Human_Safety_in_Clinical_Research

Recently, a great deal has been written about clinical research involving human subjects. Unfortunately, much of the news has been bad—fraudulent investigators in academia exposed, fined, and sent to prison;1–2 institutional review boards (watchdog groups for ethics and safety in research) examined and restrained or shut down by the U.S. government because of inappropriate practices;3–6 a physician failing to follow regulatory guidelines and treating cancer subjects with a vaccine manufactured with a “lack of control;”7 the death of a young man in a university clinical trial testing a gene therapy. 8 The FDA reports that the number of complaints filed against clinical investigators by their own staff members, pharmaceutical sponsors, or FDA investigators markedly increased in 1999.9 Reports and recommendations have issued from government agencies. The Office of Inspector General of the U.S. Department of Health and Human Services published a report on recruiting subjects into clinical trials that pointed to some possible reasons for problems and suggested some changes.10–11 Editorials have been written.12 Academia, as represented by a task force on research accountability sponsored by the Association of American Universities, has also investigated and analyzed the current state of clinical research practices. Very clear “conclusions and calls to action” are stated in their report.13 Some private focus groups, such as PRIM&R (Public Responsibility in Medicine and Research), are coming forth with performance standards, self-assessment tools, and peer-based accreditation of institutional review boards (IRBs) and institutions engaged in human research.14 Education, testing, and accreditation for clinical research physicians and their staff members are being considered, and new regulations or guidelines for oversight of clinical research seem imminent.15 Speaking from the highest level, former Health and Human Services secretary Donna Shalala, PhD, voiced her opinion about recent problems in the execution of clinical research and provided specific recommendations for change,16 as did former FDA commissioner Jane Henney, MD.17 The analyses and recommendations in these reports may lead readers to question whether clinical research is being conducted safely, and to ask how the welfare of human subjects is being maintained. The public literature contains little about the standards and practices in place designed to ensure subject safety and wellbeing in industry-sponsored trials, 18 although much, in fact, is being done. With this in mind, this article describes the process of drug discovery and development in the pharmaceutical industry, with special emphasis on the regulations and practices in place to ensure that people who volunteer to participate in clinical research on new drugs are treated with respect and dignity, and that all measures are taken to ensure their safety and well-being. Specifically, • What is the process of drug discovery, research, and development in the pharmaceutical industry' • What are the research standards that protect subjects' • How do pharmaceutical companies ensure that human protection standards are in place and followed' Core philosophy of drug development Patient well-being and safety are a constant concern throughout the long (up to 15 years), expensive (perhaps $500 million), detailed (about 400,000 pages in a typical NDA) development process for a new drug. In fact, safety is a powerful business and marketing driving force. The reason is simple and practical: Unsafe or troublesome drugs don’t remain long on the market because they do not serve customers well. As a result, along with finding drugs for untreated medical conditions, improving the safety or side-effect profile of existing drugs is a target of drug discovery scientists.