Job F. M. van Boven

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.

Comorbidome, Pattern, and Impact of Asthma-COPD Overlap Syndrome in Real Life

BACKGROUND Asthma-COPD overlap syndrome (ACOS) has been described and acknowledged as a distinct clinical entity; however, its characteristics in daily clinical practice are largely unknown. The aim of this study was to identify the prevalence of ACOS in the real-life population, its pattern of comorbidities, and its impact on hospitalization risk. METHODS Data for this retrospective cohort study were extracted from the Majorca Real-Life Investigation in COPD and Asthma cohort, including primary care, hospitalization, and pharmacy data from the Balearic Islands, Spain. Patients who had received a physician-confirmed diagnosis of both asthma and COPD were identified as having ACOS and compared with a COPD-only population. In subanalyses, more stringent diagnostic criteria (Global Initiative for Asthma-Global Initiative for Chronic Obstructive Lung Disease) were applied. The pattern and impact of comorbidities on all-cause hospitalization were compared by multivariate logistic regression. RESULTS In total, 5,093 patients with ACOS (prevalence, 5.55 per 1,000 inhabitants) were compared with 22,778 patients with COPD (30.40 per 1,000 inhabitants). Patients with ACOS were more frequently female (53.4%) than were patients with COPD (30.8%), younger (ACOS, 64.0 years; COPD, 65.8 years), and differed by nonsmoking status (ACOS, 41.4%; COPD, 22.1%) (all, P < .001). In adjusted analyses, allergic rhinitis (OR, 1.81; 95% CI, 1.63-2.00), anxiety (OR, 1.18; 95% CI, 1.10-1.27), gastroesophageal reflux disease (OR, 1.18; 95% CI, 1.04-1.33), and osteoporosis (OR, 1.14; 95% CI, 1.04-1.26) were more frequent in ACOS than COPD. In contrast, chronic kidney disease (OR, 0.79; 95% CI, 0.66-0.95) and ischemic heart disease (OR, 0.88; 95% CI, 0.79-0.98) were less frequent. In patients with ACOS, cardiovascular diseases showed the strongest association with hospitalization. CONCLUSIONS ACOS is prevalent in the general population, and it affects to a large extent females with less smoking exposure compared with patients with COPD only. Cardiovascular comorbidities in particular contribute most to overall hospitalization risk of patients with ACOS.

Economic Evaluations of Pharmacogenetic and Pharmacogenomic Screening Tests: A Systematic Review. Second Update of the Literature

Objective Due to extended application of pharmacogenetic and pharmacogenomic screening (PGx) tests it is important to assess whether they provide good value for money. This review provides an update of the literature. Methods A literature search was performed in PubMed and papers published between August 2010 and September 2014, investigating the cost-effectiveness of PGx screening tests, were included. Papers from 2000 until July 2010 were included via two previous systematic reviews. Studies’ overall quality was assessed with the Quality of Health Economic Studies (QHES) instrument. Results We found 38 studies, which combined with the previous 42 studies resulted in a total of 80 included studies. An average QHES score of 76 was found. Since 2010, more studies were funded by pharmaceutical companies. Most recent studies performed cost-utility analysis, univariate and probabilistic sensitivity analyses, and discussed limitations of their economic evaluations. Most studies indicated favorable cost-effectiveness. Majority of evaluations did not provide information regarding the intrinsic value of the PGx test. There were considerable differences in the costs for PGx testing. Reporting of the direction and magnitude of bias on the cost-effectiveness estimates as well as motivation for the chosen economic model and perspective were frequently missing. Conclusions Application of PGx tests was mostly found to be a cost-effective or cost-saving strategy. We found that only the minority of recent pharmacoeconomic evaluations assessed the intrinsic value of the PGx tests. There was an increase in the number of studies and in the reporting of quality associated characteristics. To improve future evaluations, scenario analysis including a broad range of PGx tests costs and equal costs of comparator drugs to assess the intrinsic value of the PGx tests, are recommended. In addition, robust clinical evidence regarding PGx tests’ efficacy remains of utmost importance.

Towards tailored and targeted adherence assessment to optimise asthma management

In this paper, we aim to emphasise the need for a more comprehensive and tailored approach to manage the broad nature of non-adherence, to personalise current asthma management. Although currently several methods are available to measure the extent of asthma patients’ adherence, the vast majority do not incorporate confirmation of the actual inhalation, dose and inhalation technique. Moreover, most current measures lack detailed information on the individual consequences of non-adherence and on when and how to take action if non-adherence is identified. Notably, one has to realise there are several forms of non-adherence (erratic non-adherence, intelligent non-adherence and unwitting non-adherence), each requiring a different approach. To improve asthma management, more accurate methods are needed that integrate measures of non-adherence, asthma disease control and patient preferences. Integrating information from the latest inhaler devices and patient-reported outcomes using mobile monitoring- and feedback systems (‘mHealth’) is considered a promising strategy, but requires careful implementation. Key issues to be considered before large-scale implementation include patient preferences, large heterogeneity in patient and disease characteristics, economic consequences, and long-term persistence with new digital technologies.

