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Abstract
Introduction Traditional phase IIIb randomised trials may not reflect routine clinical practice. The Salford Lung Study in chronic obstructive pulmonary disease (SLS COPD) allowed broad inclusion criteria and followed patients in routine practice. We assessed whether SLS COPD approximated the England COPD population and evidence for a Hawthorne effect.
Methods This observational cohort study compared patients with COPD in the usual care arm of SLS COPD (2012–2014) with matched non-trial patients with COPD in England from the Clinical Practice Research Datalink database. Generalisability was explored with baseline demographics, clinical and treatment variables; outcomes included COPD exacerbations in adjusted models and pretrial versus peritrial comparisons.
Results Trial participants were younger (mean, 66.7 vs 71.1 years), more deprived (most deprived quintile, 51.5% vs 21.4%), more current smokers (47.5% vs 32.1%), with more severe Global initiative for chronic Obstructive Lung Disease stages but less comorbidity than non-trial patients. There were no material differences in other characteristics. Acute COPD exacerbation rates were high in the trial population (98.37th percentile).
Conclusion The trial population was similar to the non-trial COPD population. We observed some evidence of a Hawthorne effect, with more exacerbations recorded in trial patients; however, the largest effect was observed through behavioural changes in patients and general practitioner coding practices.
- COPD pharmacology
- clinical epidemiology
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Footnotes
Contributors AP: involved with data handling and planning/leading the statistical analyses, codrafted the manuscript with author MS, and incorporated comments from other authors. MB: data processing, data analysis and editing of the manuscript. DW: contributed to study design, data analysis and interpretation, and manuscript writing/review. JMP: contributed to study design, protocol writing, interpretation of results and manuscript development. KJD: contributed to study design, data analysis plan, data interpretation and editing of the manuscript. RW: contributed to study design, data extraction, interpretation of study results and manuscript review/revision. TVS: contributed to study design, data analysis and interpretation, and manuscript development. MS: contributed to study design and analysis plan, supervised the data analysis, contributed to data interpretation, codrafted the manuscript with author AP, and revised the manuscript critically for intellectual content. All authors approved the final version of the manuscript for submission. The corresponding author had full access to the study data. Analyses were led by the academic partners (AP, MB, TVS and MS), who made the final decision to submit for publication. All authors vouch for the accuracy and completeness of the data/analyses. Manuscript drafting was led by AP and MS, and all authors collaborated to prepare the final content for publication.
Funding This analysis was funded by GSK (study PRJ2282/201491; EUPAS registration number EUPAS10376). SLS COPD was also funded by GSK (HZC115151; NCT01551758). Medical and treatment codelists for this study will be available at https://www.gsk-clinicalstudyregister.com. The sponsor, GlaxoSmithKline, contributed to the study design, analysis plan, analyses and data interpretation.
Competing interests AP: grants, personal fees and non-financial support from GSK during the conduct of the study. MB: grants, personal fees and non-financial support from GSK during the conduct of the study. DW: employed by and holds stocks in GSK. JMP: employed by and holds stocks in GSK. KJD: employed by and holds stocks in GSK. RW: grants from GSK during the conduct of the study and grants from various organisations, outside the submitted work; employed by CPRD. CPRD received funding from GSK for access to the CPRD data and research services used in this study. CPRD also received payments from the University of Manchester for access to data and research services for studies outside the submitted work. CPRD is a research organisation offering interventional and observational research services. TVS: grants from GSK during the conduct of the study, and grants from National Osteoporosis Society, outside the submitted work. MS: grants from GSK during the conduct of the study.
Patient consent Not required.
Ethics approval This study is based in part on data from the Clinical Practice Research Datalink obtained under licence from the UK Medicines and Healthcare products Regulatory Agency. The data are provided by the patients and collected by the NHS as part of their care and support. The Office for National Statistics (ONS) is the provider of the ONS data contained within the CPRD data. Hospital Episode data and the ONS data (2014) are reused with the permission of the Health and Social Care Information Centre. All rights reserved.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The data in this study cannot be published as we do not have permission.
Author note Quality control: This study is registered in the European Post Authorisation Safety studies registry of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP/SDPP/10376). The methodology in this study has been awarded with the ENCePP study seal approval.