<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/NCT01696994</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2012-01758</org_study_id>
    <secondary_id>NCI-2012-01758</secondary_id>
    <secondary_id>CDR0000078532</secondary_id>
    <secondary_id>NCI-P93-0050</secondary_id>
    <secondary_id>PLCO-1</secondary_id>
    <secondary_id>PLCO-Ovarian</secondary_id>
    <nct_id>NCT01696994</nct_id>
  </id_info>
  <brief_title>Screening for Ovarian Cancer in Older Patients (PLCO Screening Trial)</brief_title>
  <official_title>Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <brief_summary>
    <textblock>
      This clinical trial studies whether screening methods used to diagnose cancer of the&#xD;
      prostate, lung, colon, rectum, or ovaries can reduce deaths from these cancers. Screening&#xD;
      tests may help doctors find cancer cells early and plan better treatment for ovarian cancer.&#xD;
      The ovarian cancer screening tests are part of a trial that addresses the screening of four&#xD;
      cancer sites, each with their own results record: prostate (NCT00002540), lung (NCT01696968),&#xD;
      colorectal (NCT01696981), and ovarian (NCT01696994).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine whether screening with CA125 and transvaginal ultrasound (TVU) can reduce&#xD;
      mortality from ovarian cancer in women aged 55-74 at entry.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To assess screening variables, other than mortality, for each of the interventions&#xD;
      including sensitivity, specificity, and positive predictive value.&#xD;
&#xD;
      II. To assess the incidence, stage, and survival of cancer cases. III. To investigate the&#xD;
      mortality predictive value of biologic and/or prognostic characterizations of tumor tissue as&#xD;
      intermediate endpoints.&#xD;
&#xD;
      IV. To conduct biomolecular and genetic research into factors associated with cancer&#xD;
      carcinogenesis and promotion, as well as the early detection of these factors.&#xD;
&#xD;
      OUTLINE: Participants in the overall PLCO study are stratified by screening center, gender,&#xD;
      and age (55-59 vs 60-64 vs 65-69 vs 70-74). Participants are randomized to 1 of 2 arms&#xD;
      (control vs screening).&#xD;
&#xD;
      ARM I (Control): Participants receive standard medical care. Participants complete a Diet&#xD;
      History Questionnaire (DHQ) at baseline.&#xD;
&#xD;
      ARM II (Ovarian Screening): Participants undergo blood sample collection for CA125 analysis&#xD;
      at baseline annually for 5 years. Serum that is not used in the study will be stored in an&#xD;
      NCI biorepository. Participants also undergo an ovarian palpation exam (OVR, discontinued in&#xD;
      December 1998) and TVU at baseline and annually for 3 years. A scheduling and tracking&#xD;
      procedure is implemented to ensure regular attendance at repeat screens for participants&#xD;
      screened negative or for those who are designated suspicious or positive at screening but for&#xD;
      whom subsequent diagnostic procedures do not reveal ovarian cancer (follow-up diagnostic&#xD;
      procedures are through their own medical care environment). Participants diagnosed with&#xD;
      ovarian cancer via a screening test are referred for treatment in accordance with current&#xD;
      accepted practice for appropriate stage of disease, patient age, and medical condition; a&#xD;
      procedure is provided for contact with qualified medical personnel to insure appropriate&#xD;
      therapy.&#xD;
&#xD;
      Participants complete a Dietary Questionnaire (DQX) at baseline and DHQ at year 3. An Annual&#xD;
      Study Update (ADU) (previously referred to as the Periodic Survey of Health [PSH]&#xD;
      questionnaire) is mailed to each participant annually for 13 years to identify all prevalent&#xD;
      and incident cancers of the ovaries as all deaths that occur among both screened and control&#xD;
      subjects during the trial.&#xD;
&#xD;
      After completion of screening, participants are followed up for at least 13 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">November 16, 1993</start_date>
  <primary_completion_date type="Actual">May 21, 2012</primary_completion_date>
  <phase>N/A</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>Screening</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ovarian Cancer Deaths (Including Primary Peritoneal and Fallopian Tube Cancers)</measure>
    <time_frame>Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.</time_frame>
    <description>Ovarian cancer deaths confirmed in participants by a death review committee if available, otherwise by death certificate.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ovarian Cancer Death Rates (Including Primary Peritoneal and Fallopian Tube Cancers)</measure>
    <time_frame>Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.</time_frame>
    <description>Ovarian cancer deaths confirmed in participants by a death review committee if available, otherwise by death certificate. Rate is the number of deaths divided by person years of follow-up in the study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Deaths From All Causes</measure>
    <time_frame>Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.</time_frame>
    <description>Deaths from all causes were compared between the ovarian cancer screening arm and the usual care arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death Rates From All Causes</measure>
    <time_frame>Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.</time_frame>
    <description>Deaths from all causes were compared between the ovarian cancer screening arm and the usual care arm. Rate is the number of deaths divided by person years of follow-up in the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ovarian Cancer Incidence (Including Primary Peritoneal and Fallopian Tube Cancers)</measure>
    <time_frame>Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.</time_frame>
    <description>Ovarian cancer diagnoses confirmed by medical record abstraction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ovarian Cancer Incidence Rates (Including Primary Peritoneal and Fallopian Tube Cancers).</measure>
    <time_frame>Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.</time_frame>