Enhancing Respiratory Medication Adherence: The Role of Health Care Professionals and Cost-Effectiveness Considerations

Adherence to medication comprises a multiphased temporal process involving (1) initiation of prescribed therapy, (2) implementation as prescribed, and (3) subsequent persistence. Medication adherence remains suboptimal in most patients with long-term respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD). Interventions have been shown to effectively improve treatment initiation, implementation, and persistence when delivered at the health care professional level or the system level, but demonstration of the cost-effectiveness of these interventions is necessary to ensure their widespread use. This review summarizes how health care professionals can intervene to improve medication adherence in patients with asthma and COPD, provides some examples of effective primary care interventions, and illustrates some of the challenges to optimal implementation arising from cost-effectiveness modeling. Improving adherence is shown to be an economically viable treatment option for patients with asthma and COPD, but there are differences in the health economics pertaining to each condition and setting that can affect whether an intervention is considered cost-effective. Targeting adherence interventions at patients with the greatest to gain, and tailoring them to individual patient needs, may help to optimize cost-effectiveness ratios and improve the probability of positive reimbursement decisions, systemwide implementation, and resultant health benefits.

Proactive Pharmaceutical Care Interventions Improve Patients’ Adherence to Lipid-Lowering Medication

Bachground: Lipid-lowering drugs are effective preventive medication for patients at risk of cardiovascular complications. However, medication adherence is suboptimal, thereby decreasing therapy effectiveness. Pharmaceutical care interventions may increase therapy adherence. Objective: To assess the effect of a proactive pharmaceutical care intervention program, Medication Monitoring and Optimization (MeMO), on therapy discontinuation and adherence with lipid-lowering drugs as well as patients’ satisfaction with the intervention program. Methods: This prospective intervention study included 1002 patients initiating lipid-lowering drug therapy from 9 Dutch community pharmacies. In the intervention group (n = 500), the MeMO program was used, comprising continuous monitoring of patients’ adherence to lipid-lowering drugs and personal counseling with nonadherent patients. The intervention group was compared with a historical reference group (n = 502) receiving usual care. Outcomes were therapy discontinuation and adherence. Results: Discontinuation rates with lipid lowering drugs in the first year after drug initiation were 13.6% for the intervention group and 25.9% in the usual care group; continued but non-adherent use was 3.2% and 7.6% in these groups. Patients in the MeMO program had a decreased risk to discontinue medication of 51% (95% confidence interval: 34%-63%). Results were not affected by potential confounders. Patient satisfaction with MeMO was very high; one quarter of patients mentioned that they only received information about their medication from their pharmacy. Conclusions: Improving adherence to lipid lowering drugs can be achieved by a proactive pharmaceutical care program. Pharmacists can contribute to optimal use of chronic medication, which is likely to reduce healthcare costs.

Associations between chronic comorbidity and exacerbation risk in primary care patients with COPD

BackgroundCOPD often coexists with chronic conditions that may influence disease prognosis. We investigated associations between chronic (co)morbidities and exacerbations in primary care COPD patients.MethodRetrospective cohort study based on 2012–2013 electronic health records from 179 Dutch general practices. Comorbidities from patients with physician-diagnosed COPD were categorized according to International Classification of Primary Care (ICPC) codes. Chi-squared tests, uni- and multivariable logistic, and Cox regression analyses were used to study associations with exacerbations, defined as oral corticosteroid prescriptions.ResultsFourteen thousand six hundred three patients with COPD could be studied (mean age 67 (SD 12) years, 53% male) for two years. At baseline 12,826 (88%) suffered from ≥1 comorbidities, 3263 (22%) from ≥5. The most prevalent comorbidities were hypertension (35%), coronary heart disease (19%), and osteoarthritis (18%). Several comorbidities showed statistically significant associations with frequent (i.e., ≥2/year) exacerbations: heart failure (odds ratio [OR], 95% confidence interval: 1.72; 1.38–2.14), blindness & low vision (OR 1.46; 1.21–1.75), pulmonary cancer (OR 1.85; 1.28–2.67), depression 1.48; 1.14–1.91), prostate disorders (OR 1.50; 1.13–1.98), asthma (OR 1.36; 1.11–1.70), osteoporosis (OR 1.41; 1.11–1.80), diabetes (OR 0.80; 0.66–0.97), dyspepsia (OR 1.25; 1.03–1.50), and peripheral vascular disease (OR 1.20; 1.00–1.45). From all comorbidity categories, having another chronic respiratory disease beside COPD showed the highest risk for developing a new exacerbation (Cox hazard ratio 1.26; 1.17–1.36).ConclusionChronic comorbidities are highly prevalent in primary care COPD patients. Several chronic comorbidities were associated with having frequent exacerbations and increased exacerbation risk.

