Analysis of survival data from a randomized trial with all-or-none compliance: Estimating the cost-effectiveness of a cancer screening program

Many randomized cancer screening trials involve all-or-none compliance. Some subjects randomized to an offer of screening refuse screening, and some subjects randomized to no offer of screening obtain Screening outside the trial. The primary analysis to test whether or not cancer screening reduces cancer mortality is by intent-to-treat. To estimate the cost-effectiveness of screening, it is necessary to adjust for all-or-none compliance. Heretofore, adjustments for all-or-none compliance have been limited to a fixed-time endpoint. Estimating cost-effectiveness as dollars per life year saved requires an extension to the analysis of yearly survival data. In general, this involves modeling both the hazard for death from cancer and death from competing risk. Unconstrained estimates and variances can be written in closed-form notation. For the four yearly breast cancer screens with physical examination and mammography in the Health Insurance Plan of Greater New York study, the estimated cost-effectiveness for a $100 mammogram and $900 biopsy is $16,000 per life year saved with 95% confidence interval ($10,000, $45,000): In contrast, under an inappropriate intent-to-treat analysis, the estimated cost-effectiveness is $23,000 with 95% confidence interval ($14,000, $66,000).