    <description>Ovarian cancer diagnoses confirmed by medical record abstraction. Incidence rate (cumulative) defined as ovarian cancer diagnoses divided by person years at risk for ovarian cancer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complications of Diagnostic Evaluation (DE) Following a Positive Screening Test</measure>
    <time_frame>One year from screening examination</time_frame>
    <description>Number of positive screens with complications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T0 (Baseline) CA-125 Screening Results</measure>
    <time_frame>T0 (at study entry)</time_frame>
    <description>Cancer Antigen 125 (CA-125) result.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T0 (Baseline) TVU Screening Results</measure>
    <time_frame>T0 (at study entry)</time_frame>
    <description>Transvaginal Ultrasound (TVU) result.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T1 CA-125 Screening Results</measure>
    <time_frame>T1 (one year after entry)</time_frame>
    <description>Cancer Antigen 125 (CA-125) result.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T1 TVU Screening Results</measure>
    <time_frame>T1 (one year after entry)</time_frame>
    <description>Transvaginal Ultrasound (TVU) result.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T2 CA-125 Screening Results</measure>
    <time_frame>T2 (two years after entry)</time_frame>
    <description>Cancer Antigen 125 (CA-125) result.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T2 TVU Screening Results</measure>
    <time_frame>T2 (one year after entry)</time_frame>
    <description>Transvaginal Ultrasound (TVU) result.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T3 CA-125 Screening Results</measure>
    <time_frame>T3 (three years after entry)</time_frame>
    <description>Cancer Antigen 125 (CA-125) result.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T3 TVU Screening Results</measure>
    <time_frame>T3 (three years after entry)</time_frame>
    <description>Transvaginal Ultrasound (TVU) result.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T4 CA-125 Screening Results</measure>
    <time_frame>T4 (four years after entry)</time_frame>
    <description>Cancer Antigen 125 (CA-125) result.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T5 CA-125 Screening Results</measure>
    <time_frame>T5 (five years after entry)</time_frame>
    <description>Cancer Antigen 125 (CA-125) result.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">78216</enrollment>
  <condition>Ovarian Carcinoma</condition>
  <condition>Ovarian Germ Cell Tumor</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Participants receive standard medical care. Participants complete a DHQ at baseline.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ovarian Screening</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants undergo blood sample collection for CA125 analysis at baseline annually for 5 years. Serum that is not used in the study will be stored in an NCI biorepository. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years. Participants complete a DQX at baseline and DHQ at year 3. An ADU (previously referred to as the PSH questionnaire) is mailed to each participant annually for 13 years to identify all prevalent and incident cancers of the ovaries as all deaths that occur among both screened and control subjects during the trial.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Ovarian Screening</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Screening Questionnaire Administration</intervention_name>
    <description>Undergo questionnaire assessments</description>
    <arm_group_label>Ovarian Screening</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Ultrasound Imaging</intervention_name>
    <description>Undergo TVU</description>
    <arm_group_label>Ovarian Screening</arm_group_label>
    <other_name>2-Dimensional Grayscale Ultrasound Imaging</other_name>
    <other_name>2-Dimensional Ultrasound Imaging</other_name>
    <other_name>2D-US</other_name>
    <other_name>Ultrasonography</other_name>
    <other_name>Ultrasound</other_name>
    <other_name>Ultrasound Test</other_name>
    <other_name>Ultrasound, Medical</other_name>
    <other_name>US</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who at the time of randomization are less than 55 or greater than or equal to 75&#xD;
             years of age&#xD;
&#xD;
          -  Individuals undergoing treatment for cancer at this time, excluding basal-cell and&#xD;
             squamous-cell skin cancer&#xD;
&#xD;
          -  Individuals with known prior cancer of the colon, rectum, lung, or ovary&#xD;
&#xD;
               -  This includes primary or metastatic PLCO cancers&#xD;
&#xD;
          -  Individuals with previous surgical removal of the entire colon or one lung&#xD;
&#xD;
               -  Until October 1996, women with previous surgical removal of both ovaries were&#xD;
                  excluded from the trial. In order to increase the enrollment of women into the&#xD;
                  trial, beginning in October 1996, these women were no longer excluded for this&#xD;
                  reason.&#xD;
&#xD;
          -  Individuals who are participating in another cancer screening or cancer primary&#xD;
             prevention trial&#xD;
&#xD;
          -  Prior to April 1, 1999 women were excluded from the trial if they were currently&#xD;
             taking or had taken Tamoxifen or Evista\Raloxifene in the past 6 months. As of April&#xD;
             1999 based on a decision from the PLCO Ovary Subcommittee, women who have or are&#xD;
             currently taking Tamoxifen or Evista\Raloxifene are not excluded from participation.&#xD;
&#xD;
          -  Individuals who are unwilling or unable to sign the informed consent form&#xD;
&#xD;
          -  Individuals who have had a colonoscopy, sigmoidoscopy, or barium enema in the past&#xD;
             three years&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>74 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christine D Berg</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Institute (NCI)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>September 28, 2012</study_first_submitted>
  <study_first_submitted_qc>October 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2012</study_first_posted>
  <results_first_submitted>August 30, 2013</results_first_submitted>
