Healthy Skepticism Library item: 19301

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Publication type: Journal Article

Zarin DA, Tse T, Williams RJ, Califf RM, Ide NC
The ClinicalTrials.gov Results Database — Update and Key Issues
NEJM 2011 Mar 3; 364:852-860
http://www.nejm.org/doi/full/10.1056/NEJMsa1012065#t=articleBackground

Abstract:

The ClinicalTrials.gov trial registry was launched more than a decade ago. Since that time, it has been evolving in response to various policy initiatives. The registry now contains information on more than 100,000 clinical studies and has emerged as a key element of many public health policy initiatives aimed at improving the clinical research enterprise. In 2008, a database for reporting summary results was added to the registry. In this article, we present an update on relevant policies, summarize the structure and contents of the results database, and show how ClinicalTrials.gov data can be used to gain insight into the state of clinical research.
KEY TRIAL-REPORTING POLICIES
Section 801 of the Food and Drug Administration Amendments Act (FDAAA)1 expanded the legal requirements for trial reporting at ClinicalTrials.gov. It was passed into law amid concerns about ethical and scientific issues affecting the design, conduct, and reporting of clinical trials,2 including the suppression and selective reporting of results based on the interests of sponsors,3 unacknowledged alterations of prespecified outcome measures,4 “offshoring” of human-subjects research,5 and failure to report relevant adverse events.6 Among other things, the FDAAA mandates the submission of summary results data for certain trials of drugs, biologics, and devices to ClinicalTrials.gov, whether the results are published or not,7 and imposes substantial penalties for noncompliance. The law’s scope is not limited to industry-sponsored trials intended to support marketing applications but includes studies not intended to inform FDA action (e.g., comparative-effectiveness trials of approved drugs or devices), regardless of sponsorship. Table 1TABLE 1
Scope of Interventional Studies Covered by Major Reporting Policies. summarizes the scope of key reporting requirements of the FDAAA and two other policies: the registration policy of the International Committee of Medical Journal Editors8 and regulations being implemented by the European Medicines Agency for registration and results reporting of clinical drug trials conducted in the European Union.9,10
DESCRIPTION OF CLINICALTRIALS.GOV
Data in ClinicalTrials.gov are self-reported by trial sponsors or investigators by means of a Web-based system.7 Registration information is generally reported at trial inception. Each record contains a set of mandatory data elements that describe the study’s purpose, recruitment status, design, eligibility criteria, and locations, as well as other key protocol details.11 Additional information may be provided with the use of optional data elements. Before public posting, ClinicalTrials.gov conducts a quality review of the submitted information. Each trial (regardless of the number of study sites) is represented by a single record, which is assigned a unique identifier (i.e., NCT number). Each record is expected to be corrected or updated throughout the trial’s life cycle, and all changes are tracked on a public archive site that is accessible from each record (through a “History of Changes” link). Summary results data are entered in the results database after a trial is completed or terminated (Table 2TABLE 2
Summary Objectives and Description of Requirements for the ClinicalTrials.gov Results Database.
). Once posted, results records are displayed with corresponding registry (summary protocol) information for each study. Resources and links to additional information are inserted by the National Library of Medicine to enhance the overall usefulness of the database. ClinicalTrials.gov is designed to benefit the general public by expanding access to trial information, but different parts of the database are likely to be of more or less direct use to different audiences.
Quality Assurance
ClinicalTrials.gov uses automated business rules to alert data providers when required information is missing or when certain data elements are internally inconsistent. After passing automated validation, all submissions are individually reviewed before public posting to assess whether entries are complete, informative, internally consistent, and not obviously invalid; specific criteria for this assessment are described on the Web site.15 Although the review of summary protocol information is generally straightforward, that of results submissions is more complex. The goal, at a minimum, is to determine whether entries provide an accurate depiction of the study design and whether the results can be understood by an educated reader of the medical literature. Some invalid data can be detected by ClinicalTrials.gov staff; however, other data cannot be verified because ClinicalTrials.gov does not have an independent source of study data (e.g., “624 years” is clearly an invalid results entry for mean age, whereas “62.4 years” may or may not be the true mean age). Submissions are not posted on the public site until quality requirements are met; if any important problems are detected (Table 3TABLE 3
ClinicalTrials.gov Quality Review Criteria.
), results records are returned to the data providers for revision. However, individual record review has inherent limitations, and posting does not guarantee that the record is fully compliant with either ClinicalTrials.gov or legal requirements. …