Challenges in Systematic Reviews and Meta-Analyses of Mediation Analyses

Vo, Tat‐Thang; Vansteelandt, Stijn

doi:10.1093/aje/kwac028

Cited by 8 publications

(1 citation statement)

References 32 publications

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“…Under the assumption that the selected mediator-outcome confounders appropriately represent all outcome and mediator predictors that are differentially distributed across RCTs, current analyses adequately address potential heterogeneity between included RCTs. 17 The lack of a measure for radiographic OA in several RCTs could obviously challenge these assumptions.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of action of therapeutic exercise for knee and hip OA remain a black box phenomenon: an individual patient data mediation study with the OA Trial Bank

Runhaar,

Holden,

Hattle

et al. 2023

RMD Open

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ObjectivesTo evaluate mediating factors for the effect of therapeutic exercise on pain and physical function in people with knee/hip osteoarthritis (OA).MethodsFor Subgrouping and TargetEd Exercise pRogrammes for knee and hip OsteoArthritis (STEER OA), individual participant data (IPD) were sought from all published randomised controlled trials (RCTs) comparing therapeutic exercise to non-exercise controls in people with knee/hip OA. Using the Counterfactual framework, the effect of the exercise intervention and the percentage mediated through each potential mediator (muscle strength, proprioception and range of motion (ROM)) for knee OA and muscle strength for hip OA were determined.ResultsData from 12 of 31 RCTs of STEER OA (1407 participants) were available. Within the IPD data sets, there were generally statistically significant effects from therapeutic exercise for pain and physical function in comparison to non-exercise controls. Of all potential mediators, only the change in knee extension strength was statistically and significantly associated with the change in pain in knee OA (β −0.03 (95% CI −0.05 to −0.01), 2.3% mediated) and with physical function in knee OA (β −0.02 (95% CI −0.04 to −0.00), 2.0% mediated) and hip OA (β −0.03 (95% CI −0.07 to −0.00), no mediation).ConclusionsThis first IPD mediation analysis of this scale revealed that in people with knee OA, knee extension strength only mediated ±2% of the effect of therapeutic exercise on pain and physical function. ROM and proprioception did not mediate changes in outcomes, nor did knee extension strength in people with hip OA. As 98% of the effectiveness of therapeutic exercise compared with non-exercise controls remains unexplained, more needs to be done to understand the underlying mechanisms of actions.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of action of therapeutic exercise for knee and hip OA remain a black box phenomenon: an individual patient data mediation study with the OA Trial Bank

Runhaar,

Holden,

Hattle

et al. 2023

RMD Open

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Challenges

Kumar

2023

Meta-Analysis in Clinical Research: Principles and Procedures

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Practical challenges in mediation analysis: a guide for applied researchers

Schuler,

Coffman,

Stuart

et al. 2024

Health Serv Outcomes Res Method

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Mediation analysis is a statistical approach that can provide insights regarding the intermediary processes by which an intervention or exposure affects a given outcome. Mediation analyses rose to prominence, particularly in social science research, with the publication of Baron and Kenny’s seminal paper and is now commonly applied in many research disciplines, including health services research. Despite the growth in popularity, applied researchers may still encounter challenges in terms of conducting mediation analyses in practice. In this paper, we provide an overview of conceptual and methodological challenges that researchers face when conducting mediation analyses. Specifically, we discuss the following key challenges: (1) Conceptually differentiating mediators from other “third variables,” (2) Extending beyond the single mediator context, (3) Identifying appropriate datasets in which measurement and temporal ordering support the hypothesized mediation model, (4) Selecting mediation effects that reflect the scientific question of interest, (5) Assessing the validity of underlying assumptions of no omitted confounders, (6) Addressing measurement error regarding the mediator, and (7) Clearly reporting results from mediation analyses. We discuss each challenge and highlight ways in which the applied researcher can approach these challenges.

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Challenges in Systematic Reviews and Meta-Analyses of Mediation Analyses

Cited by 8 publications

References 32 publications

Mechanisms of action of therapeutic exercise for knee and hip OA remain a black box phenomenon: an individual patient data mediation study with the OA Trial Bank

Mechanisms of action of therapeutic exercise for knee and hip OA remain a black box phenomenon: an individual patient data mediation study with the OA Trial Bank

Challenges

Practical challenges in mediation analysis: a guide for applied researchers

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