Choice of Evaluation Criteria in a Clinical Trial

The choice of proper evaluation criteria is a key aspect of any clinical trial. The efficacy, tolerance and safety of symptomatic treatments can be evaluated by assessing clinical symptoms and/ or signs (vital functions). For life-threatening diseases, the relevant evaluation criterion is morbi-mortality. However, this criterion is rarely chosen because it requires very long-term studies and a large number of patients. Then, a biomarker or other intermediary criteria can be used as a substitute endpoint. The intermediary criterion should correlate well with morbi-mortality (clinical criterion).In these last years, the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have been publishing scientific guidelines defining efficacy and safety evaluation criteria for the phase I and II “proof of concept” Randomized Clinical Trials (RCTs) and the phase III “pivotal trials” which are required for marketing authorization. The present paper describes the rationale underlying the choice of evaluation criteria, together with the advantages and limitations of their application in some selected therapeutic indications.