<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/NCT02207634</url>
  </required_header>
  <id_info>
    <org_study_id>20130385</org_study_id>
    <secondary_id>2014-001976-75</secondary_id>
    <nct_id>NCT02207634</nct_id>
  </id_info>
  <brief_title>Evaluating PCSK9 Binding antiBody Influence oN coGnitive HeAlth in High cardiovascUlar Risk Subjects</brief_title>
  <acronym>EBBINGHAUS</acronym>
  <official_title>A Double-Blind, Placebo Controlled, Multicenter Study to Assess the Effect of Evolocumab on Cognitive Function in Patients With Clinically Evident Cardiovascular Disease and Receiving Statin Background Lipid Lowering Therapy: A Study for Subjects Enrolled in the FOURIER (Study 20110118) Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Amgen</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluated change over time in neurocognitive testing in patients receiving statin&#xD;
      therapy in combination with evolocumab (AMG 145), compared with patients receiving statin&#xD;
      therapy in combination with placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants who were enrolled in study 20110118 (FOURIER; NCT01764633) at select sites in&#xD;
      select countries (selected based on study start-up timelines) were invited to participate in&#xD;
      this cognitive function study, 20130385. There was no separate randomization for Study&#xD;
      20130385; data were analyzed according to Study 20110118 randomized treatment arm.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 10, 2014</start_date>
  <completion_date type="Actual">November 11, 2016</completion_date>
  <primary_completion_date type="Actual">November 11, 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>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Change From Baseline in Spatial Working Memory Strategy Index of Executive Function (6-8 Boxes) Z Score</measure>
    <time_frame>Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months).</time_frame>
    <description>Assessments were performed with the Cambridge Neuropsychological Test Automated Battery (CANTAB), a language-independent battery of computerized tests that is used to assess cognitive function.&#xD;
The Spatial Working Memory (SWM) test assesses the cognitive domain of executive function (high-level thinking and decision making). Patients search for colored tokens hidden inside boxes on the screen by touching them. The critical instruction is that once a token has been found inside a box, there will never be a token hidden inside that box again, so patients must not return to a box where a token has been found.&#xD;
The SWM strategy index of executive function represented the number of times a subject began a search with a different box. The Z score represents the standardized measure of how far an individual subject deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Spatial Working Memory (SWM) Between-errors Z Score</measure>
    <time_frame>Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months).</time_frame>
    <description>Assessments were performed with the CANTAB, a language-independent battery of computerized tests that is used to assess cognitive function. The Spatial Working Memory (SWM) between-errors test assesses the cognitive domain of working memory (holding material in mind while that material is being actively processed). Patients search for colored tokens hidden inside boxes on the screen by touching them. The critical instruction is that once a token has been found inside a box, there will never be a token hidden inside that box again, so patients must not return to a box where a token has been found.&#xD;
The SWM between-errors score is the number of times that a patient revisited a box in which a token had previously been found. The Z score represents the standardized measure of how far an individual participant deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Paired Associated Learning (PAL) Total Errors Adjusted Z Score</measure>
    <time_frame>Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months).</time_frame>
    <description>The CANTAB PAL test assesses visuospatial episodic memory (storing/retrieving information by associating an event with a time and place). Boxes on the screen opened up one at a time to reveal a number of patterns. Participants were asked to remember the location of each pattern. After all the boxes had been opened, each pattern was then shown in the center of the screen in a randomized order, and the patient should touch the box where they think each pattern was hidden. The PAL total errors adjusted comprised the number of errors committed by a patient plus an adjustment for the estimated number of errors the patient would have made on any stages that were not reached.&#xD;
Z score represents the standardized measure of how far an individual patient deviates from the study cohort average at baseline. A higher Z score indicated better performance. The mean change from baseline averaged across all the visits is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Reaction Time (RTI) Median 5-choice Reaction Time Z Score</measure>
    <time_frame>Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months).</time_frame>
    <description>Assessments were performed with the CANTAB, a language-independent battery of computerized tests that is used to assess cognitive function. The Reaction Time (RTI) test assessed the cognitive domain of psychomotor speed (detecting and responding to a stimulus). Participants held down a button until a spot appeared in 1 of 5 circles on the screen. As soon as possible after the spot flashed up, the patient lifted their finger from the button and touched the circle in which the spot appeared. The RTI median 5-choice reaction time was the median duration between the onset of the stimulus and the release of the button. Z score represents the standardized measure of how far an individual participant deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1974</enrollment>
  <condition>Dyslipidemia</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants continued with their background statin therapy during the course of the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Evolocumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference. Participants continued with their background statin therapy during the course of the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Evolocumab</intervention_name>
    <description>Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.</description>
    <arm_group_label>Evolocumab</arm_group_label>
    <other_name>AMG 145</other_name>
    <other_name>Repatha</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Background Statin Therapy</intervention_name>
    <description>Participants were required to be on a stable, high- to moderate-intensity statin background therapy consisting of an effective statin dose, ie, at least atorvastatin 20 mg daily or equivalent, and where locally approved, highly effective statin therapy (defined as at least atorvastatin 40 mg daily or equivalent) was recommended.</description>
    <arm_group_label>Evolocumab</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Randomized into Study 20110118 (FOURIER; NCT01764633)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current or known past diagnosis of dementia or mild cognitive impairment (MCI)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MD</last_name>
    <role>Study Director</role>
    <affiliation>Amgen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Huntsville</city>
        <state>Alabama</state>
        <zip>35801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Glendale</city>
        <state>Arizona</state>
        <zip>85306</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85018</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Alhambra</city>
        <state>California</state>
        <zip>91801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Banning</city>
        <state>California</state>
        <zip>92220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Harbor City</city>
        <state>California</state>
        <zip>90710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Laguna Hills</city>
        <state>California</state>
        <zip>92653</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90807</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90822</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Oceanside</city>
        <state>California</state>
        <zip>92056</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Oxnard</city>
        <state>California</state>
        <zip>93030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Palm Springs</city>
        <state>California</state>
        <zip>92262</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Roseville</city>
        <state>California</state>
        <zip>95661</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95816</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>San Pedro</city>
        <state>California</state>
        <zip>90732</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tarzana</city>
        <state>California</state>
        <zip>91356</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Thousand Oaks</city>
        <state>California</state>
        <zip>91360</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80909</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bridgeport</city>
        <state>Connecticut</state>
        <zip>06610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Boynton Beach</city>
        <state>Florida</state>
        <zip>33472</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Crystal River</city>
        <state>Florida</state>
        <zip>34429</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Daytona Beach</city>
        <state>Florida</state>
        <zip>32117</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Deerfield Beach</city>
        <state>Florida</state>
        <zip>33442</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fleming Island</city>
        <state>Florida</state>
        <zip>32003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hollywood</city>
        <state>Florida</state>
        <zip>33021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hollywood</city>
        <state>Florida</state>
        <zip>33024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33144</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Palm Harbor</city>
