You asked for information on clinical trials, particularly information available to the public, and any proposed legislation concerning them.

SUMMARY

Registering all clinical trial in a public data bank, from start to completion and including the full disclosure of results, has become an important health policy concern given the recent negative information about certain approved and prescribed prescription drugs. The issue has garnered the attention of the federal government, state governments, the medical journal community, the American Medical Association (AMA), the pharmaceutical industry, consumers, and other interested parties. While a government registry (ClinicalTrials. gov) lists many trials that are open to people with serious diseases, many trials go unlisted and there is no comprehensive system for the public reporting of results.

The AMA has recommended that the federal government establish a comprehensive registry for all clinical trials conducted in the United States. A group of medical journals have also called for the development of such a registry.

Federal legislation was introduced in the last session of the U. S. Congress on this issue but did not pass.

CLINICAL TRIALS REGISTRATION

Background and History

In the United States, public registration is currently required for some clinical trials. These include clinical gene-transfer trials registered with the National Institutes of Health (NIH) and studies of the effectiveness of treatments for serious or life-threatening conditions conducted under the investigational new drug regulations of the federal Food and Drug Administration (FDA). But there is no system for comprehensive registration of trials or the public reporting of results. According to Robert Steinbrook, “when companies seek approval to market a new medication or to market an existing drug for an additional indication, the FDA releases extensive information about the trials that support the approval—but considers much of the other information it receives to be proprietary and never releases it. ” (See Steinbrook, “Public Registration of Clinical Trials,” The New England Journal of Medicine,” Vol. 351: 315-317, July 22, 2004).

Registering clinical trials was first proposed in the 1970s in conjunction with President Nixon’s “War on Cancer” and to reduce bias in the reporting of trial results (Steinbrook). Currently, there are government and other registries as throughout the world, including those maintained by companies and institutions. Some of these government registries include GenBank (the NIH genetic sequence database, and the Genetic Modification Clinical Research Information System (www. gemcris. od. nih. gov). This latter registry is a joint NIH and FDA project to provide information about clinical gene transfer trials and allow for prompt reporting of adverse events.

The FDA Modernization Act of 1997 (FDAMA) and ClinicaTrials. gov

The FDAMA directed FDA to establish database of clinical trials to treat serious diseases and conditions. As a result, ClinicalTrials. gov was developed by FDA and NIH, through the National Library of Medicine, and became operational in 2000. The law defines a “clinical trial” as “a research study in human volunteers to answer specific health questions. ” This definition includes interventional and observational trials, preliminary trials, and trials with and without control groups.

Sponsors of clinical trials are required to describe the purpose of each qualifying experimental drug entering Phase II efficacy studies plus eligibility criteria for participation, location of trial sites, and a point of contact. The primary aim of the registry is to make it easier for patients suffering from cancer, AIDS, and other life-threatening illnesses to enroll in studies of experimental treatments.

As of summer 2004, the registry listed 10,906 trials from 90 countries, with about 40% still recruiting subjects. NIH and other federal agencies, universities, and other organizations sponsor most of the studies listed, according to Steinbrook. About 2,230 trials are sponsored, at least partially, by industry, and about 425 companies have registered studies. Each study is given a unique registration number, regardless of the number of sites. The National Library of Medicine verifies the accuracy of the information and provides quality control.

One of the limitations of ClinicalTrials. gov, according to Steinbrook, is that it was established for studies of certain diseases and conditions, although it has accepted many other listings. More significantly, information about results is not required, however links to relevant publications may be included. Further, the registry includes only a small percentage of all clinical trials, and some studies that should be registered are not, according to some commentators. The FDAMA does not include an enforcement mechanism. The FDA provides detailed guidance to industry about registration requirements.

Actions and Recommendations of Other Organizations

In September 2004, the International Committee of Medical Journal Editors (ICMJE), a group of 11 publications including the New England Journal of Medicine, the Journal of the American Medical Association, and the Lancet, simultaneously published editorials calling for the development of a comprehensive clinical trials registration database. Also, the 11 members announced they would adopt a trials-registration policy to promote this goal; they would publish only articles that discuss studies previously listed on a public trials registry. To be eligible for publication, trials must register by the onset of patient enrollment on a public site, such as ClinicalTrials. gov, beginning July 2005 (see www. actmagazine. com/appliedclinicaltrials. )

The AMA House of Delegates recommended, in June 2004, that the federal Department of Health and Human Services (HHS) “establish a comprehensive registry for all clinical trials conducted in the United States; every clinical trial should have a unique identifier; and all results from registered clinical trials should be made publicly available through either publication or an electronic data-repository. ” The AMA also

recommended “Institutional Review Boards consider registration of clinical trials to an existing registry as condition of approval. ” (see http: //content. nejm. org/cgi/content/full/351/4/315.

The Pharmaceutical Research and Manufacturers of America (PhRMA), the pharmaceutical industry’s main trade group, announced earlier this year that its member companies will begin voluntarily posting information about ongoing clinical trials for all diseases. This is scheduled to begin this summer on ClinicalTrials. gov. Also, in October 2004, PhRMA began www. clinicalstudyresults. org, a site listing information about clinical trials completed since October 1, 2002 for drugs that are on the market. (The ClinicalTrials. gov site lists ongoing trials for drugs that are not necessarily on the market yet. )

PROPOSED LEGISLATION

Federal Bills

The “Fair Access to Clinical Trials Act” was introduced in both the U. S. House of Representatives (HR 5252) and Senate (S 2933) in the 108^th Congress, 2d Session. The bills, which did not pass, would have amended the Public Health Service Act and the Federal Food, Drug and Cosmetic Act with respect to the availability to the public of information on clinical trials to determine the safety and effectiveness of drugs, biological products and devices. Specifically, these bills would have prohibited an entity from receiving a grant, contract, or cooperative agreement to conduct a clinical trial to determine the safety of effectiveness of a use of a drug or device unless it agreed to:

1. register the trial,

2. provide the results of the trial to the HHS secretary,

3. disclose specified information regarding the trial to the public, and

4. be subject to audits.

The bills also would have required the HHS secretary, acting through the NIH director, to establish and operate a data bank of clinical trial information that is provided to the secretary. The NIH director would assign primary responsibility for operating the databank to the National Library of Medicine. The bills further required the secretary to: (1) identify false or misleading information in the databank, correct it, and make appropriate public notifications, and (2) amend regulations to

require institutional review boards to determine the safety or effectiveness of products registered under the bills and deny approval for trials that are not registered.

State Legislative Proposals

We have not identified any “model legislation” on this topic; but consumers union proposes that states consider legislation to mandate new minimum standards for the review of any new drug trial in a state and that prohibits drug trials in the state from being approved unless the drug company registers the trial in advance with the federal government’s public registry (http: //www. clincaltrials. gov) and agrees to release the results to the public.

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