anchor.diff:      <h2>References</h2>
   
       <ol>
  -      <li>Zarin, D. A., Tse, T. T., Williams, R. J., Califf, R. M., and Ide, N. C. (2011). <a href="http://www.nejm.org/doi/full/10.1056/NEJMsa1012065#t=article">The ClinicalTrials.gov results database – update and key issues</a>. N Engl J Med 364: 852–60.</li>
  -      <li><a href="http://www.fda.gov/RegulatoryInformation/Legislation/SignificantAmendmentstotheFDCAct/FoodandDrugAdministrationAmendmentsActof2007/default.htm">Food and Drug Administration Amendments Act of 2007</a>. Public Law 110-95.</li>
  -      <li>Laine, C., Horton R., DeAngelis C.D., et al. <a href="http://www.nejm.org/doi/full/10.1056/NEJMe078110#t=article">Clinical trial registration – looking back and moving ahead</a>. N Engl J Med 356: 2734–6.</li>
  -      <li><a href="http://ec.europa.eu/health/files/eudralex/vol-10/2008_07/c_16820080703en00030004_en.pdf">Communication from the Commission regarding the guideline on the data fields contained in the clinical trials database provided for in Article 11 of Directive 2001/20/EC to be included in the database on medicinal products provided for in Article 57 or Regulation (EC) No 726/2004</a>. In: European Commission, ed. Official Journal of the European Union, 2008. (2008/C 168/02.)</li>
  -      <li><a href="http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000044.jsp">Guidance on the information concerning paediatric clinical trials to be entered into the EU Database on Clinical Trials (EudraCT) and on the information to be made public by the European Medicines Agency (EMEA), in accordance with Article 41 of Regulation (EC) No 1901/2006</a>. In: European Commission, ed. Official Journal of the European Union, 2009. (2009/C 28/01.)</li>
  -      <li>Zarin, D. A., Ide, N. C., Tse, T. et al. (2007). <a href="http://www.ncbi.nlm.nih.gov/pubmed/17507347">Issues in the registration of clinical trials</a>. JAMA 297: 2112—2120.</li>
  -      <li>Moher, D., Liberati, A., Tetzlaff, J. and Altman, D. G. (for the PRISMA Group)(2009). <a href="http://annals.org/article.aspx?articleid=744664">Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement</a>, BMJ 339: 332—336.</li>
  -      <li>Tse, T., Williams, R. J., Zarin, D. A. (2009). <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821287/">Reporting “basic results” in ClinicalTrials.gov</a>. CHEST 136: 295—303.</li>
  +      <li>Zarin, D. A., Tse, T. T., Williams, R. J., Califf, R. M., and Ide, N. C. (2011). <a target='_blank' href="http://www.nejm.org/doi/full/10.1056/NEJMsa1012065#t=article">The ClinicalTrials.gov results database – update and key issues</a>. N Engl J Med 364: 852–60.</li>
  +      <li><a target='_blank' href="http://www.fda.gov/RegulatoryInformation/Legislation/SignificantAmendmentstotheFDCAct/FoodandDrugAdministrationAmendmentsActof2007/default.htm">Food and Drug Administration Amendments Act of 2007</a>. Public Law 110-95.</li>
  +      <li>Laine, C., Horton R., DeAngelis C.D., et al. <a target='_blank' href="http://www.nejm.org/doi/full/10.1056/NEJMe078110#t=article">Clinical trial registration – looking back and moving ahead</a>. N Engl J Med 356: 2734–6.</li>
  +      <li><a target='_blank' href="http://ec.europa.eu/health/files/eudralex/vol-10/2008_07/c_16820080703en00030004_en.pdf">Communication from the Commission regarding the guideline on the data fields contained in the clinical trials database provided for in Article 11 of Directive 2001/20/EC to be included in the database on medicinal products provided for in Article 57 or Regulation (EC) No 726/2004</a>. In: European Commission, ed. Official Journal of the European Union, 2008. (2008/C 168/02.)</li>
  +      <li><a target='_blank' href="http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000044.jsp">Guidance on the information concerning paediatric clinical trials to be entered into the EU Database on Clinical Trials (EudraCT) and on the information to be made public by the European Medicines Agency (EMEA), in accordance with Article 41 of Regulation (EC) No 1901/2006</a>. In: European Commission, ed. Official Journal of the European Union, 2009. (2009/C 28/01.)</li>
  +      <li>Zarin, D. A., Ide, N. C., Tse, T. et al. (2007). <a target='_blank' href="http://www.ncbi.nlm.nih.gov/pubmed/17507347">Issues in the registration of clinical trials</a>. JAMA 297: 2112—2120.</li>
  +      <li>Moher, D., Liberati, A., Tetzlaff, J. and Altman, D. G. (for the PRISMA Group)(2009). <a target='_blank' href="http://annals.org/article.aspx?articleid=744664">Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement</a>, BMJ 339: 332—336.</li>
  +      <li>Tse, T., Williams, R. J., Zarin, D. A. (2009). <a target='_blank' href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821287/">Reporting “basic results” in ClinicalTrials.gov</a>. CHEST 136: 295—303.</li>
       </ol>
   