        <state>Florida</state>
        <zip>34684</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Pembroke Pines</city>
        <state>Florida</state>
        <zip>33025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ponte Vedra</city>
        <state>Florida</state>
        <zip>32081</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <zip>33401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30909</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Gainesville</city>
        <state>Georgia</state>
        <zip>30501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Savannah</city>
        <state>Georgia</state>
        <zip>31406</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Suwanee</city>
        <state>Georgia</state>
        <zip>30024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Coeur d'Alene</city>
        <state>Idaho</state>
        <zip>83814</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Addison</city>
        <state>Illinois</state>
        <zip>60101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Belleville</city>
        <state>Illinois</state>
        <zip>62220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60616</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jerseyville</city>
        <state>Illinois</state>
        <zip>62052</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hammond</city>
        <state>Indiana</state>
        <zip>46320</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Waterloo</city>
        <state>Iowa</state>
        <zip>50702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hutchinson</city>
        <state>Kansas</state>
        <zip>67502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Owensboro</city>
        <state>Kentucky</state>
        <zip>42303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70808</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hammond</city>
        <state>Louisiana</state>
        <zip>70403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
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        <state>Louisiana</state>
        <zip>70508</zip>
        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
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        <zip>70006</zip>
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  <location>
    <facility>
      <name>Research Site</name>
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        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
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        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
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  <location>
    <facility>
      <name>Research Site</name>
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  <location>
    <facility>
      <name>Research Site</name>
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        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
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        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
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        <zip>02459</zip>
        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
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  <location>
    <facility>
      <name>Research Site</name>
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        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
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  <location>
    <facility>
      <name>Research Site</name>
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        <zip>49444</zip>
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  <location>
    <facility>
      <name>Research Site</name>
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        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
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        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
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        <state>Missouri</state>
        <zip>63117</zip>
        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
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        <state>Missouri</state>
        <zip>63128</zip>
        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
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        <zip>59405</zip>
        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
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        <zip>59901</zip>
        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
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        <zip>08043</zip>
        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Westwood</city>
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        <zip>07675</zip>
        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
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        <zip>11206</zip>
        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
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        <zip>14215</zip>
        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
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        <zip>10567</zip>
        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New Hyde Park</city>
        <state>New York</state>
        <zip>11042</zip>
        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
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        <zip>12553</zip>
        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
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        <zip>14609</zip>
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  <location>
    <facility>
      <name>Research Site</name>
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        <zip>12180</zip>
        <country>United States</country>
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  <location>
    <facility>
      <name>Research Site</name>
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        <zip>14224</zip>
        <country>United States</country>
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  <location>
    <facility>
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        <zip>14221</zip>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
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  <location>
    <facility>
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  <location>
    <facility>
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      <address>
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  <location>
    <facility>
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      <address>
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  <location>
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  <location>
    <facility>
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      <address>
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  <location>
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  <location>
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  <location>
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  <location>
    <facility>
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  <location>
    <facility>
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  <location>
    <facility>
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      <address>
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  <location>
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  <location>
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      <address>
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  <location>
    <facility>
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      <address>
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  <location>
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  <location>
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  <location>
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  <location>
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  <location>
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  <location>
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  <location>
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  <location>
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  <location>
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      <address>
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  <location>
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  <location>
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  <location>
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  <location>
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  <location>
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  <location>
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  <location>
    <facility>
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  <location>
    <facility>
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  <location>
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  <location>
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      <name>Research Site</name>
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  <location>
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  <location>
    <facility>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
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  </location>
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    </facility>
  </location>
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    <facility>
      <name>Research Site</name>
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    </facility>
  </location>
  <location>
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        <zip>YO21 1SD</zip>
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    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Worcester</city>
        <zip>WR5 1DD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Czechia</country>
    <country>Denmark</country>
    <country>Estonia</country>
    <country>Finland</country>
    <country>France</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>Hong Kong</country>
    <country>Hungary</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Latvia</country>
    <country>Lithuania</country>
    <country>Malaysia</country>
