ClinicalTrials.gov, the online registry run by the US National Institutes of Health (NIH), has now expanded to include summary results of completed trials with drugs, medical devices and biological products approved by the Food and Drug Administration (FDA).

The results information will be integrated into the clinical study records available through the ClinicalTrials.gov website (http://clinical trials.gov) and its consumer health information service, MedlinePlus (http://medlineplus.gov). The NIH’s registry already includes information on nearly 62,000 ongoing and completed trials sponsored by the US federal government, the pharmaceutical industry, academic researchers and international organisations based in the US and around the world.

Expanding the scope of ClinicalTrials.gov was one of the mandates of the Food and Drug Administration Act of 2007 (FDAAA), which came into effect on 27 September 2007. The legislation also tightened up the existing requirements for registering clinical studies.

Under the Act, sponsors have to lodge details of all ‘controlled clinical investigations’, other than Phase I studies, of compounds subject to the Federal Food, Drug, and Cosmetic Act in the NIH’s database. Previously, only federally and privately funded studies of experimental treatments for “serious or life-threatening diseases and conditions” had to be included, while registration of any other trials was voluntary.

Title VIII of the FDAA also calls for the submission of ‘basic results’ data, with effect from 27 September 2008, for all clinical trials with at least one site in the US, regardless of who sponsors, finances or conducts the trial. This mandate does not apply to Phase I trials or small feasibility studies for medical devices.

The summary results must generally be filed within 12 months of data collection being completed for the trial’s primary outcome measure, subject to fines and other punitive measures. The Act also requires submission of results for pre-specified secondary outcome measures registered at ClinicalTrials.gov.

‘Basic results’, explains registry director Dr Deborah Zarin, include summary data tables of baseline characteristics, participant flow, outcomes and adverse events. Other than a number of brief free-text fields for providing descriptions of data, no narrative information is included (e.g., there is no discussion or conclusion section).

And the downside is …

Some stakeholders, including the director of the FDA’s Center for Drug Evaluation and Research (CDER), Dr Janet Woodcock, believe the FDAA provisions for disclosure of basic trial results do not go far enough in the service of data transparency.

At the same time, there have been concerns about whether early publication will discourage medical journals from carrying trial reports. The Act does allow sponsors to delay filing results with ClinicalTrials.gov in certain circumstances, but not generally to allow for submission to journals.

An editorial in the BMJ last January suggested that journals “will continue to add value by publishing useful and readable trial reports that clinicians, the media and patients can interpret and use. And, most importantly, the results disclosed by the FDA will not have been externally peer reviewed and will be preliminary. Peer review not only provides a stamp of quality assurance, it often leads to re-analysis of results”.

A recent study on publication bias that appeared in the open-access journal PLoS Medicine warned that, while the FDAA provisions should speed up the dissemination of trial results, they could also aggravate rather than reduce bias.

With the basic results already in the public domain, sponsors may feel less compelled to undertake full publication of equivocal trials, while the time pressure under the Act to submit manuscripts within one year of approval could “focus sponsor efforts even more” on submitting positive trials and trials of most interest to journals, suggested researchers Kirby Lee, Peter Bacchetti and Ida Sim from the University of California San Francisco.