Medico-Legal Issues of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Abstract

The development of a new NSAID can take 15 years and cost US $ 200 million. Cost recovery can only be achieved by successful, safe use of the product, coupled with expert ethical marketing. Discontinuation of development of an NSAID in the late pre-marketing or early post-marketing stages, results in prohibitive financial losses for the sponsors. These losses may be compounded if the reasons for withdrawal are based on adverse drug reactions (ADR), and as a consequence, the sponsor faces litigation to compensate individuals who claim to have experienced the ADR. Drug development can be examined as 3 separate stages: (a) drug synthesis with documentation of structural chemistry; (b) biopharmaceutical studies in vitro, and animal studies, specially devised to ‘predict’ toxicity, e.g. teratogenicity, carcinogenicity; and (c) pre- and post-marketing clinical studies. All individuals involved at any stage of development have a legal responsibility related to their respective roles. Unfortunately, some of the most dramatic examples of serious drug toxicity appear to have been related to imperfect identification/interpretation/ communication of data with respect to chemical structure, metabolism, immune response, teratogenicity, and carcinogenicity, despite apparently appropriate pre-clinical and clinical investigations. In the case of benoxaprofen, despite the favourable tolerance observed in controlled clinical trials, fatalities, mainly in elderly, were linked to hepatotoxic effects. Some of the liver abnormalities had been identified in mice and rats treated over 5 days, but there was no consistent ADR identified on the human liver in controlled clinical studies.