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Pragmat Obs Res. 2017 Mar 22;8:15-30. doi: 10.2147/POR.S122563. eCollection 2017.

An evaluation of exact matching and propensity score methods as applied in a comparative effectiveness study of inhaled corticosteroids in asthma.

Author information

Observational and Pragmatic Research Institute Pte Ltd, Singapore.
University Paris Descartes (EA2511), Cochin Hospital Group (AP-HP), Paris, France.
Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen.
PHARMO Institute for Drug Outcomes Research, Utrech, the Netherlands.
Takeda Development Centre Europe Ltd, London, UK.
Takeda Pharmaceuticals International GmbH, Zurich, Switzerland.
Observational and Pragmatic Research Institute Pte Ltd, Singapore; Academic Primary Care, University of Aberdeen, Aberdeen, UK.



Cohort matching and regression modeling are used in observational studies to control for confounding factors when estimating treatment effects. Our objective was to evaluate exact matching and propensity score methods by applying them in a 1-year pre-post historical database study to investigate asthma-related outcomes by treatment.


We drew on longitudinal medical record data in the PHARMO database for asthma patients prescribed the treatments to be compared (ciclesonide and fine-particle inhaled corticosteroid [ICS]). Propensity score methods that we evaluated were propensity score matching (PSM) using two different algorithms, the inverse probability of treatment weighting (IPTW), covariate adjustment using the propensity score, and propensity score stratification. We defined balance, using standardized differences, as differences of <10% between cohorts.


Of 4064 eligible patients, 1382 (34%) were prescribed ciclesonide and 2682 (66%) fine-particle ICS. The IPTW and propensity score-based methods retained more patients (96%-100%) than exact matching (90%); exact matching selected less severe patients. Standardized differences were >10% for four variables in the exact-matched dataset and <10% for both PSM algorithms and the weighted pseudo-dataset used in the IPTW method. With all methods, ciclesonide was associated with better 1-year asthma-related outcomes, at one-third the prescribed dose, than fine-particle ICS; results varied slightly by method, but direction and statistical significance remained the same.


We found that each method has its particular strengths, and we recommend at least two methods be applied for each matched cohort study to evaluate the robustness of the findings. Balance diagnostics should be applied with all methods to check the balance of confounders between treatment cohorts. If exact matching is used, the calculation of a propensity score could be useful to identify variables that require balancing, thereby informing the choice of matching criteria together with clinical considerations.


asthma; exact matching; observational; propensity score

Conflict of interest statement

Disclosure AB and CM were employees of Research in Real-Life (RiRL), Cambridge, UK. Research in Real-Life was subcontracted by Observational and Pragmatic Research Institute Pte Ltd, Singapore, to conduct this study and has conducted paid research in respiratory disease on behalf of the following other organizations in the past 5 years: Aerocrine, AKL Ltd, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Meda, Mundipharma, Napp, Novartis, Orion, Takeda, Teva, and Zentiva, a Sanofi company. NR has received over the past 3 years: 1) fees for speaking, organizing education, participation in advisory boards or consulting from 3M, Aerocrine, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, MSD-Chibret, Mundipharma, Novartis, Pfizer, Sanofi, Sandoz, Teva; 2) research grants from Novartis, Boehringer Ingelheim and Pfizer. EVH is a consultant to RiRL and has received payment for writing and editorial support to Merck. The University of Groningen has received money for DSP regarding an unrestricted educational grant for research from AstraZeneca, Chiesi. Travel to conferences for the European Respiratory Society (ERS) and/or the American Thoracic Society (ATS) has been partially funded by AstraZeneca, Chiesi, GSK, Takeda. Fees for consultancies were given to the University of Groningen by AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Takeda, and TEVA. Travel and lectures in China were paid by Chiesi. RMCH and JAO are employees of the PHARMO Institute. This independent research institute performs financially supported studies for government and related health care authorities and several pharmaceutical companies. DvE and JMK are employees of Takeda. DBP has Board Membership with Aerocrine, Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Meda, Mundipharma, Napp, Novartis, and Teva. Consultancy: Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Meda, Mundipharma, Napp, Novartis, Pfizer, Teva, and Zentiva; Grants/Grants Pending with UK National Health Service, British Lung Foundation, Aerocrine, AstraZeneca, Boehringer Ingelheim, Chiesi, Eli Lilly, GlaxoSmithKline, Meda, Merck, Mundipharma, Novartis, Orion, Pfizer, Respiratory Effectiveness Group, Takeda, Teva, and Zentiva; Payments for lectures/speaking: Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoS-mithKline, Kyorin, Meda, Merck, Mundipharma, Novartis, Pfizer, SkyePharma, Takeda, and Teva; Payment for manuscript preparation: Mundipharma and Teva; Patents (planned, pending or issued): AKL Ltd.; payment for the development of educational materials: GlaxoSmithKline, Novartis; Stock/Stock options: Shares in AKL Ltd which produces phyto-pharmaceuticals and owns 80% of Research in Real-Life Ltd, 75% of the social enterprise Optimum Patient Care Ltd and 75% of Observational and Pragmatic Research Institute Pte Ltd; received payment for travel/accommodations/meeting expenses from Aerocrine, Boehringer Ingelheim, Mundipharma, Napp, Novartis, and Teva; funding for patient enrolment or completion of research: Almirral, Chiesi, Teva, and Zentiva; peer reviewer for grant committees: Medical Research Council (2014), Efficacy and Mechanism Evaluation programme (2012), HTA (2014); and received unrestricted funding for investigator-initiated studies from Aerocrine, AKL Ltd, Almirall, Boehringer Ingelheim, Chiesi, Meda, Mundi-pharma, Napp, Novartis, Orion, Takeda, Teva, and Zentiva. The authors report no other conflicts of interest in this work.

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