<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/NCT01665144</url>
  </required_header>
  <id_info>
    <org_study_id>CBAF312A2304</org_study_id>
    <nct_id>NCT01665144</nct_id>
  </id_info>
  <brief_title>Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)</brief_title>
  <official_title>A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Variable Treatment Duration Study Evaluating the Efficacy and Safety of Siponimod (BAF312) in Patients With Secondary Progressive Multiple Sclerosis Followed by Extended Treatment With Open-label BAF312.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <brief_summary>
    <textblock>
      Evaluate the safety and efficacy of Siponimod (BAF312) versus placebo in a variable treatment&#xD;
      duration in patients with secondary progressive multiple sclerosis (Core Part) followed by&#xD;
      extended treatment with open-label BAF312 to obtain data on long-term safety, tolerability&#xD;
      and efficacy (Extension Part).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 20, 2012</start_date>
  <completion_date type="Anticipated">March 1, 2024</completion_date>
  <primary_completion_date type="Actual">April 29, 2016</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>Percentage of Participants With 3-month Confirmed Disibility Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS)</measure>
    <time_frame>Baseline, every 3 month up to the maximum of approximately 3 years</time_frame>
    <description>The EDSS uses an ordinal scale to assess neurologic impairment in MS based on a neurological examination. Scores in each of 7 functional systems (Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel &amp; Bladder, and Cerebral) and an ambulation score were combined to determine the EDSS steps, ranging from 0 (normal) to 10 (death due to MS). Confirmed disability is defined as an increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy of BAF312 Relative to Placebo in Confirmed Worsening of 25 Foot Walk Test</measure>
    <time_frame>Baseline , every 3 months up to the maximum of approximately 3 years</time_frame>
    <description>Delay in time to 3 month confirmed worsening of at least 20% from baseline in the timed 25 foot walk test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy of BAF312 Relative to Placebo in Reducing the Increase in T2 Lesion Volume</measure>
    <time_frame>Baseline, every year up to the maximum of approximately 3 years</time_frame>
    <description>Efficacy is shown by the reduction of the increase in T1 lesion volume.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Delay in Time to Confirmed Disability Progression as Measured by EDSS.</measure>
    <time_frame>Baseline, every 6 months up to the maximum of approximately 3 years</time_frame>
    <description>Confirmed disability is defined as increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy of BAF Relative to Placebo in Annualized Relapses Rate and Time to the First Relapse</measure>
    <time_frame>Baseline every 3 months up to the maximum of approximately 3 years</time_frame>
    <description>Efficacy of BAF312 relative to placebo was measured by the effect on confirmed relapses rate, the time to the first relapse, and proportion of patient free from relapses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate on the MSWS-12.</measure>
    <time_frame>Baseline, every 6 months up to the maximum of approximately 3 years</time_frame>
    <description>The overall response of the effect of BAF312 compared to placebo patients on the patient reported outcome form MSWS-12.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect on Inflammatory Disease Activity and Burden of Disease as Measured by MRI</measure>
    <time_frame>Baseline, every 12 month up to the maximum of approximately 3 years</time_frame>
    <description>Effect of BAF312 relative to placebo on disease activity and burden of disease as measured by Gd-T1 lesion, new/enlarged T2 lesion, and brain atrophy on brain MRI scans.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect on 3-month Confirmed Disability Progression as Defined by EDSS in Predefined Sub-groups</measure>
    <time_frame>Baseline, every 3 months up to the maximum of approximately 3 years</time_frame>
    <description>effect on confirmed disability progression in pre-defined subgroups, including patients with or without superimposed relapses, rapidly evolving patients with 1.5 point or greater change in EDSS score in 2 years prior to enrollment into the study. Patients with score of 4 or more in MSSS and those who don't meet this criteria.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1652</enrollment>
  <condition>Secondary Progressive Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Siponimod (BAF312)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants started on Day 1 and were uptitrated from 0.25 mg to 2 mg of BAF312 orally over a period of 6 days. After Day 7, participants continued on the treatment epoch for 3 months. During the Core Part of the study, participants participated in a maximum of 3 epochs. Following the Core Part, eligible patients enter the Extension Part during which all receive open-label BAF312.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching placebo to BAF312 was administered orally during the Core Part of the trial. Following the Core Part, eligible participants enter the Extension Part during which all receive open-label BAF312.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BAF312</intervention_name>
    <description>0.25, 0.5, 1, and 2 mg film-coated tablets</description>
    <arm_group_label>Siponimod (BAF312)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Film-coated tablets</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Prior history of relapsing remitting MS&#xD;
&#xD;
          -  SPMS defined as progressive increase of disability over at least 6 months&#xD;
&#xD;
          -  EDSS score of 3.0 to 6.5&#xD;
&#xD;
          -  No relapse of corticosteroid treatment within 3 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women of child bearing potential must use reliable forms of contraception.&#xD;
&#xD;
          -  Diagnosis of Macular edema during screening period&#xD;
&#xD;
          -  Any medically unstable condition determined by investigator.&#xD;
&#xD;
          -  Unable to undergo MRI scans&#xD;
&#xD;
          -  Hypersensitivity to any study drugs or drugs of similar class Other protocol defined&#xD;
             inclusion/exclusion may apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berkeley</city>
        <state>California</state>
        <zip>94705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Oceanside</city>
        <state>California</state>
        <zip>92056</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Basalt</city>
        <state>Colorado</state>
        <zip>81621</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Boulder</city>
        <state>Colorado</state>
        <zip>80301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80907</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Englewood</city>
        <state>Colorado</state>
        <zip>80113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Fairfield</city>
        <state>Connecticut</state>
        <zip>06824</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Delray Beach</city>
        <state>Florida</state>
        <zip>33445</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Maitland</city>
        <state>Florida</state>
        <zip>32751</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ormond Beach</city>
        <state>Florida</state>
        <zip>32174</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Port Charlotte</city>
        <state>Florida</state>
        <zip>33952</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sunrise</city>
        <state>Florida</state>
        <zip>33351</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Vero Beach</city>
        <state>Florida</state>
        <zip>32960</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <zip>60201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Flossmoor</city>
        <state>Illinois</state>
        <zip>60422</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lenexa</city>
        <state>Kansas</state>
        <zip>66212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Golden Valley</city>
        <state>Minnesota</state>
        <zip>55422</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63131</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Freehold</city>
        <state>New Jersey</state>
        <zip>07728</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87131-0001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Patchogue</city>
        <state>New York</state>
        <zip>11772</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Stony Brook</city>
        <state>New York</state>
        <zip>11794</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Akron</city>