     </div>
  
positive.code: 
      <p>The presence of a record in a dataset indicates that information was submitted to ClinicalTrials.gov for at least one variable in that data set before the data were downloaded from ClinicalTrials.gov. Some data elements are more/less likely than others to have missing information, depending on several known factors. For example:</p>
  
      <ul>
        <li><b>The data element being required by the FDAAA and/or the ClinicalTrials.gov website.</b> Refer to data element definitions xxxxxxxxxxxfor specifics regarding these requirements. Requirements may have changed over the history of the ClincalTrials.gov database.</li>
        <li><b>The date when the data element was introduced.</b> Not all data elements were included in the database at the time of its launch in 2000, but were added later. Studies registered after FDAAA when into effect must meet more requirements than studies registered earlier in the life of ClinicalTrials.gov.</li>
        <li><b>The branching structure of questions.</b> The availability of certain questions to the person submitting data depends on answers to previous questions. For example, questions about bio-specimen retention are only available for observational studies. Therefore, interventional studies should be excluded when analyzing data elements pertaining to bio-specimens.</li>
        <li><b>The list of possible answers for data elements with a fixed set of responses.</b> For example, questions that include “N/A” as a possible response are likely to have fewer missing values than questions that do not provide a “N/A” response.</li>
  
negative.code: 
    <div class="basicHero">
      <h1>Guide to Using Aggregate Analysis of ClinicalTrials.gov (AACT) for Statistical and Aggregate Analysis</h1>
    </div>
  
  </div>
  
  <section class="pointsToConsider">
    <div class="wrap">
  
      <h2>What is AACT?</h2>
  
      <p>AACT is the database for Aggregate Analysis of <a target='_blank' href='clinicaltrials.gov'>ClinicalTrials.gov</a>. Version 2 of AACT is a postgreSQL relational database containing information about clinical studies that have been been registered at ClinicalTrials.gov. AACT includes all of the protocol and results data elements for studies that are publicly available at ClinicalTrials.gov. Content is downloaded daily from ClinicalTrials.gov and loaded into AACT.</p>
  
      <p> <a target='_blank' href="http://ec2-52-87-233-209.compute-1.amazonaws.com/aact_points_to_consider.docx" download>Download a word document</a> containing the   information on this page.</p>
  
      <h2>What population of studies is represented in AACT?</h2>
  
      <p>All studies registered and publicly available at ClinicalTrials.gov are included in AACT. The ClinicalTrials.gov was released for the registration of studies on February 29, 2000. The registry accepts interventional studies in which participants are assigned according to a research protocol to receive specific interventions, as well as observational studies. It also includes Expanded Access records which describe the procedure for obtaining an experimental drug or device for patients who are not adequately treated by existing therapy and who are unable to participate in a controlled clinical study.</p>
  
      <p>The registration of studies and reporting of results and adverse events has been mandated to a large extent by requirements (both legal and institutional) implemented as part of the Food and Drug Administration Amendments Act (FDAAA), as well as by requirements introduced by the International Committee of Medical Journal Editors (ICMJE) and the European Medicines Agency (EMA) regarding registration of clinical studies. Table 1 describes the scope of these requirements.</p>
  
      <h4>Table 1: Scope of Interventional Studies Covered by Major Reporting Policies*</h4>
  
    <table class='pointsToConsider'>
      <tr>
        <th>Policy Requirements</th>
        <th>Registration & Results Reporting Requirements</th>
        <th>Effective Date</th>
      </tr>
  
      <tr>
        <td><p><a target='_blank' href='http://grants.nih.gov/grants/guide/notice-files/NOT-CA-15-011.html'>NCI Access Policy</a></p></td>
        <td><p>The NCI, NIH, issued its Policy Ensuring Public Availability of Results from NCI-supported Clinical Trials. Generally, for "all initiated or commenced NCI-Supported Interventional Clinical Trials whether extramural or intramural" (Covered Trials), "Final Trial Results are expected to be reported in a publicly accessible manner within 12 months of the Trial's Primary Completion Date regardless of whether the clinical trial was completed as planned or terminated earlier." This policy "will be incorporated as a Term and Condition of the award."</p></td>
        <td><p><b>January, 2015</b></p></td>
    </tr>
  
