The efficient stored specimen design for evaluating multiple screening technologies: Application to multicancer...

ObjectiveMulticancer detection (MCD) tests use blood specimens to screen for various cancers with the hope of reducing cancer mortality. Various companies are developing MCD tests, each with a different technology. For evaluating k MCD tests, a traditional design randomizes participants to either a group with no MCD testing or one of k groups each receiving a different immediate (administered at blood draw) MCD test. To reduce sample size, investigators can store some specimens for delayed MCD testing. A standard stored specimen (SSS) design randomizes participants to either a control group with k different delayed MCD tests applied to the same stored specimen or one of k groups each receiving a different immediate MCD test. Our goal was to further increase efficiency via a novel design and analysis.MethodsThe efficient stored specimen (ESS) design randomizes participants to delayed MCD testing, as in the SSS design, or a single group with k different immediate MCD tests applied to the same specimen. We developed a simple method to separately evaluate each MCD test when any positive MCD test yields a work-up.ResultsThe sample size per randomization group is the same for the ESS and SSS designs. For evaluating k MCD tests, the ESS design involves 2 randomization groups while the SSS design involves k + 1 randomization groups of the same size.ConclusionThe ESS design is superior to the SSS design because, without additional assumptions, it substantially reduces sample size when evaluating multiple MCD tests.