
doi: 10.1111/rssc.12163
SummaryGroup sequential study designs have been proposed as an approach to conserve resources in biomarker validation studies. Typically, group sequential study designs allow both ‘early termination to reject the null hypothesis’ and ‘early termination for futility’ if there is evidence against the alternative hypothesis. In contrast, several researchers have advocated for using group sequential study designs that allow only early termination for futility in biomarker validation studies because of the desire to obtain a precise estimate of marker performance at study completion. This suggests a loss function that heavily weights the precision of the estimate that is obtained at study completion at the expense of an increased sample size when there is strong evidence against the null hypothesis. We propose a formal approach to comparing designs that allow early termination for futility, superiority or both by developing a loss function that incorporates the expected sample size under the null and alternative hypotheses, as well as the mean-squared error of the estimate that is obtained at study completion. We then use our loss function to compare several candidate designs and derive optimal two-stage designs for a recently reported validation study of a novel prostate cancer biomarker.
group sequential testing, optimal designs, diagnostic biomarkers, Applications of statistics, prostate cancer
group sequential testing, optimal designs, diagnostic biomarkers, Applications of statistics, prostate cancer
| selected citations These citations are derived from selected sources. This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | 2 | |
| popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Average | |
| influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Average | |
| impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Average |
