Hurry up and slow down: lessons in drug development from the COX-2 inhibitors.

摘要

A Google~(TM) search performed for this editorial using the terms "COX-2 inhibitor" and "lawyer" had 292,000 hits. Certainly a swarm of legal attention has marked the end of a six-year period that saw the introduction of cyclooxygenase (COX)-2 inhibitor analgesics (1999), their growth to include millions of prescriptions annually worldwide at an estimated cost exceeding dollarCdn 6 billion, and the equally sudden almost complete disappearance of these agents from the market due to safety concerns. The apparent blind spot in drug development methods exposed by this course of events has raised serious concerns. How did a process designed to provide assurance of safety and efficaq' in the search for new drugs simultaneously fail in so many countries, including Canada, the United States, and European countries? The consequences of this misadventure have resulted in patient harm, physician alarm and concern, and litigious actions that are still playing out for the large drug companies. Furthermore, these events have eroded confidence regarding already available drugs (e.g., aprotinin),3 questioning the sufficiency of safety evaluations based on the large randomized double-blind controlled trials traditionally used as evidence for regulatory approval. There are obvious and important implications for all disciplines of medicine, including anesthesia and perioperative medicine.