High risk subjects and the cost of large field trials

The relationship between subject selection criteria, sample size and the cost of a field trial is discussed and it is shown that the use of higher risk subjects in clinical trials is not generally effective in increasing statistical power or decreasing costs and in certain circumstances can actually decrease the power of the trial.

Abstract

It is well known that individuals can vary widely in their disease susceptibilities. One potential source of this variation is the genetic makeup of individuals, which can confer either protection or susceptibility to disease. Here we examine the effects of protective genotypes on the sample sizes and time required to detect differences between clinical trial arms. We show that including individuals with protective genotypes in a clinical trial can increase required sample sizes and trial duration. One can deal with this issue by pregenotyping subjects and selectively enrolling them based on their genotype. Thus we also calculate the number of individuals that must be recruited and pregenotyped to fulfill sample size requirements. The benefits of genotypically screening study subjects will depend on numerous factors, including ease of patient recruitment, cost of genotyping, long-term costs of study (or long-term cost per subject), and the strength of the protective effect. We present several examples that show the potential value of incorporating information about protective genotypes into a clinical trial. Control Clin Trials 2000;21:7–20