Translating research to promote healthy aging: the complementary role of longitudinal studies and clinical trials.

An important challenge in epidemiology is the difficulty in inferring causality from observational studies. Even the best longitudinal studies have limitations in this regard, and when clinical trials are feasible, they will provide more-definite evidence of causality, but even when clinical trials are feasible, a large amount can be learned about the disease process, assessment techniques, subject selection criteria, and the effect of potential interventions from longitudinal studies. This review covers the theoretical issues supporting the value and limitations of longitudinal studies, the practical utilization in clinical trials of different aspects of knowledge that can be gained from longitudinal studies, critical issues in the translation of longitudinal observational studies into clinical trials, and the value of observational studies in broadening the applicability of specific trials. Relevant issues are illustrated with examples of unsuccessful and successful trials, with a major emphasis on clinical trials of physical activity in older persons.