        <state>Ohio</state>
        <zip>44320</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dayton</city>
        <state>Ohio</state>
        <zip>45408</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Springfield</city>
        <state>Oregon</state>
        <zip>97477</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lubbock</city>
        <state>Texas</state>
        <zip>79410</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78258</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Burlington</city>
        <state>Vermont</state>
        <zip>05401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <zip>1425</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <zip>C1181ACH</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <zip>C1428AQK</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Capital Federal</city>
        <state>Buenos Aires</state>
        <zip>1424</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Buenos Aires</city>
        <zip>1061</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Cordoba</city>
        <zip>X5000FAL</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Camperdown</city>
        <state>New South Wales</state>
        <zip>2050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kogarah</city>
        <state>New South Wales</state>
        <zip>2217</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Liverpool</city>
        <state>New South Wales</state>
        <zip>2170</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Heidelberg</city>
        <state>Victoria</state>
        <zip>3084</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Klagenfurt</city>
        <zip>9020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Wien</city>
        <zip>1010</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Edegem</city>
        <state>Antwerpen</state>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Brugge</city>
        <zip>8000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bruxelles</city>
        <zip>1070</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Fraiture En Condroz</city>
        <zip>4557</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pelt</city>
        <zip>3900</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sijsele</city>
        <zip>8340</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sofia</city>
        <zip>1113</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sofia</city>
        <zip>1413</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sofia</city>
        <zip>1431</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Varna</city>
        <zip>9010</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 2T9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2G3</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Burnaby</city>
        <state>British Columbia</state>
        <zip>V5G 2X6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3H 4K4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kingston</city>
        <state>Ontario</state>
        <zip>K7L 2V7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Greenfield Park</city>
        <state>Quebec</state>
        <zip>J4V 2J2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2X 0A9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3A 2B4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100034</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Changchun</city>
        <state>Jilin</state>
        <zip>130021</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taiyuan</city>
        <state>Shanxi</state>
        <zip>030001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Xi'an</city>
        <state>Shanxi</state>
        <zip>710038</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <zip>100028</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shanghai</city>
        <zip>200040</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Brno</city>
        <state>Czech Rep.</state>
        <zip>625 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Teplice</city>
        <state>Czech Republic</state>
        <zip>415 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>JIhlava</city>
        <zip>586 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Prague 5</city>
        <zip>150 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Praha</city>
        <zip>12808</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tallinn</city>
        <zip>10138</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tallinn</city>
        <zip>10617</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nancy</city>
        <state>Cedex</state>
        <zip>54035</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bordeaux Cedex</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>CAEN Cedex</city>
        <zip>14033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lille Cedex</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Marseille Cedex 05</city>
        <zip>13885</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nimes</city>
        <zip>30029</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Paris Cedex 13</city>
        <zip>75651</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Rennes</city>
        <zip>35043</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>St Herblain</city>
        <zip>44800</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Strasbourg</city>
        <zip>67091</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Regensburg</city>
        <state>Bavaria</state>
        <zip>93053</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Aschaffenburg</city>
        <zip>63739</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bad Mergentheim</city>
        <zip>97980</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bayreuth</city>
        <zip>95445</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berg</city>
        <zip>82335</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>10713</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>13347</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bielefeld</city>
        <zip>33647</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Boblingen</city>
        <zip>71032</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bochum</city>
        <zip>44791</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bonn</city>
        <zip>53111</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Erbach</city>
        <zip>64711</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Erlangen</city>
        <zip>91054</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Frankfurt</city>
        <zip>60313</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Freiburg</city>
        <zip>79106</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hamburg</city>
        <zip>20249</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hamburg</city>
        <zip>22083</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hannover</city>
        <zip>30171</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hannover</city>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Homburg</city>
        <zip>66421</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Itzehoe</city>
        <zip>25524</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Jena</city>
        <zip>07740</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kassel</city>
        <zip>34121</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Leipzig</city>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Leipzig</city>
        <zip>04107</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Muenchen</city>
        <zip>80377</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Muenster</city>
        <zip>48149</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Neuburg an der Donau</city>
        <zip>86633</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Oldenburg</city>
        <zip>26122</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Potsdam</city>
        <zip>14471</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Prien</city>
        <zip>83209</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Rostock</city>
        <zip>18057</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Schwendi</city>
        <zip>88477</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Siegen</city>
        <zip>57076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Stade</city>
        <zip>21682</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Stadtroda</city>
        <zip>07646</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Teupitz</city>
        <zip>15755</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ulm</city>
        <zip>89073</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Unterhaching</city>
        <zip>82008</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Wiesbaden</city>
