Clinical relevance of target identity and biology: implications for drug discovery and development

Many of the most commonly used drugs precede techniques for target identification and drug specificity and were developed on the basis of efficacy and safety, an approach referred to as classical pharmacology and, more recently, phenotypic drug discovery. Although substantial gains have been made during the period of focus on target-based approaches, particularly in oncology, these approaches have suffered a high overall failure rate and lower productivity in terms of new drugs when compared with phenotypic approaches. This review considers the importance of target identity and biology in clinical practice from the prescriber's viewpoint. In evaluating influences on prescribing behavior, studies suggest that target identity and mechanism of action are not significant factors in drug choice. Rather, patients and providers consistently value efficacy, safety, and tolerability. Similarly, the Food and Drug Administration requires evidence of safety and efficacy for new drugs but does not require knowledge of drug target identity or target biology. Prescribers do favor drugs with novel mechanisms, but this preference is limited to diseases for which treatments are either not available or suboptimal. Thus, while understanding of drug target and target biology is important from a scientific perspective, it is not particularly important to prescribers, who prioritize efficacy and safety.