A Word to the Wise...

Implications: 1. Sponsors need to be "squeaky clean" with respect to their assessment of signals of toxicity in drug develpment programs. 2. This assessment should be made at the preclinical and early clinical stages of the process, irrespective of political and financial considerations. 3. The per cent of failures in Phase 2 and 3 will be higher unless programs are honestly and thoroughly assessed according to the above. Even so, there will likely be more failures in late-stage programs as clinical data are generated. The FDA will spend more time and effort on safety assessment to avoid large populations being exposed in the marketing environment to new drugs.

Analysis: Until valid computerized or in vitro models are developed that can accurately and reproducibly assess, in advance,  the potential for long-term safety (particular cardiovascular) of new long-term treatments for chronic or chronic progressive disease will need to be examined more aggresivly by sponsors, not just FDA reviewers. Otherwise, more and more programs will be delayed in approval; have imposed "black box" warnings on product labels; lead to failed drugs in the postmarketing environment; and fail prior to approval after most clinical data have been generated. One way to avoid this is for sponsors to aggresively assess, in the preclinical and early clinical environments, potential safety signals that could lead to trouble later. Political considerations, investor concerns and other non-data based issues should not mitigate against a clear, aggresive and intensive assessment of safety signals early in drug development. The waste of time, money and resources could be avoided by the "killing," particularly of "me-too" programs, should signals of toxicity be identified and dealt with early on.