Orlewska, E.

Real-world health care costs of relapsed/refractory multiple myeloma during the era of novel cancer agents (Article)

2013-02-01T00:00:00Z

What is known and objective: High costs of novel agents increasingly put pressure on limited healthcare budgets. Demonstration of their real-world costs and cost-effectiveness is often required for reimbursement. However, few published economic evaluations of novel agents for multiple myeloma exist. Moreover, existing cost analyses were heavily based on conventionally treated patients. We investigated real-world health care costs of relapsed/refractory multiple myeloma in Dutch daily practice. Methods: A retrospective medical chart review was conducted for 139 patients treated between January 2001 and May 2009. Total monthly costs attributable to each cost component were described across all regimens and for bortezomib-, thalidomide- and lenalidomide-based treatment regimens. Results: Mean monthly total costs (€3,981) varied depending on the sequence of therapy (range: €442-€31,318). Significant cost drivers across all regimens included costs of therapy and hospital admissions. The acquisition costs for novel agents in particular accounted for 32% of mean total monthly costs. Prognostic factors associated with increased mean total monthly costs in multivariate regression analysis included low platelet counts (P = 0·01) and worsening performance status (P < 0·001). Mean total monthly costs of bortezomib- and lenalidomide-based regimens were significantly higher than those for thalidomide-based regimens in second, third and fourth treatment line. What is new and conclusions: Real-world costs during treatment of relapsed/refractory multiple myeloma vary greatly. Cost drivers include hospital admissions and acquisition costs of novel agents. Costs also vary by prognostic factors and treatment-related resource use. Future studies assessing the costs of combination therapy consisting of two or more novel agents are encouraged.

Long-term anticoagulant effects of CYP2C9 and VKORC1 genotypes in phenprocoumon users (Article)

2012-12-01T00:00:00Z

Anticoagulant treatment with phenprocoumon is challenging because of the narrow therapeutic range and the wide inter- and intra-patient variability in dose response. Frequent monitoring of the international normalized ratio (INR) is therefore required. Polymorphisms in two genes, CYP2C9 and VKORC1 explain approximately one third of the variation in dose requirements [1-3]. CYP2C9 encodes the main metabolizing enzyme of coumarins, the cytochrome P450 2C9 enzyme (CYP2C9), while VKORC1 encodes the pharmacodynamic target enzyme for coumarins, vitamin K epoxide reductase multiprotein complex 1 (VKORC1).

The effect of omeprazole and esomeprazole on the maintenance dose of phenprocoumon (Letter To Editor)

2012-12-01T00:00:00Z

The response to vitamin K antagonists (VKAs) is determined by many different factors like age, weight, height, vitamin K intake and genetic polymorphisms [1]. The proton pump inhibitors (PPIs) omeprazole and esomeprazole may enhance the effect of VKAs by inhibition of the hepatic metabolism of coumarins [2]. Some isolated cases have been reported of clinically significant elevated INRs in patients concomitantly using omeprazole and phenprocoumon, a VKA frequently used in Europe [3].Practical experience suggests an interaction between omeprazole or esomeprazole and phenprocoumon, but scientific evidence is still lacking.

Explaining length of stay variation of episodes of care in the Netherlands (Article)

2012-10-22T00:00:00Z

Objectives: Diagnosis Related Group (DRG) systems aim to classify patients into mutually exclusive groups of patients, with the patients in each group having the same expected length of stay (LOS). We examined the ability of current classification variables to explain LOS variation between DRG-like Diagnosis Treatment Combination (DBC)s for ten episodes of care in the Netherlands, including breast cancer, stroke and inguinal hernia repair. Additionally, we assessed the predictive ability of some other classification variables. Methods: For each episode of care, the relevant DBC codes of all hospitalizations in 2008 were identified and all available determinants that may serve as classification variables were acquired from the national database. Ordinary least squares regression was used to examine the predictive ability of these classification variables. Results: The current classification variables are not sufficiently distinct to classify patients into mutually exclusive groups of patients. ICU admissions and hospital type may serve as valuable classification variables. Additionally, episode-specific variables may improve the Dutch grouping algorithm. Conclusions: Although it may not be feasible in the short term, grouping algorithms would benefit greatly from the introduction of classification variables tailored to the needs of specific episodes of care. A first step would be to focus on 'general' classification variables meaningful for specific episodes of care.

