Use of biomarkers and surrogate endpoints in drug development and regulatory decision making: Criteria, validation, strategies

In the future, biomarkers will play an increasingly important role in all p hases of drug development, including regulatory review. However, only a few of these biomarkers will become established well enough to serve in regula tory decision making as surrogate endpoints, thereby substituting for tradi tional clinical endpoints. Even generally accepted surrogate endpoints are unlikely to capture all the therapeutic benefits and potential adverse effe cts a drug will have in a diverse patient population. Accordingly, combinat ions of biomarkers probably will be needed to provide a more complete chara cterization of the spectrum of pharmacologic response. In the future, pharm acogenomic approaches, including those based on differential expression of gene arrays, will provide panels of relevant biomarkers that can be expecte d to transform the drug development process.