Designing studies that would address the multilayered nature of health care

We review design and analytic methods available for multilevel interventions in cancer research with particular attention to study design, sample size requirements, and potential to provide statistical evidence for causal inference. The most appropriate methods will depend on the stage of development of the research and whether randomization is possible. Early on, fractional factorial designs may be used to screen intervention components, particularly when randomization of individuals is possible. Quasi-experimental designs, including time-series and multiple baseline designs, can be useful once the intervention is designed because they require few sites and can provide the preliminary evidence to plan efficacy studies. In efficacy and effectiveness studies, group-randomized trials are preferred when randomization is possible and regression discontinuity designs are preferred otherwise if assignment based on a quantitative score is possible. Quasi-experimental designs may be used, especially when combined with recent developments in analytic methods to reduce bias in effect estimates.