Surrogate endpoints: A basis for a rational approach
- 144 Downloads
In clinical trials, the clinical endpoint is often replaced by an intermediate endpoint, known in some instances as a “surrogate” endpoint. The reasons for the substitution are often both practical and financial. At present, no theoretical basis or practical guidelines exist to help in the choice of surrogate endpoints.
An approach is proposed here, based on three provisos which can be verified using one of a series of equations, if sufficient data on the pathophysiology and epidemiology of the disease are available. It is shown that even a strong statistical correlation is not a sufficient criterion for the definition of a surrogate endpoint.
It is apparent that results obtained with the commonly used “surrogate” endpoints should be cautiously considered and that the assessment of treatments should, when possible, be based on clinical rather than intermediate endpoints.
Key wordsSurrogate endpoints Clinical trials risk/benefiratio assessment
Unable to display preview. Download preview PDF.
- 1.Friedman L, Furberg CD, DeMets DL (1984) Fundamentals of clinical trials, 2nd edn. PSG Publishing, LittletonGoogle Scholar
- 2.Moleur P, Boissel JP (1987) Definition of a surrogate endpoint. Controlled Clinical Trials 8: 304Google Scholar
- 3.Herson J (1989) The use of surrogate endpoints in clinical trials (an introduction to a series of four papers). Stat Med 8: 403–404Google Scholar
- 8.Winkle RA (1980) Detection of patients at high risk for sudden death: the role of electrocardiographic monitoring. In: Kulbertus HE, Wellens HJJ (eds) Sudden death. Martinus Nijhof, The HagueGoogle Scholar
- 9.The CAST investigators (1989) Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. New Engl J Med 321: 406–412Google Scholar
- 11.Pooling Project Research Group (1978) Relationship of blood pressure, serum cholesterol, smoking habit, relative weight and ECG abnormalities to incidence of major coronary events: final report of the Pooling Project. J Chron Dis 31: 201–306Google Scholar
- 12.MacMahon S, Petro R, Cutler J, Collins R, Sorlie P, Neaton J, Abbott R, Godwin J, Dyer A, Stamler J (1990) Blood pressure, stroke, and coronary heart disease. Part 1. prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 335: 765–774CrossRefPubMedGoogle Scholar
- 13.Boissel JP, Gueyffier F (1990) High blood pressure and clinical events linked with atherosclerosis. In: Atkinson J, Capdeville C, Zannad F (eds) Coronary and cerebrovascular effects of antihypertensive drugs. Transmedico Europe Ltd, UK, p 240–252Google Scholar
- 14.Collins R, Peto R, MacMahon S, Hebert P, Fiebach NH, Eberlein KA, Godwin J, Qizilbash N, Taylor JO, Hennekens CH (1990) Blood pressure, stroke, and coronary heart disease. Part 2. short term reductions in blood pressure: overview of randomized drug trials in epidemiological context. Lancet 335: 827–838PubMedGoogle Scholar
- 15.Okamoto K, Yamori Y, Nagaoka A (1974) Establishment of the stroke-prone spontaneously hypertensive rat (SHR). Circ Res 34: 1143–1153Google Scholar