Cost-effectiveness of pharmacogenetics in anticoagulation: International differences in healthcare systems and costs (Article)

2012-09-01T00:00:00Z

Genotyping patients for CYP2C9 and VKORC1 polymorphisms can improve the accuracy of dosing during the initiation of anticoagulation with vitamin K antagonists (coumarin derivatives). The anticipated degree of improvement in the safety of anticoagulation with coumarins through genotyping may vary depending on the quality of patient care, which varies both with and among countries. The management and the cost of anticoagulant care can therefore influence the cost-effectiveness of genotyping within any given country. In this article, we provide an overview of the cost-effectiveness of pharmacogenetics-guided dosing of coumarin derivatives. We describe the organization of anticoagulant care in the UK, Sweden, The Netherlands, Greece, Germany and Austria, where a genotype-guided dosing algorithm is currently being investigated as part of the EU-PACT trial. We also explore the costs of anticoagulant care for the treatment of atrial fibrillation in these countries.

Novel anticancer agents for multiple myeloma: A review of the evidence for their therapeutic and economic value (Article)

2012-06-01T00:00:00Z

Recent advances in oncology treatment have improved patient outcomes at the expense of increasing healthcare costs. The indication multiple myeloma is especially characterized by a recent and continuing flood of expensive novel agents. A review encompassing all elements necessary to perform an economic evaluation of novel agents for multiple myeloma was conducted for thalidomide, bortezomib and lenalidomide. Improvements in efficacy have led to a switch from conventional therapy to novel agents as standard therapy. Incremental cost-effectiveness ratios for novel agents alone or in combination with conventional agents were generally regarded to be within acceptable ranges. Conflicting results were reported for the incremental cost-effectiveness of bortezomib versus lenalidomide, as unresolved questions remain regarding their comparative effectiveness. Future economic evaluations will require an assessment of the cost-effectiveness of these agents in terms of sequence within the treatment paradigm and in combination with one another.

Long-term anticoagulant effects of the CYP2C9 and VKORC1 genotypes in acenocoumarol users (Article)

2012-04-01T00:00:00Z

Background: The required acenocoumarol dose and the risk of underanticoagulation and overanticoagulation are associated with the CYP2C9 and VKORC1 genotypes. However, the duration of the effects of these genes on anticoagulation is not yet known. Objectives: In the present study, the effects of these polymorphisms on the risk of underanticoagulation and overanticoagulation over time after the start of acenocoumarol were investigated. Patients/methods: In three cohorts, we analyzed the relationship between the CYP2C9 and VKORC1 genotypes and the incidence of subtherapeutic or supratherapeutic International Normalized Ratio (INR) values (<2 and >3.5) or severe overanticoagulation (INR>6) for different time periods after treatment initiation. Results: Patients with polymorphisms in CYP2C9 and VKORC1 had a higher risk of overanticoagulation (up to 74%) and a lower risk of underanticoagulation (down to 45%) in the first month of treatment with acenocoumarol, but this effect diminished after 1-6months. Conclusions: Knowledge of the patient's genotype therefore might assist physicians to adjust doses in the first month(s) of therapy.

Adjuvant chemotherapy in stage III colon cancer: Guideline implementation, patterns of use and outcomes in daily practice in the Netherlands (Article)

2012-01-01T00:00:00Z

Background. Little is known about how well guidelines about adjuvant chemotherapy in colon cancer are followed in daily practice. We evaluated the current guideline, which is based on the MOSAIC trial, by examining implementation, treatment patterns and disease-free survival. Material and methods. We analysed a population-based cohort of 391 patients treated with adjuvant chemotherapy for stage III colon cancer in 20052006. Data were gathered from the Dutch Cancer Registry and medical records of 19 hospitals. Patients were classified according to whether or not they fulfilled MOSAIC trial eligibility criteria. Results. The administered regimens were: fluorouracil-leucovorin (17 patients), capecitabine (93), fluorouracil- leucovorin plus oxaliplatin (145), and capecitabine plus oxaliplatin (136). After its inclusion in national guidelines, oxaliplatin was prescribed in 16 hospitals within six months. Patients receiving oxaliplatin were younger and had less comorbidity than other patients. Dose schedules corresponded well with guidelines. Two-year disease-free survival probability of oxaliplatin patients meeting MOSAIC eligibility criteria was 78.4% (95% CI 72.584.3), which was comparable to MOSAIC trial results. Conclusion. Guidelines for adjuvant chemotherapy in stage III colon cancer are generally well followed in daily practice. However, uncertainty remains regarding the optimal treatment of elderly patients and patients with comorbidities, which underscores the need for practical clinical trials including these patients.

