Introduction Chronic obstructive pulmonary disease (COPD) is a progressive disease affecting 3 million people in the UK, in which patients exhibit airflow obstruction that is not fully reversible. COPD treatment guidelines are largely informed by randomised controlled trial results, but it is unclear if these findings apply to large patient populations not studied in trials. Non-interventional studies could be used to study patient groups excluded from trials, but the use of these studies to estimate treatment effectiveness is in its infancy. In this study, we will use individual trial data to validate non-interventional methods for assessing COPD treatment effectiveness, before applying these methods to the analysis of treatment effectiveness within people excluded from, or under-represented in COPD trials.
Methods and analysis Using individual patient data from the landmark COPD Towards a Revolution in COPD Health (TORCH) trial and validated methods for detecting COPD and exacerbations in routinely collected primary care data, we will assemble a cohort in the UK Clinical Practice Research Datalink (selecting people between 1 January 2004 and 1 January 2017) with similar characteristics to TORCH participants and test whether non-interventional data can generate comparable results to trials, using cohort methodology with propensity score techniques to adjust for potential confounding. We will then use the methodological template we have developed to determine risks and benefits of COPD treatments in people excluded from TORCH. Outcomes are pneumonia, COPD exacerbation, mortality and time to treatment change. Groups to be studied include the elderly (>80 years), people with substantial comorbidity, people with and without underlying cardiovascular disease and people with mild COPD.
Ethics and dissemination Ethical approval has been granted by the London School of Hygiene & Tropical Medicine Ethics Committee (Ref: 11997). The study has been approved by the Independent Scientific Advisory Committee of the UK Medicines and Healthcare Products Regulatory Agency (protocol no. 17_114R). An application to use the TORCH trial data made to clinicalstudydatarequest.com has been approved. In addition to scientific publications, dissemination methods will be developed based on discussions with patient groups with COPD.
- chronic airways disease
- clinical pharmacology
- primary care
- public health
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Contributors KW, EW, JRC, LW, SS, LS, JKQ and ID contributed to study question and design. KW wrote the first draft of the protocol manuscript (based on original grant/scientific approval applications to NIHR and ISAC that KW, EW, JRC, LW, SS, LS, JKQ and ID all contributed to). KW, EW, JRC, LW, SS, LS, JKQ and ID contributed to further drafts and approved the final version.
Funding This work was supported by NIHR grant number 15/80/28.
Competing interests JRC is funded 60% by a grant from the MRC, via a secondment to the MRC Clinical Trials Unit. The remaining funding is a combination of HEFCE and small contributions from various NIHR, ESRC, MRC and EU funds. He undertakes methodological consultancy work for Novartis and GlaxoSmithKline (GSK), and has given missing data courses for GSK, Bayer and Boehringer. Professor Smeeth reports grants from Wellcome, MRC, NIHR, BHF, Diabetes UK, ESRC and the EU; grants and personal fees for advisory work from GSK, and personal fees for advisory work from AstraZeneca. He is a Trustee of the British Heart Foundation. LW is an independent consultant to the pharmaceutical industry and is employed to provide advice by a number of different companies, none of which is involved in this therapeutic area. SS is a consultant to WHISCON and to Aetion, a software manufacturer of which he also owns equity. He is principal investigator of investigator-initiated grants to the Brigham and Women’s Hospital from Bayer, Genentech and Boehringer Ingelheim unrelated to the topic of this study. He does not receive personal fees from biopharmaceutical companies. LS reports grants from Wellcome, MRC, NIHR, BHF, Diabetes UK, ESRC and the EU; grants and personal fees for advisory work from GSK, and personal fees for advisory work from AstraZeneca. He is a Trustee of the British Heart Foundation. JKQ research group has received funding from MRC, Wellcome, BLF, GSK, BI, AZ and Insmed for other projects, none of which relate to this work. ID is funded by an unrestricted grant from, has consulted for and holds stock in GSK.
Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.
Ethics approval Ethical approval for this study has been obtained from the London School of Hygiene & Tropical Medicine Ethics Committee (Ref: 11997) and the clinicalstudydatarequest.com review panel.
Provenance and peer review Not commissioned; externally peer reviewed.
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