Good clinical practice, or GCP, is defined by the Food and Drug Administration as “a standard for the design, conduct, performance, monitoring, auditing, recording, analysis and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity and confidentiality of trial subjects are protected.” Good clinical practice is not only vital to data integrity and human subject protection; it is the foundation of clinical trials’ success in driving research in both private and public sectors. In the past few years, the FDA and other regulatory authorities have halted research activities at major academic institutions as a result of violations of clinical research regulations.
Clinical research oversight comes from private and public sectors. The government’s regulatory bodies that oversee the conduct of clinical trials are branches within the U.S. Department of Health and Human Services, such as the FDA and the National Institutes of Health. In 1996, the International Conference on the Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use published a set of standards that would harmonize research efforts across the United States, the European Union and Japan; these standards ensure ethical research conduct and robustness of research data worldwide.The Washington-based Pharmaceutical Research and Manufacturers of America also recently published its own guidance updating the principles of clinical trial conduct and communication of clinical trial results. Regulatory bodies at clinical research sites, such as institutional review boards, serve as additional safeguards of ethical research conduct.
Financial disclosure
Growing concerns over the true risk-to-benefit ratio of selective serotonin reuptake inhibitors in children have stemmed from the publication of clinical research results. A recent review of unpublished data on antidepressants’ effects in children and adolescents suggested a shift in the risk-to-benefit ratio from favorable to unfavorable. Physicians weigh risks against benefits in their prescribing practices and when enrolling participants in clinical trials. Tenets of GCP specify the ethical obligations of researchers and publishers to preserve the accuracy of results, and publish both “negative” and “positive” research results (I use quotes with these qualifiers because, in the scientific sense, even a “negative” result is a result and contributes to scientific progress).
Clinical study investigators must disclose, and be identified according to, their financial interests relative to the study sponsor. Clinical investigators should be paid per fair-market value, and only for services rendered for the clinical study. Clinical investigators — and their immediate family — should not have a direct financial interest in the drug they are studying.
Investigator responsibilities
Clinical trial conduct and GCP are delineated under Title 21 of the Code of Federal Regulations. Sponsor and investigator responsibilities are coveredin Part 312 of Title 21. Sponsors are responsible for selecting qualified investigators, providing the information needed to conduct an investigation properly, ensuring proper monitoring of the investigation, ensuring that the investigation is conducted in accordance with the general investigational plan and protocols contained in the investigational new drug application, and ensuring that the FDA and all participating investigators are promptly informed of significant new adverse effects or risks with respect to the drug.
Investigators are responsible for conducting the study according to protocol, personally overseeing the study, obtaining informed consent from subjects prior to enrolling them in the study, reporting adverse events in a timely manner, overseeing subinvestigators (as in the case of large, multicenter clinical trials), keeping good records and obtaining institutional review board approval prior to initiating the study. Failure to fulfill these responsibilities can result in court warning letters and, most seriously, harm to study participants, as was the case at Johns Hopkins University in 2001, when a healthy study subject died. Clinical research at the university was suspended as regulators unearthed numerous clinical research conduct violations.
Clinical trials have become a multibillion-dollar business. Scandals and government investigations are costly and erode public trust in the pharmaceutical business. Yet, the solution to these challenges is readily available in rigorous implementation of, and strict adherence to, good clinical practice.