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Title: Incorporating adherence in cost-effectiveness analysis: using asthma as a case study
บัญชัย จงมีลักษมี
Piyameth Dilokthornsakul
ปิยะเมธ ดิลกธรสกุล
Naresuan University. Faculty of Pharmaceutical Sciences
Keywords: Asthma; adherence; severe exacerbation; systematic review; meta-analysis; cost-effectiveness analysis
Issue Date: 2019
Publisher: Naresuan University
Abstract: Introduction: Cost-effectiveness analysis (CEA) is a well-established framework that is used to estimate the incremental costs per unit of the benefit provided by an intervention. While CEA is increasingly used to inform value assessment of the interventions by healthcare professionals and policy makers, most do not take into account medication adherence in their analyses. One important aspect that still lacks clarity is how to incorporate adherence in the analysis. This dissertation is conducted to acknowledge the abovementioned gap in current understanding in regard to the method of incorporating medication adherence in the CEA by using asthma as a case study. It is comprised of three individual studies chapter by chapter. The first study is to (1) explore the extent of CEA of asthma considering adherence as part of their analyses, and (2) summarize the methods of incorporating adherence in the economic models. The second study is to (3) associate medication adherence and severe asthma exacerbation, and its findings would deliver current evidence of such quantitative interrelations that were incorporated in the CEA of an added on omalizumab compared with the standard care in the third study, which is to (4) evaluate the impact of incorporating medication adherence affecting exacerbation on the results of cost-effectiveness analysis. Methods: In the first study, a systematic review was conducted in 4 databases; PubMed, EMBASE, NHS EED, and the Tufts CEA registry. Model-based CEA of asthma were identified, while the outcomes of interest were the number of studies incorporating adherence in the analysis, and the incorporating methods. All the CEA were reviewed to summarize adherence data, methods of incorporating adherence, and the impact of adherence on the cost-effectiveness results. In the second study, another systematic review was undertaken in the following databases; PubMed, Cochrane CENTRAL, EMBASE and Randomized-controlled trials, cohort and case-control studies which investigated the effect of adherence to controller medications on severe asthma exacerbation were included. A pairwise meta-analysis under a random-effects model was performed to provide pooled estimates of the associations between adherence and severe exacerbation. Lastly, a Markov model economic evaluation was conducted to determine the impact of incorporating adherence on the CEA’s results among patients with severe persistent asthma using an added on omalizumab compared to the standard care treatment in Thailand. A quantitative interrelations between adherence and exacerbation were incorporated in the Markov model, and the outcomes of interest were the numbers of exacerbations, life years (LY), quality-adjusted life years (QALY), lifetime costs, and the incremental cost-effectiveness ratios (ICER) of individual adherence levels. Results: In the first study, from 1,587 articles, 23 studies were decision model-based CEA of asthma, of which, four CEA (17.4%) incorporated adherence in the analyses. Only the method of incorporating adherence by adjusting treatment effectiveness according to adherence levels was demonstrated in this review in which two approaches were used to derive the associations; the first was to apply a mathematical formula developed by an expert panel, and the second was to extrapolate the associations from previous published studies. Secondly, the meta-analyses revealed that the odd of exacerbation among the patients with greater than or equal to (≥) 80% adherence was lowered by 47% [odds ratio, OR = 0.53 (95% confidence interval, CI: 0.42, 0.66), P < 0.001] compared to less than (<) 80%. When compared to < 20% adherence, a 33% reduction in the odds [OR = 0.67 (95% CI: 0.53, 0.86), P = 0.001] was associated with the patients achieving ≥ 50% adherence, while a decrease in exacerbation was not associated with 20 - 49% adherence [OR = 0.94 (95% CI: 0.85, 1.04), P = 0.22]. In addition, a 2.4 fold increase in the odds [OR = 2.4 (95% CI: 2.1, 2.7), P < 0.001] was associated with the discontinuation of treatment. Lastly, the economic evaluation of incorporating adherence among 100 severe asthmatic patients showed that patients using an added on omalizumab with ≥ 80% adherence experienced a lower number of exacerbations [-43.88% (95% credible interval, CrI: -47.94%, -39.26%)] compared with the standard care, while those with < 80% adherence experienced a higher number [13.51% (95% CrI: 5.58%, 23.11%)]. All patients were associated with increased LY, and demonstrated a trend towards an increase in QALY, however, their lifetime costs were substantial, resulting in considerable ICER. Conclusion: In this dissertation, we gather all relevant evidence regarding the current knowledge of the methods used to incorporate adherence in the CEA of asthma, demonstrate the method of incorporating adherence using the associations of adherence affecting severe exacerbation, as well as evaluate its impact on the results of cost-effectiveness. Our findings are evidence which will allow researchers, healthcare professionals and policy makers to incorporate adherence in their economic analysis for a better informed policy decision-making and future research development in regard to this area.
Description: Doctor of Philosophy (Ph.D.)
ปรัชญาดุษฎีบัณฑิต (ปร.ด.)
Appears in Collections:กลุ่มวิทยาศาสตร์สุขภาพ

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