title: Smaller sample sizes for phase II trials based on exact tests with actual error rates by trading-off their nominal levels of significance and power.
abstract: BACKGROUND
  Sample sizes for single-stage phase II clinical trials in the literature are often based on exact (binomial) tests with levels of significance (alpha (α) <5% and power >80%). This is because there is not always a sample size where α and power are exactly equal to 5% and 80%, respectively. Consequently, the opportunity to trade-off small amounts of α and power for savings in sample sizes may be lost.
  
  
  METHODS
  Sample-size tables are presented for single-stage phase II trials based on exact tests with actual levels of significance and power. Trade-off in small amounts of α and power allows the researcher to select from several possible designs with potentially smaller sample sizes compared with existing approaches. We provide SAS macro coding and an R function, which for a given treatment difference, allow researchers to examine all possible sample sizes for specified differences are provided.
  
  
  RESULTS
  In a single-arm study with P(0) (standard treatment)=10% and P(1) (new treatment)=20%, and specified α=5% and power=80%, the A'Hern approach yields n=78 (exact α=4.53%, power=80.81%). However, by relaxing α to 5.67% and power to 77.7%, a sample size of 65 can be used (a saving of 13 patients).
  
  
  CONCLUSIONS
  The approach we describe is especially useful for trials in rare disorders, or for proof-of-concept studies, where it is important to minimise the trial duration and financial costs, particularly in single-arm cancer trials commonly associated with expensive treatment options.
authors.affiliation: Cancer Research UK and UCL Cancer Trials Centre, University College London, 90 Tottenham Court Road (fifth floor), London, UK. I.Khan@ucl.ac.uk
authors.forename: I
authors.initials: I
authors.lastname: Khan
authors.forename: S-J
authors.initials: SJ
authors.lastname: Sarker
authors.forename: A
authors.initials: A
authors.lastname: Hackshaw
mesh_terms: D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D018401:Sample Size