        <zip>65191</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Athens</city>
        <zip>106 76</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Heraklion Crete</city>
        <zip>711 10</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Thessaloniki</city>
        <zip>GR 54636</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Budapest</city>
        <state>HUN</state>
        <zip>1135</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Budapest</city>
        <state>HUN</state>
        <zip>1145</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Budapest</city>
        <state>HUN</state>
        <zip>1204</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Esztergom</city>
        <state>HUN</state>
        <zip>2500</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Balassagyarmat</city>
        <zip>2660</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Budapest</city>
        <zip>1085</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Budapest</city>
        <zip>1106</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Eger</city>
        <zip>H-3300</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Miskolc</city>
        <zip>3526</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nyiregyhaza</city>
        <zip>4400</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Veszprem</city>
        <zip>H 8200</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dublin 9</city>
        <state>D9</state>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dublin 4</city>
        <zip>D04 T6F</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Jerusalem</city>
        <zip>9112001</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ramat Gan</city>
        <zip>52621</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Genova</city>
        <state>GE</state>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Cefalu</city>
        <state>PA</state>
        <zip>90015</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00152</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00161</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00179</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Toon-city</city>
        <state>Ehime</state>
        <zip>791-0295</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Asahikawa-city</city>
        <state>Hokkaido</state>
        <zip>070-8644</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Morioka</city>
        <state>Iwate</state>
        <zip>020-8505</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kyoto-city</city>
        <state>Kyoto</state>
        <zip>616-8147</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Suita</city>
        <state>Osaka</state>
        <zip>565 0871</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kawagoe</city>
        <state>Saitama</state>
        <zip>350 8550</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tokorozawa city</city>
        <state>Saitama</state>
        <zip>359 8513</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kodaira</city>
        <state>Tokyo</state>
        <zip>187-8551</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ota-ku</city>
        <state>Tokyo</state>
        <zip>145-0065</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shinjuku ku</city>
        <state>Tokyo</state>
        <zip>162 8666</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shinjuku-ku</city>
        <state>Tokyo</state>
        <zip>160 8582</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Aomori</city>
        <zip>030 8553</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chiba</city>
        <zip>260 8677</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Osaka</city>
        <zip>556-0016</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Riga</city>
        <state>LV</state>
        <zip>LV-1005</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Riga</city>
        <zip>LV 1002</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Riga</city>
        <zip>LV-1038</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kaunas</city>
        <state>LTU</state>
        <zip>LT 50161</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Klaipeda</city>
        <zip>LT-92288</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Vilnius</city>
        <zip>LT-08661</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Breda</city>
        <state>CK</state>
        <zip>4818 CK</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Amsterdam</city>
        <zip>1105 AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Eindhoven</city>
        <zip>5623 EJ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hoorn</city>
        <zip>1624 NP</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sittard-Geleen</city>
        <zip>6162 BG</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tilburg</city>
        <zip>5022 GC</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Grudziadz</city>
        <zip>86 300</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Katowice</city>
        <zip>40 571</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kielce</city>
        <zip>25 726</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Konskie</city>
        <zip>26 200</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Krakow</city>
        <zip>31-637</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lodz</city>
        <zip>90 324</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Poznan</city>
        <zip>60-355</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Warszawa</city>
        <zip>02-957</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Amadora</city>
        <zip>2720-276</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Braga</city>
        <zip>4710243</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Coimbra</city>
        <zip>3000 075</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lisboa</city>
        <zip>1600190</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Porto</city>
        <zip>4099-001</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Constanta</city>
        <state>Jud. Constanta</state>
        <zip>900591</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bucharest</city>
        <zip>020125</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bucharest</city>
        <zip>050098</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Suceava</city>
        <zip>727525</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Targu Mures</city>
        <zip>540136</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Timisoara</city>
        <zip>300736</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barnaul</city>
        <zip>656024</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kazan</city>
        <zip>420043</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Moscow</city>
        <zip>119049</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Moscow</city>
        <zip>127018</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Novosibirsk</city>
        <zip>630007</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>194044</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>St. Petersburg</city>
        <zip>197110</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>St. Petersburg</city>
        <zip>197376</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ufa</city>
        <zip>450000</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Banska Bystrica</city>
        <zip>97517</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bratislava</city>
        <zip>813 69</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bratislava</city>
        <zip>826 06</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Martin</city>
        <zip>036 59</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nitra</city>
        <zip>94911</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Presov</city>
        <zip>081 81</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Trencin</city>
        <zip>91171</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Trnava</city>
        <zip>917 75</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Malaga</city>
        <state>Andalucia</state>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sevilla</city>
        <state>Andalucia</state>
        <zip>41009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barcelona</city>
        <state>Cataluna</state>
        <zip>08026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Badalona</city>
        <state>Catalunya</state>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barcelona</city>
        <state>Catalunya</state>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barcelona</city>
        <state>Catalunya</state>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>L Hospitalet De Llobregat</city>
        <state>Catalunya</state>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Valencia</city>
