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 difficult, many investigators have proposed using alternate measures (namely, surrogate end points) that may indicate the probable effect of a drug on symptoms or survival but are not direct measures of clinical benefit. Surrogate end points are usually physiologic variables that are known to be statistically associated and are believed to be pathophysiologically related to the clinical outcome. Although the adoption of such surrogate end points would dramatically facilitate the evaluation of new drugs, experience to date has shown that the effect of a drug on a surrogate end point is not a reliable predictor of the clinical utility of the drug, usually because the assumption that the end point is pathophysiologically related to the outcome proves to be invalid. Consequently, the evaluation of the effect of a drug on a surrogate end point provides us with a hypothesis rather than data about the possible effect of a drug on clinical events; such a hypothesis can be tested in controlled clinical trials that directly measure the clinical benefit of the therapeutic intervention. In the area of heart failure, no surrogate end point currently exists that can be used in lieu of the direct assessment of a drug on symptoms or survival, ideally in the context of a placebo-controlled trial.
Division of Cardio-Renal Drug Products, Food and Drug Administration, Rockville, Maryland 20857.
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D015415:Biomarkers; D002986:Clinical Trials as Topic; D017277:Drug Approval; D015507:Drugs, Investigational / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D015203:Reproducibility of Results; D016896:Treatment Outcome
D015415:Biomarkers; D015507:Drugs, Investigational