ABSTRACT
Objectives
Single-inhaler triple therapies (SITTs) have never been directly compared in randomized controlled trials (RCTs) in chronic obstructive pulmonary disease (COPD). Cochrane recommends the Bayesian approach for indirect comparisons but a frequentist network meta-analysis (NMA) reported superiority of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) over other SITT. We assessed the most appropriate inference method for NMA characterized by between-study heterogeneity on SITT in COPD.
Methods
Bayesian and frequentist NMA were performed on RCTs investigating the effect of SITT on exacerbations and trough forced expiratory volume in the 1st second (FEV1) in COPD.
Results
The included RCTs (ETHOS, FULFIL, IMPACT, KRONOS 200812) reported significant between-study heterogeneity (I2 > 99%, p < 0.001). The Bayesian random-effect NMA provided unbiased evidence that FF/UMEC/VI was not superior to other SITT on exacerbations and trough FEV1. The frequentist fixed-effect NMA indicated that FF/UMEC/VI was significantly (p < 0.05) more effective than other SITT, although results were affected by dispersion, asymmetry, and significant risk of bias. Frequentist random-effect NMA provided effect estimates rather similar but not equal to those of Bayesian approach.
Conclusion
Indirect comparison should be performed via Bayesian approach instead of frequentist inference with a fixed-effect model. Claiming the superiority of a specific medication over other therapies should be confirmed by findings originating from well-designed RCTs.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/17476348.2024.2316167