The value of surrogate endpoints for evaluation of therapeutic efficacy

Pivotal trials on morbidity and mortality (eg, in coronary heart disease, AIDS, cancer) are not only desirable but also necessary for definitive corroboration of new therapies. Since the immense investment and long duration of such trials frequently make it impossi-ble to await the results and use them as the decisive criteria for registration of new and innovative therapeutic principles, howeveq scientific recognition has also been granted to study designs in which the surrogate endpoint is substituted as a target variable for the definitive clinical endpoint. The problems associated with these therapeutic trials based on surrogate endpoints will be discussed by means of positive and negative exam-ples, citing examples of drug development processes for which clearance for new medi-cines or indications has been granted on the basis of surrogate endpoints which generally exhibited a positive-positive relationship. There are also examples, howevec of positive-negative relationships for surrogate endpoints and clinical endpoints. An attempt will be made to describe the limitations and the appropriate role of surrogate endpoints