How drug development is changing
Traditionally, drug development proceeded from single-dose safety studies in volunteers to repeat doses in volunteers and then to short-term studies in patients. The early studies in patients would be considered 'proof of concept' and the endpoints would be similar to those in long-term large-scale (Phase III) studies that would support the licensing of the new drug. However, this straightforward scheme is not suitable for many of the new drugs and novel therapeutic agents under development today. This is because the endpoints from early studies cannot be translated directly to later studies.
For example, a drug that that stabilises atherosclerotic plaques requires a large outcome study to show that this stabilisation translates into few cardiac events. Early clinical studies will therefore focus on pharmacodynamic (PD) markers ('biomarkers') in the target patient population (Fig 8). As a result, early studies are now, as a rule, smaller but more complex than they have been in the past. Later 'confirmatory' studies are commonly larger than in the past because they need measure the drug's effect in terms of clinical outcomes (e.g. fractures) that, although important, are relatively rare events.
The new drug development process
Fig 8 The changing drug development. There is now increasing focus on the use of biomarkers as surrogate markers of clinical benefit in early pharmacodynamic studies with the clinical benefits demonstrated in larger long-term 'proof of concept' studies
