Comparative effectiveness of pharmacological treatments for patients with diarrhea-predominant irritable bowel syndrome: Protocol of a systematic review and network meta-analysis

BACKGROUND: Several pharmacological treatments are recommended by guidelines with moderate to high evidence for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D), but the comparative effectiveness and safety among these treatments are unknown. The review is to assess the comparative effectiveness and safety of pharmacological treatments for IBS-D using network meta-analysis. METHODS: We will search Ovid Medline, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) for relevant randomized controlled trials (RCTs) that compare guideline-recommended pharmacological treatments with placebo or one of the treatments. We will include RCTs that recruit patients with IBS-D, RCTs that assess the improvement in IBS-D global symptoms, abdominal pain, stool frequency, or stool consistency, and RCTs that assess the responder rate and adverse event rate. We will use standardized mean difference to synthesize continuous variables and use odds ratio to synthesize categorical variables. Traditional meta-analysis will be performed to assess the comparative effectiveness of the pharmacological treatments in direct evidence, and network meta-analysis will be performed to combine both direct and indirect evidence. Transitivity of the evidence in the network will be assessed by using a generalized Cochrane Q statistic and net-heat plot. CONCLUSIONS: The result of the review will inform clinical decisions for clinicians, patients, and police makers in the treatment of IBS-D. RESULTS: Ethical approval and informed consent are not required for this systematic review. We will disseminate the result through a peer-reviewed journal and conference abstracts. PROSPERO REGISTRATION NUMBER: PROSPERO CDR42018099294.