Protocol: a systematic review+ (SR+) to combine associative and mechanistic evidence on the efficacy of face masks in reducing transmission of respiratory diseases

Journal article

Background: Mechanistic evidence is evidence about how an intervention works. A 2023 Cochrane review, which was restricted to randomised controlled trials (RCTs), concluded that evidence on the efficacy of face masks was weak, conflicting and non-definitive. A 2024 narrative review, which included RCTs plus mechanistic evidence on masks and mask mandates, concluded that evidence of efficacy was strong, consistent and definitive. These strikingly contrasting conclusions reflect differences in how evidence is valued. Orthodox synthesis methods (e.g. those used for Cochrane reviews, informed by GRADE criteria) classify mechanistic evidence as lower quality than RCT evidence, but this position has been challenged by (among others) philosophers, non-RCT researchers and advocacy groups. We seek to include mechanistic evidence in a systematic review of mask efficacy. Method: Three overlapping work packages (methodology, review, philosophical analysis) will run concurrently. We will extend and refine the philosophical approach of Evidential Pluralism, which has been applied in a technique known as EBM+, to develop Systematic Review+ (SR+). SR+ will use Bayesian methods to support judgements of whether and to what extent interventions are effective. We will apply SR+ to face mask (and mask mandate) efficacy studies purposively selected for their epistemic contribution (the most robust and influential studies in each evidential category). We will consider whether SR+ adequately addresses philosophical objections to orthodox systematic review, including epistemological (does it adequately incorporate mechanistic evidence into reviews of efficacy?) and ethical (does it adequately address epistemic injustice, in which someone is wronged in their capacity as knower?). Discussion: We hope to produce a robust synthesis of evidence on face masks that will inform policy and a general methodology for incorporating mechanistic evidence into systematic reviews. We also hope to contribute to the scholarly literature on the philosophy of causality. Causal claims generally require at least two kinds of evidence: associative (to show that a change in one phenomenon is associated with a change in another) and mechanistic (to be confident that observed associations are causal). We hypothesise that orthodox systematic review, enhanced with mechanistic evidence, will be able to support stronger and more nuanced causal claims. Systematic review registration: INPLASY202550024, INPLASY202540045.

Authors: Greenhalgh, T; Helm, R; Poliseli, L; Ratnayake, S; Trofimov, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BioMed Central
• Journal: Systematic Reviews
• Volume: 14
• Issue: 1
• Article number: 226
• Publication date: 2025-11-17
• Acceptance date: 2025-10-01
• DOI: 10.1186/s13643-025-02973-2
• EISSN: 2046-4053
• ISSN: 2046-4053
• Language: English
• Keywords: Evidential Pluralism; Systematic review; Hierarchy of evidence; EBM+; GRADE; Epistemic justice; Risk of bias; Systematic review + (SR+); Mechanism-informed systematic review; Narrative review