PT - JOURNAL ARTICLE AU - Kevin Wing AU - Elizabeth Williamson AU - James R Carpenter AU - Lesley Wise AU - Sebastian Schneeweiss AU - Liam Smeeth AU - Jennifer K Quint AU - Ian Douglas TI - Real world effects of COPD medications: a cohort study with validation against RCT results AID - 10.1183/13993003.01586-2020 DP - 2020 Jan 01 TA - European Respiratory Journal PG - 2001586 4099 - http://erj.ersjournals.com/content/early/2020/10/02/13993003.01586-2020.short 4100 - http://erj.ersjournals.com/content/early/2020/10/02/13993003.01586-2020.full AB - Real-world data provide the potential for generating evidence on drug treatment effects in groups excluded from trials, but rigorous, validated methodology for doing so is lacking. We investigated whether non-interventional methods applied to real-world data could reproduce results from the landmark TORCH COPD trial.We performed a historical cohort study (2000–2017) of COPD drug treatment effects in the UK Clinical Practice Research Datalink (CPRD). Two control groups were selected from CPRD by applying TORCH inclusion/exclusion criteria and 1:1 matching to TORCH participants: control group 1- people with COPD not prescribed fluticasone propionate-salmeterol (FP-SAL), control group 2- people with COPD prescribed salmeterol (SAL). FP-SAL exposed groups were then selected from CPRD by propensity-score matching to each control group. Outcomes studied were COPD exacerbations, death from any cause and pneumonia.2652 FP-SAL exposed people were propensity-score matched to 2652 FP-SAL unexposed people while 991 FP-SAL exposed people were propensity-score matched to 991 SAL exposed people. Exacerbation rate ratio was comparable to TORCH for FP-SAL versus SAL (0.85, 95% CI 0.74–0.97 versus 0.88, 0.81–0.95) but not for FP-SAL versus no FP-SAL (1.30, 1.19–1.42 versus 0.75, 0.69–0.81). Active comparator results were also consistent with TORCH for mortality (hazard ratio 0.93, 0.65–1.32 versus 0.93, 0.77–1.13) and pneumonia (risk ratio 1.39, 1.04–1.87 versus 1.47, 1.25–1.73).We obtained very similar results to the TORCH trial for active comparator analyses, but were unable to reproduce placebo-controlled results. Application of these validated methods for active comparator analyses to groups excluded from RCTs provides a practical way for contributing to the evidence base and supporting COPD treatment decisions.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Wing has nothing to disclose.Conflict of interest: Dr. Williamson has nothing to disclose.Conflict of interest: Dr. Carpenter reports grants from MRC, grants from MRC, personal fees from Novartis, personal fees from GSK, other from GSK, other from Bayer, other from Boehringer, outside the submitted work;.Conflict of interest: Dr. Wise reports personal fees from Pharmaceutical industry, outside the submitted work;.Conflict of interest: Dr. Schneeweiss reports personal fees from WHISCON LLC, personal fees from Aetion, other from Aetion, grants from Bayer, grants from Genentech, grants from Boehringer, outside the submitted work;.Conflict of interest: Dr. Smeeth reports grants from Wellcome, grants from MRC, grants from NIHR, grants from BHF, grants from Diabetes UK, grants from ESRC, grants from EU, grants from GSK, personal fees from GSK, personal fees from AstraZeneca, other from British Heart Foundation, outside the submitted work;.Conflict of interest: Dr. Quint reports grants from MRC, grants from Wellcome, grants from BLF, grants from GSK, grants from Boehringer, grants from AstraZeneca, grants from Insmed, outside the submitted work;.Conflict of interest: Dr. Douglas reports grants from GSK, personal fees from GSK, other from GSK, outside the submitted work;.