Clinical and economic impact of non-adherence in COPD:A systematic review

BACKGROUND: Medication for Chronic Obstructive Pulmonary Disease (COPD) has shown to substantially reduce symptoms and slow progression of disease. However, non-adherence to medication is common and associated with worsened clinical and economic outcomes. OBJECTIVE: The objective of this study was to perform a systematic review of published literature to assess the impact of non-adherence to COPD medication on clinical and economic outcomes. METHODS: A search in PubMed and Web of Science databases was conducted of original studies published from database inception to 2012. Studies must report on the association between adherence to COPD medication and outcomes, published in English in peer-reviewed journals and full texts needed to be available. RESULTS: Twelve full articles were included in the review. Most studies were retrospective database studies. Seven studies reported on the association between adherence and clinical outcomes, two on mortality, three on costs, four on quality of life and one on work productivity. Results indicated a clear association between adherence and both clinical and economic outcomes. Evidence from studies revealed increased hospitalizations, mortality, quality of life and loss of productivity among non-adherent patients. CONCLUSION: This review revealed a clear association between non-adherence to COPD medication and worsened clinical and economic outcomes making non-adherent patients a priority for cost-effective interventions.</p

Systematic Review and Quality Appraisal of Cost-Effectiveness Analyses of Pharmacologic Maintenance Treatment for Chronic Obstructive Pulmonary Disease:Methodological Considerations and Recommendations

Worldwide, chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic lung disease with considerable clinical and socioeconomic impact. Pharmacologic maintenance drugs (such as bronchodilators and inhaled corticosteroids) play an important role in the treatment of COPD. The cost effectiveness of these treatments has been frequently assessed, but studies to date have largely neglected the impact of treatment sequence and the exact stage of disease in which the drugs are used in real life. We aimed to systematically review recently published articles that reported the cost effectiveness of COPD maintenance treatments, with a focus on key findings, quality and methodological issues. We performed a systematic literature search in Embase, PubMed, the UK NHS Economic Evaluation Database (NHS-EED) and EURONHEED (European Network of Health Economics Evaluation Databases) and included all relevant articles published between 2011 and 2015 in either Dutch, English or German. Main study characteristics, methods and outcomes were extracted and critically assessed. The Quality of Health Economic Studies (QHES) instrument was used as basis for quality assessment, but additional items were also addressed. The search identified 18 recent pharmacoeconomic analyses of COPD maintenance treatments. Papers reported the cost effectiveness of long-acting muscarinic antagonist (LAMA) monotherapy (n = 6), phosphodiesterase (PDE)-4 inhibitors (n = 4), long-acting beta agonist/inhaled corticosteroid (LABA/ICS) combinations (n = 4), LABA monotherapy (n = 2) and LABA/LAMA combinations (n = 2). All but two studies were funded by the manufacturer, and all studies indicated favourable cost effectiveness; however, the number of quality-adjusted life-years (QALYs) gained was small. Less than half of the studies reported a COPD-specific outcome in addition to a generic outcome (mostly QALYs). Exacerbation and mortality rates were found to be the main drivers of cost effectiveness. According to the QHES, the quality of the studies was generally sufficient, but additional assessment revealed that most studies poorly represented the cost effectiveness of real-life medication use. The majority of studies showed that pharmacologic COPD maintenance treatment is cost effective, but most studies poorly reflected real-life drug use. Consistent and COPD-specific methodology is recommended

A health policy model for COPD:Effects of smoking cessation

Objectives: 1) To improve an existing COPD model by incorporating the distinction between mild, moderate, severe and very severe COPD and by quantifying the progression of COPD over these stages 2) To use the improved model to estimate the potential impact of smoking cessation programs offered to COPD patients and project their effect on the future burden of COPD. Methods: An existing population model for COPD, which is a module of the RIVM Chronic Disease model, was extended with disease progression over time. Prevalent cases in the starting year were distributed over 4 severity stages mild (28%), moderate (54%), severe (15%) and very severe (3%) (GOLD-classification). The severity distribution was based on data from GP registrations. The COPD incidence was 