SAMPLE-SIZE ESTIMATION: A SENSITIVITY ANALYSIS IN THE CONTEXT OF A CLINICAL TRIAL FOR TREATMENT OF MILD HYPERTENSION1

Abstract

The effectiveness of treatment for mild hypertension (diastolic pressures of 85 to 105 mm Hg) has not been conclusively demonstrated. Both the costs of a carefully designed clinical trial and the likelihood that it will produce definitive answers will depend importantly on the sample size. This paper presents sample-size estimates under a variety of assumptions regarding the characteristics of the population to be studied, the degree of blood pressure control to be achieved, and the health benefits to be expected. Under a central set of assumptions, the estimated sample size per group is 22,700 with death as an endpoint and 14,000 with morbid events (CHD and stroke) as endpoints. As individual assumptions are varied one at a time, required sample sizes range from 10,900 to 101,100 and from 6,800 to 63,100 for the respective endpoints. Results are most sensitive to the degree of blood pressure control actually achieved to the expected health benefits from blood pressure control. They are also highly sensitive to the sex composition of the population and to expected dropout rates. The choice of sample size will depend on the decision maker's assessment of the likelihood that each assumption will be fulfilled and on the degree of willingness to risk an inconclusive study result. By making explicit the effect of variation in each assumption, decision making is rendered more susceptible to critical examination by outside reviewers.