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 phases of drug development, including regulatory review. However, only a few of these biomarkers will become established well enough to serve in regulatory decision making as surrogate endpoints, thereby substituting for traditional clinical endpoints. Even generally accepted surrogate endpoints are unlikely to capture all the therapeutic benefits and potential adverse effects a drug will have in a diverse patient population. Accordingly, combinations of biomarkers probably will be needed to provide a more complete characterization of the spectrum of pharmacologic response. In the future, pharmacogenomic approaches, including those based on differential expression of gene arrays, will provide panels of relevant biomarkers that can be expected to transform the drug development process.