The role of scientific evidence of risks and benefits in determining risk management policies for medications

Recent changes in the regulatory environment have called attention to the need for and potential benefits of greater and more detailed evidence to inform decisions based on the risk-benefit profile of medications. Nevertheless, access to potentially beneficial therapies continues to be impeded by a lack of sufficient information that could help optimize benefits and minimize risks of treatments for patients. Over-reliance on pre-marketing clinical trials and the FDA's spontaneous reporting adverse event system to support regulatory decisions has sustained an information void. Clinical trials are the gold standard for demonstrating efficacy, but they cannot fully predict safety when drugs are used in the real world. Spontaneous reporting can identify new signals, but cannot quantify those signals or place them in appropriate clinical context. In the face of new safety signals, absence of better information on how medications are used and how they perform in the real world setting, regulators are often limited to either continuing drug marketing without significant changes or withdrawing a medication from the market. Experience shows that information collected proactively, to better understand the background risks associated with the underlying disease and to better quantify the product risks, can influence these decisions to include a wider range of options regarding a product's availability, labeling and additional risk management strategies. This article presents several case studies of medications, including those in which insufficient data were available to address important safety signals and decisions were made to withdraw products, as well as those in which epidemiologic data were available to provide reassurance of product safety and allow continued product use, even though some may be marketed with additional risk management programs. More extensive and earlier epidemiologic assessment of risks and benefits of new products will create a new standard of evidence for industry and regulators and is likely to result in more effective and balanced regulatory actions, thereby affording better care for patients. Copyright (C) 2003 John Wiley Sons, Ltd.