955)</name>
      <address>
        <city>Firenze</city>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori ( Site 0950)</name>
      <address>
        <city>Milano</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Europeo di Oncologia ( Site 0953)</name>
      <address>
        <city>Milano</city>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera San Paolo ( Site 0952)</name>
      <address>
        <city>Milano</city>
        <zip>20142</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0951)</name>
      <address>
        <city>Napoli</city>
        <zip>80121</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Oncologico Veneto ( Site 0957)</name>
      <address>
        <city>Padova</city>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS - Policlinico San Matteo ( Site 0960)</name>
      <address>
        <city>Pavia</city>
        <zip>27100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital East ( Site 0350)</name>
      <address>
        <city>Kashiwa</city>
        <state>Chiba</state>
        <zip>277-8577</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hokkaido University Hospital ( Site 0351)</name>
      <address>
        <city>Sapporo</city>
        <state>Hokkaido</state>
        <zip>060-8648</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hyogo Cancer Center ( Site 0354)</name>
      <address>
        <city>Akashi</city>
        <state>Hyogo</state>
        <zip>673-8558</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kagawa University Hospital ( Site 0359)</name>
      <address>
        <city>Kita-gun</city>
        <state>Kagawa</state>
        <zip>761-0793</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miyagi Cancer Center ( Site 0353)</name>
      <address>
        <city>Natori</city>
        <state>Miyagi</state>
        <zip>981-1293</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chiba Cancer Center ( Site 0358)</name>
      <address>
        <city>Chiba</city>
        <zip>260-8717</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hiroshima University Hospital ( Site 0352)</name>
      <address>
        <city>Hiroshima</city>
        <zip>734-8551</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Osaka International Cancer Institute ( Site 0355)</name>
      <address>
        <city>Osaka</city>
        <zip>541-8567</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Hospital, Tokyo Medical And Dental University ( Site 0356)</name>
      <address>
        <city>Tokyo</city>
        <zip>113-8519</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Cancer Institute Hospital of JFCR ( Site 0357)</name>
      <address>
        <city>Tokyo</city>
        <zip>135-8550</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chungbuk National University Hospital ( Site 0454)</name>
      <address>
        <city>Cheongju si</city>
        <state>Chungcheongbuk Do</state>
        <zip>28644</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital ( Site 0453)</name>
      <address>
        <city>Seongnam-si</city>
        <state>Gyeonggi-do</state>
        <zip>13620</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chungnam National University Hospital ( Site 0455)</name>
      <address>
        <city>Daejeon</city>
        <zip>35015</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital Yonsei University Health System ( Site 0452)</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center ( Site 0450)</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Noordwest Ziekenhuisgroep NWZ ( Site 1350)</name>
      <address>
        <city>Alkmaar</city>
        <zip>1815 JD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VU Medisch Centrum ( Site 1352)</name>
      <address>
        <city>Amsterdam</city>
        <zip>1081 HV</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMCG ( Site 1351)</name>
      <address>
        <city>Groningen</city>
        <zip>9713 GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMC St. Radboud ( Site 1356)</name>
      <address>
        <city>Nijmegen</city>
        <zip>6525 GA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasmus University Medical Center ( Site 1354)</name>
      <address>
        <city>Rotterdam</city>
        <zip>3015 GD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Capital &amp; Coast District Health Board - Wellington Hospital ( Site 0400)</name>
      <address>
        <city>Wellington</city>
        <state>Newtown</state>
        <zip>6021</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dolnoslaskie Centrum Onkologii. ( Site 1001)</name>
      <address>
        <city>Wroclaw</city>
        <state>Dolnoslaskie</state>
        <zip>53-413</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mazowiecki Szpital Onkologiczny ( Site 1015)</name>
      <address>
        <city>Wieliszew</city>
        <state>Mazowieckie</state>
        <zip>05-135</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 1005)</name>
      <address>
        <city>Bielsko-Biala</city>
        <zip>43-300</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 1007)</name>
      <address>
        <city>Gdynia</city>
        <zip>81-519</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Onkologii. Instytut im. Marii Sklodowskiej-Curie ( Site 1010)</name>
      <address>
        <city>Gliwice</city>
        <zip>44-101</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie ( Site 1008)</name>
      <address>
        <city>Krakow</city>
        <zip>31-826</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zachodniopomorskie Centrum Onkologii ( Site 1013)</name>
      <address>
        <city>Szczecin</city>
        <zip>71-730</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie ( Site 1000)</name>
      <address>
        <city>Warszawa</city>
        <zip>02-781</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H.U. Vall de Hebron ( Site 1052)</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Duran i Reynals ( Site 1053)</name>
      <address>
        <city>Hospitalet de Llobregat</city>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Doce de Octubre ( Site 1054)</name>
      <address>
        <city>Madrid</city>
        <zip>28024</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramon y Cajal ( Site 1055)</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico San Carlos ( Site 1051)</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de la Victoria ( Site 1056)</name>
      <address>
        <city>Malaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Gral Universitario de Valencia ( Site 1050)</name>
      <address>
        <city>Valencia</city>
        <zip>46014</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chang Gung Medical Foundation - Kaohsiung ( Site 0501)</name>
      <address>
        <city>Kaohsiung</city>
        <zip>83301</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taichung Veterans General Hospital ( Site 0506)</name>
      <address>
        <city>Taichung</city>
        <zip>407</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cheng Kung University Hospital ( Site 0503)</name>
      <address>
        <city>Tainan</city>
        <zip>70403</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital ( Site 0500)</name>
      <address>
        <city>Taipei</city>
        <zip>10048</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MacKay Memorial Hospital ( Site 0505)</name>
      <address>
        <city>Taipei</city>
        <zip>105</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital ( Site 0504)</name>
      <address>
        <city>Taipei</city>
        <zip>112</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Linkou Chang Gung Memorial Hospital ( Site 0502)</name>
      <address>
        <city>Taoyuan</city>
        <zip>333</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Basken Adana Dr.Turgut Noyan Uygulama ve Arastirma Merkezi ( Site 1103)</name>
      <address>
        <city>Adana</city>
        <zip>01250</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1102)</name>
      <address>
        <city>Ankara</city>
        <zip>06100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ankara Sehir Hastanesi ( Site 1108)</name>
      <address>
        <city>Ankara</city>
        <zip>06800</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istanbul Universitesi Istanbul Tip Fakultesi ( Site 1100)</name>
      <address>
        <city>Istanbul</city>
        <zip>34093</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medipol Universite Hastanesi ( Site 1104)</name>
      <address>
        <city>Istanbul</city>
        <zip>34214</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Park Izmir Hastanesi ( Site 1109)</name>
      <address>
        <city>Izmir</city>
        <zip>35520</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kocaeli Universitesi Tip Fakultesi ( Site 1106)</name>
      <address>
        <city>Kocaeli</city>
        <zip>41380</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inonu Universitesi Tip Fakultesi ( Site 1101)</name>
      <address>
        <city>Malatya</city>
        <zip>44280</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norfolk &amp; Norwich University Hospital NHS Foundation Trust ( Site 1206)</name>
      <address>
        <city>Norwich</city>
        <state>Norfolk</state>
        <zip>NR4 7UY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital of North Staffordshire ( Site 1202)</name>
      <address>
        <city>Stoke-On-Trent</city>
        <state>Staffordshire</state>
        <zip>ST4 6QG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ipswich Hospital ( Site 1207)</name>
