Conclusions and implications for practice
Our findings and analysis of interpretive frameworks demonstrates the pharmacovigilance principle that no one study or pooled analysis of studies can adequately determine whether the harm risk of drug therapy is real. A convergence of proof using data from various sources and study designs is needed. Considering the data from the COMPASS RCT together with the pharmaco-epidemiology observational studies leads us to conclude that on balance, it is likely that long-term PPI use increases all-cause mortality. Given the high prevalence of long-term PPI utilization, this message needs to be conveyed to health professionals and patients.
Competing interests: None declared.
Contributors: The authors are a group of Clinician-scientists (Ben-Eltriki, Green, Musini, Bassett and Wright), medical researcher and epidemiologist (Maclure) as well as Cochrane Hypertension authors and reviewers (Musini, Bassett and Wright). The authors are experts in analyzing clinical trials of drugs, and clarifying the state of scientific evidence regarding effectiveness and safety of drug therapy. All authors participated in the study design. Mohamed Ben-Eltriki and Carolyn Green screened studies for eligibility, performed data extraction, assessed the risk of bias, performed data analysis. All authors interpreted the data analysis and assessed the certainty of evidence. Mohamed Ben-Eltriki and Carolyn Green wrote the first draft of the manuscript, and all other authors revised the manuscript.
Funding: Funds provided to Therapeutic Initiative by the Ministry of Health of British Columbia through a grant provided to the University of British Columbia, Vancouver, Canada. The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Acknowledgements: The authors thank the BJCP reviewers for peer reviewing the study. The authors thank Cochrane Hypertension for the help provided by Douglas Salzwedel, Information Specialist for Cochrane Hypertension, for designing and conducting the searches, and for his assistance.