Deciding whether a substance is ready for a study in humans (the so-called move from bench to bedside) involves an understanding for the risk\benefit for the human subject involved. An extensive guidance has been developed to ensure that preclinical (non in human) studies will yield sufficient safety, (toxicity), mode of action (pharmacokinetic\pharmacodynamic) and efficacy (proof of concept) information.
For a novel drug a wide range of doses, formulations, and mode of administration of the drug are tested using in vitro (test tube or cell culture) and in vivo (animal) experiments. To reduce the use of animal, it is also possible to perform in silico profiling using computer models of the drug–target interactions and of PK\PD.
For a drug already authorised for another clinical indication, a reduced set of information will be required focused on the new clinical target.
Clinical trials are formalised studies performed on human subjects intended to discover or verify the effects of one or more investigational substances (Investigational New Drug (IND) or Investigational Medicinal Product (IMP). Specific rules are applied to performing a Clinical Trial usually referred as Good Clinical Practices (GCP).
The passage from pre-clinical to clinical studies is subject to an authorization from the National Competent Authority (usually Health Ministry or agency) or of the local Ethical Review Board according to the type of studies involved.
The procedure (a Clinical Trial Application – CTA) might be local, national or centralised according to regulatory requirement which are legally enforced.
The evaluation process of an Initial CTA is divided into three main phases: Validation1 , Assessment, and Decision. The Assessment phase is divided into two parts (Part I and Part II), which may or may not run in parallel. Each phase has its own timelines and activities to be performed.