      <address>
        <city>Ipswich</city>
        <state>Suffolk</state>
        <zip>IP4 5PD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Bartholomew s Hospital ( Site 1205)</name>
      <address>
        <city>London</city>
        <zip>EC1A 7BE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal Marsden Foundation Trust ( Site 1200)</name>
      <address>
        <city>London</city>
        <zip>SW3 6JJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 1204)</name>
      <address>
        <city>London</city>
        <zip>W6 8RF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lancashire Teaching Hospitals NHS Foundation Trust ( Site 1208)</name>
      <address>
        <city>Preston</city>
        <zip>PR2 9HT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Southampton NHS Foundation Trust ( Site 1203)</name>
      <address>
        <city>Southampton</city>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Marsden NHS Foundation Trust ( Site 1201)</name>
      <address>
        <city>Sutton</city>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>Colombia</country>
    <country>Czechia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>New Zealand</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Argentina</country>
    <country>Chile</country>
    <country>Czech Republic</country>
    <country>Hungary</country>
    <country>Mexico</country>
    <country>Puerto Rico</country>
    <country>Ukraine</country>
  </removed_countries>
  <link>
    <url>http://merckoncologyclinicaltrials.com</url>
    <description>Merck Oncology Clinical Trial Information</description>
  </link>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>February 1, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <results_first_submitted>May 12, 2023</results_first_submitted>
  <results_first_submitted_qc>May 12, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">June 8, 2023</results_first_posted>
  <last_update_submitted>May 12, 2023</last_update_submitted>
  <last_update_submitted_qc>May 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Head and Neck Squamous Cell Carcinoma</keyword>
  <keyword>Programmed Cell Death Receptor 1 (PD-1)</keyword>
  <keyword>Programmed Cell Death Receptor Ligand 1 (PD-L1)</keyword>
  <keyword>Programmed Cell Death Receptor Ligand 2 (PD-L2)</keyword>
  <keyword>PD1</keyword>
  <keyword>PD-1</keyword>
  <keyword>PDL1</keyword>
  <keyword>PD-L1</keyword>
  <keyword>PDL2</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Head and Neck Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cisplatin</mesh_term>
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 16, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/99/NCT03040999/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled who had locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) and who were eligible for definitive chemoradiation therapy (CRT) and not considered for primary surgery based on investigator decision; had an Eastern Cooperative Oncology Group performance score of 0 or 1; had no distant metastases; and no active autoimmune disease or infection requiring systemic therapy.</recruitment_details>
      <pre_assignment_details>A total of 1093 participants were screened, across 130 study sites in 21 countries.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Pembrolizumab + Cisplatin + CRT</title>
          <description>Participants received a priming dose of pembrolizumab before initiating CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.</description>
        </group>
        <group group_id="P2">
          <title>Placebo + Cisplatin + CRT</title>
          <description>Participants received placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="402"/>
                <participants group_id="P2" count="402"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="398"/>
                <participants group_id="P2" count="398"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="402"/>
                <participants group_id="P2" count="402"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="128"/>
                <participants group_id="P2" count="138"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participants Ongoing in Trial</title>
              <participants_list>
                <participants group_id="P1" count="266"/>
                <participants group_id="P2" count="252"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Pembrolizumab + Cisplatin + CRT</title>
          <description>Participants received a priming dose of pembrolizumab before initiating CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.</description>
        </group>
        <group group_id="B2">
          <title>Placebo + Cisplatin + CRT</title>
          <description>Participants received placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.</description>
        </group>
        <group group_id="B3">
          <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="402"/>
            <count group_id="B2" value="402"/>
            <count group_id="B3" value="804"/>
          </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="58.8" spread="9.0"/>
                    <measurement group_id="B2" value="58.6" spread="7.8"/>
                    <measurement group_id="B3" value="58.7" spread="8.4"/>
                  </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="71"/>
                    <measurement group_id="B2" value="73"/>
                    <measurement group_id="B3" value="144"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="331"/>
                    <measurement group_id="B2" value="329"/>
                    <measurement group_id="B3" value="660"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</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="47"/>
                    <measurement group_id="B2" value="59"/>
                    <measurement group_id="B3" value="106"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="324"/>
                    <measurement group_id="B2" value="311"/>
                    <measurement group_id="B3" value="635"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="54"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="102"/>
                  </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="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="311"/>
                    <measurement group_id="B2" value="311"/>
                    <measurement group_id="B3" value="622"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="47"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Event-free Survival (EFS)</title>
        <description>EFS is the time from date of randomization to the date of first record of any of the following events: death due to any cause; progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR) or biopsy as indicated for locoregional progression or recurrence or distant metastasis. As well as the first record of the following types of surgery: salvage surgery for persistent or residual disease at the primary tumor site requiring surgical removal when invasive cancer is present on final pathology; neck dissection or surgery (performed for clinical or radiological disease progression per RECIST 1.1) ≤ 20 weeks from end of CRT when invasive cancer is present; or neck dissection or surgery &gt;20 weeks from end of CRT when invasive cancer is present. From product-limit (Kaplan-Meier) method for censored data.</description>
        <time_frame>Up to approximately 62 months</time_frame>
        <population>All randomized participants based on the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab + Cisplatin + CRT</title>
            <description>Participants received a priming dose of pembrolizumab before initiating CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + Cisplatin + CRT</title>
            <description>Participants received placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.</description>
          </group>
        </group_list>
        <measure>
          <title>Event-free Survival (EFS)</title>
          <description>EFS is the time from date of randomization to the date of first record of any of the following events: death due to any cause; progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR) or biopsy as indicated for locoregional progression or recurrence or distant metastasis. As well as the first record of the following types of surgery: salvage surgery for persistent or residual disease at the primary tumor site requiring surgical removal when invasive cancer is present on final pathology; neck dissection or surgery (performed for clinical or radiological disease progression per RECIST 1.1) ≤ 20 weeks from end of CRT when invasive cancer is present; or neck dissection or surgery &gt;20 weeks from end of CRT when invasive cancer is present. From product-limit (Kaplan-Meier) method for censored data.</description>
          <population>All randomized participants based on the treatment group to which they were randomized.</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="402"/>
                <count group_id="O2" value="402"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="44.7" upper_limit="NA">NA = median and upper limit not reached due to insufficient number of participants with an event.</measurement>
                    <measurement group_id="O2" value="46.6" lower_limit="27.5" upper_limit="NA">NA = upper limit not reached due to insufficient number of participants with an event.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by HPV status and overall cancer stage. Hypothesis: Pembrolizumab in combination with CRT is superior to placebo in combination with CRT.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0429</p_value>