Effectiveness and success factors of educational inhaler technique interventions in asthma & COPD patients: a systematic review

With the current wealth of new inhalers available and insurance policy driven inhaler switching, the need for insights in optimal education on inhaler use is more evident than ever. We aimed to systematically review educational inhalation technique interventions, to assess their overall effectiveness, and identify main drivers of success. Medline, Embase and CINAHL databases were searched for randomised controlled trials on educational inhalation technique interventions. Inclusion eligibility, quality appraisal (Cochrane’s risk of bias tool) and data extraction were performed by two independent reviewers. Regression analyses were performed to identify characteristics contributing to inhaler technique improvement. Thirty-seven of the 39 interventions included (95%) indicated statistically significant improvement of inhaler technique. However, average follow-up time was relatively short (5 months), 28% lacked clinical relevant endpoints and all lacked cost-effectiveness estimates. Poor initial technique, number of inhalation procedure steps, setting (outpatient clinics performing best), and time elapsed since intervention (all, p < 0.05), were shown to have an impact on effectiveness of the intervention, explaining up to 91% of the effectiveness variation. Other factors, such as disease (asthma vs. chronic obstructive pulmonary disease), education group size (individual vs. group training) and inhaler type (dry powder inhalers vs. pressurised metered dose inhalers) did not play a significant role. Notably, there was a trend (p = 0.06) towards interventions in adults being more effective than those in children and the intervention effect seemed to wane over time. In conclusion, educational interventions to improve inhaler technique are effective on the short-term. Periodical intervention reinforcement and longer follow-up studies, including clinical relevant endpoints and cost-effectiveness, are recommended.

Mapping the clinical chronic obstructive pulmonary disease questionnaire onto generic preference-based EQ-5D values

OBJECTIVES To develop a model to predict EuroQol five-dimensional questionnaire (EQ-5D) values from clinical chronic obstructive pulmonary disease (COPD) questionnaire (CCQ) scores. METHODS We used data from three clinical trials (the Randomized Clinical Trial on Effectiveness of Integrated COPD Management in Primary Care [RECODE], the Assessment Of Going Home Under Early Assisted Discharge [GO-AHEAD], and the Health Status Guided COPD Care [MARCH]). Data were randomly split into an estimation sample and a validation sample. The conceptual similarity between patient-reported CCQ and preference-based EQ-5D scores was assessed using correlation and principal-component analysis. Different types of models were estimated with increasing complexity. We selected the final models on the basis of mean absolute error and root mean square error when comparing predicted and observed values from the same population (internal validity) and from different trial populations (external validity). We also developed models for different country-specific EQ-5D value sets. RESULTS The principal-component analysis showed that the CCQ domains functional state and mental state are associated with four dimensions of the EQ-5D. The EQ-5D dimension pain/discomfort formed a separate construct on which no CCQ item loaded. The mean observed EQ-5D values were not significantly different from the mean predicted EQ-5D values in internal validation samples but did significantly differ in external validation samples. The models underestimated EQ-5D values in milder health states and overestimated them in more severe health states. The predictive ability of the models was similar across different EQ-5D value sets. CONCLUSIONS The models can predict mean EQ-5D values that are similar to observed mean values in a similar population. The overestimating/underestimating of the low/high EQ-5D values, however, limits its use in Markov models. Therefore, mapping should be used cautiously.

Higher Adherence During Reimbursement of Pharmacological Smoking Cessation Treatments

INTRODUCTION In the Netherlands, pharmacologic Smoking Cessation Treatments (pSCTs) were reimbursed in 2011. In 2012 the reimbursement was discontinued. As of 2013, pSCTs were again reimbursed, provided they are accompanied by behavioral counseling. The aim of this article is to assess the impact of changes in reimbursement policy on use of-and adherence to-pSCTs. METHODS A retrospective dispensing database analysis was performed on real-world observational data (2010-2013) from the Netherlands. Data on use and adherence was collected, in patients who were dispensed bupropion or varenicline in community pharmacies for the first time. Using the InterActionDataBase (iadb.nl), adherence per patient that initiated varenicline or bupropion was calculated by adding up all dispenses between initiation of the therapy and the 120 days thereafter. Good adherence was defined as using minimal 80% of the recommended duration and intensity of use. RESULTS The prevalence of patients initiating pSCTs was stable at 0.4 per 1000 inhabitants per quarter during 2010. In 2011, the prevalence was on average 0.7, with peaks in the first (0.8 per 1000) and fourth (1.0 per 1000) quarters of 2011. In 2012, the prevalence was stable again at 0.3. In 2013, prevalence was on average 0.4, with a small peak in the first quarter. Adherence was 15.4% in 2010 versus 20.1% in 2011 (P = .002). In 2012, adherence was 13.9%, compared with 18.9% in 2013 (P = .008). CONCLUSIONS Not only the likelihood of initiating pSCTs, but also the extent of adherence to these treatments, although generally low, seems higher during reimbursement.