        <state>Comunidad Valenciana</state>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Valencia</city>
        <state>Comunidad Valenciana</state>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>El Palmar</city>
        <state>Murcia</state>
        <zip>30120</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bilbao</city>
        <state>Pais Vasco</state>
        <zip>48013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Sebastian</city>
        <state>Pais Vasco</state>
        <zip>20080</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Madrid</city>
        <zip>28222</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Goeteborg</city>
        <zip>413 45</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Stockholm</city>
        <zip>102 35</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Stockholm</city>
        <zip>10235</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Aarau</city>
        <state>CH</state>
        <zip>5001</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Basel</city>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lausanne</city>
        <zip>1011</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lugano</city>
        <zip>6900</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Luzern</city>
        <zip>6000</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>St Gallen</city>
        <zip>9007</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Zuerich</city>
        <zip>8091</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Istanbul</city>
        <state>TUR</state>
        <zip>34098</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Altunizade</city>
        <zip>34662</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Haseki / Istanbul</city>
        <zip>34096</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kocaeli</city>
        <zip>41380</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Mecidiyekoy/Istanbul</city>
        <zip>34394</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Samsun</city>
        <zip>55139</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Trabzon</city>
        <zip>61080</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Salford</city>
        <state>Manchester</state>
        <zip>M6 8HD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Headington</city>
        <state>Oxfordshire</state>
        <zip>OX3 9DU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sheffield</city>
        <state>South Yorkshire</state>
        <zip>S10 2JF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bristol</city>
        <zip>BS10 5NB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Glasgow</city>
        <zip>G51 4TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Leeds</city>
        <zip>LS1 3EX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Leicester</city>
        <zip>LE5 4PW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>London</city>
        <zip>EC1A 7BE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>London</city>
        <zip>W8 6RF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Newcastle Upon Tyne</city>
        <zip>NE1 4LP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Bulgaria</country>
    <country>Canada</country>
    <country>China</country>
    <country>Czechia</country>
    <country>Estonia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>Hungary</country>
    <country>Ireland</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Latvia</country>
    <country>Lithuania</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Romania</country>
    <country>Russian Federation</country>
    <country>Slovakia</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Switzerland</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
    <country>Egypt</country>
  </removed_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>August 3, 2012</study_first_submitted>
  <study_first_submitted_qc>August 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2012</study_first_posted>
  <results_first_submitted>August 6, 2018</results_first_submitted>
  <results_first_submitted_qc>October 4, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">October 31, 2018</results_first_posted>
  <last_update_submitted>January 11, 2023</last_update_submitted>
  <last_update_submitted_qc>January 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Secondary Progressive Multiple Sclerosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Multiple Sclerosis, Chronic Progressive</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Siponimod</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com&#xD;
Locations: central Contact Info Novartis.email@novartis.com</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>During the core, eligible patients were randomized in a 2:1 ratio to siponimod (BAF312) or placebo.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Siponimod (BAF312)</title>
          <description>Participants started on Day 1 and were uptitrated from 0.25 mg to 2 mg of BAF312 orally over a period of 6 days. After Day 7, participants continued on 2 mg BAF312 daily for a variable duration.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Matching placebo to BAF312 was administered orally during the Core Part of the trial.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1105"/>
                <participants group_id="P2" count="546"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Set</title>
              <participants_list>
                <participants group_id="P1" count="1099"/>
                <participants group_id="P2" count="546"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Full Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="1099"/>
                <participants group_id="P2" count="546"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="903"/>
                <participants group_id="P2" count="424"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="202"/>
                <participants group_id="P2" count="122"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>New therapy for study indication</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Technical problems</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol deviation</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliance w/study treatment</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive disease</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="96"/>
                <participants group_id="P2" count="77"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Siponimod (BAF312)</title>
          <description>Participants started on Day 1 and were uptitrated from 0.25 mg to 2 mg of BAF312 orally over a period of 6 days. After Day 7, participants continued on 2 mg BAF312 daily for a variable duration.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Matching placebo to BAF312 was administered orally during the Core Part of the trial.</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="1105"/>
            <count group_id="B2" value="546"/>
            <count group_id="B3" value="1651"/>
          </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="48.0" spread="7.84"/>
                    <measurement group_id="B2" value="48.1" spread="7.94"/>
                    <measurement group_id="B3" value="48.0" spread="7.87"/>
                  </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="669"/>
                    <measurement group_id="B2" value="323"/>
                    <measurement group_id="B3" value="992"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="436"/>
                    <measurement group_id="B2" value="223"/>
                    <measurement group_id="B3" value="659"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="49"/>
                  </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="7"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1050"/>
                    <measurement group_id="B2" value="513"/>
                    <measurement group_id="B3" value="1563"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With 3-month Confirmed Disibility Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS)</title>
        <description>The EDSS uses an ordinal scale to assess neurologic impairment in MS based on a neurological examination. Scores in each of 7 functional systems (Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel &amp; Bladder, and Cerebral) and an ambulation score were combined to determine the EDSS steps, ranging from 0 (normal) to 10 (death due to MS). Confirmed disability is defined as an increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5.</description>
        <time_frame>Baseline, every 3 month up to the maximum of approximately 3 years</time_frame>
        <population>The Full analysis set (FAS), which comprised all randomized patients with assigned treatments who took at least one dose of study medication, was considered for the analysis. Only participants from the FAS with non-missing covariates were analyzed for this outcome.</population>