    <country>Netherlands</country>
    <country>New Zealand</country>
    <country>Norway</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Russian Federation</country>
    <country>Slovakia</country>
    <country>South Africa</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
  </removed_countries>
  <link>
    <url>http://www.amgentrials.com</url>
    <description>AmgenTrials clinical trials website</description>
  </link>
  <reference>
    <citation>Giugliano RP, Mach F, Zavitz K, Kurtz C, Schneider J, Wang H, Keech A, Pedersen TR, Sabatine MS, Sever PS, Honarpour N, Wasserman SM, Ott BR; EBBINGHAUS Investigators. Design and rationale of the EBBINGHAUS trial: A phase 3, double-blind, placebo-controlled, multicenter study to assess the effect of evolocumab on cognitive function in patients with clinically evident cardiovascular disease and receiving statin background lipid-lowering therapy-A cognitive study of patients enrolled in the FOURIER trial. Clin Cardiol. 2017 Feb;40(2):59-65. doi: 10.1002/clc.22678. Epub 2017 Feb 16.</citation>
    <PMID>28207168</PMID>
  </reference>
  <reference>
    <citation>Giugliano RP, Mach F, Zavitz K, Kurtz C, Im K, Kanevsky E, Schneider J, Wang H, Keech A, Pedersen TR, Sabatine MS, Sever PS, Robinson JG, Honarpour N, Wasserman SM, Ott BR; EBBINGHAUS Investigators. Cognitive Function in a Randomized Trial of Evolocumab. N Engl J Med. 2017 Aug 17;377(7):633-643. doi: 10.1056/NEJMoa1701131.</citation>
    <PMID>28813214</PMID>
  </reference>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>July 31, 2014</study_first_submitted>
  <study_first_submitted_qc>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 4, 2014</study_first_posted>
  <results_first_submitted>December 15, 2017</results_first_submitted>
  <results_first_submitted_qc>December 15, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">January 16, 2018</results_first_posted>
  <disposition_first_submitted>June 19, 2017</disposition_first_submitted>
  <disposition_first_submitted_qc>June 19, 2017</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">June 21, 2017</disposition_first_posted>
  <last_update_submitted>December 15, 2017</last_update_submitted>
  <last_update_submitted_qc>December 15, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">January 16, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>High cholesterol</keyword>
  <keyword>Treatment for high cholesterol</keyword>
  <keyword>Lowering cholesterol</keyword>
  <keyword>Lowering high cholesterol</keyword>
  <keyword>Hypercholesterolemia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dyslipidemias</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Evolocumab</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants enrolled in Study 20110118 (FOURIER; NCT01764633) at select sites in select countries (based on study start-up timelines) were invited to participate in this cognitive function study.&#xD;
Participants were enrolled at 340 centers in 29 countries in Europe, North America, and Asia Pacific from September 2014 to July 2015.</recruitment_details>
      <pre_assignment_details>There was no separate randomization in this study; each participant received their assigned treatment per Protocol 20110118. Data were analyzed according to Study 20110118 randomized treatment arm.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants continued with their background statin therapy during the course of the study.</description>
        </group>
        <group group_id="P2">
          <title>Evolocumab</title>
          <description>Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference. Participants continued with their background statin therapy during the course of the study.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="990"/>
                <participants group_id="P2" count="984"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Treatment</title>
              <participants_list>
                <participants group_id="P1" count="990"/>
                <participants group_id="P2" count="983"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="968"/>
                <participants group_id="P2" count="953"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="31"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="31"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Demographic data are provided for all enrolled participants. Baseline Cambridge Neuropsychological Test Automated Battery (CANTAB®) data are provided for all dosed participants enrolled in the study with a baseline cognitive function assessment prior to or on the first dose date of study drug and ≥ 1 post-baseline cognitive measure.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants continued with their background statin therapy during the course of the study.</description>
        </group>
        <group group_id="B2">
          <title>Evolocumab</title>
          <description>Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference. Participants continued with their background statin therapy during the course of the study.</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="990"/>
            <count group_id="B2" value="984"/>
            <count group_id="B3" value="1974"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="990"/>
                    <count group_id="B2" value="984"/>
                    <count group_id="B3" value="1974"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.7" spread="8.7"/>
                    <measurement group_id="B2" value="62.9" spread="8.7"/>
                    <measurement group_id="B3" value="62.8" spread="8.7"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="990"/>
                    <count group_id="B2" value="984"/>
                    <count group_id="B3" value="1974"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="274"/>
                    <measurement group_id="B2" value="269"/>
                    <measurement group_id="B3" value="543"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="716"/>
                    <measurement group_id="B2" value="715"/>
                    <measurement group_id="B3" value="1431"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="990"/>
                    <count group_id="B2" value="984"/>
                    <count group_id="B3" value="1974"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="976"/>
                    <measurement group_id="B2" value="975"/>
                    <measurement group_id="B3" value="1951"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="990"/>
                    <count group_id="B2" value="984"/>
                    <count group_id="B3" value="1974"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="59"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="60"/>
                  </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="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="910"/>
                    <measurement group_id="B2" value="908"/>
                    <measurement group_id="B3" value="1818"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Multiple</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</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>
          <title>Spatial Working Memory (SWM) Strategy Index of Executive Function Raw Score</title>
          <description>CANTAB is a series of computerized tests to assess cognitive function. The SWM test assesses the cognitive domain of executive function (high-level thinking and decision making). Patients search for colored tokens hidden inside boxes on the screen. Tokens were never hidden inside the same box twice, so patients must not return to a box where a token was already found. The SWM strategy index of executive function represents the number of times a patient began a search with a different box. A high score represents an inefficient use of strategy and planning. The raw score ranges from 4 to 28.</description>
          <population>All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="618"/>
                    <count group_id="B2" value="586"/>
                    <count group_id="B3" value="1204"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17.8" spread="3.4"/>
                    <measurement group_id="B2" value="17.8" spread="3.5"/>
                    <measurement group_id="B3" value="17.8" spread="3.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Spatial Working Memory (SWM) Strategy Index of Executive Function Z Score</title>
          <description>The CANTAB SWM test assesses the cognitive domain of executive function (high-level thinking and decision making). Patients search for colored tokens hidden inside boxes on the screen. Tokens were never hidden inside the same box twice, so patients must not return to a box where a token was already found. The SWM strategy index of executive function represents the number of times a patient began a search with a different box. The Z score represents the standardized measure of how far an individual deviates from the study cohort average at baseline. A higher Z score reflects better performance.</description>
          <population>All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.</population>
          <units>Z score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="618"/>
                    <count group_id="B2" value="586"/>
                    <count group_id="B3" value="1204"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="-0.0106" spread="0.9910"/>
                    <measurement group_id="B2" value="0.0166" spread="1.0066"/>
                    <measurement group_id="B3" value="0.0026" spread="0.9983"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Spatial Working Memory Between Errors Raw Score</title>
          <description>The CANTAB Spatial Working Memory (SWM) between-errors score test assesses the cognitive domain of working memory (holding material in mind while that material is being actively processed). Patients search for colored tokens hidden inside boxes on the screen. Tokens were never hidden inside the same box twice, so patients must not return to a box where a token was already found. The SWM between-errors score is the number of times that a patient revisited a box in which a token had previously been found. A lower score indicates better performance. The raw score ranges from 0 to 279.</description>
          <population>All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="618"/>
