Related Experiment Video
Updated: Nov 2, 2025
In Vitro Application of a Wireless Sensor in Flexion-Extension Gap Balance of Unicompartmental Knee Arthroplasty
Published on: May 5, 2023
Bounding the Implications of Noncompliance in Randomized Controlled Trials in Orthopaedics: An Example in
Shaun P Forbes1, Roy K Aaron, Thomas A Trikalinos
1From the Department of Health Services, Policy & Practice, Brown University School of Public Health (Forbes, Trikalinos), the Center for Evidence Synthesis in Health (CESH), Brown University School of Public Health (Forbes, Trikalinos), and the Department of Orthopedics, Warren Alpert Medical School of Brown University, Providence, RI (Aaron).
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 -0.01 to 0.04 (-0.16 to 0.16); for ATE with no assumptions, 0.38 (-0.58 to 0.43) to 0.62 (0.56 to 0.70); for ATE with minimum assumptions, -0.50 (-0.22 to 0.10) to 0.61 (0.53 to 0.57); and for complier ATE, -0.01 to 0.07 (-0.22 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).
More Related Videos
Related Concept Videos
01:23Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...
01:11Blinding