Creating an NIH Clinical Trials Registry: A User Friendly Approach to Health Care

The National Institutes of Health (NIH) is surveying its existing information networks with the aim of assembling an easily accessed database of NIH-funded clinical trials-- ongoing, completed but unpublished, and published.

Building on the impetus of a Congressional mandate to create a clinical trials registry for women's health, NIH's Office of Medical Applications of Research (OMAR), the Office of Research on Women's Health (ORWH), and the National Library of Medicine (NLM) are working to assemble a database of trials relevant not only to women's health, but across the spectrum of research. "The goal," says John Ferguson, MD, director of OMAR, "is to improve health care outcomes, and you want to have the best information across the board on which to base patient care decisions."

A December 1993 meeting at NIH, co-sponsored by the Agency for Health Care Policy and Research, convened health officials, patient advocates, researchers, and administrators of clinical trials registries to review the rationale for registries, exchange information on existing registries, identify users' needs, and explore the problems in set-ting up and maintain-ing registries. The logistical obstacles involved in managing registries are formidable, but among the benefits would be a health care system in which evidence from clinical trials can be more rapidly incorporated into clinical practice.

The Case for Clinical Trials Registries

The scientific evidence that clinical trials provide on treatment safety and efficacy is only useful when it reaches the practitioners who can apply the information in clinical care. A previous column addressed the use of clinical alerts under certain conditions to expedite the dissemi-nation of results from major trials to health practitioners (JAMA. 1993;269:3096). The accumulation of data from smaller-scale trials could offer more timely information than larger ones, according to Thomas C. Chalmers, MD, a speaker at the meeting who is chairman of MetaWorks, Inc., Boston, Mass, and a leading authority on clinical trials and meta-analysis. Access to data from com-pleted trials is not easy, however. "If we had had a registry of clinical trials for the last 20 years, we would have saved, I believe, some large number of lives," said Chalmers. In a study that compared the results of meta-analyses and the recommendations of clinical experts over time, Chalmers and colleagues found, for example, that cumulative meta-analysis of clinical trials could have shown by 1973 that use of thrombolytic drugs in acute myocardial infarction (AMI) reduced total mortality significantly (JAMA. 1992;268:240-248). It was not until 1982 that a meta-analysis was published showing a significant reduction in mortality; 1986, before the results of the first large-scale mortality trial were published; and 1988, before the majority of reviewers in a literature survey recommended the treatment. Timely meta-analyses could have sped changes in treatment paradigms for other conditions as well.

Registries document the fact that trials took place, and whether they had negative or positive results. Clinical trials with negative outcomes are often not published. The easy retrievability of this information could shape future trials and meta-analyses by making readily accessible what has already been investigated. An added benefit, says Vivian Pinn, MD, director of the ORWH, is that the NIH registry "must report the proportions in trials of women and men by age, race, and ethnic group, data that are vital for recruit- ment, analysis, and application but have often been difficult or impossible to retrieve." Finally, registries can give patients of diverse backgrounds and their physicians in any location access to information on state-of-the-art treatment and research.

One of the key resources to registries of published clinical trials is the NLM. In recent years, NLM has expanded the number and variety of terms that can be used in indexing and searching the clinical trial literature. In addition, because indexers must rely solely on authors' explicit descriptions of research, the NLM is taking steps to emphasize to editors and authors the need to use terms specific to clinical trials. The NLM, OMAR, and the University of Maryland's Baltimore Cochrane Center are collabo-rating to "retro-tag" already published randomized controlled clinical trial reports that were not so indexed, and are asking journal editors to contribute to the massive task of back searching for such papers.

Ongoing Trials a Greater Challenge Than Those Already Published

Experience with existing U.S. and European databases discussed at the meeting highlighted common problems of managing a database of ongoing clinical trials. At present, registries vary in both the types of studies they include and the information on each trial. The International Collaborative Group on Clinical Trials Registries, a consortium of registry keepers, has suggested a standard core content that could make data collection among registries more consistent.

Gathering and updating the information--and ensuring the resources needed to do so--are difficult challenges. OMAR is looking at its existing inventory of NIH-funded clinical trials with a view toward streamlining data acquisition with an empha-sis on protocols, rather than program and funding information, which had been its focus, and making the database easier to update and use.

NIH already has two on-line clinical trials databases, AIDSTRIALS and PDQ. AIDSTRIALS, a collaborative effort of the National Institute of Allergy and Infectious Diseases, the Food and Drug Administration, the Centers for Disease Control and Prevention, and the NLM, currently provides information on about

540 AIDS-related trials. The National Cancer Institute's PDQ provides information on cancer research protocols as well as other resources. (For more information, call the AIDS Clinical Trials Information Service at [800] TRIALS-A, or, for PDQ, [800] 422-6237.)

Internationally, there are about 24 clinical trials registries, most of which focus on AIDS. Registry advocates envision a time when anyone will be able to obtain information on-line on international clinical trials, if not through one unified registry then through a directory of registries like that at the University of Maryland. This registry is not yet on-line, but information is available by contacting Kay Dickersin, PhD, (E-mail [email protected], or fax [410] 706-8013). A systematic means of archiving and retrieving the experience of previous and ongoing research is central to wise, timely, and ethical use of therapies and health resources which is essential to health care system reform.

• -- by Willam R. Harlan, MD
• Associate Director for Disease Prevention, NIH

Editor's Note: Inquiries may be directed to Charlotte Armstrong, Writer-Editor, NIH, Bldg 31, Room 2B19, Bethesda, MD 20892; Telephone: (301) 496-8855.