                    <count group_id="B2" value="586"/>
                    <count group_id="B3" value="1204"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21.0" spread="10.6"/>
                    <measurement group_id="B2" value="20.9" spread="10.2"/>
                    <measurement group_id="B3" value="21.0" spread="10.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Spatial Working Memory Between Errors Z Score</title>
          <description>The CANTAB Spatial Working Memory (SWM) between-errors score test assesses the cognitive domain of working memory (holding material in mind while that material is being actively processed). Patients search for colored tokens hidden inside boxes on the screen. Tokens were never hidden inside the same box twice, so patients must not return to a box where a token was already found The SWM between-errors score is the number of times a patient revisited a box in which a token had already been found. A higher Z score reflects better performance.</description>
          <population>All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.</population>
          <units>Z score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="618"/>
                    <count group_id="B2" value="586"/>
                    <count group_id="B3" value="1204"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="-0.0130" spread="1.0075"/>
                    <measurement group_id="B2" value="0.0024" spread="0.9675"/>
                    <measurement group_id="B3" value="-0.0055" spread="0.9879"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Paired Associates Learning (PAL) Total Errors Adjusted Raw Score</title>
          <description>The CANTAB PAL test assesses memory function (storing/retrieving information by associating an event with a time and place). Boxes on the screen open in turn to reveal a number of patterns. After all the boxes were opened, each pattern was shown in a randomized order and the patient asked to touch the box where they think the pattern was hidden. The PAL total errors adjusted score is the number of errors made plus an adjustment for the estimated number of errors the patient would have made on any stages not reached. A lower score indicates better performance. The raw score ranges from 0 to 70.</description>
          <population>All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="618"/>
                    <count group_id="B2" value="586"/>
                    <count group_id="B3" value="1204"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25.2" spread="18.4"/>
                    <measurement group_id="B2" value="26.5" spread="19.3"/>
                    <measurement group_id="B3" value="25.8" spread="18.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Paired Associates Learning Total Errors Adjusted Z Score</title>
          <description>The CANTAB PAL test assesses memory function (storing/retrieving information by associating an event with a time and place). Boxes on the screen open in turn to reveal a number of patterns. After all the boxes have been opened, each pattern was shown in a randomized order and the patient asked to touch the box where they think each pattern was hidden. The PAL total errors adjusted is the number of errors committed plus an adjustment for the estimated number of errors the patient would have made on any stages not reached. Higher Z scores indicate better performance.</description>
          <population>All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.</population>
          <units>Z score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="618"/>
                    <count group_id="B2" value="586"/>
                    <count group_id="B3" value="1204"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.0442" spread="0.9834"/>
                    <measurement group_id="B2" value="-0.0272" spread="1.0294"/>
                    <measurement group_id="B3" value="0.0095" spread="1.0063"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Reaction Time Median 5-Choice Reaction Time Raw Score</title>
          <description>The CANTAB Reaction Time (RTI) test assessed psychomotor speed (detecting and responding to a stimulus). Participants held down a button until a spot appeared in 1 of 5 circles on the screen. As soon as possible after the spot flashed up, the patient lifted their finger from the button and touched the circle in which the spot appeared. The RTI median 5-choice reaction time was the median duration between the onset of the stimulus and the release of the button. A lower score indicates better performance. The raw score ranges from 100 to 5100 msec.</description>
          <population>All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.</population>
          <units>msec</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="614"/>
                    <count group_id="B2" value="585"/>
                    <count group_id="B3" value="1199"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="355.10" spread="77.60"/>
                    <measurement group_id="B2" value="356.74" spread="65.01"/>
                    <measurement group_id="B3" value="355.90" spread="71.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Reaction Time Median 5-Choice Reaction Time Z Score</title>
          <description>The CANTAB Reaction Time (RTI) test assessed psychomotor speed (detecting and responding to a stimulus). Participants held down a button until a spot appeared in 1 of 5 circles on the screen. As soon as possible after the spot flashed up, the patient moved their finger from the button to the circle in which the spot appeared. The RTI median 5-choice reaction time is the median duration between the onset of the stimulus and the release of the button. A higher Z score reflects better performance.</description>
          <population>All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="614"/>
                    <count group_id="B2" value="585"/>
                    <count group_id="B3" value="1199"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="-0.0271" spread="1.0829"/>
                    <measurement group_id="B2" value="-0.0500" spread="0.9072"/>
                    <measurement group_id="B3" value="-0.0383" spread="1.0007"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Change From Baseline in Spatial Working Memory Strategy Index of Executive Function (6-8 Boxes) Z Score</title>
        <description>Assessments were performed with the Cambridge Neuropsychological Test Automated Battery (CANTAB), a language-independent battery of computerized tests that is used to assess cognitive function.&#xD;
The Spatial Working Memory (SWM) test assesses the cognitive domain of executive function (high-level thinking and decision making). Patients search for colored tokens hidden inside boxes on the screen by touching them. The critical instruction is that once a token has been found inside a box, there will never be a token hidden inside that box again, so patients must not return to a box where a token has been found.&#xD;
The SWM strategy index of executive function represented the number of times a subject began a search with a different box. The Z score represents the standardized measure of how far an individual subject deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported.</description>
        <time_frame>Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months).</time_frame>
        <population>All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.&#xD;
Cognitive function assessments after an on-study stroke event were excluded from the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants continued with their background statin therapy during the course of the study.</description>
          </group>
          <group group_id="O2">
            <title>Evolocumab</title>
            <description>Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference. Participants continued with their background statin therapy during the course of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Spatial Working Memory Strategy Index of Executive Function (6-8 Boxes) Z Score</title>
          <description>Assessments were performed with the Cambridge Neuropsychological Test Automated Battery (CANTAB), a language-independent battery of computerized tests that is used to assess cognitive function.&#xD;
The Spatial Working Memory (SWM) test assesses the cognitive domain of executive function (high-level thinking and decision making). Patients search for colored tokens hidden inside boxes on the screen by touching them. The critical instruction is that once a token has been found inside a box, there will never be a token hidden inside that box again, so patients must not return to a box where a token has been found.&#xD;
The SWM strategy index of executive function represented the number of times a subject began a search with a different box. The Z score represents the standardized measure of how far an individual subject deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported.</description>
          <population>All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.&#xD;
Cognitive function assessments after an on-study stroke event were excluded from the analysis.</population>
          <units>Z score</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="616"/>
                <count group_id="O2" value="586"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1206" lower_limit="0.0535" upper_limit="0.1877"/>
                    <measurement group_id="O2" value="0.1134" lower_limit="0.0449" upper_limit="0.1820"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A repeated measures mixed-effect linear model was used to estimate treatment difference (placebo - evolocumab) in change from baseline and associated 95% confidence intervals (CI). The model included stratification factors for Study 20110118 (final screening low-density lipoprotein cholesterol [LDL-C] and geographical region), age, education level, baseline SWM strategy index Z score, treatment group, visit, and treatment by visit interaction.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>The non-inferiority margin was 0.19, calculated as 20% of the observed common standard deviation, which was estimated from observations in the placebo group by a repeated measured mixed-effect linear model with visit as a covariate. If the upper bound of the 95% CI for the difference between the placebo and evolocumab group in mean change from baseline for Z score averaged across the visits was less than the non-inferiority margin non-inferiority criteria were met.</non_inferiority_desc>