            <p_value_desc>P-value crossing boundary of 0.0242 required for statistical significance.</p_value_desc>
            <method>Log Rank</method>
            <method_desc>One-sided p-value based on log-rank test stratified by human papilloma virus (HPV) status and overall cancer stage.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.83</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.68</ci_lower_limit>
            <ci_upper_limit>1.03</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>OS is the time from randomization to death due to any cause, from product-limit (Kaplan-Meier) method for censored data. The hypothesis was that pembrolizumab in combination with CRT is superior to placebo in combination with CRT; but based on the protocol, because the statistical criterion for success in the primary EFS hypothesis was not met, the OS hypothesis was not tested</description>
        <time_frame>Up to approximately 62 months</time_frame>
        <population>All randomized participants based on the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab + Cisplatin + CRT</title>
            <description>Participants received a priming dose of pembrolizumab before initiating CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + Cisplatin + CRT</title>
            <description>Participants received placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>OS is the time from randomization to death due to any cause, from product-limit (Kaplan-Meier) method for censored data. The hypothesis was that pembrolizumab in combination with CRT is superior to placebo in combination with CRT; but based on the protocol, because the statistical criterion for success in the primary EFS hypothesis was not met, the OS hypothesis was not tested</description>
          <population>All randomized participants based on the treatment group to which they were randomized.</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="402"/>
                <count group_id="O2" value="402"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">NA = median, upper limit, and lower limit were not reached due to insufficient number of participants with an event.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">NA = median, upper limit, and lower limit were not reached due to insufficient number of participants with an event.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events (AEs)</title>
        <description>An AE is any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE is any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy.</description>
        <time_frame>From time of first dose of study treatment until 90 days after last dose (up to approximately 19 months)</time_frame>
        <population>All randomized participants who received at least one dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab + Cisplatin + CRT</title>
            <description>Participants received a priming dose of pembrolizumab before initiating CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + Cisplatin + CRT</title>
            <description>Participants received placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events (AEs)</title>
          <description>An AE is any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE is any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy.</description>
          <population>All randomized participants who received at least one dose of study treatment.</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="398"/>
                <count group_id="O2" value="398"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="398"/>
                    <measurement group_id="O2" value="397"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Discontinuing Study Drug Due to an AE</title>
        <description>An AE is any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE is any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy.</description>
        <time_frame>From time of first dose of study treatment until the end of treatment (up to approximately 16 months)</time_frame>
        <population>All randomized participants who received at least one dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab + Cisplatin + CRT</title>
            <description>Participants received a priming dose of pembrolizumab before initiating CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + Cisplatin + CRT</title>
            <description>Participants received placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Discontinuing Study Drug Due to an AE</title>
          <description>An AE is any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE is any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy.</description>
          <population>All randomized participants who received at least one dose of study treatment.</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="398"/>
                <count group_id="O2" value="398"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="164"/>
                    <measurement group_id="O2" value="132"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Global Health Status/Quality of Life (GHS/QoL)</title>
        <description>The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) contains 30 items and measures five functional dimensions (physical, role, emotional, cognitive and social), three symptom items (fatigue, nausea/vomiting, and pain), six single items (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and QoL scale. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, so that a higher score indicates a better overall GHS. A change from baseline of 10 points on the 100-point EORTC QLQ-C30 scale is considered as clinically relevant. Based on a constrained longitudinal data analysis (cLDA) model with the patient reported outcomes (PRO) scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of human papilloma virus (HPV) status and overall cancer stage.</description>
        <time_frame>Prior to the first dose of study treatment (Baseline) and up to Week 45</time_frame>
        <population>Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention based on in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab + Cisplatin + CRT</title>
            <description>Participants received a priming dose of pembrolizumab before initiating CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + Cisplatin + CRT</title>
            <description>Participants received placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Global Health Status/Quality of Life (GHS/QoL)</title>
          <description>The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) contains 30 items and measures five functional dimensions (physical, role, emotional, cognitive and social), three symptom items (fatigue, nausea/vomiting, and pain), six single items (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and QoL scale. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, so that a higher score indicates a better overall GHS. A change from baseline of 10 points on the 100-point EORTC QLQ-C30 scale is considered as clinically relevant. Based on a constrained longitudinal data analysis (cLDA) model with the patient reported outcomes (PRO) scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of human papilloma virus (HPV) status and overall cancer stage.</description>
          <population>Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention based on in the treatment group to which they were randomized.</population>
          <units>Score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="395"/>
                <count group_id="O2" value="397"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.95" lower_limit="-0.10" upper_limit="4.00"/>
                    <measurement group_id="O2" value="6.08" lower_limit="4.02" upper_limit="8.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0019</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least squares mean</param_type>
            <param_value>-4.13</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.73</ci_lower_limit>
            <ci_upper_limit>-1.53</ci_upper_limit>
            <estimate_desc>Pembrolizumab minus Placebo</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Swallowing, Speech, and Pain Symptoms</title>
        <description>EORTC QLQ Head and Neck Questionnaire (H&amp;N35) consists of 7 multi-item scales (pain in the mouth, problems with swallowing, senses, speech, social eating, social contact, and sexuality), Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Change from baseline in swallowing, speech, and pain symptoms was measured. A change from baseline of 10 points on the 100-point EORTC QLQ-H&amp;N35 is considered as clinically relevant. Based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.</description>
        <time_frame>Prior to the first dose of study treatment (Baseline) and up to Week 45</time_frame>
        <population>Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention based on in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab + Cisplatin + CRT</title>
            <description>Participants received a priming dose of pembrolizumab before initiating CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + Cisplatin + CRT</title>
            <description>Participants received placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Swallowing, Speech, and Pain Symptoms</title>
