Group sequential methods and sample size savings in biomarker-disease association studies.

Molecular epidemiological association studies use valuable biosamples and incur costs. Statistical methods for early genotyping termination may conserve biosamples and costs. Group sequential methods (GSM) allow early termination of studies on the basis of interim comparisons. Simulation studies evaluated the application of GSM using data from a case-control study of GST genotypes and prostate cancer. Group sequential boundaries (GSB) were defined in the EAST-2000 software and were evaluated for study termination when early evidence suggested that the null hypothesis of no association between genotype and disease was unlikely to be rejected. Early termination of GSTM1 genotyping, which demonstrated no association with prostate cancer, occurred in >90% of the simulated studies. On average, 36.4% of biosamples were saved from unnecessary genotyping. In contrast, for GSTT1, which demonstrated a positive association, inappropriate termination occurred in only 6.6%. GSM may provide significant cost and sample savings in molecular epidemiology studies.