        <group_list>
          <group group_id="O1">
            <title>Siponimod (BAF312)</title>
            <description>Participants started on Day 1 and were uptitrated from 0.25 mg to 2 mg of BAF312 orally over a period of 6 days. After Day 7, participants continued on 2 mg BAF312 daily for a variable duration.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo to BAF312 was administered orally during the Core Part of the trial.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With 3-month Confirmed Disibility Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS)</title>
          <description>The EDSS uses an ordinal scale to assess neurologic impairment in MS based on a neurological examination. Scores in each of 7 functional systems (Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel &amp; Bladder, and Cerebral) and an ambulation score were combined to determine the EDSS steps, ranging from 0 (normal) to 10 (death due to MS). Confirmed disability is defined as an increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5.</description>
          <population>The Full analysis set (FAS), which comprised all randomized patients with assigned treatments who took at least one dose of study medication, was considered for the analysis. Only participants from the FAS with non-missing covariates were analyzed for this outcome.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1096"/>
                <count group_id="O2" value="545"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.3"/>
                    <measurement group_id="O2" value="31.7"/>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0134</p_value>
            <method>Cox proportional hazards model</method>
            <param_type>Cox Proportional Hazard</param_type>
            <param_value>0.79</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.65</ci_lower_limit>
            <ci_upper_limit>0.95</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy of BAF312 Relative to Placebo in Confirmed Worsening of 25 Foot Walk Test</title>
        <description>Delay in time to 3 month confirmed worsening of at least 20% from baseline in the timed 25 foot walk test.</description>
        <time_frame>Baseline , every 3 months up to the maximum of approximately 3 years</time_frame>
        <posting_date>07/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy of BAF312 Relative to Placebo in Reducing the Increase in T2 Lesion Volume</title>
        <description>Efficacy is shown by the reduction of the increase in T1 lesion volume.</description>
        <time_frame>Baseline, every year up to the maximum of approximately 3 years</time_frame>
        <posting_date>07/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Delay in Time to Confirmed Disability Progression as Measured by EDSS.</title>
        <description>Confirmed disability is defined as increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5.</description>
        <time_frame>Baseline, every 6 months up to the maximum of approximately 3 years</time_frame>
        <posting_date>07/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy of BAF Relative to Placebo in Annualized Relapses Rate and Time to the First Relapse</title>
        <description>Efficacy of BAF312 relative to placebo was measured by the effect on confirmed relapses rate, the time to the first relapse, and proportion of patient free from relapses.</description>
        <time_frame>Baseline every 3 months up to the maximum of approximately 3 years</time_frame>
        <posting_date>07/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Response Rate on the MSWS-12.</title>
        <description>The overall response of the effect of BAF312 compared to placebo patients on the patient reported outcome form MSWS-12.</description>
        <time_frame>Baseline, every 6 months up to the maximum of approximately 3 years</time_frame>
        <posting_date>07/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Effect on Inflammatory Disease Activity and Burden of Disease as Measured by MRI</title>
        <description>Effect of BAF312 relative to placebo on disease activity and burden of disease as measured by Gd-T1 lesion, new/enlarged T2 lesion, and brain atrophy on brain MRI scans.</description>
        <time_frame>Baseline, every 12 month up to the maximum of approximately 3 years</time_frame>
        <posting_date>07/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Effect on 3-month Confirmed Disability Progression as Defined by EDSS in Predefined Sub-groups</title>
        <description>effect on confirmed disability progression in pre-defined subgroups, including patients with or without superimposed relapses, rapidly evolving patients with 1.5 point or greater change in EDSS score in 2 years prior to enrollment into the study. Patients with score of 4 or more in MSSS and those who don't meet this criteria.</description>
        <time_frame>Baseline, every 3 months up to the maximum of approximately 3 years</time_frame>
        <posting_date>07/2024</posting_date>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3.5 years.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Siponimod (BAF312)</title>
          <description>Participants started on Day 1 and were uptitrated from 0.25 mg to 2 mg of BAF312 orally over a period of 6 days. After Day 7, participants continued on 2 mg BAF312 daily for a variable duration.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Matching placebo to BAF312 was administered orally during the Core Part of the trial.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (19.0)</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="4" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="197" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="83" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>ANAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>LEUKOPENIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>THROMBOCYTOPENIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>ACUTE CORONARY SYNDROME</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>ACUTE MYOCARDIAL INFARCTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>ANGINA PECTORIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>ATRIAL FIBRILLATION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>ATRIOVENTRICULAR BLOCK SECOND DEGREE</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>BRADYCARDIA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>BUNDLE BRANCH BLOCK LEFT</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>CORONARY ARTERY DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>MYOCARDIAL ISCHAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>PALPITATIONS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SINUS TACHYCARDIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SUPRAVENTRICULAR TACHYCARDIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>VERTIGO</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>BLINDNESS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>CATARACT</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>DIPLOPIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>MACULAR OEDEMA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>RETINAL DETACHMENT</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>RETINOSCHISIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>ABDOMINAL PAIN UPPER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>ANAL FISSURE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>CONSTIPATION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>DIARRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>DUODENAL ULCER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>GASTRIC ULCER PERFORATION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>GASTRITIS EROSIVE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>INCARCERATED INGUINAL HERNIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>INGUINAL HERNIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>INTESTINAL OBSTRUCTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>OESOPHAGITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>PANCREATITIS ACUTE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SMALL INTESTINAL OBSTRUCTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>UMBILICAL HERNIA, OBSTRUCTIVE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>VOMITING</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>ASTHENIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>FATIGUE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>GAIT DISTURBANCE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>OEDEMA PERIPHERAL</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>PYREXIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>BILIARY COLIC</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>CHOLECYSTITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>CHOLECYSTITIS