Bounding the Implications of Noncompliance in Randomized Controlled Trials in Orthopaedics: An Example in Arthroscopic Surgery

Abstract

Introduction: Randomized controlled trials (RCTs) are not impervious to bias especially when there are substantial numbers of patients who cross over from the treatment assigned by randomization to another treatment group, leading to loss of confidence in study results. The goals of this study were to (1) quantify the effects of crossovers on RCTs, (2) describe the specific effects of crossovers on RCTs for arthroscopic meniscectomy for osteoarthritis of the knee (APM/OAK), and (3) assess the confidence in APM/OAK in which there have been substantial numbers of patients crossing over to another treatment group than that assigned. Methods: Studies were included that were RCTs of APM/OAK with intention-to-treat (ITT) analysis and illustrated the problem of crossovers on confidence in the analysis. Studies were excluded if they consisted of APM for conditions other than OAK or had unavailability of data needed for the analysis. For eligible RCTs, the ITT effect was calculated; bounds for the average treatment effect (ATE) and the complier ATE were assessed by estimating confidence intervals for the bound through robust Bayesian analysis. Results: The eligible studies had different comparators and, therefore, were analyzed individually. Data were not pooled. The most extreme point estimates (with 95% confidence interval) for ITT ranged from 20.01 to 0.04 (20.16 to 0.16); for ATE with no assumptions, 0.38 (20.58 to 0.43) to 0.62 (0.56 to 0.70); for ATE with minimum assumptions, 20.50 (20.22 to 0.10) to 0.61 (0.53 to 0.57); and for complier ATE, 20.01 to 0.07 (20.22 to 0.24). Discussion: These data suggest large bounds, crossing the threshold of "no effect," which indicates a high degree of uncertainty and low confidence in the RCTs studied. The results demonstrate that when there are crossovers, ITT analyses do not estimate the ATE and confidence in the results of these RCTs is low. Data Availability: All analyzed data are provided in the article. Level of Evidence: Level I (therapeutic study = RCT

Letter to the Editor: Editorial: The New AAOS Guidelines on Knee Arthroscopy for Degenerative Meniscus Tears Are a Step in the Wrong Direction

“…The crossover percentages in recent studies on surgical meniscectomy varied from 19% to 33%, a significant confounder and source of potential bias [10,17]. In a recent analysis of the Level I evidence regarding knee osteoarthritis and arthroscopic partial meniscectomy, Forbes et al [6] found that "the extensive crossovers from one group to another diminish confidence in the precision of the results" in Level I studies. Finally, only two of the randomized controlled trials had a defined and mandatory prerandomization period of nonoperative care.…”