The evaluation of the results of clinical trials: surrogate end points and composite end points.

The evaluation of the clinical outcome of patients enrolled in randomised controlled studies should always be accurate and objective. The methods used to assess and report patients' results must consequently be indicated a priori in the design of the clinical experimentation. Major (hard) individual end points currently constitute the gold standard in the definition of outcome measures, yet surrogate and composite end points are spreading diffusely as alternative/complementary outcome measures. Surrogate end points are minor outcome measures that are easier to record and are being adopted instead of major end points. They may be considered acceptable substitutes of hard end points when capable of predicting major events reliably, and when it may be demonstrated that the intervention on such surrogate end points consistently modifies the incidence of the event. In other cases they cannot represent predictive elements of major clinical outcomes. Composite (combined) primary end points may contribute to improve the statistical precision of a clinical trial; moreover, since clinical trials are particularly expensive, their identification permits more limited samples of patients to be enrolled. Their limits include the possibility that the direction in which the different outcome measures composing the combined end point are modified is not the same. Biomedical researchers are called upon to design studies adopting major (hard) end points, rather than solitary surrogate end points, in order to provide really useful information for the care of patients. The selection of composite end points requires notable methodological attention so as to retrieve the most reliable estimates on the efficacy and the effectiveness of treatments.