Overall Postmarketing Risk Assessment Is Complex
Under the current system, FDA shares responsibility for postmarketing risk assessment with manufacturers, healthcare providers, user facilities, and patients. Each participant has a role in monitoring and evaluating adverse events associated with medical products, as well as taking appropriate corrective action. The roles assigned to manufacturers and the FDA are defined primarily by statute, while the roles of other stakeholders are more flexible in most cases.
The specific objectives of FDA's postmarketing risk assessment programs are to detect adverse events not previously observed, improve understanding of the potential severity of previously anticipated risks, detect events resulting from drug interactions or drug effects in particular populations, and assess the potential for causal relationships.
Manufacturers of prescription medical products are required to submit adverse event reports to the FDA. In addition, drug and biological product manufacturers must submit either error and accident reports or drug quality reports when deviations from current good manufacturing practice (CGMP) regulations occur. For medical devices, manufacturers must report to the Agency the voluntary recall of any products that are in violation of the Act and that pose a risk to health.
FDA is responsible for inspecting the manufacturing facilities to determine if they comply with the regulations, including the regulations that require reports to the Agency. The Agency may issue warning letters and take other regulatory actions when a manufacturer fails to comply with the reporting requirements.1
For a number of reasons, changes are occurring that will affect the Agency's current postmarketing system. First, PDUFA and the Modernization Act of 1997 have resulted in some changes in postmarketing reporting requirements. For example, with regard to medical devices, the Modernization Act directs the FDA to move away from universal, mandatory adverse event reporting by user facilities to a system based on reporting by a representative sample of facilities. 2 The Modernization Act also provides for sponsors of a drug that have entered into an agreement with the Agency to conduct a postmarketing study to report annually to the Agency on the progress of the study or the reasons for the failure of the sponsor to conduct the study.3
In addition, shifts in the healthcare environment and in international marketplaces are affecting the potential for adverse events caused by medical interventions. For example, with patients now being treated by multiple healthcare providers, a single provider may not have full knowledge of the patient's medical history and use of various medicines. Prescribers' lack of information can lead to increased risk of drug interactions, as one physician may not be aware of what another has prescribed. The increasingly global marketplace for medical products also could result in a greater potential for rapid, large-scale patient exposure to new products and carries a proportional potential for more unexpected adverse events. Finally, the rapid development of new medical interventions for a variety of previously untreatable (or less satisfactorily treatable) conditions results in more individuals using medical products. The availability of a new class of antidepressants leading to a substantial increase in the number of individuals receiving drug treatment for depression is just one example. These shifts in the healthcare environment are challenging the existing risk management system and should be considered in each party's approach to postmarketing risk assessment.
One concern raised by the healthcare community is whether the Agency can rapidly collect and analyze the vast amount of postmarketing risk assessment information and respond in a timely manner to findings of postmarketing surveillance.