Prevention Trials: Challenges in Design, Analysis, and Interpretation of Prevention Trials

Designing a prevention trial requires understanding the natural history of the disease, and the likely length of intervention required to achieve a reduction in incidence. The population suitable to contribute meaningful information to the outcomes under study, the intervention is appropriate and likely will generate a balance of risks and benefits for the typically disease free population, and the primary outcome is biologically plausible and clinically relevant. Given the relatively long evolution of chronic diseases, prevention trials bring extra pressures on two fundamental issues in the design of the trial: adherence to the preventive intervention among participants who are otherwise healthy, and sustained follow-up of trial participants. With growing emphasis on the composition of the trial participant population reflecting the overall population for ultimate application of the results, there is the need for additional attention to recruitment and retention of participants. This is fundamental to planning a prevention trial. Planning for follow-up after the intervention is completed helps place the intervention and outcomes in the context of the disease process but adds complexity to recruitment. Never the less this adds to insights from prevention trials. Improving risk stratification for identification of eligible participants for recruitment to prevention trials can improve efficiency of the trials and fit prevention trials in the context of precision prevention.