ACUTE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>CHOLELITHIASIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HEPATOTOXICITY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>NON-ALCOHOLIC STEATOHEPATITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERSENSITIVITY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>APPENDICEAL ABSCESS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>APPENDICITIS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>BACTERAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>CAMPYLOBACTER GASTROENTERITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>CELLULITIS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>CHORIORETINITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>DIVERTICULITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>ESCHERICHIA URINARY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>GASTROENTERITIS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>GASTROENTERITIS PROTEUS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HEPATITIS E</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HERPES ZOSTER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HERPES ZOSTER MENINGITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>INFLUENZA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>LABYRINTHITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>NASAL ABSCESS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>ORAL VIRAL INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>PNEUMONIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>POSTOPERATIVE WOUND INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>PYELONEPHRITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>PYELONEPHRITIS CHRONIC</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SEPSIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SEPTIC SHOCK</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>URINARY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>UROSEPSIS</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>WOUND INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>ANKLE FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>CERVICAL VERTEBRAL FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>CLAVICLE FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>CONCUSSION</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>CONTUSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>EYE CONTUSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>FALL</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>FEMORAL NECK FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>FRACTURE DISPLACEMENT</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HEAD INJURY</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HIP FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>INJURY CORNEAL</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>LACERATION</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>LOWER LIMB FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>MENISCUS INJURY</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>RADIUS FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>RIB FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SPINAL COMPRESSION FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SPLENIC RUPTURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SUBDURAL HAEMATOMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>TENDON RUPTURE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>THERMAL BURN</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>TIBIA FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>TRAUMATIC FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>TRAUMATIC HAEMORRHAGE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>TRAUMATIC HAEMOTHORAX</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>TRAUMATIC LIVER INJURY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>ALANINE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>ASPARTATE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>BLOOD BILIRUBIN INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>BLOOD GLUCOSE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>CARBON MONOXIDE DIFFUSING CAPACITY DECREASED</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>COLUMBIA SUICIDE SEVERITY RATING SCALE ABNORMAL</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HEART RATE DECREASED</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HEPATIC ENZYME ABNORMAL</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HEPATIC ENZYME INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>LIVER FUNCTION TEST ABNORMAL</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>PULMONARY FUNCTION TEST DECREASED</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>WALKING DISTANCE TEST ABNORMAL</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>WEIGHT DECREASED</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>DEHYDRATION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HAEMOCHROMATOSIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SHOCK HYPOGLYCAEMIC</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ARTHRALGIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>ARTHRITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>BACK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>BURSITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>FOOT DEFORMITY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>INTERVERTEBRAL DISC PROTRUSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>LUMBAR SPINAL STENOSIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>MUSCULAR WEAKNESS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>MUSCULOSKELETAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>MUSCULOSKELETAL STIFFNESS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>OSTEOARTHRITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>PATELLOFEMORAL PAIN SYNDROME</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SPINAL DEFORMITY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SYNOVIAL CYST</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </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" subjects_affected="11" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>BENIGN NEOPLASM OF THYROID GLAND</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>BLADDER CANCER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>BOWEN'S DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>BREAST CANCER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>CENTRAL NERVOUS SYSTEM LYMPHOMA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>COLON CANCER STAGE IV</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>ENDOMETRIAL CANCER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>GASTRIC CANCER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>GASTROINTESTINAL MELANOMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>GLIOMA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>LIP SQUAMOUS CELL CARCINOMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>LUNG ADENOCARCINOMA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>LUNG ADENOCARCINOMA METASTATIC</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>MALIGNANT MELANOMA IN SITU</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>MELANOCYTIC NAEVUS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>NEUROFIBROMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>PROSTATE CANCER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>RENAL ONCOCYTOMA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SEMINOMA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SQUAMOUS CELL CARCINOMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>UTERINE LEIOMYOMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>ALLODYNIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>AMNESTIC DISORDER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>APHASIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>ATAXIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>BRAIN INJURY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>BRAIN STEM INFARCTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>CEREBROVASCULAR ACCIDENT</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>DISTURBANCE IN ATTENTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>DYSAESTHESIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>EPILEPSY</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>GENERALISED TONIC-CLONIC SEIZURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HAEMORRHAGIC STROKE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HEAD TITUBATION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HEMIPARESIS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HYPOAESTHESIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>INTENTION TREMOR</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>INTRACRANIAL ANEURYSM</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>ISCHAEMIC STROKE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>MERALGIA