Registering before a clinical trial begins and reporting basic results
after the trial are now mandatory, thanks to the Food and Drug Administration
Amendment Act of 2007 (FDAAA).
the free, searchable, and open online registry administered by the National
Library of Medicine (NLM) will begin to post clinical trial results as early
as this September, according to Rebecca Williams, Pharm.D., an assistant
Williams presented an overview of the implications of the new law and
specific timelines for implementing the FDAAA mandates during the annual
meeting of the New Clinical Drug Evaluation Unit (NCDEU) conference in May in
Phoenix. The meeting was sponsored by the National Institute of Mental Health
and American Society of Clinical Psychopharmacology.
Previous legislation had required public registration for trials of drugs
to treat life-threatening diseases. After the International Committee of
Medical Journal Editors began to require clinical trial registration in 2005
as a condition for consideration for publication in prominent medical
journals, most researchers or sponsors have registered their clinical trials
Nevertheless, the process remained voluntary. The legislation enacted in
September 2007 imposed legal requirements that mandate registering trials
before they begin as well as reporting their results at their end.
Prospective trial registration is intended to reduce the underreporting of
trials with negative results, especially such trials sponsored by drug
companies. Recent analyses showing that underpublication of negative trial
results may have inflated the perception of the effectiveness of
antidepressants and other medications, which has generated demands from the
research community for more transparent reporting and open access to
industry-sponsored trial data. Making trial results open to public access will
increase the transparency of industry data and allow researchers to have
easier access to more complete clinical evidence.
Since December 26, 2007, all phase 2 through phase 4 drug trials and
medical-device trials conducted for all diseases are required to be registered
before enrolling patients.
"[The new law] not only expanded the types of trials that should be
registered but also added data elements required to be registered,"
Williams explained. Clinical trial protocols posted on the Web site must
contain specific study elements consistent with the standards issued by the
World Health Organization and International Committee of Medical Journal
Editors, including primary outcome measures.
In addition, the FDAAA requires that the sponsor or investigator report the
results of some of these trials within 12 months after the estimated or actual
date of trial completion, whichever is earlier. This requirement does not
apply to drugs or devices that have not been approved by the FDA. Once the FDA
approves or issues an approvable or not approvable letter, the results of
clinical trials conducted previously must be posted within 30 days of the
The NLM is currently expanding the registry database and building the
results database, Williams said. She encouraged meeting attendees to review
the proposed data presentation formats and submit comments and suggestions. A
public meeting will be held by March 2009 to help develop specific rules and
The reporting of "basic results" will begin on September 27, as
required by the legislation. In these datasets, the public and researchers can
find trial participants' demographic and baseline characteristics, primary and
secondary outcomes, point of contact (personnel from whom scientific
information can be obtained), and main statistical analyses in clear and
According to Williams, the database for trial results will include links to"
existing results" such as FDA approval packages, advisory
committee information, and journal publications.
On September 27, 2009, the reporting of safety results will become
mandatory and include at least the following data summaries: rates of all
serious adverse events, adverse events that occurred in more than 5 percent of
subjects in any treatment arm, and adverse events in the active-treatment
group that are at least twice as frequent as those in the placebo arm.
Protocol registration and reporting of results are required for not only
industry-sponsored trials but also for academic and publicly funded trials.
will become the central repository for all clinical trials conducted in the
United States, it remains unclear whether the NLM will have the resources and
authority to monitor and enforce the accuracy of trial registration
information and results data posted on the Web site. At present, it is the
responsibility of sponsors and/or investigators to ensure that all information
submitted to the databases is correct.
The NLM does not restrict the submission of information, and clinical
trials conducted outside of the United States are encouraged to register as
The complete set of final rules about clinical trial registration and
results reporting, including the data format, guidelines, and enforcement,
will be released by the director of the National Institutes of Health (NIH) by
September 27, 2010.
In a separate presentation, Jean Baum from the National Institute of Mental
Health's Office of Communication, pointed grant-receiving investigators to
assistance provided on the Web sites of NIH and her agency on registering and
reporting their studies.
Additional information about
and instructions for submitting comments are posted at<prsinfo.clinicaltrials.gov/fdaaa.html>.
The text of the FDAAA 2007 is posted at<www.fda.gov/oc/initiatives/hr3580.pdf>.
Guidance for researchers funded by NIMH grants can be accessed at<www.nimh.nih.gov/health/trials/researchers/index.shtml>.▪