The safety of drugs for OTC use: what evidence is required for an NSAID switch?

In recent years there has been a growing demand for safe and effective over-the-counter (OTC) drugs. The demonstration of the safety of OTC products in actual conditions of use is crucial for their wide distribution, since the circumstances of their use may be different from the prescription-only setting. A group of experts met in Geneva, Switzerland, with the aim of exploring the criteria required to show safety equivalence of OTC medications, with specific reference to low-dose non-steroidal anti-inflammatory drugs (NSAIDs) used for analgesia. It was agreed that an acceptable surrogate marker for safety as the primary endpoint in a study designed to show that a new NSAID was not inferior to a current NSAID would be any adverse event leading the patient to consult a physician. A sample size of 10 000 patients in each arm of a two-arm study would be sufficient to show non-inferiority with acceptable relative risk equal to 1.2 with at least 90% power for an event rate of 5%. An example of a possible pharmacy-based randomized study design to demonstrate safety equivalence of OTC analgesics is given. Copyright (C) 2002 John Wiley Sons, Ltd.