Principles of Designing a Cohort Study in Orthopaedics By Dianne M. Bryant, MSc, PhD, Kevin Willits, MD, FRCSC, and Beate P. Hanson, MD, MPH A well-designed and executed prospective cohort study can provide high-quality evidence in the evaluation of the effec- tiveness of surgical interventions. In designing a cohort study to evaluate orthopaedic interventions, it is important to recognize the limitations of the design as well as the methodological features that can be incorporated to strengthen the validity of the conclusions. In this article, we discuss the importance of the appropriate selection of participants for a control group, the management of confounders, the selection of outcomes with established measurement properties (reliability, validity, and sensitivity to change), the blinded assessment of outcomes, and the impact of nonparticipants and patients lost to follow-up. Introduction D etermining whether one thing causes another is a challenging task. The randomized controlled trial is widely accepted as the most definitive research design for examining the effectiveness of treatments 1 . By controlling the timing or the amount of the intervention or which subjects receive the intervention and which do not, the chances are minimized that factors outside of the control of the researcher could have affected the results 2,3 . An advantage of using a ran- domized controlled trial rather than other study designs is that a randomized controlled trial can definitively establish a cause and effect relationship and limit sources of systematic error 2 . In many situations, use of a randomized controlled trial is not feasible. The next most powerful method to introduce ev- idence comes from cohort studies 1,2 . In a cohort study, the re- searcher does not control the intervention but rather observes the effects of different interventions on outcomes as they occur naturally following the intervention 4 . The minimum design feature of the cohort study is the existence of two treatment groups: an active group, and a comparison, or control, group. In a cohort study concerned with the effect of a surgical in- tervention, the investigator starts with a group of individuals who are apparently free of the outcome of interest. This group, or cohort, consists of individuals who have been given a par- ticular diagnosis and who receive either the experimental in- tervention, an alternative active intervention (for example, usual care), or no treatment at all. Participants are then followed over the course of time to determine the prevalence of the outcome in each group. In a prospective cohort study, the investigator collects in- formation about the patient and the intervention from the time that the study begins and then identifies new occurrences of the outcome from that time forward. In contrast, in a retrospec- tive cohort study, the investigator collects patient-related and intervention-related information that has been recorded at some time in the past and then determines outcome on the basis of events that have occurred between that time and the present. Compared with prospective cohort studies, retrospective cohort studies offer the advantage of a relatively short time frame to completion, thus resulting in considerably less cost. The advantage of prospective data collection lies in the nature of the collected data: checklists to establish a diagnosis are oper- ationalized, careful documentation of the intervention and any co-interventions are standardized, and information on poten- tial confounding factors is specified before the commencement of data collection and these factors remain constant throughout the course of the study. In retrospective studies, the definitions of symptoms of disease may have been modified over time, units of measurement may have changed, old methods for diagnosis may have been replaced, and follow-up times may be incon- sistent between patients, thereby resulting in greater variability in the data. Perhaps the most important advantage associated with prospective studies is that they allow a determination of a temporal sequence of events (i.e., a determination of whether the intervention came before the outcome) 2,4 . Other advantages of cohort studies are related to their increased feasibility as compared with the feasibility of ran- domized controlled trials. For example, cohort studies do not usually interfere with the regular clinical diagnostic and treat- ment decision-making process. Clinicians are not asked to com- promise their clinical judgment and can treat patients as they would usually treat them. Further, clinicians are not asked to Disclosure: The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. 10 COPYRIGHT Ó 2009 BY THE J OURNAL OF BONE AND J OINT SURGERY,INCORPORATED J Bone Joint Surg Am. 2009;91 Suppl 3:10-4 d doi:10.2106/JBJS.H.01597