Clinical development plan drug interactions

Where does man insert himself back into the process Once the hit is detected, the molecule has to be checked for stability, acute toxicity, and possible drug interactions with commonly used other drugs. Various structural changes may then be introduced by some of the 1,000 medicinal chemists at the company. The pharmacokinetics and toxicology are then determined to create the clinical candidate, and, if one sensibly plans ahead, an alternative as backup is developed in parallel. 

If we are required to prove significance in two trials, as is usually believed to be necessary in phase III for a successful NDA application, then from the practical point of view it may be the power of the combined requirement which is important, rather than that for individual trials. On the assumption that the trials are competent and that the background planning has been carried out appropriately and that trial by treatment interactions may be dismissed, then the power to detect the clinically relevant difference in both of two trials, each with power 80%, is 64% since 0.8 x 0.8 = 0.64. This means that 1 — 0.64 = 0.36, or more than one-third, of such drug development programmes would fail in phase III for failure of one or both clinical trials on this basis. (This does not mean that one-third of drug developments will fall in phase III, since many drugs which survive that far may, indeed, have an effect which is superior to the clinically relevant difference. On the other hand, there may be other reasons for failure.) If it is desired to have 80% power overall, then it is necessary to run each trial with 90% power since 0.9 x 0.9 = 0.80. 

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