Reporting Discrepancies between the ClinicalTrials.gov Results Database and Peer Reviewed Publications

BACKGROUND: Result summaries are now required to be reported in ClinicalTrials.gov for many 1 trials of drugs and devices. PURPOSE: To evaluate the consistency of reporting in trials that are both registered in the ClinicalTrials.gov results database and published in the literature. DATA SOURCES: ClinicalTrials.gov results database, matched publications identified through both ClinicalTrials.gov and a manual search of two electronic databases. STUDY SELECTION: 10% random sample of Phase III or IV trials with results in the ClinicalTrials.gov results database, completed before January 1, 2009, with two or more arms. DATA EXTRACTION: One reviewer extracted data from ClinicalTrials.gov results database and matching publications. A subsample was independently verified. Basic design features and results were compared between reporting sources and discrepancies were summarized. DATA SYNTHESIS: Of 110 reviewed trials with results, most were industry-sponsored, parallel design, drug studies. The most common inconsistency was the number of secondary outcome measures reported (80%). There were 16 trials (15%) that reported the primary outcome description inconsistently and 22 (20%) in which the primary outcome value was reported inconsistently. A total of 38 trials inconsistently reported the number of individuals with a serious adverse event (SAE), of which 33 (87%) reported more SAEs in ClinicalTrials.gov. Among the 84 trials that reported SAEs in ClinicalTrials.gov, 11 publications did not mention SAEs, 5 reported SAEs as zero or not occurring, and 21 reported a different number of SAEs. In 29 trials that reported deaths in ClinicalTrials.gov, 28% differed with the matched publication. LIMITATIONS: Small sample that includes earliest results posted to the database and therefore may reflect inexperience with the submission process. CONCLUSIONS: Reporting discrepancies between the ClinicalTrials.gov results database and matching publications are common. It is unclear which reporting source contains the most accurate account of trial results. ClinicalTrials.gov may provide a more comprehensive description of trial adverse events than the publication.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the American College of Physicians and can be found at: http://annals.org/

Considering Usual Medical Care in Clinical Trial Design

Liza Dawson and colleagues discuss the scientific and ethical issues associated with choosing clinical trial designs when there is no consensus on what constitutes usual care

Sharing Individual Participant Data (IPD) within the Context of the Trial Reporting System (TRS).

Deborah Zarin and Tony Tse of ClinicalTrials.Gov consider how sharing individual participant data can and cannot help improve the reporting of clinical trials

Data from: Trial-results reporting and academic medical centers.

To the Editor: Reporting of aggregate results helps mitigate disclosure biases affecting medical research. Although the reporting of summary results is currently mandated by the Food and Drug Administration Amendments Act of 2007 (FDAAA), published findings suggest underreporting. Two recent proposals are aimed at improving public reporting of aggregate results. These are a Notice of Proposed Rulemaking (NPRM) to expand FDAAA requirements to include the results of trials of unapproved products, and a draft policy requiring the results of all National Institutes of Health (NIH)-funded trials, including those not subject to the FDAAA

Schematic depicting information granularity for different types of data [12].

<p>Schematic depicting information granularity for different types of data [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001946#pmed.1001946.ref012" target="_blank">12</a>].</p

Schematic depicting ClinicalTrials.gov as an “information scaffold” using the record unique identifier (NCT number) to link to various online resources.

<p>Schematic depicting <a href="http://ClinicalTrials.gov" target="_blank">ClinicalTrials.gov</a> as an “information scaffold” using the record unique identifier (NCT number) to link to various online resources.</p

Data from: Terminated trials in the ClinicalTrials.gov results database: evaluation of availability of primary outcome data and reasons for termination

Background: Clinical trials that end prematurely (or “terminate”) raise financial, ethical, and scientific concerns. The extent to which the results of such trials are disseminated and the reasons for termination have not been well characterized. Methods and Findings: A cross-sectional, descriptive study of terminated clinical trials posted on the ClinicalTrials.gov results database as of February 2013 was conducted. The main outcomes were to characterize the availability of primary outcome data on ClinicalTrials.gov and in the published literature and to identify the reasons for trial termination. Approximately 12% of trials with results posted on the ClinicalTrials.gov results database (905/7,646) were terminated. Most trials were terminated for reasons other than accumulated data from the trial (68%; 619/905), with an insufficient rate of accrual being the lead reason for termination among these trials (57%; 350/619). Of the remaining trials, 21% (193/905) were terminated based on data from the trial (findings of efficacy or toxicity) and 10% (93/905) did not specify a reason. Overall, data for a primary outcome measure were available on ClinicalTrials.gov and in the published literature for 72% (648/905) and 22% (198/905) of trials, respectively. Primary outcome data were reported on the ClinicalTrials.gov results database and in the published literature more frequently (91% and 46%, respectively) when the decision to terminate was based on data from the trial. Conclusions: Trials terminate for a variety of reasons, not all of which reflect failures in the process or an inability to achieve the intended goals. Primary outcome data were reported most often when termination was based on data from the trial. Further research is needed to identify best practices for disseminating the experience and data resulting from terminated trials in order to help ensure maximal societal benefit from the investments of trial participants and others involved with the study