Classification of chronic obstructive pulmonary disease (COPD) severity according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD): Variations in the definition of GOLD groups and their impact on stage assignment Gottschalk F1, Mueller S1, Groth A1, Driessen M2, Wilke T3 1 IPAM, University of Wismar, Alter Holzhafen 19, 23966 Wismar, Germany. Electronic address: kontakt@ipam-wismar.de 2 GlaxoSmithKline, Value Evidence & Outcomes, Brentford, Middlesex, United Kingdom. 3 Ingress-Health HWM GmbH, Alter Holzhafen 19, 23966 Wismar, Germany. Chronic obstructive pulmonary disease (COPD) is a common disease characterized by persistent respiratory symptoms. COPD treatment guidelines recommend disease management strategies based on the disease severity as described by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups classification. However, a correct examination of the disease severity seems to be challenging in real-life treatment of COPD patients. The aim of this investigation was to examine the impact on patient distributions of (1) different criteria for the definition of GOLD groups, and (2) the use of information from different data sources on the distribution of patients in the GOLD classification in Germany. Background In this study, primary care data was collected by using 3 methods: (1) study physician documentation (2) patient questionnaires and (3) German claims data (sickness fund AOK Nordost). All collected primary data (physician documentation and patient questionnaires) was linked to the claims data on a patient level. Primary data included all information relevant for GOLD group classification (exacerbations, airflow limitation (FEV1), COPD assessment test (CAT) and modified Medical Research Council (mMRC) scale). Exacerbation frequency was obtained from the claims data for the same patients. Based on all available data, four different methods were applied for the assessment of GOLD groups, as proposed by the German COPD guideline 2014(1). By varying (a) either primary data or claims data information about exacerbations to define the degree of risk; and (b) using either the CAT or the mMRC to define the degree of symptoms, the distribution of patients included in different GOLD categories was reviewed. The four different classification approaches are explained below: Methods (1) CAT + FEV1 value or exacerbations (whichever indicates a higher severity); exacerbations obtained from primary data A = CAT<10 and FEV1 >=50 and max. 1 exacerbation in the previous year B = CAT>=10 and FEV1 >=50 and max. 1 exacerbation in the previous year C = CAT<10 and FEV1 <50 or more than 1 exacerbation in the previous year D = CAT>=10 and FEV1 <50 or more than 1 exacerbation in the previous year (2) CAT + FEV1 value or exacerbations (whichever indicates a higher severity); exacerbations obtained from claims data Severity level defined as described for classification approach (1) (3) mMRC + FEV1 value or exacerbations (whichever indicates a higher severity); exacerbations obtained from primary data A = mMRC 0-1 and FEV1 >=50 and max. 1 exacerbation in the previous year B = mMRC >1 and FEV1 >=50 and max. 1 exacerbation in the previous year C = mMRC 0-1 and FEV1 <50 or more than 1 exacerbation in the previous year D = mMRC >1 and FEV1 <50 or more than 1 exacerbation in the previous year (4) mMRC + FEV1 value or exacerbations (whichever indicates a higher severity); exacerbations obtained from claims data Severity level defined as described for classification approach (3) Furthermore, the difference in the assignment of a patient’s GOLD group by patient’s age, sex or the type of physician treating the patient (general practitioners vs. pneumonologists), was tested. Results In this post-hoc analysis 497 patients with COPD (mean age: 58.2 years, female: 36.0%) were included. 270 patients (54.3%) were uniformly assigned to the same severity category in all four classification approaches. For 26 patients (5.2%) each of the four classification approaches assigned the patient to another level of severity. Generally, patient distributions varied, ranging between: 13.1-38.4% (A), 19.1-44.9% (B), 2.4- 20.7% (C) and 23.7-42.5% (D) as presented in Figure 1. Overall, a higher proportion of patients were assigned to severity level A and C (representing COPD patients with less symptoms) when using the mMRC instead of the CAT. As an example, 14.3% of the patients have been assigned to group A by utilization of the (1) categorization which applies the CAT, compared to 38.4% when using the (3) categorization which applies the mMRC. The deviation due to utilization of different data sources turned out to be smaller, assigning slightly more patients to higher risk groups (C and D) when using claims data instead of primary data information about the exacerbation frequency. In total, the degree of deviation between categorizations using either claims data or primary data for the risk assessment (categorization (1) vs. (2) and (3) vs. (4)) is 9.7%, whereas it is 41.3% between categorizations using either CAT or mMRC (categorization (1) vs. (3) and (2) vs. (4)). The statistical comparison showed that the difference between primary and claims data categorizations is significantly higher for female patients (13.4% vs. 7.6%, p = 0.034). No significant influence on the degree of deviation was found for the comparison of general practitioners and pneumonologists as the treating physician nor for the age of the patient. Classification (1): CAT and exacerbations from primary data Classification (2): CAT and exacerbations from claims data Classification (3): mMRC and exacerbations from primary data Classification (4): mMRC and exacerbations from claims data Less symptoms More symptoms High risk Low risk Figure 1 GOLD group assignment of patients according to different criteria Linked dataset; N = 497 patients for whom all data was available C D A B The GOLD classification can vary as a result of the used data sources (primary collected data/claims data) and especially, according to the method used to assess COPD symptoms (CAT/mMRC). This may have a substantial impact on COPD patients’ treatment, as GOLD treatment recommendations vary for different GOLD groups. The use of multiple data sources may be considered by researchers in order to estimate more precisely the GOLD groups within a COPD population. Conclusion This study (HO12-12-8607) is funded by GlaxoSmithKline. Maurice Driessen is an employee of GlaxoSmithKline and holds stock in GlaxoSmithKline. Sabrina Mueller, Fränce Gottschalk and Antje Groth participated in this study as staff members of IPAM; IPAM work in this study was sponsored by GSK. Thomas Wilke has received honoraria from several pharmaceutical/consultancy companies e.g. Novo Nordisk, Abbvie; Merck; GSK, BMS, LEO Pharma, Astra Zeneca, Bayer, Boehringer Ingelheim, Pharmerit. Acknowledgement Keywords Observational research, claims data analysis, chronic obstructive pulmonary disease, real-world evidence study, linked data study (1) Global Initiative For Chronic Obstructive Lung Disease: Global Strategy For The Diagnosis, Management, And Prevention Of Chronic Obstructive Lung Disease (Updated 2014). References www.ingress-health.com www.twitter.com/ingressh info@ingress-health.com www.linkedin.com/company/ingress-health © Ingress-Health HWM GmbH E-Mail: info@ingress-health.com / Tel.: +49 (0)3841-758-1010