PARAESTHETICA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>MULTIPLE SCLEROSIS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>MULTIPLE SCLEROSIS RELAPSE</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>MUSCLE SPASTICITY</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>PARAPARESIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>PARTIAL SEIZURES</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>POLYNEUROPATHY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>PUTAMEN HAEMORRHAGE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>RADICULOPATHY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SEIZURE</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>STATUS MIGRAINOSUS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SUBARACHNOID HAEMATOMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SYNCOPE</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>TRANSIENT ISCHAEMIC ATTACK</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>TREMOR</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>TRIGEMINAL NEURALGIA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>ABORTION SPONTANEOUS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>ANXIETY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>ANXIETY DISORDER DUE TO A GENERAL MEDICAL CONDITION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>COMPLETED SUICIDE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>DEPRESSED MOOD</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>DEPRESSION</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>DEPRESSION SUICIDAL</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>DEPRESSIVE SYMPTOM</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>EUPHORIC MOOD</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HALLUCINATION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>MANIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>MENTAL STATUS CHANGES</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>PANIC ATTACK</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>PSYCHOTIC DISORDER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SUICIDAL BEHAVIOUR</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SUICIDAL IDEATION</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SUICIDE ATTEMPT</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="546"/>
              </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" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>BLADDER DYSFUNCTION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>CALCULUS BLADDER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HYDRONEPHROSIS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>NEPHROLITHIASIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>NEUROGENIC BLADDER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>SINGLE FUNCTIONAL KIDNEY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>URETEROLITHIASIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>URETHRAL STENOSIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>URGE INCONTINENCE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>URINARY INCONTINENCE</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>URINARY RETENTION</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>CERVICAL DYSPLASIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>MENORRHAGIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>METRORRHAGIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>OVARIAN DISORDER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>TESTICULAR ATROPHY</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>PNEUMONIA ASPIRATION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>PULMONARY EMBOLISM</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>PULMONARY HYPERTENSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>RESPIRATORY DEPRESSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>RESPIRATORY DISORDER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ACTINIC KERATOSIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>DECUBITUS ULCER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>RASH</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>RASH PAPULAR</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Social circumstances</title>
            <event_list>
              <event>
                <sub_title>IMMOBILE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>WALKING DISABILITY</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>CIRCULATORY COLLAPSE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>DEEP VEIN THROMBOSIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HAEMATOMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HYPERTENSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>ORTHOSTATIC HYPOTENSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>VENOUS THROMBOSIS LIMB</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (19.0)</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="698" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="311" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>DIARRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="69" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" subjects_affected="73" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>FATIGUE</sub_title>
                <counts group_id="E1" subjects_affected="100" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="51" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>INFLUENZA</sub_title>
                <counts group_id="E1" subjects_affected="72" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="40" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>NASOPHARYNGITIS</sub_title>
                <counts group_id="E1" subjects_affected="149" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="79" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="89" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="41" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>URINARY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="128" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="75" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>FALL</sub_title>
                <counts group_id="E1" subjects_affected="126" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="59" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>ALANINE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="58" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ARTHRALGIA</sub_title>
                <counts group_id="E1" subjects_affected="49" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>BACK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="66" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="43" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>PAIN IN EXTREMITY</sub_title>
                <counts group_id="E1" subjects_affected="60" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" subjects_affected="74" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="546"/>
              </event>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" subjects_affected="159" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="71" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>DEPRESSION</sub_title>
                <counts group_id="E1" subjects_affected="44" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="546"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERTENSION</sub_title>
                <counts group_id="E1" subjects_affected="114" subjects_at_risk="1099"/>
                <counts group_id="E2" subjects_affected="41" subjects_at_risk="546"/>
              </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 terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Novartis Pharmaceuticals</organization>
      <phone>862-778-8300</phone>
      <email>novartis.email@novartis.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/NCT01665144
org study id: CBAF312A2304
nct id: NCT01665144
lead sponsor: 
Evaluate the safety and efficacy of Siponimod (BAF312) versus placebo in a variable treatment
      duration in patients with secondary progressive multiple sclerosis (Core Part) followed by
      extended treatment with open-label BAF312 to obtain data on long-term safety, tolerability
      and efficacy (Extension Part).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Percentage of Participants With 3-month Confirmed Disibility Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS)
time frame: Baseline, every 3 month up to the maximum of approximately 3 years
description: The EDSS uses an ordinal scale to assess neurologic impairment in MS based on a neurological examination. Scores in each of 7 functional systems (Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel & Bladder, and Cerebral) and an ambulation score were combined to determine the EDSS steps, ranging from 0 (normal) to 10 (death due to MS). Confirmed disability is defined as an increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5.