41% in mild, 55% in moderate and 4% in severe. Disease progression was modelled as annual decline in lung function in FEV1% predicted. The Lung Health Study was used to estimate gender, age, smoking and baseline FEV1% predicted dependent values of lung function decline and one-time increase in lung function associated with smoking cessation. A meta-analysis was done to obtain severity stage specific mortality rates. The new model was used to project COPD prevalence, mortality and costs by COPD severity stage over the period 2000-2025 (the base-case scenario). A series of sensitivity analyses was performed to assess the robustness of the results to changes in input data and assumptions. The new model was used to compare two scenarios on increased implementation of two smoking cessation interventions, minimal counselling by the general practioner (H-MIS) and intensive counselling with bupropion (IC+Bupr). They were compared to the base-case scenario in terms of life-years, QALYs, interventions costs and savings of COPD-related costs. In the scenarios H-MIS or IC+Bupr was implemented for a period of either 1 year, 10 years or 25 years and reached 25% of the smokers. Smoking cessation results in a one-time increase in lung function and a lower annual decline in FEV1% predicted, which results in less disease progression and less mortality among COPD patients who quit smoking. Future costs and effects of these scenarios were discounted at 4%. Incremental cost-effectiveness ratios were calculated as (additional intervention costs minus the savings in COPD-related health care costs)/ gain in health outcomes. Results: In the base-case scenario, the total number of COPD patients increases from 300 thousand in 2000 to 490 thousand patients in 2025. Between 2000 and 2025 the prevalence rate of mild COPD increases from 5 to 11 per 1000 inhabitants. The prevalence rate of moderate COPD increases from 11 to 14. For severe COPD the rate increases from 3.0 to 3.9 and for very severe COPD the rate increases from 0.5 to 1.3. In absolute numbers the increase is highest in mild COPD, but the largest relative increase in prevalence rate is seen in very severe COPD. As a result of the increase in COPD prevalence and aging of the COPD population, all-cause mortality rates per 1000 inhabitants increase in all severity stages. In 2000, total COPD-related health care costs are estimated to be 280 million Euros. In 2025 total costs are projected to be 495 million Euros. Costs for very severe COPD have the highest relative increase. The sensitivity analyses show that the model projections were most sensitive to assumptions about the severity distribution of incidence. Implementation of H-MIS and IC+Bupr results in more mild and moderate and less severe and very severe COPD patients compared to the base-case scenario after 25 years. Costs per additional quitter are 700 for H-MIS and 2700 for IC+Bupr. Irrespective of the duration of implementation, H-MIS generates net savings, which indicates that the intervention costs of H-MIS are offset by the savings in COPD-related costs. For IC+Bupr savings do not outweigh the interventions costs. For the years 2000 to 2025 the costs per life-year gained of implementing IC+Bupr for 10 years are estimated to be 12000 Euros. Conclusions: Modelling COPD progression over time proves feasible. The model showed that implementation of H-MIS among COPD patients results in better health outcomes and is cost saving. Implementation of IC+Bupr has higher costs than savings, but is still cost-effective with costs per life-year ranging from 10600 to 24500 depending on the duration of implementation. +12Figure content uploaded by Talitha FeenstraAuthor contentPublic Full-text (1) 53e8d65d0cf25d674ea87058.pdfContent uploaded by Talitha FeenstraAuthor contentpage 1page 2A Health Policy Model for COPD: Effects of Smoking Cessation 2A health policy model for COPD: effects of smoking cessation Martine Hoogendoorn1, MSc Talitha Feenstra1,2, PhD Rudolf Hoogenveen2, MSc Marianne van Genugten2, MSc Maureen Rutten-van Mölken1, PhD 1 Institute for Medical Technology Assessment (IMTA), Erasmus Medical Center, Rotterdam, The Netherlands 2 Department for prevention and health services research, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands Correspondence: Institute for Medical Technology Assessment Erasmus Medical Center Rotterdam P.O. Box 1738 3000 DR Rotterdam The Netherlands Phone: (010) 408 85 71 Fax: (010) 408 90 81 E-mail: [email protected] for Medical Technology Assessment, November 2003 Report number: 03.68 This study was financially supported by The Dutch Asthma Foundation, project number: 3.4.01.75. Copyright. All rights reserved. Save exceptions stated by the law, no part of this publication may be reproduced in any form without the prior written permission of iMTApage 3A Health Policy Model for COPD: Effects of Smoking Cessation 3Table of Contents