A new test of the construct validity of the CarerQol instrument: Measuring the impact of informal care giving (Article)

2011-08-01T00:00:00Z

Purpose: Most economic evaluations of health care programmes do not consider the effects of informal care, while this could lead to suboptimal policy decisions. This study investigates the construct validity of the CarerQol instrument, which measures and values carer effects, in a new population of informal caregivers. Methods: A questionnaire was distributed by mail (n = 1,100, net response rate = 21%) to regional informal care support centers throughout the Netherlands. Two types of construct validity, i.e., convergent and clinical validity, have been analyzed. Convergent validity was assessed with Spearman's correlation coefficients and multivariate correlation between the burden dimensions (CarerQol-7D) and the valuation component (CarerQol-VAS) of the CarerQol. Additionally, convergent validity was analyzed with Spearman's correlation coefficients between the CarerQol and other measures of subjective caregiver burden (SRB, PU). Clinical validity was evaluated with multivariate correlation between CarerQol-VAS and CarerQol-7D, characteristics of caregivers, care recipients and care situation among the whole sample of caregivers and subgroups. Results: The positive (negative) dimensions of CarerQol-7D were positively (negatively) related to CarerQol-VAS, and almost all had moderate strength of convergent validity. CarerQol-VAS was positively associated with PU and negatively with SRB. The CarerQol-VAS reflects differences in important background characteristics of informal care: type of relationship, age of the care recipient and duration of care giving were associated with higher CarerQol-VAS scores. These results confirmed earlier tests of the construct validity of the CarerQol. Furthermore, the dimensions of CarerQol-7D significantly explained differences in CarerQol-VAS scores among subgroups of carers. Conclusion: Notwithstanding the limitations of our study, such as the low response rate, this study shows that the CarerQol provides a valid means to measure carer effects for use in economic evaluations. Future research should derive a valuation set for the CarerQol and further address the instrument's content validity, sensitivity and reliability.

Critical review of economic evaluations in multiple myeloma: An overview of the economic evidence and quality of the methodology (Article)

2011-07-01T00:00:00Z

Continued expansion in the availability of costly alternative therapies in multiple myeloma will enhance the role of economic evaluations in reimbursement decisions and amendments to the treatment guidelines. The quality of economic evaluations should be taken into account by clinicians involved in decision-making. A systematic review and critique of the methodology was performed to assess the trends and quality in economic evaluations in multiple myeloma to date. A literature search was conducted to identify full economic evaluations in multiple myeloma as of December 2009. Details of the economic evaluation methods applied were extracted. Each study underwent a quality assessment based on the Drummond checklist for appraisal of high-quality economic evaluations in health care. Eighteen published economic evaluations were identified. Stem cell transplantation in combination with intensive chemotherapy has been demonstrated to be cost-effective, while interferon alpha is generally ineffective at additional costs. Evaluations have become less frequent in the last decade, especially for newer therapies despite their important contribution to improvements in outcomes. The quality of the methodology applied and its documentation can be improved in many aspects. As users of the results of economic evaluations, clinicians involved in guiding decision-making should be critical of the quality of economic evaluations in multiple myeloma. To ensure access to and identification of high-quality studies, researchers conducting economic evaluations of future advances should strive towards evaluations that fulfil the Drummond criteria and are properly documented.