measure: Efficacy of BAF312 Relative to Placebo in Confirmed Worsening of 25 Foot Walk Test
time frame: Baseline , every 3 months up to the maximum of approximately 3 years
description: Delay in time to 3 month confirmed worsening of at least 20% from baseline in the timed 25 foot walk test.
measure: Efficacy of BAF312 Relative to Placebo in Reducing the Increase in T2 Lesion Volume
time frame: Baseline, every year up to the maximum of approximately 3 years
description: Efficacy is shown by the reduction of the increase in T1 lesion volume.
measure: The Delay in Time to Confirmed Disability Progression as Measured by EDSS.
time frame: Baseline, every 6 months up to the maximum of approximately 3 years
description: Confirmed disability is defined as increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5.
measure: Efficacy of BAF Relative to Placebo in Annualized Relapses Rate and Time to the First Relapse
time frame: Baseline every 3 months up to the maximum of approximately 3 years
description: Efficacy of BAF312 relative to placebo was measured by the effect on confirmed relapses rate, the time to the first relapse, and proportion of patient free from relapses.
measure: Overall Response Rate on the MSWS-12.
time frame: Baseline, every 6 months up to the maximum of approximately 3 years
description: The overall response of the effect of BAF312 compared to placebo patients on the patient reported outcome form MSWS-12.
measure: Effect on Inflammatory Disease Activity and Burden of Disease as Measured by MRI
time frame: Baseline, every 12 month up to the maximum of approximately 3 years
description: Effect of BAF312 relative to placebo on disease activity and burden of disease as measured by Gd-T1 lesion, new/enlarged T2 lesion, and brain atrophy on brain MRI scans.
measure: Effect on 3-month Confirmed Disability Progression as Defined by EDSS in Predefined Sub-groups
time frame: Baseline, every 3 months up to the maximum of approximately 3 years
description: effect on confirmed disability progression in pre-defined subgroups, including patients with or without superimposed relapses, rapidly evolving patients with 1.5 point or greater change in EDSS score in 2 years prior to enrollment into the study. Patients with score of 4 or more in MSSS and those who don't meet this criteria.
arm group label: Siponimod (BAF312)
arm group type: Experimental
description: Participants started on Day 1 and were uptitrated from 0.25 mg to 2 mg of BAF312 orally over a period of 6 days. After Day 7, participants continued on the treatment epoch for 3 months. During the Core Part of the study, participants participated in a maximum of 3 epochs. Following the Core Part, eligible patients enter the Extension Part during which all receive open-label BAF312.
arm group label: Placebo
arm group type: Placebo Comparator
description: Matching placebo to BAF312 was administered orally during the Core Part of the trial. Following the Core Part, eligible participants enter the Extension Part during which all receive open-label BAF312.
intervention type: Drug
intervention name: BAF312
description: 0.25, 0.5, 1, and 2 mg film-coated tablets
arm group label: Siponimod (BAF312)
intervention type: Drug
intervention name: Placebo
description: Film-coated tablets
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Argentina
country: Australia
country: Austria
country: Belgium
country: Bulgaria
country: Canada
country: China
country: Czechia
country: Estonia
country: France
country: Germany
country: Greece
country: Hungary
country: Ireland
country: Israel
country: Italy
country: Japan
country: Latvia
country: Lithuania
country: Netherlands
country: Poland
country: Portugal
country: Romania
country: Russian Federation
country: Slovakia
country: Spain
country: Sweden
country: Switzerland
country: Turkey
country: United Kingdom
country: United States
country: Czech Republic
country: Egypt
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Multiple Sclerosis
mesh term: Multiple Sclerosis, Chronic Progressive
mesh term: Sclerosis
mesh term: Siponimod
sharing ipd: Yes
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Locations: central Contact Info Novartis.email@novartis.com
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 