          <description>EORTC QLQ Head and Neck Questionnaire (H&amp;N35) consists of 7 multi-item scales (pain in the mouth, problems with swallowing, senses, speech, social eating, social contact, and sexuality), Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Change from baseline in swallowing, speech, and pain symptoms was measured. A change from baseline of 10 points on the 100-point EORTC QLQ-H&amp;N35 is considered as clinically relevant. Based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.</description>
          <population>Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention based on in the treatment group to which they were randomized.</population>
          <units>Score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="395"/>
                <count group_id="O2" value="396"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Swallowing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.88" lower_limit="-6.57" upper_limit="-1.18"/>
                    <measurement group_id="O2" value="-3.56" lower_limit="-6.26" upper_limit="-0.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Speech</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.23" lower_limit="-8.90" upper_limit="-3.57"/>
                    <measurement group_id="O2" value="-4.97" lower_limit="-7.64" upper_limit="-2.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.62" lower_limit="-12.94" upper_limit="-8.31"/>
                    <measurement group_id="O2" value="-12.07" lower_limit="-14.39" upper_limit="-9.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Swallowing</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.</non_inferiority_desc>
            <p_value>0.8582</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least squares mean</param_type>
            <param_value>-0.31</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.75</ci_lower_limit>
            <ci_upper_limit>3.13</ci_upper_limit>
            <estimate_desc>Pembrolizumab minus Placebo</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Speech</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.</non_inferiority_desc>
            <p_value>0.4555</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least squares mean</param_type>
            <param_value>-1.27</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.60</ci_lower_limit>
            <ci_upper_limit>2.07</ci_upper_limit>
            <estimate_desc>Pembrolizumab minus Placebo</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Pain</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.</non_inferiority_desc>
            <p_value>0.2965</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least squares mean</param_type>
            <param_value>1.44</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.27</ci_lower_limit>
            <ci_upper_limit>4.15</ci_upper_limit>
            <estimate_desc>Pembrolizumab minus Placebo</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Physical Functioning</title>
        <description>Participant responded to 5 questions from the EORTC QLQ-C30 about their physical functioning scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100, where a higher score indicates a better quality of life. A change from baseline of 10 points on the 100-point scale is considered as clinically relevant. Based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.</description>
        <time_frame>Prior to the first dose of study treatment (Baseline) and up to Week 45</time_frame>
        <population>Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention based on in the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab + Cisplatin + CRT</title>
            <description>Participants received a priming dose of pembrolizumab before initiating CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.</description>
          </group>
          <group group_id="O2">
            <title>Placebo + Cisplatin + CRT</title>
            <description>Participants received placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Physical Functioning</title>
          <description>Participant responded to 5 questions from the EORTC QLQ-C30 about their physical functioning scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100, where a higher score indicates a better quality of life. A change from baseline of 10 points on the 100-point scale is considered as clinically relevant. Based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.</description>
          <population>Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention based on in the treatment group to which they were randomized.</population>
          <units>Score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="395"/>
                <count group_id="O2" value="397"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.54" lower_limit="-7.34" upper_limit="-3.73"/>
                    <measurement group_id="O2" value="-3.46" lower_limit="-5.26" upper_limit="-1.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0954</p_value>
            <method>cLDA</method>
            <param_type>Difference in Least squares mean</param_type>
            <param_value>-2.07</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.51</ci_lower_limit>
            <ci_upper_limit>0.36</ci_upper_limit>
            <estimate_desc>Pembrolizumab minus Placebo</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events : From time of first dose of study treatment until 90 days after last dose (up to approximately 19 months). All-Cause Mortality: From randomization to last Follow Up visit (up to approximately 62 months)</time_frame>
      <desc>The population analyzed for all-cause mortality consisted of all randomized participants. The population for AEs consisted of all allocated participants who received ≥1 dose of study drug. Per protocol disease progression of cancer was not considered an AE unless related to study drug. Therefore the following AE preferred terms not related to the drug were excluded: Neoplasm progression, Malignant neoplasm progression and Disease progression.</desc>
      <group_list>
        <group group_id="E1">
          <title>Pembrolizumab + CRT Followed by Pembrolizumab</title>
          <description>Participants received a priming dose of pembrolizumab before initiating CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.</description>
        </group>
        <group group_id="E2">
          <title>Placebo + CRT Followed by Placebo</title>
          <description>Participants received placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants received 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also received up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 25.0</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="129" subjects_at_risk="402"/>
                <counts group_id="E2" subjects_affected="143" subjects_at_risk="402"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="245" subjects_at_risk="398"/>
                <counts group_id="E2" subjects_affected="197" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Agranulocytosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="26" subjects_affected="24" subjects_at_risk="398"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Lymphadenitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Lymphadenopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pancytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Atrioventricular block complete</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Cardiopulmonary failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Ischaemic cardiomyopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Sinus node dysfunction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoacusis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hypophysitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eyelid ptosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Vitreous detachment</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Achlorhydria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="398"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Duodenal perforation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Duodenal ulcer haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="11" subjects_affected="11" subjects_at_risk="398"/>
                <counts group_id="E2" events="13" subjects_affected="12" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Enterocolitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Gastric haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Gastric perforation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Gastric ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Gastric ulcer haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Gastric ulcer perforation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Lower gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Mouth haemorrhage</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="19" subjects_affected="17" subjects_at_risk="398"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Neutropenic colitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Odynophagia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Oesophageal obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Oesophageal stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Oesophagitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pneumatosis intestinalis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Salivary hypersecretion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Small intestinal haemorrhage</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="12" subjects_affected="12" subjects_at_risk="398"/>
