Group testing can improve the cost-efficiency of prospective-retrospective biomarker studies

BACKGROUND: Cancer treatment is increasingly dependent on biomarkers for prognostication and treatment selection. Potential biomarkers are frequently evaluated in prospective-retrospective studies in which biomarkers are measured retrospectively on archived specimens after completion of prospective clinical trials. In light of the high costs of some assays, random sampling designs have been proposed that measure biomarkers for a random sub-sample of subjects selected on the basis of observed outcome and possibly other variables. Compared with a standard design that measures biomarkers on all subjects, a random sampling design can be cost-efficient in the sense of reducing the cost of the study substantially while achieving a reasonable level of precision. METHODS: For a biomarker that indicates the presence of some molecular alteration (e.g., mutation in a gene), we explore the use of a group testing strategy, which involves physically pooling specimens across subjects and assaying pooled samples for the presence of the molecular alteration of interest, for further improvement in cost-efficiency beyond random sampling. We propose simple and general approaches to estimating the prognostic and predictive values of biomarkers with group testing, and conduct simulation studies to validate the proposed estimation procedures and to assess the cost-efficiency of the group testing design in comparison to the standard and random sampling designs. RESULTS: Simulation results show that the proposed estimation procedures perform well in realistic settings and that a group testing design can have considerably higher cost-efficiency than a random sampling design. CONCLUSIONS: Group testing can be used to improve the cost-efficiency of biomarker studies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12874-021-01239-4.