Increasing power in screening trials by testing stored specimens in the control arm: Assessing and relaxing assumptions

Music City Center 

Screening trials have required very large sample sizes and long time-horizons to definitively demonstrate mortality reductions. We and others have recently demonstrated that statistical power can be greatly increased by testing stored material in the control-arm and considering trial outcomes only among those who ever test positive. In the "targeted" analysis, one only tests control-arm cancer-cases, whereas the "Intended Effect" (IE) analysis tests all control-arm specimens. We extend both analyses to account for loss-of-signal in stored specimens by storing and retesting specimens in the screen-arm. Although the targeted analysis tests many fewer control-arm specimens (saving money), we show that it is sensitive to non-compliance in specimen collections that is differential by arm. We extend the IE analysis to only test a representative subsample of the control-arm while maintaining nearly all statistical power. With careful attention to assumptions, there is much scope for novel analyses to substantially increase power in screening trials.

Screening Trial Design

Intended Effect