Clinical Trials Registry Falling Short of Goal

Researchers at Canada’s University of British Columbia say that U.S. efforts to create greater transparency in clinical research by requiring that all clinical trials be catalogued in a registry—and that information about the results of these trials be made public— are failing.

The largest clinical trials registry, ClinicalTrials.gov, is run by the U.S. National Institutes of Health (NIH) and contains information on more than 100,000 trials. The database was made public in February 2000 to improve patient access to information on clinical trials for rare and serious conditions.

In July 2005, the International Committee of Medical Journal Editors made registration prior to patient enrollment a prerequisite for publication for all studies started after that date. Then, the September 2007 Food and Drug Administration Amendments Act mandated that either the study sponsor or the principal investigator register with ClinicalTrials.gov all phase-2 and higher drug and biologic trials that meet either or both of two criteria: that the trial has one or more study sites located in the United States and that the trial is being conducted under a U.S. investigational new drug application.

The act also mandated that trials already under way be registered by December 2007 and required that researchers post a summary of basic results—including outcome measures and adverse events—within a year of the completion of data collection or within 30 days after the U.S. Food and Drug Administration (FDA) first approved the drug. Failure to comply can result in civil penalties of up to $10,000 per day if the violations remain uncorrected 30 days after being cited by the FDA.

However, the act permits researchers to delay reporting results for up to three years for trials conducted before drugs are initially approved and for studies of unapproved clinical indications for already approved drugs.

In the December 2011 Health Affairs, Michael Law, Ph.D., an assistant professor in the Centre for Health Service and Policy Research at the University of British Columbia, and colleagues pointed out that the overall value of clinical trial registries for the clinical and scientific communities depends on how comprehensively those registries document completed and ongoing studies, particularly those that will never be published.

Law and colleagues studied the longer-term impact of the federal mandate and found that the number of trials registered with ClinicalTrials.gov increased, but also that “39 percent of trials were registered late, and only 12 percent of completed studies reported results within one year.”

Furthermore, they found that trials funded by industry were more than three times as likely to report results as were trials funded by NIH. They theorized that this may reflect the capacity of industry researchers to meet posting requirements, the fact that they—unlike academic researchers—are paid to post results, or the strong incentive that manufacturers have to publicize positive results about their products.

But what about those penalties for failure to register? Although Law and colleagues pointed out that fines for failing to submit clinical trial information are supposed to be on the order of $10,000 per day, manufacturers weigh those penalties against possible risks to revenue streams that are often orders of magnitude larger, and—as of February 2010—no fines had been levied for noncompliance with the federal mandate. And journals’ publication requirements are often a moot point, since many studies will never be published.

Overall, Law and colleagues found that the federal mandate did, in fact, increase the registration of medication trials on ClinicalTrials.gov, at least for a short period of time, but additional mechanisms may be required to ensure the completeness of trial registration and results reporting.

“Transparency in clinical trial design and reporting is very important, particularly in light of several high-profile withdrawals of drugs from the market after safety problems were identified,” Law told Psychiatric News. “A complete database of all clinical trials and their results would be an incredibly powerful resource for discovering important new information on drug safety and efficacy.”

Jarilyn Dupont, J.D., director of Regulatory Policy for the FDA, told Psychiatric News, “We always have concerns if we discover someone who hasn’t submitted results, and we have followed up on many of these.”

Dupont also pointed out that NIH has the responsibility for implementation of regulations that will then be enforced by the FDA: “It is our understanding that [NIH is] working on proposed rules. Although we’ve been doing compliance activities all along, we need the regulations to clarify certain statutory requirements.”

An abstract of “Despite Law, Fewer Than One in Eight Completed Studies of Drugs and Biologics are Reported on Time on ClinicalTrials.gov” is posted at http://content.healthaffairs.org/content/30/12/2338.