Cardiovascular disease prevention in rural Nigeria in the context of a community based health insurance scheme: QUality improvement cardiovascular care Kwara-I (QUICK-I) (Article)

2011-03-31T00:00:00Z

Background: Cardiovascular diseases (CVD) are a leading contributor to the burden of disease in low- and middle-income countries. Guidelines for CVD prevention care in low resource settings have been developed but little information is available on strategies to implement this care. A community health insurance program might be used to improve patients' access to care. The operational research project "QUality Improvement Cardiovascular care Kwara - I (QUICK-I)" aims to assess the feasibility of CVD prevention care in rural Nigeria, according to international guidelines, in the context of a community based health insurance scheme. Methods/Design. Design: prospective observational hospital based cohort study. Setting: a primary health care centre in rural Nigeria. Study population: 300 patients at risk for development of CVD (patients with hypertension, diabetes, renal disease or established CVD) who are enrolled in the Hygeia Community Health Plan. Measurements: demographic and socio- economic data, physical and laboratory examination, CVD risk profile including screening for target organ damage. Measurements will be done at 3 month intervals during 1 year. Direct and indirect costs of CVD prevention care will be estimated. Outcomes: 1) The adjusted cardiovascular quality of care indicator scores based on the "United Kingdom National Health Services Quality and Outcome Framework". 2) The average costs of CVD prevention and treatment per patient per year for patients, the clinic and the insurance company. 3) The estimated net health care costs of standard CVD prevention care per quality-adjusted life year gained. Analysis: The primary outcomes, the score on CVD quality indicators and cost data will be descriptive. The quality scores and cost data will be used to describe the feasibility of CVD prevention care according to international guidelines. A cost-effectiveness analysis will be done using a Markov model. Discussion. Results of QUICK-I can be used by policy makers and professionals who aim to implement CVD prevention programs in settings with limited resources. The context of the insurance program will provide insight in the opportunities community health insurance may offer to attain sustainable chronic disease management programs in low resource settings. Trial registration. This protocol has been registered at ISRCTN, ID number: ISRCTN47894401.

Application of cost-effectiveness ana lysis to demonstrate the potential value of companion diagnostics in chronic myeloid leukemia (Article)

2011-03-01T00:00:00Z

Aim: A cost-effectiveness analysis was performed to assess the potential value of companion diagnostics in supporting treatment decisions for dasatinib and nilotinib in chronic myeloid leukemia. Materials & methods: A decision model was developed, and model inputs were taken from the literature and publicly available sources. The perspective of the healthcare sector in the Netherlands was used. Sensitivity and scenario analyses were performed to assess uncertainty in the results. Results: Companion diagnostics could improve health and reduce costs, despite the estimates being uncertain owing to limited evidence for comparative effectiveness between dasatinib and nilotinib. The results were sensitive to the cost of treatment, utility of progression and progression-free survival. Conclusion: This case demonstrates the use of cost-â€"effectiveness analysis at an early stage of health technology assessment to generate economic evidence for the use of companion diagnostics in treatment decisions and to support decision-making for their development.

Comparison of Macroscopic Pathology Measurements with Magnetic Resonance Imaging and Assessment of Microscopic Pathology Extension for Colorectal Liver Metastases (Article)

2010-12-23T00:00:00Z

Purpose: To compare pathology macroscopic tumor dimensions with magnetic resonance imaging (MRI) measurements and to establish the microscopic tumor extension of colorectal liver metastases. Methods and Materials: In a prospective pilot study we included patients with colorectal liver metastases planned for surgery and eligible for MRI. A liver MRI was performed within 48 hours before surgery. Directly after surgery, an MRI of the specimen was acquired to measure the degree of tumor shrinkage. The specimen was fixed in formalin for 48 hours, and another MRI was performed to assess the specimen/tumor shrinkage. All MRI sequences were imported into our radiotherapy treatment planning system, where the tumor and the specimen were delineated. For the macroscopic pathology analyses, photographs of the sliced specimens were used to delineate and reconstruct the tumor and the specimen volumes. Microscopic pathology analyses were conducted to assess the infiltration depth of tumor cell nests. Results: Between February 2009 and January 2010 we included 13 patients for analysis with 21 colorectal liver metastases. Specimen and tumor shrinkage after resection and fixation was negligible. The best tumor volume correlations between MRI and pathology were found for T1-weighted (w) echo gradient sequence (rs= 0.99, slope = 1.06), and the T2-w fast spin echo (FSE) single-shot sequence (rs= 0.99, slope = 1.08), followed by the T2-w FSE fat saturation sequence (rs= 0.99, slope = 1.23), and the T1-w gadolinium-enhanced sequence (rs= 0.98, slope = 1.24). We observed 39 tumor cell nests beyond the tumor border in 12 metastases. Microscopic extension was found between 0.2 and 10 mm from the main tumor, with 90% of the cases within 6 mm. Conclusions: MRI tumor dimensions showed a good agreement with the macroscopic pathology suggesting that MRI can be used for accurate tumor delineation. However, microscopic extensions found beyond the tumor border indicate that caution is needed in selecting appropriate tumor margins.

