Risk management and post-marketing surveillance of CNS drugs.

ABSTRACT

Drugs affecting the central nervous system span a broad range of chemical entities, dosage forms, indications, and risks. Unintended consequences include potential abuse and overdose in non-patient drug abusers, deliberate tampering of drug dosage forms, and criminal behavior associated with diversion. Regulators must consider diverse factors to find the appropriate conditions of approval to minimize unintended consequences while enabling a level of access desired by health care providers and patients. This commentary appears as part of a special issue of Drug and Alcohol Dependence that focuses on risk management and post-marketing surveillance and addresses key issues that pose real-world challenges to pharmaceutical sponsors and regulators in particular. For example, in the U.S., Controlled Substances Act drug scheduling can be considered a risk management strategy but its legal authorities and administrative processes are independent from those of risk management (including Risk Evaluation and Mitigation Strategies or REMS); better harmonization of these approaches is vital from drug development and regulatory perspectives. Risk management would ideally be implemented on a strong science foundation demonstrating that the tools employed to mitigate risks and ensure safe use are effective. In reality, research and evaluation of tools in this area is in its infancy and will necessarily be an evolutionary process; furthermore, there is little precedent for linking interventions and program evolution to unintended consequences such as regional outbreaks of abuse and diversion. How such issues are resolved has the potential to stimulate or stifle innovations in drug development and advance or imperil health care.