PerspectivesAre you interested in submitting a Perspective Article? Be sure to read The Science Advisory Board's Editorial Guides for Perspective Articles. Click here. Knock Knock, Who’s There? The FDA! by Katrina A. Bramstedt, Ph.D. Cleveland Clinic Foundation Evan J. Topol, B.S. cand., University of Virginia Warning letters (WL) issued to clinical investigators by the Food and Drug Administration (FDA) reveal common ethical concerns associated with clinical trials and serve as a resourceful tool in educating researchers. By studying WLs (available online at www.fda.gov/foi/warning.htm), clinical investigators can gain a more realistic view of research ethics, while learning of the consequences they may face if they fail to adhere to the FDA’s standards. The value of these warning letters can be realized when researchers take advantage of them and translate their information into maintaining the safety and integrity of clinical research. The FDA regulates clinical research by ensuring study integrity and protecting the safety and welfare of human research subjects. Clinical investigators are expected to adhere to the standards of good clinical practice (GCP), which provide guidelines for designing, conducting, recording and reporting research studies that involve human subjects. Each year, the FDA conducts about 1000 clinical trial-related inspections, issuing WLs to those researchers who do not comply with the GCP standards. Investigators may be disqualified or restricted from clinical research if they fail to comply with FDA regulations. In a recent study examining FDA WLs (Clin Invest Med 2004; 27:129-134), the majority were issued for studies of medical devices. WLs were issued most frequently to research studies of pulmonary medicine, followed by oncology and cardiology. The common violations of research ethics included: deviation from the research plan, flawed or nonexistent consent processes, and failure to report or late reporting of adverse events. Other problems were related to study supervision, institutional review board approval, and misconduct. Study deviations necessary for the safety of research subjects are appropriate and should be implemented in a timely fashion. However, deviations are problematic when they involve changing the goal of the research study or when they aim to massage the study data to meet stated goals. Inappropriate study changes have potential to put research subjects at risk, delay study progress and waste research resources due to flawed study design. Thus, oversight by an institutional review board is essential in considering study deviations unless immediate action is required to ensure the safety of human subjects. Another ethical concern is the use of a proper informed consent process. It is inappropriate for research subjects to sign consent forms after study participation, and for members of the research team to sign consent forms “on behalf” of research subjects. Also, consent forms must be up to date in order to provide accurate information regarding the study’s procedures, risks and alternatives. The text in the consent form should be easy to understand and the terminology should consistently remind the reader that the study is an “experiment” or “research project,” thus making no implications or promises of clinical benefit. Underreporting and untimely reporting of adverse events (AE) is also inappropriate. AEs are incidents where the use of a drug, biological or medical device is suspected or known to have resulted in an undesirable outcome (e.g., injury). The FDA requires AEs to be reported to one or more overseeing bodies within defined timeframes, yet burdensome reporting processes and fears of blame or liability often interfere with proper reporting. Researchers often underplay the importance of AEs; however, as a result, they overlook issues of research subject safety. Research misconduct is potentially harmful to research subjects, future clinical patients and the integrity of science as a profession. Desire for the prestige of “successful” trial results, peer pressure to be competitive, and pressure for rapid trial enrollment and data collection, all contribute to the likelihood of misconduct. The use of falsified data can skew results and have a detrimental effect upon further research. Furthermore, if the integrity of the science profession is harmed by misconduct, funding could become more difficult to obtain and human subjects more difficult to recruit, which would slow clinical developments that could benefit society. Through the use of easily attainable WLs, researchers can gain a practical tool to learn from the mistakes of others. WLs bring the theories of research ethics to life for clinical investigators who must recognize the importance of research subject safety as well as the integrity of their research. “Front-loading” the research process with research ethics will enhance clinical investigation, not hinder it, for the risks of conducting research unethically are hefty and include harm to research subjects, collection of invalid data, poor stewardship of research resources, and diminished credibility of research as a profession. ### << Previous Next >> [ View All Perspectives ] |
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