                <counts group_id="E2" events="13" subjects_affected="12" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Tongue oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="17" subjects_affected="15" subjects_at_risk="398"/>
                <counts group_id="E2" events="11" subjects_affected="10" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Complication associated with device</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Condition aggravated</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="398"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Face oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Facial pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Fibrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="398"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Impaired healing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Multiple organ dysfunction syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="398"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Vascular device occlusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Vascular stent thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholangitis sclerosing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Cholecystitis acute</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hepatitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hepatitis fulminant</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Immune-mediated hepatitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abdominal abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Abscess jaw</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Abscess neck</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Arthritis infective</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Bacterial sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="398"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Bronchitis bacterial</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Candida sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Catheter site abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Catheter site infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="398"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Clostridium difficile colitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Dermatitis infected</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Device related sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Empyema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Enterocolitis infectious</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Epiglottitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Erysipelas</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Fungaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Gangrene</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Genitourinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hepatitis B reactivation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Infected fistula</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Infectious pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Infective exacerbation of chronic obstructive airways disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Intervertebral discitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Lung abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Mediastinitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Meningitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Meningitis aseptic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Neutropenic sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Ophthalmic herpes zoster</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Oral bacterial infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Parotitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="49" subjects_affected="43" subjects_at_risk="398"/>
                <counts group_id="E2" events="33" subjects_affected="25" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" events="12" subjects_affected="12" subjects_at_risk="398"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Post procedural infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Respiratory syncytial virus bronchitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="12" subjects_affected="12" subjects_at_risk="398"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Skin bacterial infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Staphylococcal infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Stoma site cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Stoma site infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Streptococcal bacteraemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Systemic infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Tracheitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Tracheobronchitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Tracheostomy infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Tuberculosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Vascular access site infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Vascular device infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Accidental overdose</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Alcohol poisoning</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Arterial injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Chest injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Gastrostomy failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Gastrostomy tube site complication</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Humerus fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Osteoradionecrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Radiation associated pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Radiation necrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Radiation skin injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Stoma complication</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Tracheal obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Tracheostomy malfunction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Unintentional medical device removal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Vascular pseudoaneurysm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Wound dehiscence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="398"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>C-reactive protein increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="398"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="398"/>
                <counts group_id="E2" events="9" subjects_affected="7" subjects_at_risk="398"/>
              </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="4" subjects_affected="4" subjects_at_risk="398"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="398"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Diabetic ketoacidosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="398"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="398"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hypophagia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Latent autoimmune diabetes in adults</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Malnutrition</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Tumour lysis syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Type 1 diabetes mellitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Type 2 diabetes mellitus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Joint effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pathological fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Spinal osteoarthritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Trismus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Follicular lymphoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Follicular thyroid cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Infected neoplasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Lip and/or oral cavity cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Lung adenocarcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Neoplasm swelling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Neuroendocrine carcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Non-small cell lung cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Oesophageal squamous cell carcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Prostate cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Rectal adenocarcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of lung</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of skin</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Tumour associated fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Tumour haemorrhage</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Tumour inflammation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Tumour pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral venous sinus thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="398"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Vocal cord paralysis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Device breakage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Device dislocation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Alcohol abuse</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Alcohol withdrawal syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Alcoholism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Drug abuse</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Panic attack</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Suicidal ideation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="42" subjects_affected="33" subjects_at_risk="398"/>
