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21 September 2009

Why Do So Many Phase 3 Clinical Trials Fail?

Part 1: The Effect of Deficient Phase 2 Trials in Therapeutic Areas with High Failure Rates in Phase 3 Studies

Anastassios D. Retzios, Ph.D.


The development of new drugs in oncology and in stroke, both leading causes of mortality and disability is exceedingly important both for the pharmaceutical industry and the general public.  It should be a public health priority. However, the number of Phase 3 clinical trials that fail in these critical areas is very high, raising the costs of development and delaying or canceling the introduction of new and more effective therapies.  

Although on the surface it may appear that the challenges in oncology and stroke drug development are very different, in fact, the causal factors that lead to failure in Phase 3 trials are very much the same.  A major contributor to the high failure rate is inadequate Phase 2 programs that provide sub-optimal information for the “go/no go” decision to move to Phase 3 and the design of the Phase 3 trials. 

Deficient Phase 2 programs are either inadequately designed, do not contain the full complement of studies, incorporate endpoints that provide limited or misleading information regarding the efficacy of the test agent, or are improperly executed.  The specific challenges vary with the therapeutic area. In oncology, trial designs and endpoints utilized for cytotoxic compounds may not be appropriate in the development of the newer targeted, cytostatic therapeutic agents.  In the treatment of stroke, the designs and the endpoints typically employed so far may not have the sensitivity and reliability to allow investigators to define the effects of neuroprotective compounds,

In this article, some of the problems plaguing the Phase 2 programs in oncology and stroke are summarized and certain proposed solutions are presented and evaluated.  Despite the rather narrow focus of this article in terms of therapeutic areas, the fault lines in Phase 2 studies have a universal dimension in clinical research.


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