    <tr>
      <td><a target='_blank' href='http://www.fda.gov/RegulatoryInformation/Legislation/SignificantAmendmentstotheFDCAct/FoodandDrugAdministrationAmendmentsActof2007/default.htm'>FDAAA</a></td>
      <td>The following must be registered in ClinicalTrials.gov:
        <ul class='pointsToConsider'>
          <li>Interventional studies of drugs, biologics, or devices (whether or not approved for marketing)</li>
          <li>Studies phases 2 through 4</li>
          <li>Studies with at least 1 US site or conducted under IND/IDE</li>
        </ul>
  
        <p>Results and adverse event reporting is required for studies that meet the above registration requirements if they study drugs, biologics, or devices that are approved, licensed, or cleared by the FDA.</p>
      </td>
  
      <td>
        <b>September 27, 2007.</b> Studies initiated after this date, or with a completion date later than December 25, 2007 are subject to FDAAA requirements. Registration is required no later than 21 days after first patient is enrolled. Results and adverse events must be reported for these studies (if required) within 1 year of completing data collection for the pre-specified primary outcome.
        <br><br>
        <b>September, 2008.</b> Results reporting launched with optional adverse event reporting.
        <br><br>
        <b>September, 2009.</b>  Adverse event information became required.
      </td>
    </tr>
  
    <tr>
      <td><a target='_blank' href='http://www.icmje.org/about-icmje/faqs/clinical-trials-registration/'>ICMJE</a></td>
      <td>
        Interventional studies of any intervention type, phase, or geographical location must be registered in ClinicalTrials.gov or other approved registry.
        <br>No results reporting requirements.
      </td>
      <td>
        <b>July 1, 2005</b>.  Studies initiated after this date must be registered before first patient enrolled; studies initiated before this date must be retrospectively registered to be considered for publication.
      </td>
    </tr>
  
    <tr>
      <td><a target='_blank' href='http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000629.jsp&mid=WC0b01ac05808768df'>EMA</a></td>
      <td><p>The following must be registered in ClinicalTrials.gov or other approved registry:
        <ul class='pointsToConsider'>
          <li>Interventional studies of drugs or biologics (whether or not approved for marketing)</li>
          <li>Pediatric phase 1 studies;</li>
          <li>Studies in phases 2 through 4</li>
          <li>Studies taking place in at least 1 EU site</li>
        </ul>
        <p>Results reporting required for all studies that meet registration requirements.</p>
      </td>
      <td>
          <p>
            <b>May 1, 2004</b>. EMA launched <a target='_blank' href='https://eudract.ema.europa.eu/'>EudraCT</a>
            <br><br>
            <b>March 22, 2011</b>. The <a target='_blank' href='https://www.clinicaltrialsregister.eu/'>EU Clinical Trials Register</a> was launched by the EMA
         </p>
      </td>
    </tr>
  
  </table>
  
  <p>* Adapted from <a target='_blank' href="http://www.nejm.org/doi/full/10.1056/NEJMsa1012065#t=article">The ClinicalTrials.gov results database – update and key issues</a>. For complete descriptions of policy requirements, see the references cited. EMA denotes European Medicines Agency; EU, European Union; FDAAA, Food and Drug Administration Amendments Act; ICMJE, International Committee of Medical Journal Editors; IDE, investigational device exemption; IND, investigational new drug application, NCI, National Cancer Institute; NIH, National Institutes of Health; US, United States.</p>
  
      <p>Based on these requirements, the following are examples of characteristics that may influence the likelihood that a study is included in the ClinicalTrials.gov registry:</p>
  
      <ul class='pointsToConsider'>
        <li>Interventional studies are more likely to be registered than observational studies.</li>
        <li>Studies that began before the ICMJE requirement in <b>July, 2005</b> are less likely to be registered, especially if their results are unpublished (e.g., negative studies).</li>
        <li>Studies with drug, biological, or device interventions are more likely to be registered than studies of other interventions.</li>
        <li>Studies with at least one site in the United States or European Union are more likely to be registered than studies with no such sites.</li>
        <li>Studies involving a drug or device that is manufactured in the United States are more likely to be registered than studies involving a drug or device manufactured outside of the United States.</li>
  