                <counts group_id="E2" events="33" subjects_affected="30" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Chronic kidney disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>End stage renal disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Renal injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Tubulointerstitial nephritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute pulmonary oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Epiglottic oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Laryngeal cyst</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Laryngeal fistula</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Laryngeal haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Laryngeal necrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Laryngeal oedema</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="398"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Oropharyngeal fistula</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pharyngeal haemorrhage</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="398"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pharyngeal inflammation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="398"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pharyngeal necrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pharyngeal oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pharyngeal swelling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pharyngeal ulceration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pneumonia lipoid</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="11" subjects_affected="10" subjects_at_risk="398"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="398"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Respiratory acidosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Respiratory distress</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Stridor</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Tracheal stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Angioedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Drug reaction with eosinophilia and systemic symptoms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pemphigoid</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Rash macular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Jugular vein thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="398"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Peripheral artery thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Peripheral ischaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Phlebitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Venous thrombosis limb</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="398"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 25.0</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="398" subjects_at_risk="398"/>
                <counts group_id="E2" subjects_affected="396" subjects_at_risk="398"/>
              </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="298" subjects_affected="229" subjects_at_risk="398"/>
                <counts group_id="E2" events="287" subjects_affected="205" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" events="29" subjects_affected="28" subjects_at_risk="398"/>
                <counts group_id="E2" events="35" subjects_affected="33" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hypoacusis</sub_title>
                <counts group_id="E1" events="84" subjects_affected="80" subjects_at_risk="398"/>
                <counts group_id="E2" events="51" subjects_affected="49" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="83" subjects_affected="75" subjects_at_risk="398"/>
                <counts group_id="E2" events="92" subjects_affected="88" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" events="43" subjects_affected="40" subjects_at_risk="398"/>
                <counts group_id="E2" events="35" subjects_affected="33" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="109" subjects_affected="99" subjects_at_risk="398"/>
                <counts group_id="E2" events="58" subjects_affected="54" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="23" subjects_affected="22" subjects_at_risk="398"/>
                <counts group_id="E2" events="13" subjects_affected="13" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="218" subjects_affected="179" subjects_at_risk="398"/>
                <counts group_id="E2" events="213" subjects_affected="174" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="121" subjects_affected="88" subjects_at_risk="398"/>
                <counts group_id="E2" events="106" subjects_affected="82" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="206" subjects_affected="191" subjects_at_risk="398"/>
                <counts group_id="E2" events="194" subjects_affected="173" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="32" subjects_affected="25" subjects_at_risk="398"/>
                <counts group_id="E2" events="26" subjects_affected="25" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="190" subjects_affected="177" subjects_at_risk="398"/>
                <counts group_id="E2" events="185" subjects_affected="165" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" events="31" subjects_affected="30" subjects_at_risk="398"/>
                <counts group_id="E2" events="21" subjects_affected="19" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="324" subjects_affected="222" subjects_at_risk="398"/>
                <counts group_id="E2" events="337" subjects_affected="232" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Odynophagia</sub_title>
                <counts group_id="E1" events="96" subjects_affected="87" subjects_at_risk="398"/>
                <counts group_id="E2" events="98" subjects_affected="89" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="30" subjects_affected="28" subjects_at_risk="398"/>
                <counts group_id="E2" events="23" subjects_affected="22" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Saliva altered</sub_title>
                <counts group_id="E1" events="23" subjects_affected="22" subjects_at_risk="398"/>
                <counts group_id="E2" events="26" subjects_affected="26" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="279" subjects_affected="249" subjects_at_risk="398"/>
                <counts group_id="E2" events="259" subjects_affected="232" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="204" subjects_affected="131" subjects_at_risk="398"/>
                <counts group_id="E2" events="168" subjects_affected="116" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="93" subjects_affected="74" subjects_at_risk="398"/>
                <counts group_id="E2" events="89" subjects_affected="73" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="150" subjects_affected="126" subjects_at_risk="398"/>
                <counts group_id="E2" events="137" subjects_affected="118" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Localised oedema</sub_title>
                <counts group_id="E1" events="29" subjects_affected="26" subjects_at_risk="398"/>
                <counts group_id="E2" events="29" subjects_affected="28" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="26" subjects_affected="21" subjects_at_risk="398"/>
                <counts group_id="E2" events="20" subjects_affected="18" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="94" subjects_affected="64" subjects_at_risk="398"/>
                <counts group_id="E2" events="55" subjects_affected="43" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="15" subjects_affected="14" subjects_at_risk="398"/>
                <counts group_id="E2" events="20" subjects_affected="20" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" events="85" subjects_affected="77" subjects_at_risk="398"/>
                <counts group_id="E2" events="71" subjects_affected="60" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="25" subjects_affected="23" subjects_at_risk="398"/>
                <counts group_id="E2" events="23" subjects_affected="21" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="35" subjects_affected="26" subjects_at_risk="398"/>
                <counts group_id="E2" events="21" subjects_affected="17" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Radiation skin injury</sub_title>
                <counts group_id="E1" events="260" subjects_affected="254" subjects_at_risk="398"/>
                <counts group_id="E2" events="244" subjects_affected="242" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="100" subjects_affected="79" subjects_at_risk="398"/>
                <counts group_id="E2" events="74" subjects_affected="60" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="78" subjects_affected="59" subjects_at_risk="398"/>
                <counts group_id="E2" events="49" subjects_affected="41" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="127" subjects_affected="91" subjects_at_risk="398"/>
                <counts group_id="E2" events="128" subjects_affected="87" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" events="61" subjects_affected="47" subjects_at_risk="398"/>
                <counts group_id="E2" events="40" subjects_affected="36" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="142" subjects_affected="94" subjects_at_risk="398"/>