  <results_first_submitted_qc>December 4, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">December 12, 2014</results_first_posted>
  <last_update_submitted>August 9, 2022</last_update_submitted>
  <last_update_submitted_qc>August 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms, Germ Cell and Embryonal</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled between November 1993 and July 2001 at 10 study centers.</recruitment_details>
      <pre_assignment_details>Participants signed a study informed consent prior to being randomized to a study arm.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Control</title>
          <description>Participants receive standard medical care.</description>
        </group>
        <group group_id="P2">
          <title>Ovarian Screening</title>
          <description>Participants undergo blood sample collection for CA-125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="39111"/>
                <participants group_id="P2" count="39105"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="33919"/>
                <participants group_id="P2" count="30668"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5192"/>
                <participants group_id="P2" count="8437"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Cancer Before Rand. (Ovarian Screening)</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Died Before Randomization</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Died Before ASU (Control)</title>
              <participants_list>
                <participants group_id="P1" count="73"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>No Ovaries at Baseline</title>
              <participants_list>
                <participants group_id="P1" count="4807"/>
                <participants group_id="P2" count="4851"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Refused ASU (Control)</title>
              <participants_list>
                <participants group_id="P1" count="311"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Refused Screen (Ovarian Screening)</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3582"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Control</title>
          <description>Participants receive standard medical care. Participants complete a baseline questionnaire (BQ) at entry and a dietary history questionnaire (DHQ) during study years 0-6.</description>
        </group>
        <group group_id="B2">
          <title>Ovarian Screening</title>
          <description>Participants undergo blood sample collection for Cancer Antigen 125 (CA-125) analysis at baseline and annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</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="39111"/>
            <count group_id="B2" value="39105"/>
            <count group_id="B3" value="78216"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25222"/>
                    <measurement group_id="B2" value="25233"/>
                    <measurement group_id="B3" value="50455"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13889"/>
                    <measurement group_id="B2" value="13872"/>
                    <measurement group_id="B3" value="27761"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.5" spread="5.4"/>
                    <measurement group_id="B2" value="62.5" spread="5.4"/>
                    <measurement group_id="B3" value="62.5" spread="5.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39111"/>
                    <measurement group_id="B2" value="39105"/>
                    <measurement group_id="B3" value="78216"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</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>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39111"/>
                    <measurement group_id="B2" value="39105"/>
                    <measurement group_id="B3" value="78216"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Ovarian Cancer Deaths (Including Primary Peritoneal and Fallopian Tube Cancers)</title>
        <description>Ovarian cancer deaths confirmed in participants by a death review committee if available, otherwise by death certificate.</description>
        <time_frame>Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants receive standard medical care.</description>
          </group>
          <group group_id="O2">
            <title>Ovarian Screening</title>
            <description>Participants undergo blood sample collection for CA-125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
          </group>
        </group_list>
        <measure>
          <title>Ovarian Cancer Deaths (Including Primary Peritoneal and Fallopian Tube Cancers)</title>
          <description>Ovarian cancer deaths confirmed in participants by a death review committee if available, otherwise by death certificate.</description>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34304"/>
                <count group_id="O2" value="34253"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100"/>
                    <measurement group_id="O2" value="188"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Deaths From All Causes</title>
        <description>Deaths from all causes were compared between the ovarian cancer screening arm and the usual care arm.</description>
        <time_frame>Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants receive standard medical care.</description>
          </group>
          <group group_id="O2">
            <title>Ovarian Screening</title>
            <description>Participants undergo blood sample collection for CA-125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
          </group>
        </group_list>
        <measure>
          <title>Deaths From All Causes</title>
          <description>Deaths from all causes were compared between the ovarian cancer screening arm and the usual care arm.</description>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34304"/>
                <count group_id="O2" value="34253"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3542"/>
                    <measurement group_id="O2" value="3508"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Death Rates From All Causes</title>
        <description>Deaths from all causes were compared between the ovarian cancer screening arm and the usual care arm. Rate is the number of deaths divided by person years of follow-up in the study.</description>
