Stakeholders are pushing for a national clinical trial registry, and efforts by UnitedHealth Group are in the forefront. Medical journals are setting hard and fast rules.
The creation of a publicly accessible national registry of clinical trials — recording both successes and failures — is an idea whose time certainly appears to have finally arrived. The National Institutes of Health, the American Medical Association, the Pharmaceutical Research and Manufacturers of America, Congress, and many drug companies are calling for public disclosure of clinical trials, including drug trials.
Roche, for example, launched a public database of clinical trials at «www.roche-trials.com» in April. Merck and GlaxoSmithKline have said that they support the idea of a national database, and GSK said that it will post the results of clinical trials since the beginning of 2001 on its own Web site by the end of the year.
Several health plans — including Aetna, HealthPartners, Harvard Pilgrim, Kaiser, and UnitedHealth Group's subsidiary Ingenix — have research centers that conduct post-marketing surveillance studies of drug interactions, says Carmella Bocchino, senior vice president for medical affairs for America's Health Insurance Plans.
"The kind of data gathered includes drug interactions with a variety of disease processes, wider age cohorts, and the effect of drugs on patients suffering from medical conditions other than the disease the drugs are meant to treat," says Bocchino. "National plans have a tremendous amount of claims and administrative data they can use to evaluate the effect of a specific drug."
It was, in fact, a large study made public last August by the FDA and Kaiser Permanente that led to the recall of Vioxx. Kaiser operates its own hospitals and employs its own doctors and has long conducted safety studies that draws from its database of claims and the clinical experience of its physicians. According to Kaiser CEO George Halverson, the health plan is currently conducting studies using its claims data and will make more information public as the reports are completed. "Patient safety will continue to be a driving market force in our industry for some time to come," said Halverson. "Public disclosure is ... inevitable."
In its joint initiative with Kaiser, the FDA announced on June 13 that it will support efforts by CMS to use data from claims related to the new Medicare drug benefit to pinpoint drug safety problems. "[We] strongly support the use of data from Medicare ... to identify safety risks for recently approved medications and to learn more about the real-world outcomes of medication use," said Janet Woodcock, MD, FDA acting deputy commissioner for operations, in a public statement. CMS Administrator Mark McClellan, MD, formerly the head of the FDA, said his agency wants to create a computerized system to gather data about the safety and effectiveness of the drugs that the government will begin subsidizing for Medicare enrollees next year.
That kind of scrutiny could significantly enhance the drug safety data, according to McClellan, because 4 out of every 10 prescriptions written in the country is for a patient 65 years or older. CMS officials say that problems resulting from "off-label" use of medications could also be detected.
"I expect several health plans will be willing to work with Medicare to help make this information available," says AHIP's Bocchino.
A subsidiary of Ingenix, I3, is marketing a drug safety registry that contains data from members' claims. The I3 Aperio Drug Registry will provide faster access to data for researchers at pharmaceutical companies, regulators, managed care organizations, and others. It will draw on a database that has 11 million members with prescription-drug coverage and will rise to 13 million as the company incorporates data from Oxford Health Plans, which it acquired recently.
The subsidiary will monitor its claims data on drugs introduced since 2004. The resulting data will be available in quarterly Web-based files, and annual reports and will be consistent with HIPAA regulations, say company officials. The reports will not be available to the public, but FDA officials say the data will be used to support public disclosure of drug safety data.
"Clinical trials are a powerful and essential step in testing drug safety, but by necessity are generally performed on limited numbers of people who don't have other diseases or take other medications," says K. Arnold Chan, MD, senior scientist for I3. "We offer researchers the data to analyze real-world prescription drug experience, including the health experiences of patients with comorbidities and those taking multiple medications. And the registry provides a greater scope of data, allowing researchers to identify rare side effects."
The FDA has been in discussions with I3 and others about making use of the information "to the extent we have the funding," says Steven Galson, MD, acting director for the FDA's Center for Drug Evaluation and Research. "The kind of data available from these databases represents an evolution in drug-safety information." The agency's monitoring system relies largely on reports by pharmaceutical companies of side effects and injuries caused by their products. But the companies' information comes mostly from doctors, who are under no obligation to report anything to the manufacturers and sometimes worry about their own potential liability if they report problems.
The agency receives 400,000 reports of possible bad reactions a year, but officials say there may be 10 times that number of actual events. Reports from I3 and others are worth the effort and cost, say Galson and other FDA officials. "We would like to be able to perform independent studies more frequently," said Janet Woodcock, deputy FDA commissioner, in a recent public statement. "We don't really have a robust program that can do that."
Journal editors issue list of minimum clinical trial reporting requirements
Clinical trials, including drug trials, gain medical and market credibility primarily through publication in a peer-reviewed journal. Several journals, including the New England Journal of Medicine and the Journal of the American Medical Association, announced last September that they would only publish the results of clinical trials that begin on or after July 1, 2005 if the trials are publicly registered. In June, the International Committee of Medical Journal Editors published an article in JAMA that reiterated that position, and provided extensive criteria for a minimal data set for publication. The editors define a clinical trial as "any research project that prospectively assigns human subjects to intervention and comparison groups to study the cause-and-effect relationship between a medical intervention and a health outcome." They define a "medical intervention" as any intervention used to modify an outcome, including drugs, surgeries, medical devices, and protocols.
Criteria include at minimum:
a unique identifying number, a statement of intervention, and comparison of the study hypothesis to existing data,
definitions of all outcome measures,
the target number of subjects,
the funding source, and
contact information for the principal investigator.
Trials must have at least one concurrent control or comparison group, which in essence requires contemporary data in order to be publishable. As of now, the only clinical trial registry meeting criteria is at «www.clinicaltrials.gov», which is sponsored by the United States National Library of Medicine. That registry is voluntary. Legislation is pending in Congress that would make registration in a national registry of all clinical trials mandatory and move the registry to the Food and Drug Administration.
More information is available in an editorial titled "Clinical Trial Registration: A Statement from the International Committee of Medical Journal Editors" in the Sept. 16, 2004 issue of NEJM and an editorial titled "Is This Clinical Trial Fully Registered? A Statement From the International Committee of Medical Journal Editors" in the June 8, 2005 issue of JAMA.
Contributing Editor Martin Sipkoff is a health care journalist who lives in Gettysburg, Pa.