ABSTRACT
By the time a drug candidate has evolved through the developmental pipeline to
submission for regulatory approval to begin phase I clinical trials, an average of
999 other candidates have been discarded. And the odds of that selected drug
ultimately receiving marketing approval are estimated at approximately one in
five [1]. A 20% clinical drug development success rate from that point suggests
that the interface created by drug development approaches and regulatory review
requirements being used over the past decades are in need of great improvement.
Unacceptable toxicities and safety concerns are cited to account for 20-40% of
the failures [2]. One factor for this may be that many of the assumptions implicit
in current practice may be flawed or that the data generated are insufficiently
informative. Once a compound has been selected to advance to the stage of
initiation of clinical trials, its fate has essentially been cast. The clinical stages of
investigation remain primarily to match the patient population to the indication,
establish optimal dosing and use, and demonstrate proof of safety and efficacy for
that selected molecule. The selection of the molecule is based on all of the study
information preceding clinical trial initiation-discovery data, mechanistic
studies, chemistry, biology, in vitro toxicology, and the animal toxicology study
findings.
