Surrogate end points in heart failure.
Because of the increasing number of pharmacologic strategies available for treatment of heart failure (HF), the time has come to reassess the adequacy of end points used to evaluate therapeutic efficacy. Interest in the use of surrogate end points in clinical studies is increasing. A surrogate end point is defined as a measurement that can substitute for a true end point for the purpose of comparing specific interventions or treatments in a clinical trial. A true end point is one that is of clinical importance to the patient (e.g., mortality or quality of life), whereas a surrogate end point is one biologically closer to the disease process (e.g., ejection fraction or left ventricular volume in HF). The prime motivation for the use of a surrogate end point concerns the possible reduction in sample size or trial duration. Such reductions have important cost implications and in some cases may influence trial feasibility. Another, perhaps more important, aspect of measuring surrogate end points is that they increase our understanding of the mechanism of action of drugs and thus may help physicians to take a more enlightened approach in managing their patients. In this article we have analyzed the possible potentials of the surrogate end points in clinical studies of patients with chronic HF. Other uses of possible surrogates are discussed, and the limitations in finding true surrogates are mentioned. At this time we conclude there is no well established surrogate in HF.
Anand
Inder S
IS
University of Minnesota Medical School and Veterans Affairs Medical Center, Minneapolis, Minnesota, USA. anand001@tc.umn.edu
Florea
Viorel G
VG
Fisher
Lloyd
L
D015415:Biomarkers / Q000097:blood; D002986:Clinical Trials as Topic; D017277:Drug Approval; D015507:Drugs, Investigational / Q000494:pharmacology; D005080:Exercise Test; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D009638:Norepinephrine / Q000097:blood; D017063:Outcome Assessment, Health Care / Q000379:methods*; D011788:Quality of Life; D012107:Research Design; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D015415:Biomarkers; D015507:Drugs, Investigational; D009638:Norepinephrine