ROLE OF SURROGATE END-POINTS IN THE EVALUATION OF DRUGS FOR HEART-FAILURE

To be of clinical value in the treatment of heart failure, a drug must permit patients either to feel better or to live longer, or both. Yet , because the assessment of both quality and quantity of life is diffi cult, many investigators have proposed using alternate measures (namel y, surrogate end points) that may indicate the probable effect of a dr ug on symptoms or survival but are not direct measures of clinical ben efit. Surrogate end points are usually physiologic variables that are known to be statistically associated and are believed to be pathophysi ologically related to the clinical outcome. Although the adoption of s uch surrogate end points would dramatically facilitate the evaluation of new drugs, experience to date has shown that the effect of a drug o n a surrogate end point is not a reliable predictor of the clinical ut ility of the drug, usually because the assumption that the end point i s pathophysiologically related to the outcome proves to be invalid. Co nsequently, the evaluation of the effect of a drug on a surrogate end point provides us with a hypothesis rather than data about the possibl e effect of a drug on clinical events; such a hypothesis can be tested in controlled clinical trials that directly measure the clinical bene fit of the therapeutic intervention. In the area of heart failure, no surrogate end point currently exists that can be used in lieu of the d irect assessment of a drug on symptoms or survival, ideally in the con text of a placebo-controlled trial.