Explaining Ethnic Differences in Late Antenatal Care Entry by Predisposing, Enabling and Need Factors in the Netherlands. The Generation R Study (Article)

2010-06-09T00:00:00Z

Despite compulsory health insurance in Europe, ethnic differences in access to health care exist. The objective of this study is to investigate how ethnic differences between Dutch and non-Dutch women with respect to late entry into antenatal care provided by community midwifes can be explained by need, predisposing and enabling factors. Data were obtained from the Generation R Study. The Generation R Study is a multi-ethnic population-based prospective cohort study conducted in the city of Rotterdam. In total, 2,093 pregnant women with a Dutch, Moroccan, Turkish, Cape Verdean, Antillean, Surinamese Creole and Surinamese Hindustani background were included in this study. We examined whether ethnic differences in late antenatal care entry could be explained by need, predisposing and enabling factors. Subsequently, logistic regression analysis was used to assess the independent role of explanatory variables in the timing of antenatal care entry. The main outcome measure was late entry into antenatal care (gestational age at first visit after 14 weeks). With the exception of Surinamese-Hindustani women, the percentage of mothers entering antenatal care late was higher in all non-Dutch compared to Dutch mothers. We could explain differences between Turkish (OR = 0.95, CI: 0.57-1.58), Cape Verdean (OR = 1.65. CI: 0.96-2.82) and Dutch women. Other differences diminished but remained significant (Moroccan: OR = 1,74, CI: 1.07-2.85; Dutch Antillean OR 1.80, CI: 1.04-3.13). We found that non-Dutch mothers were more likely to enter antenatal care later than Dutch mothers. Because we are unable to explain fully the differences regarding Moroccan, Surinamese-Creole and Antillean women, future research should focus on differences between 1st and 2nd generation migrants, as well as on language barriers that may hinder access to adequate information about the Dutch obstetric system.

Costs and effects of secondary prevention with perindopril in stable coronary heart disease in Poland: An analysis of the EUROPA study including 1251 Polish patients (Article)

2008-09-25T00:00:00Z

Objectives: To estimate the long-term impact of treatment with perindopril on costs and health effects in patients with stable coronary artery disease in Poland. Methods: The cost-effectiveness analysis was based on data from a randomized double-blind, placebo-controlled trial. A decision-tree analysis was employed, including Monte Carlo and bootstrapping techniques. This study was a sub-study of the EUROPA (European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease) trial (n = 12 218; mean follow-up 4.2 years). Resource use was based on data from Polish EUROPA study patients (n = 1251), while effectiveness was based on the whole EUROPA study. The health gain of perindopril in life-years was based on overall EUROPA study results, and the adapted Polish life expectancy of patients not dying during the trial. Costs were calculated in new Polish zloty (PLN), year 2003 values; €1 = PLN4.053. Only direct healthcare costs related to cardiovascular events and medication use were studied. Results: When observed mortality was combined with life expectancy beyond the end of the study, perindopril use showed a gain in life expectancy of 0.182 life-years (SD ± 0.129) at a cost of PLN1983 (SD ± 103) with discounting of 5% per annum on costs and no discounting on effects. This resulted in an incremental cost-effectiveness ratio (ICER) of PLN10 896 per life-year gained. The probability that the ICER for perindopril was below the threshold of PLN60 000 was 88%. The overall results were insensitive to discount rates for costs and life-years. Conclusions: Perindopril leads to a reduction in the risk of coronary events among patients with stable heart disease. When the expected improvement in life expectancy is combined with associated medical costs, there is a high probability that perindopril is cost effective, given the threshold of PLN60 000 per life-year gained.