        <time_frame>Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.</time_frame>
        <population>Female participants, excluding females without ovaries at baseline, were analyzed. An intention-to-treat analysis was performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants receive standard medical care.</description>
          </group>
          <group group_id="O2">
            <title>Ovarian Screening</title>
            <description>Participants undergo blood sample collection for CA125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
          </group>
        </group_list>
        <measure>
          <title>Death Rates From All Causes</title>
          <description>Deaths from all causes were compared between the ovarian cancer screening arm and the usual care arm. Rate is the number of deaths divided by person years of follow-up in the study.</description>
          <population>Female participants, excluding females without ovaries at baseline, were analyzed. An intention-to-treat analysis was performed.</population>
          <units>Deaths per 10,000 PY</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34304"/>
                <count group_id="O2" value="34253"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.6"/>
                    <measurement group_id="O2" value="91.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.99</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.95</ci_lower_limit>
            <ci_upper_limit>1.04</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ovarian Cancer Incidence (Including Primary Peritoneal and Fallopian Tube Cancers)</title>
        <description>Ovarian cancer diagnoses confirmed by medical record abstraction.</description>
        <time_frame>Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.</time_frame>
        <population>Female participants, excluding females without ovaries at baseline, were analyzed. An intention-to-treat analysis was performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants receive standard medical care.</description>
          </group>
          <group group_id="O2">
            <title>Ovarian Screening</title>
            <description>Participants undergo blood sample collection for CA-125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
          </group>
        </group_list>
        <measure>
          <title>Ovarian Cancer Incidence (Including Primary Peritoneal and Fallopian Tube Cancers)</title>
          <description>Ovarian cancer diagnoses confirmed by medical record abstraction.</description>
          <population>Female participants, excluding females without ovaries at baseline, were analyzed. An intention-to-treat analysis was performed.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34304"/>
                <count group_id="O2" value="34253"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="176"/>
                    <measurement group_id="O2" value="212"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ovarian Cancer Incidence Rates (Including Primary Peritoneal and Fallopian Tube Cancers).</title>
        <description>Ovarian cancer diagnoses confirmed by medical record abstraction. Incidence rate (cumulative) defined as ovarian cancer diagnoses divided by person years at risk for ovarian cancer.</description>
        <time_frame>Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.</time_frame>
        <population>Female participants, excluding females without ovaries at baseline, were analyzed. An intention-to-treat analysis was performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants receive standard medical care.</description>
          </group>
          <group group_id="O2">
            <title>Ovarian Screening</title>
            <description>Participants undergo blood sample collection for CA125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
          </group>
        </group_list>
        <measure>
          <title>Ovarian Cancer Incidence Rates (Including Primary Peritoneal and Fallopian Tube Cancers).</title>
          <description>Ovarian cancer diagnoses confirmed by medical record abstraction. Incidence rate (cumulative) defined as ovarian cancer diagnoses divided by person years at risk for ovarian cancer.</description>
          <population>Female participants, excluding females without ovaries at baseline, were analyzed. An intention-to-treat analysis was performed.</population>
          <units>Diagnoses per 10,000 PY</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34304"/>
                <count group_id="O2" value="34253"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7"/>
                    <measurement group_id="O2" value="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.21</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.99</ci_lower_limit>
            <ci_upper_limit>1.48</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Complications of Diagnostic Evaluation (DE) Following a Positive Screening Test</title>
        <description>Number of positive screens with complications</description>
        <time_frame>One year from screening examination</time_frame>
        <population>The units analyzed were positive screening exams with documented diagnostic follow-up. If a participant received 3 positive screens with documented follow-up after each one, she would be counted 3 times in the number of units analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Ovarian Screening</title>
            <description>Participants undergo blood sample collection for CA125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
          </group>
        </group_list>
        <measure>
          <title>Complications of Diagnostic Evaluation (DE) Following a Positive Screening Test</title>
          <description>Number of positive screens with complications</description>
          <population>The units analyzed were positive screening exams with documented diagnostic follow-up. If a participant received 3 positive screens with documented follow-up after each one, she would be counted 3 times in the number of units analyzed.</population>
          <units>Positive screens w/ complications</units>
          <param>Number</param>
