Regulation on Clinical Development Programs

The statement that the proof of effectiveness would be derived from well-controlled investigations has been the cornerstone of the FDA s position for the requirement of two positive adequate and well-controlled clinical trialS/ both of which must demonstrate effectiveness at the P 0.05 level (16). However/ in practice/ most clinical development plans include more than just two studies to document efficacy and evaluate safety. In a pilot study reported by Peck (1) of a cohort of 12 of the 51 NDAs that were approved by the FDA in 1994-1995/ the total number of clinical trials in each submission ranged from 23 to 150. In those trials that were designed to establish efficacy and evaluate safety/ the number of study participants ranged from 1/000 to 13/000. Peck has pointed out that these NDAs probably reflect clinical plans that were designed in the mid-1980s. 

In the 1999 annual report from Monsanto/ it was stated that the development and NDA submission 

Drug Indication (years) Trials Participants Trials Participants Trials Participants Trials Participants  

Phase I includes all of the clinical pharmacology studies that in many cases were conducted within 12 months of the NDA BLA submission. 

Two key resources for input into the design of a successful clinical development program are the corresponding therapeutic FDA Guidance (25,26) and the publicly available reviews by FDA reviewers for 

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