Adjustment for compliance behavior in trials of epidural analgesia in labor using instrumental variable meta-analysis

Abstract

Objectives: Intention-to-treat (ITT) analysis of randomized controlled trials (RCTs) may cause bias when compliance is poor. Noncompliance describes failure to comply with allocation in the intervention arm, and contamination describes uptake of the intervention in the control arm. Instrumental variable (IV) analysis can be applied in addition to the primary ITT analysis to estimate the causal effect adjusted for noncompliance and contamination, assuming that noncompliers would have had the same treatment benefit as compliers. We aimed to compare ITT and IV meta-analysis of the association between epidural analgesia in labor and cesarean section.

Study design and setting: The study was restricted to 27 trials in a Cochrane Systematic Review. The association between epidural analgesia in labor and cesarean section was calculated using ITT and IV analyses. Pooled risk ratios (RRs) were calculated using fixed-effects meta-analysis.

Results: In 18 trials with compliance data, noncompliance was 23% and contamination was 27%. In 10 trials with outcome data stratified by compliance, the pooled RR for cesarean section following epidural analgesia was 1.37 [95% confidence interval (CI): 1.00, 1.89; P = 0.049] using IV compared with 1.19 (95% CI: 0.93, 1.51; P = 0.16) using ITT.

Conclusion: ITT meta-analysis underestimates the effect of receiving epidural analgesia in labor on cesarean section compared with IV meta-analysis.

Keywords: Cesarean section; Epidural analgesia; Instrumental variables; Intention-to-treat; Noncompliance; Randomized controlled trials.