New drug development during and after a period of regulatory change: Clinical research activity of major united states pharmacxeutical firms, 1958 to 1979

Abstract

The 1962 drug amendments fundamentally changed the way in which USA pharmaceutical firms could test new drugs in man and receive New Drug Application (NDA) approval. Although it is well known that the amendments and associated events caused a profound decline in the annual number of new drugs receiving NDA approval, the amendments'' effects on clinical research into new chemical entities (NCE) have not been investigated because data were unavailable. Drug development information dating back to 1958 was obtained from 9 major USA-owned pharmaceutical firms. The introduction rate of NCE into human testing dropped sharply in the early 1960s and declined substantially thereafter. The number of NCE entering human testing fell from a mean of 89/yr in 1958-1962, to 35/yr in 1963-1972 (a reduction of 61%), and to 17/yr in the last 5 yr of the survey, 1975-1979-an overall reduction of 81%. The number of NDA approvals received by these firms fell sharply by 49% in the early 1960s and more slowly for 10 yr thereafter, from the mid-1960s to the mid-1970s. In the case of self-originated NCE, the size of this later fall was 71%. Causes of these changes in NCE flow include the amendments and the events that prompted them; changes in scientific philosophy, standards and state of the art; and economic factors.