ABSTRACT
Confirmatory controlled clinical trials, also known as Phase III clinical trials, when successful, are significant achievements in medical research as they provide evidence that new treatments (e.g., test drugs or other types of interventions) studied in these trials are clinically effective in treating targeted diseases, and are also safe as far as judgment is possible on taking into account the limited number of exposed patients. Unfortunately, many such trials fail and are unable to show that new treatments studied in these trials are better than placebo. This is surprising because Phase III clinical trials are designed and conducted after the so-called Phase II trials, which are supposed to have already shown promising evidence of treatment efficacy and safety. There can be several reasons for such failures. For example, certain weaknesses in the primary endpoints of a trial can jeopardize the success of a trial, e.g., if these endpoints are not objective, or are not validated, or are not in line with the mechanisms of actions of the treatment. A trial can also fail because of poor planning or disregarding multiplicity issues with respect to multiple endpoints and multiple comparisons.
