Registration of Clinical Trials for Pharmaceuticals

• Author: Danielle Bradus
• Position: JD candidate at American University Washington College of Law
• Pages: 06

Danielle Bradus is a second-year JD candidate at American University Washington College of Law. She is a member of the Business Law Brief and the American University Journal of Gender, Social Policy & the Law. Ms. Bradus received her undergraduate degree in Public Policy from Duke University.

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VIOXX WAS REMOVED FROM THE MARKET because its use was linked to an increased risk of heart attack and stroke. Paxil may be associated with an increased risk of suicide in children. These are only two examples of many similar stories publicized recently by the media. In light of reports and public disclosure of information, pharmaceutical companies have come under attack for failing to disclose information about the side effects of their drugs. The negative exposure has resulted in numerous lawsuits, an American Medical Association (AMA) study, Congressional Hearings, and a recent ruling by the International Committee of Medical Journal Editors (ICMJE) mandating the registration of clinical trials in a public database before member journals may publish the results of those trials. Pharmaceutical companies have not registered their studies in a timely manner, impacting the scientific community, the medical community, and the public at large. With the recent publicity of problems associated with different medications there is an increased push for the registration of clinical trials. However, registration will have a great impact on the pharmaceutical industry and will not solve all problems related to clinical trials.

Initial Registration and the Law

TO UNDERSTAND THE EFFECTS OF REGISTRATION and the ICMJE ruling, it is important to have a basic knowledge of the regulation of clinical trials. The Food and Drug Administration (FDA) governs new drug applications and trials under the Food Drug and Cosmetic Act (FDCA). The FDCA originally contained no requirements for the registration of clinical studies. The first proposal for mandatory clinical trial registration arose in the 1970s during President Nixon's "War on Cancer;"¹ however, this push for a registration requirement was unsuccessful. Congress amended the FDCA in an effort to increase the use of registries. The FDA Modernization Act of 1997 ("Modernization Act") required the registration of clinical trials for serious or life-threatening diseases.² The Modernization Act included the following requirements: A registry of clinical trials (whether federally or privately funded) of experimental treatments for serious or lifethreatening diseases and conditions . . . which provides a description of the purpose of each experimental drug[,] . . . eligibility criteria for participation in the clinical trials, a description of the location of trial sites, and a point of contact for those wanting to enroll in the trial, and shall be in a form readily understood by members of the public.³

By applying these guidelines to trials involving lifethreatening diseases and conditions, the Modernization Act was Congress' attempt to produce a register of trials for the most critical diseases. The Act led the FDA and National Institute of Health (NIH) to create a national register maintained by the United States National Library of Medicine.⁴ This registration system became operational in 2000 and contained 10,906 registered trials by June of 2004.⁵ Although the register was created for studies involving serious or life-threatening diseases, the database also accepts other listings, such as government-funded clinical trials.⁶ The pharmaceutical industry did not fully comply with the new regulations. From its point of view, the economic cost of compliance, discussed in detail below, outweighed the benefits. Therefore, the Modernization Act did not compel the industry to change its practices drastically. In addition, pharmaceutical companies likely realized that the Modernization Act did not grant the FDA funding or an enforcement mechanism. Therefore, although adhering to FDA regulations might help the industry gain the required FDA approval for new medicines, pharmaceutical companies realized that failure to comply with the mandate was unlikely to result in adverse consequences.⁷ The lack of public and media awareness of the benefits and existence of the clinical trial registries may also have contributed to the pharmaceutical companies' failure to comply.⁸

Awareness Levels

THE LACK OF PUBLIC AWARENESS about the benefits of registration may be due to minimal press coverage about the existence of bias in clinical studies. Without media coverage to alert the public to the possibility that clinical trials are skewed toward a positive outcome, there is no public outcry to change the system. Nevertheless, scientists have known of the lack of registration for years, resulting in large part to problems during the publication of study results. In Page 25 fact, for decades, scientists complained about publication bias in medical research, particularly the issue of more frequent reporting of positive results.⁹ Publication bias is often attributed to decisions made by the author, investigator, or editor, but may also be present throughout the entire trial, eventually leading to outcome bias.¹⁰ By providing the scientific and medical communities with access to initial information about studies, practitioners may better understand the objectives of each study, the comparative benefits of different study methods, and the markers for success within the studies. This information would help practitioners recognize the impact of various criteria within the published results and enable them...