            <param_type>Treatment Difference</param_type>
            <param_value>0.0072</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.0375</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.0664</ci_lower_limit>
            <ci_upper_limit>0.0808</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Spatial Working Memory (SWM) Between-errors Z Score</title>
        <description>Assessments were performed with the CANTAB, a language-independent battery of computerized tests that is used to assess cognitive function. The Spatial Working Memory (SWM) between-errors test assesses the cognitive domain of working memory (holding material in mind while that material is being actively processed). Patients search for colored tokens hidden inside boxes on the screen by touching them. The critical instruction is that once a token has been found inside a box, there will never be a token hidden inside that box again, so patients must not return to a box where a token has been found.&#xD;
The SWM between-errors score is the number of times that a patient revisited a box in which a token had previously been found. The Z score represents the standardized measure of how far an individual participant deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported.</description>
        <time_frame>Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months).</time_frame>
        <population>All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.&#xD;
Cognitive function assessments after an on-study stroke event were excluded from the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants continued with their background statin therapy during the course of the study.</description>
          </group>
          <group group_id="O2">
            <title>Evolocumab</title>
            <description>Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference. Participants continued with their background statin therapy during the course of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Spatial Working Memory (SWM) Between-errors Z Score</title>
          <description>Assessments were performed with the CANTAB, a language-independent battery of computerized tests that is used to assess cognitive function. The Spatial Working Memory (SWM) between-errors test assesses the cognitive domain of working memory (holding material in mind while that material is being actively processed). Patients search for colored tokens hidden inside boxes on the screen by touching them. The critical instruction is that once a token has been found inside a box, there will never be a token hidden inside that box again, so patients must not return to a box where a token has been found.&#xD;
The SWM between-errors score is the number of times that a patient revisited a box in which a token had previously been found. The Z score represents the standardized measure of how far an individual participant deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported.</description>
          <population>All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.&#xD;
Cognitive function assessments after an on-study stroke event were excluded from the analysis.</population>
          <units>Z score</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="616"/>
                <count group_id="O2" value="586"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1024" lower_limit="0.0373" upper_limit="0.1675"/>
                    <measurement group_id="O2" value="0.0691" lower_limit="0.0026" upper_limit="0.1355"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A repeated measures mixed-effect linear model was used to estimate treatment difference (placebo - evolocumab) in change from baseline and associated 95% confidence intervals (CI). The model included stratification factors for Study 20110118 (final screening LDL-C and geographical region), age, education level, baseline SWM between-errors Z score, treatment group, visit, and treatment by visit interaction.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Treatment Difference</param_type>
            <param_value>0.0333</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.0363</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.0378</ci_lower_limit>
            <ci_upper_limit>0.1045</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Paired Associated Learning (PAL) Total Errors Adjusted Z Score</title>
        <description>The CANTAB PAL test assesses visuospatial episodic memory (storing/retrieving information by associating an event with a time and place). Boxes on the screen opened up one at a time to reveal a number of patterns. Participants were asked to remember the location of each pattern. After all the boxes had been opened, each pattern was then shown in the center of the screen in a randomized order, and the patient should touch the box where they think each pattern was hidden. The PAL total errors adjusted comprised the number of errors committed by a patient plus an adjustment for the estimated number of errors the patient would have made on any stages that were not reached.&#xD;
Z score represents the standardized measure of how far an individual patient deviates from the study cohort average at baseline. A higher Z score indicated better performance. The mean change from baseline averaged across all the visits is reported.</description>
        <time_frame>Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months).</time_frame>
        <population>All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.&#xD;
Cognitive function assessments after an on-study stroke event were excluded from the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants continued with their background statin therapy during the course of the study.</description>
          </group>
          <group group_id="O2">
            <title>Evolocumab</title>
            <description>Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference. Participants continued with their background statin therapy during the course of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Paired Associated Learning (PAL) Total Errors Adjusted Z Score</title>
          <description>The CANTAB PAL test assesses visuospatial episodic memory (storing/retrieving information by associating an event with a time and place). Boxes on the screen opened up one at a time to reveal a number of patterns. Participants were asked to remember the location of each pattern. After all the boxes had been opened, each pattern was then shown in the center of the screen in a randomized order, and the patient should touch the box where they think each pattern was hidden. The PAL total errors adjusted comprised the number of errors committed by a patient plus an adjustment for the estimated number of errors the patient would have made on any stages that were not reached.&#xD;
Z score represents the standardized measure of how far an individual patient deviates from the study cohort average at baseline. A higher Z score indicated better performance. The mean change from baseline averaged across all the visits is reported.</description>
          <population>All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.&#xD;
Cognitive function assessments after an on-study stroke event were excluded from the analysis.</population>
          <units>Z score</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="615"/>
                <count group_id="O2" value="585"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1098" lower_limit="0.0511" upper_limit="0.1686"/>
                    <measurement group_id="O2" value="0.0873" lower_limit="0.0273" upper_limit="0.1472"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A repeated measures mixed-effect linear model was used to estimate treatment difference (placebo - evolocumab) in change from baseline and associated 95% confidence intervals (CI). The model included stratification factors for Study 20110118 (final screening LDL-C and geographical region), age, education level, baseline PAL total errors adjusted Z score, treatment group, visit, and treatment by visit interaction.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Treatment Difference</param_type>
            <param_value>0.0226</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.0330</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.0422</ci_lower_limit>
            <ci_upper_limit>0.0873</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Reaction Time (RTI) Median 5-choice Reaction Time Z Score</title>
        <description>Assessments were performed with the CANTAB, a language-independent battery of computerized tests that is used to assess cognitive function. The Reaction Time (RTI) test assessed the cognitive domain of psychomotor speed (detecting and responding to a stimulus). Participants held down a button until a spot appeared in 1 of 5 circles on the screen. As soon as possible after the spot flashed up, the patient lifted their finger from the button and touched the circle in which the spot appeared. The RTI median 5-choice reaction time was the median duration between the onset of the stimulus and the release of the button. Z score represents the standardized measure of how far an individual participant deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported.</description>
        <time_frame>Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months).</time_frame>
        <population>All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.&#xD;
Cognitive function assessments after an on-study stroke event were excluded from the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants continued with their background statin therapy during the course of the study.</description>
          </group>
          <group group_id="O2">
            <title>Evolocumab</title>
            <description>Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference. Participants continued with their background statin therapy during the course of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Reaction Time (RTI) Median 5-choice Reaction Time Z Score</title>