Long-term outcomes of continuous intrathecal baclofen infusion for treatment of spasticity: A prospective multicenter follow-up study (Article)

2008-07-01T00:00:00Z

Long-term outcomes of 115 patients treated with continuous intrathecal baclofen infusion are reported. A prospective follow-up study was conducted in eight centers. Patients were followed up over a 12-month period. The follow-up scores on the three spasticity scales (Ashworth, spasm, and clonus scales) were significantly lower at every follow-up visit in comparison to the intake score, except for the clonus scale scores at 12 months. Improvements in health-related quality of life (EQ-5D) and functionality (SIP-68, functional independence measure) were small and nonsignificant. A significant reduction in severity of self-reported personal problems rating scale was observed. Sixty-six patients had no adverse events. Types of adverse events reported were wound complications (22%), catheter problems (36%), cerebrospinal fluid leakage (25%), and other complications (17%). Intrathecal baclofen reduces spasticity and severity of patient-reported problems but its effect on quality of life and functionality is less apparent. Improvements are desired in selection criteria, design of spinal catheters, and outcome scales.

Costs and prices of single dental fillings in Europe: A micro-costing study (Article)

2008-01-01T00:00:00Z

Dental fillings represent an established procedure to treat tooth decay. The present paper provides a cost comparison of dental filling procedures across nine European countries. More specifically, the paper aims to estimate the costs and prices (i.e. reimbursement fees) of a single dental filling procedure in an approximately 12-year-old child with a toothache in a lower molar who presents at a dental practice, as described in a case vignette. Both amalgam and composite fillings were examined. Total costs were determined by identifying resource use and unit costs for the following cost components: diagnostic procedures, labour, materials, drugs, and overheads. Altogether, 49 practices provided data for the cost calculations. Mean total costs per country varied considerably, ranging from €8 to €156. Labour costs were the most important cost driver in all practices, comprising 58% of total costs. Overhead costs were the second-most important cost component in the majority of countries. Actual cost differences across practices within countries were relatively small. Cost variations between countries were primarily due to differences in unit costs, especially for labour and overheads, and only to a lesser extent to differences in resource use. Finally, cost estimates for a single dental filling procedure based on reimbursement fees led to an underestimation of the total costs by approximately 50%. Copyright

Does the pulse pressure in people of European, African and South Asian descent differ? A systematic review and meta-analysis of UK data (Article)

2007-08-01T00:00:00Z

The aim of this study was to assess whether the pulse pressures (PPs) in people of African and South Asian descent differ from those of the European-origin White (henceforth, White) in the UK. A systematic literature review was carried out using MEDLINE 1966-2006 and EMBASE 1980-2006. The meta-analysis was performed using Cochrane review manager software (RevMan version 4.2; Oxford, UK). Thirteen studies were examined. Results for African descent men (n = 9 studies) and women (n = 7) indicated that African men and women had a higher mean PP than their White counterparts. Overall weighted mean difference (WMD) in PP was 1.68 (95% confidence interval: [0.38, 2.98 mm Hg]; P < 0.01) in men and 2.01 (-0.39, 3.63 mm Hg]; P < 0.001) in women. South Asian men (n = 7 studies) had a lower mean PP than White men (-1.94; [-3.56, -0.32 mm Hg]; P = 0.02), whereas no significant difference was found between South Asian and White women (n = 5 studies) (-0.40; [-3.22, 2.39 mm Hg]; P = 0.77). Separate data were available for Indians (n=5 studies), Bangladeshis (n = 4) and Pakistanis (n = 3). Bangladeshis had a lower PP than Whites (men, -5.61; [-6.87, -4.36 mm Hg]; P < 0.001) (women, -5.21; [-8.67, -1.75 mm Hg]; P = 0.003). Pakistani men had a lower PP than White men (-3.33 mm Hg; [-5.67, -1.00]; P < 0.001). The WMD was nonsignificantly lower in Indian men (-0.76 mm Hg), Indian women (-0.80 mm Hg) and Pakistani women (-2.06 mm Hg). The higher PP found among African descent people may contribute to their more frequent hypertension complications. However, the lower PP in South Asian populations, particularly in Bangladeshis and Pakistani men, indicates that PP is unlikely to contribute to their higher risk of cardiovascular disease in the UK.