ACKNOWLEDGEMENTS................................................................................................................................4ABSTRACT...................................................................................................................................................51. INTRODUCTION ..........................................................................................................................72. UPDATE OF THE EXISTING COPD MODEL .............................................................................82.1 DEMOGRAPHY........................................................................................................................................82.2 COPD INCIDENCE, PREVALENCE AND MORTALITY...............................................................................92.3 SMOKING PREVALENCE AND TRANSITION RATES....................................................................................92.4 COPD INCIDENCE AMONG NON-SMOKERS, SMOKERS AND EX-SMOKERS.............................................103. DESCRIPTION OF THE NEW COPD MODEL ......................................................................... 113.1 DISTRIBUTION OF PREVALENCE BY SEVERITY......................................................................................123.2 DISTRIBUTION OF INCIDENCE BY SEVERITY..........................................................................................153.3 TRANSITION RATES BETWEEN SEVERITY STAGES.................................................................................163.4 MORTALITY RATES BY SEVERITY.........................................................................................................193.5 COSTS OF COPD BY SEVERITY............................................................................................................213.6 SENSITIVITY ANALYSES.......................................................................................................................264. BASE-CASE AND SMOKING CESSATION SCENARIOS...................................................... 284.1 BASE-CASE SCENARIO..........................................................................................................................284.2 SMOKING CESSATION SCENARIOS.........................................................................................................285. RESULTS: PROJECTIONS FOR THE BASE-CASE SCENARIO .......................................... 315.1 PREVALENCE OF COPD .......................................................................................................................315.2 MORTALITY.........................................................................................................................................355.3 COPD-RELATED COSTS.......................................................................................................................386. RESULTS: SENSITIVITY ANALYSIS FOR THE BASE-CASE SCENARIO ........................... 406.1 PREVALENCE OF COPD .......................................................................................................................406.2 MORTALITY.........................................................................................................................................446.3 COPD-RELATED COSTS.......................................................................................................................467. RESULTS: PROJECTIONS FOR THE SMOKING CESSATION SCENARIOS ...................... 487.1 CHANGES IN THE COPD POPULATION..................................................................................................487.2 COST-EFFECTIVENESS ANALYSES.........................................................................................................517.3 SENSITIVITY ANALYSES FOR COST-EFFECTIVENESS..............................................................................568. DISCUSSION AND CONCLUSION .......................................................................................... 59REFERENCES .............................................................................................................................. 63APPENDIX A: TABLES OF CHAPTER 2, UPDATE OF THE EXISTING COPD MODEL .......... 70APPENDIX B: TABLES OF CHAPTER 3, DESCRIPTION OF THE NEW COPD MODEL ........ 75APPENDIX C: MATHEMATICAL DESCRIPTION OF THE NEW COPD MODEL ...................... 84APPENDIX D: TABLES OF CHAPTER 5 RESULTS: PROJECTIONS FOR THE BASE-CASE SCENARIO.................................................................................................................................... 97APPENDIX E: TABLES OF CHAPTER 6 RESULTS: SENSITIVITY ANALYSIS FOR THE BASE-CASE SCENARIO ........................................................................................................... 