10 Mar 2008

Much of the data generated from drug trials on human volunteers stays hidden from view, sometimes to the detriment of patients. A new federal law will help bring more of this trial information to the public, by expanding the number of trials that must be reported to the federal clinical trial register, and by establishing the first federally funded clinical trial results database.

As explained by Deborah Zarin and Tony Tse of the National Institutes of Health, Bethesda, Maryland, in a policy paper in the 7 March Science, the law will narrow the gap between the number of clinical trials conducted and the number for which results are reported. It will not, however, cover all trials or address all the problems that come with the lack of transparency in the conduct of clinical trials.

The U.S. Legislature established the current trial registration system (accessed through www.Clinicaltrials.gov) in 1997, to increase patient access to experimental drugs. The law required public disclosure of information on a subset of trials involving medicines for serious diseases. The number of trials registered has steadily expanded due to additional pressures and policies, especially by journals that began to require registration as a precondition for publication (see ARF related news story for this reporter’s recent perusal of the database in search of Alzheimer disease trials).

Last September, the Congress passed another law, the FDA Amendments Act, which expands the type of trial that needs to be registered to include drugs, biologics, and devices for any condition. According to Zarin and Tse, this requirement is still narrower than some would like. The World Health Organization and the International Committee of Medical Journal Editors policy calls for registration of all clinical trials, regardless of type, and the WHO established its own database to support this goal.

The big impact of the law may be its requirement for a results database to be set up by September 2008. This database will collect summary results of clinical trials for all approved drugs, to be deposited within one year of trial completion or within 30 days of FDA approval of a new therapy. Eventually, the database will also display adverse event data.

These measures will improve public access to critical information from publicly and privately funded clinical research. Thus, the new law should prevent repeats of cases like Paxil, where the manufacturer did not release data on adverse effects in children and adolescents, or Vioxx, which was pulled from the market after researchers got a belated look at clinical trial data that indicated an increased risk of heart complications.

The law, however, does not address other important issues, Zarin and Tse write. The new reporting requirements will not solve problems related to the design or conduct of clinical trials, including research ethics. In addition, the law covers intervention studies, not observational studies, a class that includes post-market surveillance. Another question not addressed is how many data are needed for the FDA to take action. On that count, though, wide access to data is critical for the public to make a case for action.

Weaknesses of the law include provisions that bias reporting towards positive results, the authors caution. Trials on some devices must be registered, but the registration and results data will not be released unless and until the device is approved, insuring that only positive trials will be disclosed. The law does not require registration or reporting of Phase 1 trials, or reporting the results of unapproved medicines. Nonetheless, Zarin and Tse conclude, the law “should transform the degree of public access to critical clinical trial information from public and privately funded clinical research,” a necessary step in the evolution of transparency in clinical trials.

The increasing demands for accountability in clinical trials raise an often-overlooked problem for investigators, that is, the task of documenting their work properly to comply with the reporting laws. This can be burdensome, say Greg Fegan and Trudie Lang of the Kenya Medical Research Institute–Wellcome Trust Collaborative Research Program, Kilifi, Kenya, in an essay in the March issue of PLoS Medicine. Companies running large trials use commercial software packages for this purpose, but for smaller academic groups or investigators in poorer countries, those packages can be prohibitively expensive. Fegan and Lang suggest that open-source software could fill the need for an affordable, easy-to-use clinical trial data management system. Such a solution could help lower the barrier to conducting trials, they say, and “encourage more investigators in resource-poor settings to take part in high-standard research that would otherwise be out of reach and beyond their capacity.” They call for research organizations to combine their efforts to produce such a system, which would bring wide benefits to investigators and patients.—Pat McCaffrey

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References

News Citations

1. Clinical Trial Update: Flurry of Winter Activity 10 Mar 2008

External Citations

1. www.Clinicaltrials.gov
2. its own database

Further Reading

News

1. Clinical Trial Update: Flurry of Winter Activity 10 Mar 2008
2. Clinical Trial Data: Fit for Public Consumption 13 Mar 2007