          <description>Assessments were performed with the CANTAB, a language-independent battery of computerized tests that is used to assess cognitive function. The Reaction Time (RTI) test assessed the cognitive domain of psychomotor speed (detecting and responding to a stimulus). Participants held down a button until a spot appeared in 1 of 5 circles on the screen. As soon as possible after the spot flashed up, the patient lifted their finger from the button and touched the circle in which the spot appeared. The RTI median 5-choice reaction time was the median duration between the onset of the stimulus and the release of the button. Z score represents the standardized measure of how far an individual participant deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported.</description>
          <population>All enrolled and dosed participants who completed a baseline cognitive functional assessment prior to or on the first date of administration of study drug and who have at least one post-baseline cognitive measure.&#xD;
Cognitive function assessments after an on-study stroke event were excluded from the analysis.</population>
          <units>Z score</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="611"/>
                <count group_id="O2" value="584"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0153" lower_limit="-0.0529" upper_limit="0.0834"/>
                    <measurement group_id="O2" value="-0.0575" lower_limit="-0.1270" upper_limit="0.0121"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A repeated measures mixed-effect linear model was used to estimate treatment difference ( placebo - evolocumab) in change from baseline and associated 95% confidence intervals (CI). The model included stratification factors for Study 20110118 (final screening LDL-C and geographical region), age, education level, baseline RTI median 5-choice reaction time Z score, treatment group, visit, and treatment by visit interaction.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Treatment Difference</param_type>
            <param_value>0.0727</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.0382</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.0022</ci_lower_limit>
            <ci_upper_limit>0.1477</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the first dose of study drug to the end of study. The median duration of follow-up was 19.4 months.</time_frame>
      <desc>Although there was no separate safety data collection, recording, or reporting planned in this study, an ad-hoc analysis of safety data collected in Study 20110118 was conducted for participants in Study 20130385 and is reported here.&#xD;
Deaths by any cause were collected as adjudicated efficacy endpoints in Study 20110118 and were reported as a secondary endpoint in Study 20110118.&#xD;
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the 5% frequency threshold.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants continued with their background statin therapy during the course of the study.</description>
        </group>
        <group group_id="E2">
          <title>Evolocumab</title>
          <description>Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference. Participants continued with their background statin therapy during the course of the study.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 19.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="204" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="212" subjects_at_risk="983"/>
              </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="6" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Autoimmune haemolytic anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Haemorrhagic anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Immune thrombocytopenic purpura</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Iron deficiency anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Spleen disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </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="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Angina unstable</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Arrhythmia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Atrioventricular block</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Atrioventricular block complete</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Atrioventricular block second degree</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Bundle branch block left</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cardiac failure acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cardiac failure chronic</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cardiac tamponade</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cardiomyopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Congestive cardiomyopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Dressler's syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Heart alternation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Left ventricular dysfunction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Left ventricular failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Mitral valve incompetence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Mitral valve stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Myocarditis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pericarditis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Sinus arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Sinus node dysfunction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Ventricular extrasystoles</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Ventricular fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Ventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Intracranial lipoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </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="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Iridocyclitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Retinal detachment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Strabismus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Uveitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Visual impairment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal hernia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Abdominal pain lower</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Coeliac artery stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Colitis ischaemic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Colitis ulcerative</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Diverticulum</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Duodenal ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Duodenal ulcer haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Faecaloma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Gastric disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Gastric ulcer haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Gastric ulcer perforation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Gastritis erosive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Gastritis haemorrhagic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Gastrointestinal polyp haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Haematemesis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Hiatus hernia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Large intestine polyp</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Mesenteric artery stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Oesophageal ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pancreatic cyst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Peptic ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Reflux gastritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Retroperitoneal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Umbilical hernia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Soft tissue inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Systemic inflammatory response syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholangitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cholangitis acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cholecystitis acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cholecystitis chronic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cholelithiasis obstructive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Liver disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </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="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </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="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Burkholderia cepacia complex infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Clostridium difficile infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Device related sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Escherichia sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Escherichia urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Hepatitis C</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Hepatitis E</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Infectious pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Mastoiditis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Orchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Osteomyelitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Peritonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Post procedural sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Streptococcal sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection bacterial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Urinary tract infection bacterial</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </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="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Arterial bypass occlusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Coronary artery restenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Dislocation of sternum</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Eye injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Fibula fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Incisional hernia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Intentional overdose</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Meniscus injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Peripheral arterial reocclusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Peripheral artery restenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pneumoconiosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pneumonitis chemical</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Post concussion syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Post procedural constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Post procedural swelling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Spinal column injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Tendon rupture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Tibia fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Upper limb fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Arteriogram coronary</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Blood potassium increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Liver function test abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Myocardial necrosis marker increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Thyroid function test abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Cachexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus inadequate control</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Diabetic ketoacidosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Fluid retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Gout</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Type 2 diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </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="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Exostosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Foot deformity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Gouty arthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Lumbar spinal stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Myalgia intercostal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pain in jaw</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Polyarthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Polymyalgia rheumatica</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Rhabdomyolysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Spinal osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Synovial cyst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Tendonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Adenocarcinoma gastric</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Adenocarcinoma of colon</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Benign pancreatic neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Bladder cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Bladder transitional cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Bladder transitional cell carcinoma stage III</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Bronchial carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Colon adenoma</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Colon cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Diffuse large B-cell lymphoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Gastric cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Invasive ductal breast carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Laryngeal cancer stage 0</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Lip and/or oral cavity cancer stage III</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Lung adenocarcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Lung adenocarcinoma metastatic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Lung neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Lung neoplasm malignant</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Lung squamous cell carcinoma stage III</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Lymphoproliferative disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Meningioma benign</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Metastases to liver</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Metastatic malignant melanoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Metastatic squamous cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Non-small cell lung cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pancreatic carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Papillary thyroid cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Prostate cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Renal cancer metastatic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Renal cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Small cell lung cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of lung</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Tonsil cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Transitional cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Uterine leiomyoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Arachnoid cyst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Balance disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Carotid artery disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Carotid artery stenosis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Carpal tunnel syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cerebral ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cervical myelopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cervicobrachial syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Facial paralysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Generalised tonic-clonic seizure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Guillain-Barre syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Meralgia paraesthetica</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Paraparesis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Parkinsonism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Radiculopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Device malfunction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Device occlusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Major depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </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="6" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Calculus urethral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Chronic kidney disease</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>End stage renal disease</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Tubulointerstitial nephritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Ureterolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Urethral stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Benign prostatic hyperplasia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Metrorrhagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Postmenopausal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Asthma-chronic obstructive pulmonary disease overlap syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pleurisy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pulmonary mass</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Pulmonary oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Angioedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Decubitus ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Dermal cyst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Diabetic foot</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Eczema nummular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Psoriasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Skin ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Fracture treatment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Gastric banding reversal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Accelerated hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Aortic aneurysm</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Aortic aneurysm rupture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Aortic stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Arterial occlusive disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Circulatory collapse</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Hypertensive crisis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Iliac artery occlusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Intermittent claudication</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Leriche syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Peripheral arterial occlusive disease</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Peripheral artery occlusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Peripheral artery stenosis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Peripheral artery thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Peripheral ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Peripheral vascular disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Subclavian artery stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 19.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="257" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="272" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="74" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="101" subjects_at_risk="983"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="63" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="53" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="59" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="45" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="58" subjects_at_risk="983"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="66" subjects_at_risk="990"/>
                <counts group_id="E2" subjects_affected="61" subjects_at_risk="983"/>
              </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 Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Amgen Inc.</organization>
      <phone>866-572-6436</phone>
    </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/NCT02207634
org study id: 20130385
secondary id: 2014-001976-75
nct id: NCT02207634
lead sponsor: 
has dmc: Yes
This study evaluated change over time in neurocognitive testing in patients receiving statin
      therapy in combination with evolocumab (AMG 145), compared with patients receiving statin
      therapy in combination with placebo.