101page 4A Health Policy Model for COPD: Effects of Smoking Cessation 4Acknowledgements First of all, we would like to thank the expert panel, S. Buist, E. Wouters, J. Schouten and I. Smeele for their valuable comments and suggestions on our input data. Furthermore we would like to thank T. Schermer and A. Hesselink for providing data for the estimation of the severity distribution of prevalence and the National Heart, Lung and Blood Institute for providing us the Lung Health Study data. Finally the following persons are thanked for their help and advice: H. Boshuizen and J. Oostenbrink.page 5A Health Policy Model for COPD: Effects of Smoking Cessation 5Abstract Objectives: 1) To improve an existing COPD model by incorporating the distinction between mild, moderate, severe and very severe COPD and by quantifying the progression of COPD over these stages 2) To use the improved model to estimate the potential impact of smoking cessation programs offered to COPD patients and project their effect on the future burden of COPD. Methods: An existing population model for COPD, which is a module of the RIVM Chronic Disease model, was extended with disease progression over time. Prevalent cases in the starting year were distributed over 4 severity stages mild (28%), moderate (54%), severe (15%) and very severe (3%) (GOLD-classification). The severity distribution was based on data from GP registrations. The COPD incidence was 41% in mild, 55% in moderate and 4% in severe. Disease progression was modelled as annual decline in lung function in FEV1% predicted. The Lung Health Study was used to estimate gender, age, smoking and baseline FEV1% predicted dependent values of lung function decline and one-time increase in lung function associated with smoking cessation. A meta-analysis was done to obtain severity stage specific mortality rates. The new model was used to project COPD prevalence, mortality and costs by COPD severity stage over the period 2000-2025 (the base-case scenario). A series of sensitivity analyses was performed to assess the robustness of the results to changes in input data and assumptions. The new model was used to compare two scenarios on increased implementation of two smoking cessation interventions, minimal counselling by the general practioner (H-MIS) and intensive counselling with bupropion (IC+Bupr). They were compared to the base-case scenario in terms of life-years, QALYs, interventions costs and savings of COPD-related costs. In the scenarios H-MIS or IC+Bupr was implemented for a period of either 1 year, 10 years or 25 years and reached 25% of the smokers. Smoking cessation results in a one-time increase in lung function and a lower annual decline in FEV1% predicted, which results in less disease progression and less mortality among COPD patients who quit smoking. Future costs and effects of these scenarios were discounted at 4%. Incremental cost-effectiveness ratios were calculated as (additional intervention costs minus the savings in COPD-related health care costs)/ gain in health outcomes. page 6A Health Policy Model for COPD: Effects of Smoking Cessation 6Results: In the base-case scenario, the total number of COPD patients increases from 300 thousand in 2000 to 490 thousand patients in 2025. Between 2000 and 2025 the prevalence rate of mild COPD increases from 5 to 11 per 1000 inhabitants. The prevalence rate of moderate COPD increases from 11 to 14. For severe COPD the rate increases from 3.0 to 3.9 and for very severe COPD the rate increases from 0.5 to 1.3. In absolute numbers the increase is highest in mild COPD, but the largest relative increase in prevalence rate is seen in very severe COPD. As a result of the increase in COPD prevalence and aging of the COPD population, all-cause mortality rates per 1000 inhabitants increase in all severity stages. In 2000, total COPD-related health care costs are estimated to be 280 million Euros. In 2025 total costs are projected to be 495 million Euros. Costs for very severe COPD have the highest relative increase. The sensitivity analyses show that the model projections were most sensitive to assumptions about the severity distribution of incidence. Implementation of H-MIS and IC+Bupr results in more mild and moderate and less severe and very severe COPD patients compared to the base-case scenario after 25 years. Costs per additional quitter are 700 for H-MIS and 2700 for IC+Bupr. Irrespective of the duration of implementation, H-MIS generates net savings, which indicates that the intervention costs of H-MIS are offset by the savings in COPD-related costs. For IC+Bupr savings do not outweigh the interventions costs. For the years 2000 to 2025 the costs per life-year gained of implementing IC+Bupr for 10 years are estimated to be 12000 Euros. Conclusions: Modelling COPD progression over time proves feasible. The model showed that implementation of H-MIS among COPD patients results in better health outcomes and is cost saving. Implementation of IC+Bupr has higher costs than savings, but is still cost-effective with costs per life-year ranging from 10600 to 24500 depending on the duration of implementation. <br/