This study also highlights the type of thought that should go into determining the evaluation for a study. Since minor depression was an unknown entity at the time, one of the key questions was: how stable is this entity over time? Although 4 weeks is an arbitrary length of time, we felt for ethical
and scientific reasons, that it would be an adequate length of time for an extended MEK inhibition placebo run-in. Conclusions A careful and critical review of clinical trial methodologies is imperative for the field to move forward. Attention to many of the assumptions that are inclusively made when a trial is designed will be critical in enhancing the success of clinical trials. We must think closely about the diagnostic criteria Inhibitors,research,lifescience,medical used in the trial in the inclusion and exclusion criteria. Many of the currently accepted criteria limit the generalizability of the findings and have not been demonstrated in a systematic fashion to enhance differentiation of drug versus placebo responses. Yet, some important aspects Inhibitors,research,lifescience,medical of the very definition of these syndromes have been neglected, in particular, the importance of including functional disability and quality of
life dysfunction as part of the definition of the syndrome. Some individuals may present with a requisite number of symptoms, Inhibitors,research,lifescience,medical but may not be as adversely affected as if they had had a profound, long-lasting syndrome. It is quite likely they are suffering from a transient constellation of symptoms due to an external stressor. A second Inhibitors,research,lifescience,medical important concern is the appropriateness of the assessments that are being used in randomized controlled trials. Very often, the assessments that are employed represent “me too” assessments, because studies done by other companies have used the measures
in the past. Yet, this may not reflect our best knowledge about, the disorder being studied, nor a sufficient way of bringing a new compound onto the market. Frequently, the argument for the use of such instruments is that they are supposedly mandated by regulatory agencies. However, more often than not, this is a myth that is perpetuated rather than the outcome Inhibitors,research,lifescience,medical of frank and careful discussions with the regulatory authority. A third important issue that requires some thought is assumptions about about the stability of the syndrome over time. Many times, studies are designed with the assumption that randomization to placebo should lead to a relatively static or, if anything, disadvantageous course for patients. Yet, investigation of most medical syndromes suggests that there is an intrinsic waxing and waning to the course of the syndrome. Therefore, arbitrary assessment using instruments that investigate only one aspect of the syndrome may well lead to spurious results. A last concern, but one that can greatly influence a trial, involves appropriate statistical design. Often studies are powered based on desire, rather than available data.