                <counts group_id="E2" events="145" subjects_affected="107" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="228" subjects_affected="166" subjects_at_risk="398"/>
                <counts group_id="E2" events="241" subjects_affected="152" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="150" subjects_affected="97" subjects_at_risk="398"/>
                <counts group_id="E2" events="120" subjects_affected="83" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="192" subjects_affected="179" subjects_at_risk="398"/>
                <counts group_id="E2" events="201" subjects_affected="183" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="222" subjects_affected="125" subjects_at_risk="398"/>
                <counts group_id="E2" events="236" subjects_affected="133" subjects_at_risk="398"/>
              </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="115" subjects_affected="104" subjects_at_risk="398"/>
                <counts group_id="E2" events="126" subjects_affected="115" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="49" subjects_affected="44" subjects_at_risk="398"/>
                <counts group_id="E2" events="48" subjects_affected="38" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="43" subjects_affected="30" subjects_at_risk="398"/>
                <counts group_id="E2" events="51" subjects_affected="35" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="38" subjects_affected="27" subjects_at_risk="398"/>
                <counts group_id="E2" events="52" subjects_affected="36" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" events="41" subjects_affected="31" subjects_at_risk="398"/>
                <counts group_id="E2" events="50" subjects_affected="33" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" events="51" subjects_affected="41" subjects_at_risk="398"/>
                <counts group_id="E2" events="41" subjects_affected="33" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" events="48" subjects_affected="38" subjects_at_risk="398"/>
                <counts group_id="E2" events="42" subjects_affected="31" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="142" subjects_affected="100" subjects_at_risk="398"/>
                <counts group_id="E2" events="108" subjects_affected="74" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" events="162" subjects_affected="110" subjects_at_risk="398"/>
                <counts group_id="E2" events="144" subjects_affected="96" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="107" subjects_affected="78" subjects_at_risk="398"/>
                <counts group_id="E2" events="109" subjects_affected="71" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" events="33" subjects_affected="30" subjects_at_risk="398"/>
                <counts group_id="E2" events="32" subjects_affected="19" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="34" subjects_affected="25" subjects_at_risk="398"/>
                <counts group_id="E2" events="34" subjects_affected="28" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="26" subjects_affected="21" subjects_at_risk="398"/>
                <counts group_id="E2" events="14" subjects_affected="14" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="38" subjects_affected="35" subjects_at_risk="398"/>
                <counts group_id="E2" events="38" subjects_affected="36" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Trismus</sub_title>
                <counts group_id="E1" events="14" subjects_affected="12" subjects_at_risk="398"/>
                <counts group_id="E2" events="24" subjects_affected="22" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="42" subjects_affected="30" subjects_at_risk="398"/>
                <counts group_id="E2" events="28" subjects_affected="24" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="137" subjects_affected="132" subjects_at_risk="398"/>
                <counts group_id="E2" events="139" subjects_affected="134" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="46" subjects_affected="39" subjects_at_risk="398"/>
                <counts group_id="E2" events="54" subjects_affected="49" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="36" subjects_affected="34" subjects_at_risk="398"/>
                <counts group_id="E2" events="42" subjects_affected="39" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="24" subjects_affected="22" subjects_at_risk="398"/>
                <counts group_id="E2" events="14" subjects_affected="14" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="61" subjects_affected="57" subjects_at_risk="398"/>
                <counts group_id="E2" events="50" subjects_affected="43" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="74" subjects_affected="52" subjects_at_risk="398"/>
                <counts group_id="E2" events="53" subjects_affected="39" subjects_at_risk="398"/>
              </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="75" subjects_affected="65" subjects_at_risk="398"/>
                <counts group_id="E2" events="71" subjects_affected="64" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" events="52" subjects_affected="49" subjects_at_risk="398"/>
                <counts group_id="E2" events="69" subjects_affected="62" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="24" subjects_affected="20" subjects_at_risk="398"/>
                <counts group_id="E2" events="26" subjects_affected="20" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" events="40" subjects_affected="32" subjects_at_risk="398"/>
                <counts group_id="E2" events="32" subjects_affected="25" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Laryngeal oedema</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="398"/>
                <counts group_id="E2" events="25" subjects_affected="25" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="98" subjects_affected="91" subjects_at_risk="398"/>
                <counts group_id="E2" events="79" subjects_affected="72" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pharyngeal inflammation</sub_title>
                <counts group_id="E1" events="52" subjects_affected="51" subjects_at_risk="398"/>
                <counts group_id="E2" events="48" subjects_affected="48" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="45" subjects_affected="39" subjects_at_risk="398"/>
                <counts group_id="E2" events="50" subjects_affected="42" subjects_at_risk="398"/>
              </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="15" subjects_affected="15" subjects_at_risk="398"/>
                <counts group_id="E2" events="23" subjects_affected="22" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="18" subjects_affected="17" subjects_at_risk="398"/>
                <counts group_id="E2" events="21" subjects_affected="21" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="28" subjects_affected="27" subjects_at_risk="398"/>
                <counts group_id="E2" events="21" subjects_affected="19" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="57" subjects_affected="52" subjects_at_risk="398"/>
                <counts group_id="E2" events="34" subjects_affected="27" subjects_at_risk="398"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="70" subjects_affected="59" subjects_at_risk="398"/>
                <counts group_id="E2" events="26" subjects_affected="24" subjects_at_risk="398"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="26" subjects_affected="21" subjects_at_risk="398"/>
                <counts group_id="E2" events="38" subjects_affected="33" subjects_at_risk="398"/>
              </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>The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Vice President, Global Clinical Development</name_or_title>
      <organization>Merck Sharp &amp; Dohme LLC</organization>
      <phone>1-800-672-6372</phone>
      <email>ClinicalTrialsDisclosure@merck.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/NCT03040999
org study id: 3475-412
secondary id: MK-3475-412
secondary id: 173640
secondary id: KEYNOTE-412
secondary id: 2016-003934-25
nct id: NCT03040999
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine the efficacy and safety of pembrolizumab given
      concomitantly with chemoradiation (CRT) and as maintenance therapy versus placebo plus CRT in
      participants with locally advanced head and neck squamous cell carcinoma (LA HNSCC). The
      primary hypothesis is that pembrolizumab in combination with CRT is superior to placebo in
      combination with CRT with respect to event-free survival (EFS).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Event-free Survival (EFS)
time frame: Up to approximately 62 months
description: EFS is the time from date of randomization to the date of first record of any of the following events: death due to any cause; progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR) or biopsy as indicated for locoregional progression or recurrence or distant metastasis. As well as the first record of the following types of surgery: salvage surgery for persistent or residual disease at the primary tumor site requiring surgical removal when invasive cancer is present on final pathology; neck dissection or surgery (performed for clinical or radiological disease progression per RECIST 1.1) ≤ 20 weeks from end of CRT when invasive cancer is present; or neck dissection or surgery >20 weeks from end of CRT when invasive cancer is present. From product-limit (Kaplan-Meier) method for censored data.
