Search

Objective: To undertake meta-analysis and compare treatment effects estimated by the intention-to-treat (ITT) method and per-protocol (PP) method in randomized controlled trials (RCTs). PP excludes trial participants who are non-adherent to trial protocol in terms of eligibility, interventions, or outcome assessment., Study Design and Setting: Five high impact journals were searched for all RCTs published between July 2017 to June 2019. Primary outcome was a pooled estimate that quantified the difference between the treatment effects estimated by the two methods. Results are presented as ratio of odds ratios (ROR). Meta-regression was used to explore the association between level of trial protocol non-adherence and treatment effect. Sensitivity analyses compared results with varying within-study correlations and across various study characteristics., Results: Random-effects meta-analysis (N = 156) showed that PP estimates were on average 2% greater compared to the ITT estimates (ROR: 1.02, 95% CI: 1.00-1.04, P = 0.03). The divergence further increased with higher degree of protocol non-adherence. Sensitivity analyses reassured consistent results with various within-study correlations and across various study characteristics., Conclusion: There was evidence of larger treatment effect with PP compared to ITT analysis. PP analysis should not be used to assess the impact of protocol non-adherence in RCTs. Instead, in addition to ITT, investigators should consider randomization based casual method such as Complier Average Causal Effect (CACE)., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: The objective of this study was to review and assess the methodological quality of randomized controlled trials that test physical therapy interventions for low back pain., Study Design and Setting: This is a systematic review of trials of physical therapy interventions to prevent or treat low back pain (of any duration or type) in participants of any age indexed on the Physiotherapy Evidence Database (PEDro). Existing PEDro scale ratings were used to evaluate methodological quality., Results: This review identified 2,215 trials. The majority of trials were for adults (n = 2136, 96.4%), low back pain without specific etiology (n = 1,863, 84.1%), and chronic duration (n = 947, 42.8%). The quality of trials improved over time; however, most were at risk of bias. Less than half of the trials concealed allocation to intervention (n = 813, 36.7%), used intention-to-treat principles (n = 778, 35.1%), and blinded assessors (n = 810, 36.6%), participants (n = 174, 7.9%), and therapists (n = 39, 1.8%). These findings did not vary by the type of therapy., Conclusion: Most trials that test physical therapy interventions for low back pain have methodological limitations that could bias treatment effect estimates. Greater attention to methodological features, such as allocation concealment and the reporting of intention-to-treat effects, would improve the quality of trials testing physical therapy interventions for low back pain., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To describe the characteristics, and estimate the incidence, of trials included in systematic reviews deviating from the intention-to-treat (ITT) principle., Study Design and Setting: A 5% random sample of reviews were selected (Medline 2006-2010). Trials from reviews were classified based on the ITT: (1) ITT trials (trials reporting standard ITT analyses); (2) modified ITT (mITT) trials (modified ITT; trials deviating from standard ITT); or (3) no ITT trials., Results: Of 222 reviews, 81 (36%) included at least one mITT trial. Reviews with mITT trials were more likely to contain trials that used placebo, that investigated drugs, and that reported favorable results. The incidence of reviews with mITT trial ranged from 29% (17/58) to 48% (23/48). Of the 2,349 trials, 597 (25.4%) were classified as ITT trials, 323 (13.8%) as mITT trials, and 1,429 (60.8%) as no ITT trials. The mITT trials were more likely to have reported exclusions compared to studies classified as ITT trials and to have received funding., Conclusion: The reporting of the type of ITT may differ according to the clinical area and the type of intervention. Deviation from ITT in randomized controlled trials is a widespread phenomenon that significantly affects systematic reviews., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: In randomized trials, the primary analysis should be consistent with the intention-to-treat (ITT) principle and should address missing data appropriately to draw valid inferences. This review focuses on current practices relating to the ITT principle and methods to handle missing data in the major musculoskeletal journals., Study Design and Setting: A systematic review of randomized trials published in 2010 and 2011 in five musculoskeletal journals was performed., Results: We reviewed 91 trials: 38% performed a full ITT analysis (analyzing outcome data for all randomized participants) and 31% performed a partial ITT analysis (excluding participants with no follow-up data). The overall median dropout was 12%; 60% of trials had more than 10% dropouts, and 32% of trials had more than 20% dropouts. Among those that performed an ITT analysis, the majority adopted a form of single imputation; last observation carried forward was the designated approach in most cases. Mixed models for repeated measures and/or multiple imputations were limited to eight trials., Conclusion: It appears that many trials reporting missing data are inappropriately analyzed and may therefore be prone to biased estimates and invalid inferences., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)