Estimates for average costs and durations vary, but a reasonable approximation puts the typical duration for bringing a drug to market at 12-15 years (1) and the average cost at over $800 million (2). The reason for this is that the process is dominated by failure, with a high attrition rate of compounds and projects, even in the later and most expensive clinical phases. Therefore, the majority of the cost is associated with compounds and projects that never result in a marketed drug.

Pharmaceutical R&D is conventionally divided into three phases, as illustrated in Figure 1. Although the exact definitions of these phases may vary and the boundaries are blurred, they may broadly be described as; target discovery, drug discovery and drug development. In this article, we focus on the drug discovery phase for small molecule drugs – those with a molecular weight less than around 800Da.

DRUG DISCOVERY VERSUS DRUG DESIGN

It is interesting to note that the middle phase is termed drug discovery, which suggests a search for a solution among many possibilities and with a certain element of speculation. This is in contrast to a design process, which implies a rational process by which a small number of optimal solutions are constructed ab initio. The high attrition rates of the current state-of-the-art suggest that drug discovery has not yet become drug design. Why is this, given recent industry trends that have emphasised techniques such as ‘rational drug design’ (3), ‘structure-based drug design’ (4), and ‘de novo drug design’ (5)?