Noncompliance in cancer screening trials

Background Randomized trials evaluating new cancer screening technologies may underestimate the efficacy of screening to reduce cancer mortality if study participants are noncompliant. Participants may fail to comply with the screening itself or fail to obtain appropriate diagnostic follow-up and treatment. Noncompliance with screening has drawn wide attention, but little attention has been paid to noncompliance with diagnostic follow-up and treatment. Purpose To examine the importance of noncompliance with screening, follow-up, and treatment in cancer screening trials. Methods The unique problems associated with noncompliance in screening trials are described and provide an example illustrating the potential impact of noncompliance in a screening trial. I discuss issues that arise with measurement of follow-up and therapeutic noncompliance, and the benefit of collecting information on health system and participant characteristics associated with noncompliance. Results The estimate of the efficacy of a screening program on cancer mortality can be adjusted for screening, follow-up, and treatment noncompliance. Noncompliance needs to be measured in a rigorous, systematic manner across all arms of the trial. Information on health system and participant characteristics associated with compliance may also be incorporated into statistical models to estimate screening effects with full compliance, plan interventions to increase compliance, and extrapolate results of screening trials from one population to another. Limitations Measuring compliance with follow-up and treatment can be difficult when these occur outside the trial, and when there is variation among providers in follow-up and treatment practices. Conclusions Noncompliance may alter the estimate of a screening effect on cancer mortality in clinical trials. It is possible to adjust screening efficacy estimates for noncompliance using existing statistical techniques. It is important that data describing compliance with screening, follow-up, and treatment are collected as part of standard data collection in cancer screening trials.