Effectiveness of management strategies for uninvestigated dyspepsia: systematic review and network meta-analysis

Abstract

Objective: To determine the effectiveness of management strategies for uninvestigated dyspepsia.

Design: Systematic review and network meta-analysis.

Data sources: Medline, Embase, Embase Classic, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov from inception to September 2019, with no language restrictions. Conference proceedings between 2001 and 2019.

Eligibility criteria for selecting studies: Randomised controlled trials that assessed the effectiveness of management strategies for uninvestigated dyspepsia in adult participants (age ≥18 years). Strategies of interest were prompt endoscopy; test for Helicobacter pylori and perform endoscopy in participants who test positive; test for H pylori and eradication treatment in those who test positive ("test and treat"); empirical acid suppression; or symptom based management. Trials reported dichotomous assessment of symptom status at final follow-up (≥12 months).

Results: The review identified 15 eligible randomised controlled trials that comprised 6162 adult participants. Data were pooled using a random effects model. Strategies were ranked according to P score, which is the mean extent of certainty that one management strategy is better than another, averaged over all competing strategies. "Test and treat" ranked first (relative risk of remaining symptomatic 0.89, 95% confidence interval 0.78 to 1.02, P score 0.79) and prompt endoscopy ranked second, but performed similarly (0.90, 0.80 to 1.02, P score 0.71). However, no strategy was significantly less effective than "test and treat." Participants assigned to "test and treat" were significantly less likely to receive endoscopy (relative risk v prompt endoscopy 0.23, 95% confidence interval 0.17 to 0.31, P score 0.98) than all other strategies, except symptom based management (relative risk v symptom based management 0.60, 0.30 to 1.18). Dissatisfaction with management was significantly lower with prompt endoscopy (P score 0.95) than with "test and treat" (relative risk v "test and treat" 0.67, 0.46 to 0.98), and empirical acid suppression (relative risk v empirical acid suppression 0.58, 0.37 to 0.91). Upper gastrointestinal cancer rates were low in all trials. Results remained stable in sensitivity analyses, with minimal inconsistencies between direct and indirect results. Risk of bias of individual trials was high; blinding was not possible because of the pragmatic trial design.

Conclusions: "Test and treat" was ranked first, although it performed similarly to prompt endoscopy and was not superior to any of the other strategies. "Test and treat" led to fewer endoscopies than all other approaches, except symptom based management. However, participants showed a preference for prompt endoscopy as a management strategy for their symptoms.

Systematic review registration: PROSPERO registration number CRD42019132528.

Fig 1

Network plot for likelihood of remaining symptomatic according to intention to treat analysis at final point of follow-up

Fig 2

Forest plot for likelihood of remaining symptomatic according to intention to treat analysis at final point of follow-up. P score is probability of each treatment being ranked as best in network analysis. Higher score indicates greater probability of being ranked first

Fig 3

Summary treatment effects from network meta-analysis for likelihood of remaining symptomatic according to intention to treat analysis at final point of follow-up. Comparisons, column versus row, should be read from left to right, and are ordered relative to overall effectiveness. Treatment in top left position is ranked as best after network meta-analysis of direct and indirect effects. Direct comparisons are provided above strategy labels, and indirect comparisons are below. Values are relative risk (95% confidence interval). NA=not applicable, no randomised controlled trials making direct comparisons

Fig 4

Forest plot for likelihood of receiving endoscopy. P score is probability of each treatment being ranked as best in network analysis. Higher score indicates greater probability of being ranked first

Fig 5

Summary treatment effects from network meta-analysis for likelihood of receiving endoscopy. Comparisons, column versus row, should be read from left to right, and are ordered relative to overall effectiveness. Treatment in top left position is ranked as best after network meta-analysis of direct and indirect effects. Orange boxes indicate significant differences. Direct comparisons are provided above strategy labels, and indirect comparisons are below. Values are relative risk (95% confidence interval). NA=not applicable, no randomised controlled trials making direct comparisons