measure: Overall Survival (OS)
time frame: Up to approximately 62 months
description: OS is the time from randomization to death due to any cause, from product-limit (Kaplan-Meier) method for censored data. The hypothesis was that pembrolizumab in combination with CRT is superior to placebo in combination with CRT; but based on the protocol, because the statistical criterion for success in the primary EFS hypothesis was not met, the OS hypothesis was not tested
measure: Number of Participants With Adverse Events (AEs)
time frame: From time of first dose of study treatment until 90 days after last dose (up to approximately 19 months)
description: An AE is any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE is any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy.
measure: Number of Participants Discontinuing Study Drug Due to an AE
time frame: From time of first dose of study treatment until the end of treatment (up to approximately 16 months)
description: An AE is any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE is any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy.
measure: Change From Baseline in Global Health Status/Quality of Life (GHS/QoL)
time frame: Prior to the first dose of study treatment (Baseline) and up to Week 45
description: The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) contains 30 items and measures five functional dimensions (physical, role, emotional, cognitive and social), three symptom items (fatigue, nausea/vomiting, and pain), six single items (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and QoL scale. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, so that a higher score indicates a better overall GHS. A change from baseline of 10 points on the 100-point EORTC QLQ-C30 scale is considered as clinically relevant. Based on a constrained longitudinal data analysis (cLDA) model with the patient reported outcomes (PRO) scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of human papilloma virus (HPV) status and overall cancer stage.
measure: Change From Baseline in Swallowing, Speech, and Pain Symptoms
time frame: Prior to the first dose of study treatment (Baseline) and up to Week 45
description: EORTC QLQ Head and Neck Questionnaire (H&N35) consists of 7 multi-item scales (pain in the mouth, problems with swallowing, senses, speech, social eating, social contact, and sexuality), Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Change from baseline in swallowing, speech, and pain symptoms was measured. A change from baseline of 10 points on the 100-point EORTC QLQ-H&N35 is considered as clinically relevant. Based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.
measure: Change From Baseline in Physical Functioning
time frame: Prior to the first dose of study treatment (Baseline) and up to Week 45
description: Participant responded to 5 questions from the EORTC QLQ-C30 about their physical functioning scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100, where a higher score indicates a better quality of life. A change from baseline of 10 points on the 100-point scale is considered as clinically relevant. Based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.
arm group label: Pembrolizumab + Cisplatin + CRT
arm group type: Experimental
description: Participants receive a priming dose of pembrolizumab before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with pembrolizumab.
arm group label: Placebo + Cisplatin + CRT
arm group type: Placebo Comparator
description: Participants receive placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with placebo.
intervention type: Biological
intervention name: Pembrolizumab
description: Administered as an intravenous (IV) infusion every 3 weeks (Q3W)
arm group label: Pembrolizumab + Cisplatin + CRT
other name: KEYTRUDA®
intervention type: Drug
intervention name: Placebo
description: Normal saline or dextrose solution administered as an IV infusion Q3W
arm group label: Placebo + Cisplatin + CRT
intervention type: Drug
intervention name: Cisplatin
description: 100 mg/m^2 administered as an IV infusion Q3W
arm group label: Pembrolizumab + Cisplatin + CRT
arm group label: Placebo + Cisplatin + CRT
other name: Platinol®
other name: Platinol®-AQ
intervention type: Radiation
intervention name: Accelerated Fractionation (AFX) Radiotherapy
description: 70 Gray (Gy) given in 35 fractions over 6 weeks
arm group label: Pembrolizumab + Cisplatin + CRT
arm group label: Placebo + Cisplatin + CRT
intervention type: Radiation
intervention name: Standard Fractionation (SFX) Radiotherapy
description: 70 Gy given in 35 fractions over 7 weeks
arm group label: Pembrolizumab + Cisplatin + CRT
arm group label: Placebo + Cisplatin + CRT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
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country: Australia
country: Austria
country: Belgium
country: Brazil
country: Canada
country: Colombia
country: Czechia
country: France
country: Germany
country: Israel
country: Italy
country: Japan
country: Korea, Republic of
country: Netherlands
country: New Zealand
country: Poland
country: Spain
country: Taiwan
country: Turkey
country: United Kingdom
country: United States
country: Argentina
country: Chile
country: Czech Republic
country: Hungary
country: Mexico
country: Puerto Rico
country: Ukraine
url: http://merckoncologyclinicaltrials.com
description: Merck Oncology Clinical Trial Information
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Head and Neck Neoplasms
mesh term: Cisplatin
mesh term: Pembrolizumab
sharing ipd: Yes
ipd description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 