          <units_analyzed>Positive Screens with Follow-up</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3531"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Positive Screens with Follow-up</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5970"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>When DE Led to Ovarian Cancer Diagnosis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>When DE Did Not Lead to Ovarian Cancer Diagnosis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="226"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>T0 (Baseline) CA-125 Screening Results</title>
        <description>Cancer Antigen 125 (CA-125) result.</description>
        <time_frame>T0 (at study entry)</time_frame>
        <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T0 were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Ovarian Screening</title>
            <description>Participants undergo blood sample collection for CA-125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
          </group>
        </group_list>
        <measure>
          <title>T0 (Baseline) CA-125 Screening Results</title>
          <description>Cancer Antigen 125 (CA-125) result.</description>
          <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T0 were analyzed.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28733"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Negative (&lt;35 U/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28275"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive (&gt;= 35 U/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="400"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Inadequate screen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>T0 (Baseline) TVU Screening Results</title>
        <description>Transvaginal Ultrasound (TVU) result.</description>
        <time_frame>T0 (at study entry)</time_frame>
        <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a TVU screen at T0 were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Ovarian Screening</title>
            <description>Participants undergo blood sample collection for CA125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
          </group>
        </group_list>
        <measure>
          <title>T0 (Baseline) TVU Screening Results</title>
          <description>Transvaginal Ultrasound (TVU) result.</description>
          <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a TVU screen at T0 were analyzed.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28477"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26624"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1309"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Inadequate screen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="544"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>T1 CA-125 Screening Results</title>
        <description>Cancer Antigen 125 (CA-125) result.</description>
        <time_frame>T1 (one year after entry)</time_frame>
        <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T1 were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Ovarian Screening</title>
            <description>Participants undergo blood sample collection for CA-125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
          </group>
        </group_list>
        <measure>
          <title>T1 CA-125 Screening Results</title>
          <description>Cancer Antigen 125 (CA-125) result.</description>
          <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T1 were analyzed.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27514"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Negative (&lt;35 U/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27035"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive (&gt;= 35 U/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="433"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Inadequate screen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>T1 TVU Screening Results</title>
        <description>Transvaginal Ultrasound (TVU) result.</description>
        <time_frame>T1 (one year after entry)</time_frame>
        <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a TVU screen at T1 were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Ovarian Screening</title>
            <description>Participants undergo blood sample collection for CA-125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
          </group>
        </group_list>
        <measure>
          <title>T1 TVU Screening Results</title>
          <description>Transvaginal Ultrasound (TVU) result.</description>
          <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a TVU screen at T1 were analyzed.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27046"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25740"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="930"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Inadequate screen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="376"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>T2 CA-125 Screening Results</title>
        <description>Cancer Antigen 125 (CA-125) result.</description>
        <time_frame>T2 (two years after entry)</time_frame>
        <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T2 were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Ovarian Screening</title>
            <description>Participants undergo blood sample collection for CA-125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
          </group>
        </group_list>
        <measure>
          <title>T2 CA-125 Screening Results</title>
          <description>Cancer Antigen 125 (CA-125) result.</description>
          <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T2 were analyzed.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26555"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Negative (&lt;35 U/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26024"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive (&gt;= 35 U/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="480"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Inadequate screen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>T2 TVU Screening Results</title>
        <description>Transvaginal Ultrasound (TVU) result.</description>
        <time_frame>T2 (one year after entry)</time_frame>
        <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a TVU screen at T2 were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Ovarian Screening</title>
            <description>Participants undergo blood sample collection for CA-125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