Participants who were enrolled in study 20110118 (FOURIER; NCT01764633) at select sites in
      select countries (selected based on study start-up timelines) were invited to participate in
      this cognitive function study, 20130385. There was no separate randomization for Study
      20130385; data were analyzed according to Study 20110118 randomized treatment arm.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Mean Change From Baseline in Spatial Working Memory Strategy Index of Executive Function (6-8 Boxes) Z Score
time frame: Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months).
description: Assessments were performed with the Cambridge Neuropsychological Test Automated Battery (CANTAB), a language-independent battery of computerized tests that is used to assess cognitive function.
The Spatial Working Memory (SWM) test assesses the cognitive domain of executive function (high-level thinking and decision making). Patients search for colored tokens hidden inside boxes on the screen by touching them. The critical instruction is that once a token has been found inside a box, there will never be a token hidden inside that box again, so patients must not return to a box where a token has been found.
The SWM strategy index of executive function represented the number of times a subject began a search with a different box. The Z score represents the standardized measure of how far an individual subject deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported.
measure: Mean Change From Baseline in Spatial Working Memory (SWM) Between-errors Z Score
time frame: Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months).
description: Assessments were performed with the CANTAB, a language-independent battery of computerized tests that is used to assess cognitive function. The Spatial Working Memory (SWM) between-errors test assesses the cognitive domain of working memory (holding material in mind while that material is being actively processed). Patients search for colored tokens hidden inside boxes on the screen by touching them. The critical instruction is that once a token has been found inside a box, there will never be a token hidden inside that box again, so patients must not return to a box where a token has been found.
The SWM between-errors score is the number of times that a patient revisited a box in which a token had previously been found. The Z score represents the standardized measure of how far an individual participant deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported.
measure: Mean Change From Baseline in Paired Associated Learning (PAL) Total Errors Adjusted Z Score
time frame: Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months).
description: The CANTAB PAL test assesses visuospatial episodic memory (storing/retrieving information by associating an event with a time and place). Boxes on the screen opened up one at a time to reveal a number of patterns. Participants were asked to remember the location of each pattern. After all the boxes had been opened, each pattern was then shown in the center of the screen in a randomized order, and the patient should touch the box where they think each pattern was hidden. The PAL total errors adjusted comprised the number of errors committed by a patient plus an adjustment for the estimated number of errors the patient would have made on any stages that were not reached.
Z score represents the standardized measure of how far an individual patient deviates from the study cohort average at baseline. A higher Z score indicated better performance. The mean change from baseline averaged across all the visits is reported.
measure: Mean Change From Baseline in Reaction Time (RTI) Median 5-choice Reaction Time Z Score
time frame: Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months).
description: Assessments were performed with the CANTAB, a language-independent battery of computerized tests that is used to assess cognitive function. The Reaction Time (RTI) test assessed the cognitive domain of psychomotor speed (detecting and responding to a stimulus). Participants held down a button until a spot appeared in 1 of 5 circles on the screen. As soon as possible after the spot flashed up, the patient lifted their finger from the button and touched the circle in which the spot appeared. The RTI median 5-choice reaction time was the median duration between the onset of the stimulus and the release of the button. Z score represents the standardized measure of how far an individual participant deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants continued with their background statin therapy during the course of the study.
arm group label: Evolocumab
arm group type: Experimental
description: Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference. Participants continued with their background statin therapy during the course of the study.
intervention type: Biological
intervention name: Evolocumab
description: Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.
arm group label: Evolocumab
other name: AMG 145
other name: Repatha
intervention type: Drug
intervention name: Placebo
description: Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.
arm group label: Placebo
intervention type: Drug
intervention name: Background Statin Therapy
description: Participants were required to be on a stable, high- to moderate-intensity statin background therapy consisting of an effective statin dose, ie, at least atorvastatin 20 mg daily or equivalent, and where locally approved, highly effective statin therapy (defined as at least atorvastatin 40 mg daily or equivalent) was recommended.
arm group label: Evolocumab
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 85 Years
healthy volunteers: No
last name: MD
role: Study Director
affiliation: Amgen
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country: Australia
country: Belgium
country: Canada
country: Czechia
country: Denmark
country: Estonia
country: Finland
country: France
country: Germany
country: Greece
country: Hong Kong
country: Hungary
country: Italy
country: Japan
country: Latvia
country: Lithuania
country: Malaysia
country: Netherlands
country: New Zealand
country: Norway
country: Poland
country: Portugal
country: Russian Federation
country: Slovakia
country: South Africa
country: Spain
country: Sweden
country: Turkey
country: United Kingdom
country: United States
country: Czech Republic
url: http://www.amgentrials.com
description: AmgenTrials clinical trials website
citation: Giugliano RP, Mach F, Zavitz K, Kurtz C, Schneider J, Wang H, Keech A, Pedersen TR, Sabatine MS, Sever PS, Honarpour N, Wasserman SM, Ott BR; EBBINGHAUS Investigators. Design and rationale of the EBBINGHAUS trial: A phase 3, double-blind, placebo-controlled, multicenter study to assess the effect of evolocumab on cognitive function in patients with clinically evident cardiovascular disease and receiving statin background lipid-lowering therapy-A cognitive study of patients enrolled in the FOURIER trial. Clin Cardiol. 2017 Feb;40(2):59-65. doi: 10.1002/clc.22678. Epub 2017 Feb 16.
PMID: 28207168
citation: Giugliano RP, Mach F, Zavitz K, Kurtz C, Im K, Kanevsky E, Schneider J, Wang H, Keech A, Pedersen TR, Sabatine MS, Sever PS, Robinson JG, Honarpour N, Wasserman SM, Ott BR; EBBINGHAUS Investigators. Cognitive Function in a Randomized Trial of Evolocumab. N Engl J Med. 2017 Aug 17;377(7):633-643. doi: 10.1056/NEJMoa1701131.
PMID: 28813214
responsible party type: Sponsor
mesh term: Dyslipidemias
mesh term: Evolocumab
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