title: Clinical trials in the genomic era: effects of protective genotypes on sample size and duration of 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.
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44109, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Fijal
authors.forename: J M
authors.initials: JM
authors.lastname: Hall
authors.forename: J S
authors.initials: JS
authors.lastname: Witte
mesh_terms: D002986:Clinical Trials as Topic / Q000191:economics / Q000706:statistics & numerical data*; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000191:economics; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D006801:Humans; D018579:Patient Selection; D018401:Sample Size; D015996:Survival Rate; D013997:Time Factors