Measuring quality of life in opioid-induced constipation:mapping EQ-5D-3 L and PAC-QOL

BACKGROUND: In health economic evaluations, quality of life should be measured with preference-based utilities, such as the EuroQol 5 Dimension 3-level (EQ-5D-3 L). Non-preference-based instruments (often disease-specific questionnaires) are commonly mapped to utilities. We investigated if the relationship observed between the Patient Assessment of Constipation Quality of Life (PAC-QOL) and the EQ-5D-3 L in patients with chronic idiopathic constipation (CIC) also applies in opioid-induced constipation (OIC). METHODS: EQ-5D-3 L patient-level data from a clinical study of lubiprostone in OIC (n = 439) were scored using the UK tariff. A published mapping between the PAC-QOL and the EQ-5D-3 L was tested using these data. New mapping formulas were analysed, including PAC-QOL total and subscale scores. The root mean square error (RMSE), the adjusted R(2) and predicted/observed plots were used to test the fit. RESULTS: The utility measured with the EQ-5D-3 L was 0.450 ± 0.329, with a distinctly bimodal distribution. This significantly improved if patients responded to treatment (defined as an increase of three spontaneous bowel movements per week, with no rescue medication taken). The published mapping in CIC performed poorly in this OIC population, and the PAC-QOL could not be reliably mapped on to the EQ-5D-3 L even when re-estimating coefficients. This was shown in our two mappings (using PAC-QOL total score, and subscale scores) by a high RMSE (0.317 and 0.314) and a low R(2) (0.068 and 0.080), with high utilities underestimated and low utilities overestimated. CONCLUSIONS: Patients with OIC have a low quality of life which does improve with the resolution of symptoms. However the PAC-QOL cannot be used to estimate the EQ-5D-3 L utility - potentially as the PAC-QOL does not capture the all relevant aspects of the patients quality of life (for example the cause of the opioid use)

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

Using a genetic, observational study as a strategy to estimate the potential cost-effectiveness of pharmacological CCR5 blockade in dialysis patients

Background and objective Randomized clinical trials are expensive and time consuming. Therefore, strategies are needed to prioritise tracks for drug development. Genetic association studies may provide such a strategy by considering the differences between genotypes as a proxy for a natural, lifelong, randomized at conception, clinical trial. Previously an association with better survival was found in dialysis patients with systemic inflammation carrying a deletion variant of the CC-chemokine receptor 5 (CCR5). We hypothesized that in an analogous manner, pharmacological CCR5 blockade could protect against inflammation-driven mortality and estimated if such a treatment would be cost-effective. Methods A genetic screen and treat strategy was modelled using a decision-analytic Markov model, in which patients were screened for the CCR5 deletion 32 polymorphism and those with the wild type and systemic inflammation were treated with pharmacological CCR5 blockers. Kidney transplantation and mortality rates were calculated using patient level data. Extensive sensitivity analyses were performed. Results The cost-effectiveness of the genetic screen and treat strategy was (sic)18 557 per life year gained and (sic)21 896 per quality-adjusted life years gained. Concordance between the genetic association and pharmacological effectiveness was a main driver of cost-effectiveness. Sensitivity analyses showed that even a modest effectiveness of pharmacological CCR5 blockade would result in a treatment strategy that is good value for money. Conclusion Pharmacological blockade of the CCR5 receptor in inflamed dialysis patients can be incorporated in a potentially cost-effective screen and treat programme. These findings provide formal rationale for clinical studies. This study illustrates the potential of genetic association studies for drug development, as a source of Mendelian randomized evidence from an observational setting. Pharmacogenetics and Genomics 21: 417-425 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

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

The value of personalized approaches to improve pharmacotherapy in renal disease

Nierziekten verlagen de levensverwachting en kwaliteit van leven en zijn erg duur. Om de farmacotherapie te verbeteren worden personalized approaches, behandelingen toegespitst op de individuele patiënt, steeds belangrijker. Het werk in dit proefschrift bevat een checklist voor doelmatigheids-onderzoek van genetische strategieën; tevens werden twee genetische strategieën voor nierpatiënten onderzocht. Uit het eerste onderzoek bleek dat het ACE-(I/D)-polymorfisme de (kosten-)effectiviteit van ACE remmers bij niet-diabetische nierziekte beïnvloedt. Het tweede onderzoek richtte zich op een polymorfisme voor de CCR5 receptor; een genetisch defect van deze receptor is geassocieerd met een verbeterde overleving bij dialyse patiënten. Een model beschreven in dit proefschrift suggereert dat farmacologische blokkade van de receptor óók klinische en economische voordelen kan bieden. Dit proefschrift beschrijft ook niet-genetische strategieën om de farmacotherapie te verbeteren. Ten eerste, juiste keuzen in voorschrijven kan economische voordelen bieden, zoals blijkt uit onderzoek naar het voorschrijven van specifieke fosfaatbinders (lanthaancarbonaat) als tweedelijns therapie. Dit proefschrift onderschrijft voorschrijven van goedkope RAAS interveniërende geneesmiddelen, aangezien er geen verschil in therapietrouw werd gevonden tussen dure en goedkope middelen. Ten tweede, farmacotherapie kan verbeterd worden door nauwkeurig te letten op bijwerkingen, zoals in dit proefschrift onderzocht werd voor de bijwerking prikkelhoest bij ACE remmers. Ten derde, farmacotherapie bij nierziekten kan verbeterd worden door een hoge zoutinname te vermijden. De effectiviteit van ACE remmers bleek namelijk groter bij minder zoutinname. Er kan geconcludeerd worden dat personalized approaches veel potentie bieden bij nierziekten. Ze kunnen niet alleen de zorg voor individuele patiënten verbeteren maar ook grote economische voordelen bieden voor de samenleving als geheel