The influence of intervention fidelity on treatment effect estimates in clinical trials of complex interventions: A meta-epidemiological study.

BACKGROUND: Randomized clinical trials (RCT) provide the most reliable estimates of treatment effectiveness for therapeutic interventions. However, flaws in their design and conduct may bias treatment effect estimates, leading to over or underestimation of the true intervention effect. This is especially relevant for complex interventions, such as those in rehabilitation, which are multifaceted and tailored for individual patients or providers, leading to variations in delivery and treatment effects. OBJECTIVE: To assess whether poor intervention fidelity, the faithfulness of the intervention delivered in an RCT to what was intended in the trial protocol, influences (biases) estimates of treatment effects derived from meta-analysis of rehabilitation RCTs. METHODS: In this meta-epidemiological study of 19 meta-analyses and 204 RCTs published between 2010-2020, we evaluated the difference in intervention effects between RCTs in which intervention fidelity was monitored and those in which it was absent. We also conducted random-effects meta-regression to measure associations between intervention fidelity, risk of bias (ROB), study sample size, and treatment effect estimates. RESULTS: There was a linear relationship between fidelity and treatment effect sizes across RCTs, even after adjusting for ROB and study sample size. Higher degrees of fidelity were associated with smaller but more precise treatment effect estimates (d= -0.23 95% CI: -0.38, -0.74). Lower or absent fidelity was associated with larger, less precise estimates. Adjusting for fidelity reduced pooled treatment effect estimates in 4 meta-analyses from moderate to small or from small to no negligible or no effect, highlighting how poor fidelity can bias meta-analyses' results. CONCLUSION: Poor or absent intervention fidelity in RCTs may lead to overestimation of observed treatment effects, skewing the conclusions from individuals studies and systematic reviews with meta-analyses when pooled. Caution is needed when interpreting the results of complex intervention RCTs when fidelity is not monitored or is monitored but not reported.