          </group>
        </group_list>
        <measure>
          <title>T2 TVU Screening Results</title>
          <description>Transvaginal Ultrasound (TVU) result.</description>
          <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a TVU screen at T2 were analyzed.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26048"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24988"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="764"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Inadequate screen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="296"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>T3 CA-125 Screening Results</title>
        <description>Cancer Antigen 125 (CA-125) result.</description>
        <time_frame>T3 (three years after entry)</time_frame>
        <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T3 were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Ovarian Screening</title>
            <description>Participants undergo blood sample collection for CA-125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
          </group>
        </group_list>
        <measure>
          <title>T3 CA-125 Screening Results</title>
          <description>Cancer Antigen 125 (CA-125) result.</description>
          <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T3 were analyzed.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25401"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Negative (&lt;35 U/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24925"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive (&gt;= 35 U/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="427"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Inadequate screen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>T3 TVU Screening Results</title>
        <description>Transvaginal Ultrasound (TVU) result.</description>
        <time_frame>T3 (three years after entry)</time_frame>
        <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a TVU screen at T3 were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Ovarian Screening</title>
            <description>Participants undergo blood sample collection for CA-125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
          </group>
        </group_list>
        <measure>
          <title>T3 TVU Screening Results</title>
          <description>Transvaginal Ultrasound (TVU) result.</description>
          <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a TVU screen at T3 were analyzed.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24949"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23926"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="733"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Inadequate screen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="290"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Ovarian Cancer Death Rates (Including Primary Peritoneal and Fallopian Tube Cancers)</title>
        <description>Ovarian cancer deaths confirmed in participants by a death review committee if available, otherwise by death certificate. Rate is the number of deaths divided by person years of follow-up in the study.</description>
        <time_frame>Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.</time_frame>
        <population>Female participants, excluding females without ovaries at baseline, were analyzed. An intention-to-treat analysis was performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Participants receive standard medical care.</description>
          </group>
          <group group_id="O2">
            <title>Ovarian Screening</title>
            <description>Participants undergo blood sample collection for CA125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
          </group>
        </group_list>
        <measure>
          <title>Ovarian Cancer Death Rates (Including Primary Peritoneal and Fallopian Tube Cancers)</title>
          <description>Ovarian cancer deaths confirmed in participants by a death review committee if available, otherwise by death certificate. Rate is the number of deaths divided by person years of follow-up in the study.</description>
          <population>Female participants, excluding females without ovaries at baseline, were analyzed. An intention-to-treat analysis was performed.</population>
          <units>Deaths per 10,000 PY</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34304"/>
                <count group_id="O2" value="34253"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6"/>
                    <measurement group_id="O2" value="3.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.18</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>.91</ci_lower_limit>
            <ci_upper_limit>1.54</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>T4 CA-125 Screening Results</title>
        <description>Cancer Antigen 125 (CA-125) result.</description>
        <time_frame>T4 (four years after entry)</time_frame>
        <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T4 were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Ovarian Screening</title>
            <description>Participants undergo blood sample collection for CA-125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
          </group>
        </group_list>
        <measure>
          <title>T4 CA-125 Screening Results</title>
          <description>Cancer Antigen 125 (CA-125) result.</description>
          <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T4 were analyzed.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20115"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Negative (&lt;35 U/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19772"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive (&gt;= 35 U/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="327"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Inadequate screen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>T5 CA-125 Screening Results</title>
        <description>Cancer Antigen 125 (CA-125) result.</description>
        <time_frame>T5 (five years after entry)</time_frame>
        <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T5 were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Ovarian Screening</title>
