Table 2.

Principles to guide the inclusion of biomarkers in the drug development process

Stage in drug development processRecommendation
PreclinicalConduct comprehensive preclinical studies aimed at reliably identifying the drug target and developing a robust biomarker coupled with a sufficiently reliable and reproducible assay. At this point, efforts should be directed at developing an analytically validated assay for the biomarker.
Phase IIncorporate the biomarker in phase I testing with the goal of better characterizing the biomarker and assay performance in human samples.
Phase IIThe biomarker should be incorporated into trials for hypothesis testing. Questions of whether use of the biomarker is likely to inform treatment decisions by identifying populations likely to respond or whether it may be useful as a surrogate or correlative endpoint can be preliminarily assessed. To achieve this, larger and more complex phase II designs, including randomized designs, may be needed.
Phase IIIOnce the biomarker assay is analytically validated for use on clinical specimens, an indication of efficacy in phase II testing will allow for the design of a phase III trial that will lead to clinical validation and eventually incorporation of the biomarker into clinical use.