109th Congress

Access to Clinical Trial Information

S. 470/H.R. 3196, H.R. 5887, S. 3807

Background

The Food and Drug Administration (FDA) Modernization Act passed by Congress in 1997 required the U.S. Department of Health and Human Services, acting through the National Institutes of Health (NIH), to establish a clinical trials registry for both federally and privately funded trials “of experimental treatments for serious or life-threatening diseases or conditions.”

With input from FDA and other agencies, the National Library of Medicine (NLM) developed the ClinicalTrials.gov Web site. The first version of ClinicalTrials.gov was made available to the public on February 29, 2000. At that time, ClinicalTrials.gov included primarily NIH-sponsored trials. The site now includes more than 36,000 studies sponsored by NIH and other Federal agencies, private industry, and nonprofit organizations throughout the world.

The scientific and advocacy communities continue to support efforts to require research sponsors to publicly register all clinical trials, including outcome measures, in a centralized, standardized database. A registry of all clinical trials, not just treatment trials for serious and life-threatening conditions, would provide information to more patients and give physicians access to the most complete information available to assist them in practicing evidence-based medicine. It would also inform and speed the development of new trials, reduce the number of redundant studies, and enhance the safety of research participants.

Health-related organizations have taken several steps to encourage clinical trial registration. The International Committee of Medical Journal Editors announced that beginning in September 2005, it would require registration of “clinically directive” trials at their inception as a precondition for subsequent publication of manuscripts drawing on the results of those trials. Professional organizations such as the American Medical Association and Association of American Medical Colleges have also advocated public registration of clinical trials. Internationally, the World Health Organization (WHO) announced its support for the registration of clinical trials and recently approved standards for registration and reporting. The Institute of Medicine of the National Academies has also expressed support for registration of a broad range of clinical trials.

More recently, attention has turned to the reporting of results of clinical trials (excluding raw data), and ClinicalTrials.gov currently provides links to results reported in published, peer-reviewed journal articles. However, despite the benefits of reporting results to patients, clinicians, and researchers, significant challenges must be addressed when assembling summary information about the results of trials that have not been subject to scientific and editorial review (i.e., not published in peer-reviewed scientific journals). Processes and techniques must be developed for ensuring that reported results are complete and of high quality, and these issues must also be addressed through broad consultation among all interested parties, including patient groups, health care providers, clinical researchers, industry sponsors, regulators, and medical editors. NIH has begun exploring the feasibility of providing access to the results of the clinical trials it funds and conducts through ClinicalTrials.gov, as recommended by an internal NIH working group. Recognizing the difficulties inherent in results reporting, the working group also advised NIH to take a phased approach.

Congressional actions provide further impetus to clinical trials registration and results reporting. Senator Christopher J. Dodd (D-CT) and Representative Henry A. Waxman (D-CA) have introduced legislation that would assist in achieving universal, comprehensive clinical trials registration. Senators Michael B. Enzi (R-WY) and Edward M. Kennedy (D-MA) included provisions for clinical trials databases in legislation introduced to improve drug safety.

Provisions of the Legislation/Impact on NIH

S. 470 and H.R. 3196, the Fair Access to Clinical Trials Act of 2005 or the FACT Act, would have required the expansion of ClinicalTrials.gov. The data bank would have included a clinical trials registry accessible to patients and health care practitioners seeking information related to ongoing clinical trials for serious or life-threatening diseases and conditions, as well as a results database that would have contained results of all publicly and privately funded clinical trials, regardless of outcome. (This database would not have been limited to trials for serious or life-threatening diseases or conditions.) The results database would have been accessible to the scientific community, health care practitioners, and members of the public. In addition, FDA would have been required to make internal drug approval and safety reviews publicly available.

The ClinicalTrials.gov Web site would have continued to be run by NLM, with assistance from FDA. Provisions of the FACT Act would have applied to clinical trials for drugs, biologics, and medical devices. Clinical trials conducted outside the United States that are submitted to FDA or used in advertising or labeling to make a claim about a drug, device, or biological product would have been required to be registered at the time of submission. The Secretary of Health and Human Services (HHS) would have been permitted to impose penalties for noncompliance, including revoking a sponsor’s eligibility for further Federal funding and imposing civil money penalties.

H.R. 5887, the Vaccine and Public Confidence Assurance Act, which would have established the Agency for Vaccine Safety Evaluation, also contained a provision that would have required vaccine manufacturers to register clinical trials in a “qualified public registry.” (See separate article for more details on this measure.)

Title III of S. 3807, the Enhancing Drug Safety and Innovation Act of 2006, would have required the establishment of a clinical trials registry and results database¹ for drugs subject to FDA approval; however, inclusion of other types of intervention trials, such as devices, procedures, and behavioral interventions, would not have been required. Title III would have authorized such sums as may have been necessary to expand the registry and establish the results database within 1 year of enactment. It would have required that the public be able to search both the registry and the results database by specified categories. Registration of late Phase II, Phase III, and Phase IV clinical trials would have been required within 14 days of enrolling the first participant, and submissions would have been required to conform to the International Clinical Trial Registry Platform standards issued by WHO. The results database would have also been required to include the name of the drug studied, its approval status, and significant safety information for all Phase III and Phase IV clinical trials. Two versions of results summaries (nontechnical and technical) would have been required to be submitted within 1 year of trial completion. All submissions to the registry and results database would have been required to include “non-promotional” summary information that is not “false or misleading.”

NIH would have been required to post clinical trial information in the results database within 30 days of publication in a peer-reviewed journal or action by FDA (approval or disapproval of the application). NIH would have also been required to post clinical trial information in the results database if publication or action by FDA has not occurred within 2 years of submission to the agency.

Federal agencies would have been prohibited from releasing money for a research grant unless the responsible party has complied with the requirements for the clinical trials registry and results database. NIH, the Agency for Healthcare Research and Quality, and the U.S. Department of Veterans Affairs would have been required to certify and verify that the responsible party had provided the necessary information for the clinical trials registry and results database to NIH. If these agencies determined that clinical trial information had not been submitted, they would have been required to notify the grantee and allow 30 days for compliance. In addition, if any data elements were missing, the responsible party would have been notified and given 30 days to submit the information. If the information was not submitted, NIH would have been required to report the noncompliance to the scientific peer-review committees of the Federal research agencies and to the Office of Human Research Subjects Protections. NIH would have also been required to provide a public notice that data elements are missing. FDA would have been required to verify that information has been provided for the registry and results database before an application can be approved. FDA would have also been required to validate the content of the submitted information for a representative sample of trials.

Status and Outlook

S. 470 was introduced by Senator Dodd on February 28, 2005, and was referred to the Senate Committee on Health, Education, Labor and Pensions (HELP). No further action occurred on this legislation during the 109th Congress.

H.R. 3196 was introduced by Representative Waxman on June 30, 2005, and was referred to the House Energy and Commerce Subcommittee on Health. No further action occurred on this legislation during the 109th Congress.

H.R. 5887 was introduced by Representative Dave Weldon (R-FL), on July 25, 2006, and was referred to the House Committee on Energy and Commerce. No further action occurred on this legislation during the 109th Congress.

S. 3807 was introduced by Senator Enzi on August 3, 2006, and was referred to the Senate HELP Committee. On November 16, the HELP Committee held a hearing on the bill. No further action occurred on this legislation during the 109th Congress.

¹ Ninety days after enactment, the Secretary of HHS (after a public comment period) would have been required to publish a Federal Register notice regarding whether to expand ClinicalTrials.gov or create a new database.