            <description>Participants undergo blood sample collection for CA-125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
          </group>
        </group_list>
        <measure>
          <title>T5 CA-125 Screening Results</title>
          <description>Cancer Antigen 125 (CA-125) result.</description>
          <population>Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T5 were analyzed.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22193"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Negative (&lt;35 U/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21788"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive (&gt;= 35 U/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="366"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Inadequate screen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>During each annual screening visit.</time_frame>
      <desc>These events are solely those prompted by the screening examination.</desc>
      <group_list>
        <group group_id="E1">
          <title>Ovarian Screening</title>
          <description>Participants undergo blood sample collection for CA125 analysis at baseline annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34253"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="903" subjects_at_risk="34253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="34253"/>
              </event>
              <event>
                <sub_title>Bleeding</sub_title>
                <counts group_id="E1" events="27" subjects_affected="26" subjects_at_risk="34253"/>
              </event>
              <event>
                <sub_title>Dizzy</sub_title>
                <counts group_id="E1" events="82" subjects_affected="80" subjects_at_risk="34253"/>
              </event>
              <event>
                <sub_title>Fainted</sub_title>
                <counts group_id="E1" events="31" subjects_affected="29" subjects_at_risk="34253"/>
              </event>
              <event>
                <sub_title>Inflammation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34253"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="34253"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="26" subjects_affected="26" subjects_at_risk="34253"/>
              </event>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" events="453" subjects_affected="446" subjects_at_risk="34253"/>
              </event>
              <event>
                <sub_title>Hematoma</sub_title>
                <counts group_id="E1" events="292" subjects_affected="284" subjects_at_risk="34253"/>
              </event>
              <event>
                <sub_title>Other Adverse Event</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="34253"/>
              </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 only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Paul F. Pinsky, Ph.D.</name_or_title>
      <organization>Early Detection Research Group, NCI, NIH</organization>
      <phone>301-496-8544</phone>
      <email>pinskyp@mail.nih.gov</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01696994
org study id: NCI-2012-01758
secondary id: NCI-2012-01758
secondary id: CDR0000078532
secondary id: NCI-P93-0050
secondary id: PLCO-1
secondary id: PLCO-Ovarian
nct id: NCT01696994
lead sponsor: 
This clinical trial studies whether screening methods used to diagnose cancer of the
      prostate, lung, colon, rectum, or ovaries can reduce deaths from these cancers. Screening
      tests may help doctors find cancer cells early and plan better treatment for ovarian cancer.
      The ovarian cancer screening tests are part of a trial that addresses the screening of four
      cancer sites, each with their own results record: prostate (NCT00002540), lung (NCT01696968),
      colorectal (NCT01696981), and ovarian (NCT01696994).
PRIMARY OBJECTIVES:

      I. To determine whether screening with CA125 and transvaginal ultrasound (TVU) can reduce
      mortality from ovarian cancer in women aged 55-74 at entry.

      SECONDARY OBJECTIVES:

      I. To assess screening variables, other than mortality, for each of the interventions
      including sensitivity, specificity, and positive predictive value.

      II. To assess the incidence, stage, and survival of cancer cases. III. To investigate the
      mortality predictive value of biologic and/or prognostic characterizations of tumor tissue as
      intermediate endpoints.

      IV. To conduct biomolecular and genetic research into factors associated with cancer
      carcinogenesis and promotion, as well as the early detection of these factors.

      OUTLINE: Participants in the overall PLCO study are stratified by screening center, gender,
      and age (55-59 vs 60-64 vs 65-69 vs 70-74). Participants are randomized to 1 of 2 arms
      (control vs screening).

      ARM I (Control): Participants receive standard medical care. Participants complete a Diet
      History Questionnaire (DHQ) at baseline.

      ARM II (Ovarian Screening): Participants undergo blood sample collection for CA125 analysis
      at baseline annually for 5 years. Serum that is not used in the study will be stored in an
      NCI biorepository. Participants also undergo an ovarian palpation exam (OVR, discontinued in
      December 1998) and TVU at baseline and annually for 3 years. A scheduling and tracking
      procedure is implemented to ensure regular attendance at repeat screens for participants
      screened negative or for those who are designated suspicious or positive at screening but for
      whom subsequent diagnostic procedures do not reveal ovarian cancer (follow-up diagnostic
      procedures are through their own medical care environment). Participants diagnosed with
      ovarian cancer via a screening test are referred for treatment in accordance with current
      accepted practice for appropriate stage of disease, patient age, and medical condition; a
      procedure is provided for contact with qualified medical personnel to insure appropriate
      therapy.

      Participants complete a Dietary Questionnaire (DQX) at baseline and DHQ at year 3. An Annual
      Study Update (ADU) (previously referred to as the Periodic Survey of Health [PSH]
      questionnaire) is mailed to each participant annually for 13 years to identify all prevalent
      and incident cancers of the ovaries as all deaths that occur among both screened and control
      subjects during the trial.

      After completion of screening, participants are followed up for at least 13 years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Screening
masking: Single (Investigator)
measure: Ovarian Cancer Deaths (Including Primary Peritoneal and Fallopian Tube Cancers)
time frame: Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.
description: Ovarian cancer deaths confirmed in participants by a death review committee if available, otherwise by death certificate.
measure: Ovarian Cancer Death Rates (Including Primary Peritoneal and Fallopian Tube Cancers)
time frame: Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.
description: Ovarian cancer deaths confirmed in participants by a death review committee if available, otherwise by death certificate. Rate is the number of deaths divided by person years of follow-up in the study.
measure: Deaths From All Causes
time frame: Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.
description: Deaths from all causes were compared between the ovarian cancer screening arm and the usual care arm.
measure: Death Rates From All Causes
time frame: Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.
description: Deaths from all causes were compared between the ovarian cancer screening arm and the usual care arm. Rate is the number of deaths divided by person years of follow-up in the study.
measure: Ovarian Cancer Incidence (Including Primary Peritoneal and Fallopian Tube Cancers)
time frame: Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.
description: Ovarian cancer diagnoses confirmed by medical record abstraction.
measure: Ovarian Cancer Incidence Rates (Including Primary Peritoneal and Fallopian Tube Cancers).
time frame: Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.
description: Ovarian cancer diagnoses confirmed by medical record abstraction. Incidence rate (cumulative) defined as ovarian cancer diagnoses divided by person years at risk for ovarian cancer.
measure: Complications of Diagnostic Evaluation (DE) Following a Positive Screening Test
time frame: One year from screening examination
description: Number of positive screens with complications
measure: T0 (Baseline) CA-125 Screening Results
time frame: T0 (at study entry)
description: Cancer Antigen 125 (CA-125) result.
measure: T0 (Baseline) TVU Screening Results
time frame: T0 (at study entry)
description: Transvaginal Ultrasound (TVU) result.
measure: T1 CA-125 Screening Results
time frame: T1 (one year after entry)
description: Cancer Antigen 125 (CA-125) result.
measure: T1 TVU Screening Results
time frame: T1 (one year after entry)
description: Transvaginal Ultrasound (TVU) result.
measure: T2 CA-125 Screening Results
time frame: T2 (two years after entry)
description: Cancer Antigen 125 (CA-125) result.
measure: T2 TVU Screening Results
time frame: T2 (one year after entry)
description: Transvaginal Ultrasound (TVU) result.
measure: T3 CA-125 Screening Results
time frame: T3 (three years after entry)
description: Cancer Antigen 125 (CA-125) result.
measure: T3 TVU Screening Results
time frame: T3 (three years after entry)
description: Transvaginal Ultrasound (TVU) result.
measure: T4 CA-125 Screening Results
time frame: T4 (four years after entry)
description: Cancer Antigen 125 (CA-125) result.
measure: T5 CA-125 Screening Results
time frame: T5 (five years after entry)
description: Cancer Antigen 125 (CA-125) result.
arm group label: Control
arm group type: No Intervention
description: Participants receive standard medical care. Participants complete a DHQ at baseline.
arm group label: Ovarian Screening
arm group type: Active Comparator
description: Participants undergo blood sample collection for CA125 analysis at baseline annually for 5 years. Serum that is not used in the study will be stored in an NCI biorepository. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years. Participants complete a DQX at baseline and DHQ at year 3. An ADU (previously referred to as the PSH questionnaire) is mailed to each participant annually for 13 years to identify all prevalent and incident cancers of the ovaries as all deaths that occur among both screened and control subjects during the trial.
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Ovarian Screening
intervention type: Other
intervention name: Screening Questionnaire Administration
description: Undergo questionnaire assessments
arm group label: Ovarian Screening
intervention type: Procedure
intervention name: Ultrasound Imaging
description: Undergo TVU
arm group label: Ovarian Screening
other name: 2-Dimensional Grayscale Ultrasound Imaging
other name: 2-Dimensional Ultrasound Imaging
other name: 2D-US
other name: Ultrasonography
other name: Ultrasound
other name: Ultrasound Test
other name: Ultrasound, Medical
other name: US
criteria: 
gender: Female
minimum age: 55 Years
maximum age: 74 Years
healthy volunteers: No
last name: Christine D Berg
role: Principal Investigator
affiliation: National Cancer Institute (NCI)
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neoplasms, Germ Cell and Embryonal
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 