Johan L Severens

Erasmus Universiteit Rotterdam, Rotterdam, South Holland, Netherlands

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Publications (290)1076.07 Total impact

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    ABSTRACT: Most studies on birth settings investigate the association between planned place of birth at the start of labor and birth outcomes and intervention rates. To optimize maternity care it also is important to pay attention to the entire process of pregnancy and childbirth. This study explores the association between the initial preferred place of birth and model of care, and the course of pregnancy and labor in low-risk nulliparous women in the Netherlands. As part of a Dutch prospective cohort study (2007-2011), we compared medical indications during pregnancy and birth outcomes of 576 women who initially preferred a home birth (n = 226), a midwife-led hospital birth (n = 168) or an obstetrician-led hospital birth (n = 182). Data were obtained by a questionnaire before 20 weeks of gestation and by medical records. Analyses were performed according to the initial preferred place of birth. Low-risk nulliparous women who preferred a home birth with midwife-led care were less likely to be diagnosed with a medical indication during pregnancy compared to women who preferred a birth with obstetrician-led care (OR 0.41 95% CI 0.25-0.66). Preferring a birth with midwife-led care - both at home and in hospital - was associated with lower odds of induced labor (OR 0.51 95% CI 0.28-0.95 respectively OR 0.42 95% CI 0.21-0.85) and epidural analgesia (OR 0.32 95% CI 0.18-0.56 respectively OR 0.34 95% CI 0.19-0.62) compared to preferring a birth with obstetrician-led care. In addition, women who preferred a home birth were less likely to experience augmentation of labor (OR 0.54 95% CI 0.32-0.93) and narcotic analgesia (OR 0.41 95% CI 0.21-0.79) compared to women who preferred a birth with obstetrician-led care. We observed no significant association between preferred place of birth and mode of birth. Nulliparous women who initially preferred a home birth were less likely to be diagnosed with a medical indication during pregnancy. Women who initially preferred a birth with midwife-led care - both at home and in hospital - experienced lower rates of interventions during labor. Although some differences can be attributed to the model of care, we suggest that characteristics and attitudes of women themselves also play an important role.
    BMC Pregnancy and Childbirth 12/2015; 15(1):455. DOI:10.1186/s12884-015-0455-x · 2.19 Impact Factor
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    ABSTRACT: The National Institute for Health and Care Excellence (NICE) invited the manufacturer of lenalidomide (Celgene) to submit evidence of the clinical and cost effectiveness of the drug for treating adults with myelodysplastic syndromes (MDS) associated with deletion 5q cytogenetic abnormality, as part of the Institute's single technology appraisal (STA) process. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was commissioned to act as the Evidence Review Group (ERG). This paper describes the company's submission, the ERG review, and the NICE's subsequent decisions. The ERG reviewed the evidence for clinical and cost effectiveness of the technology, as submitted by the manufacturer to the NICE. The ERG searched for relevant additional evidence and validated the manufacturer's decision analytic model to examine the robustness of the cost-effectiveness results. Clinical effectiveness was obtained from a three-arm, European, randomized, phase III trial among red blood cell (RBC) transfusion-dependent patients with low-/intermediate-1-risk del5q31 MDS. The primary endpoint was RBC independence for ≥26 weeks, and was reached by a higher proportion of patients in the lenalidomide 10 and 5 mg groups compared with placebo (56.1 and 42.6 vs 5.9 %, respectively; both p < 0.001). The option of dose adjustments after 16 weeks due to dose-limiting toxicities or lack of response made long-term effectiveness estimates unreliable, e.g. overall survival (OS). The de novo model of the manufacturer included a Markov state-transition cost-utility model implemented in Microsoft Excel. The base-case incremental cost-effectiveness ratio (ICER) of the manufacturer was £56,965. The ERG assessment indicated that the modeling structure represented the course of the disease; however, a few errors were identified and some of the input parameters were challenged. In response to the appraisal documentation, the company revised the economic model, which increased the ICER to £68,125 per quality-adjusted life-year. The NICE Appraisal Committee (AC) did not recommend lenalidomide as a cost-effective treatment. Subsequently, the manufacturer submitted a Patient Access Scheme (PAS) that provided lenalidomide free of charge for patients who remained on treatment after 26 cycles. This PAS improved the ICER to £25,300, although the AC considered the proportion of patients who received treatment beyond 26 cycles, and hence the ICER, to be uncertain. Nevertheless, the AC accepted a commitment from the manufacturer to publish, once available, data on the proportion of patients eligible for the PAS, and believed this provided reassurance that lenalidomide was a cost-effective treatment for low- or intermediate-1-risk MDS patients.
    PharmacoEconomics 08/2015; DOI:10.1007/s40273-015-0318-3 · 2.45 Impact Factor
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    ABSTRACT: Abstract: The aim of this study was to assess the cost-effectiveness, from a health care perspective, of adding rituximab to fludarabine and cyclophosphamide scheme (FCR versus FC) for treatment-naïve and refractory/relapsed Ukrainian patients with chronic lymphocytic leukemia. A decision-analytic Markov cohort model with three health states and 1-month cycle time was developed and run within a life time horizon. Data from two multinational, prospective, open-label Phase 3 studies were used to assess patients' survival. While utilities were generalized from UK data, local resource utilization and disease-associated treatment, hospitalization, and side effect costs were applied. The alternative scenario was performed to assess the impact of lower life expectancy of the general population in Ukraine on the incremental cost-effectiveness ratio (ICER) for treatment-naïve patients. One-way, two-way, and probabilistic sensitivity analyses were conducted to assess the robustness of the results. The ICER (in US dollars) of treating chronic lymphocytic leukemia patients with FCR versus FC is US$8,704 per quality-adjusted life year gained for treatment-naïve patients and US$11,056 for refractory/relapsed patients. When survival data were modified to the lower life expectancy of the general population in Ukraine, the ICER for treatment-naïve patients was higher than US$13,000. This value is higher than three times the current gross domestic product per capita in Ukraine. Sensitivity analyses have shown a high impact of rituximab costs and a moderate impact of differences in utilities on the ICER. Furthermore, probabilistic sensitivity analyses have shown that for refractory/relapsed patients the probability of FCR being cost-effective is higher than for treatment-naïve patients and is close to one if the threshold is higher than US$15,000. State coverage of rituximab treatment may be considered a cost-effective treatment for the Ukrainian population under conditions of economic stability, cost-effectiveness threshold growth, or rituximab price negotiations.
    Cancer Management and Research 08/2015; 7. DOI:10.2147/CMAR.S79258
  • Gerardus Wj Frederix · Johan L Severens · Anke M Hövels
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    ABSTRACT: Economic evaluations have become an essential part of reimbursement decisions in a wide range of countries. To ensure high quality, a variety of checklists with different purposes have been developed and implemented enabling assessment of these evaluations. Three of these checklists are most frequently used and are recommended by the Cochrane Handbook for Systematic Reviews for critical appraisal (Drummond, CHEC and Philips). Every checklist is developed with a different purpose having, for example, a focus on reporting or conducting and on modeling or trial-based evaluations. This review outlines the heterogeneity in choice and implementation of these quality checklists in an incorrect manner. This ultimately results in under- and even possibly overestimation of quality of included economic evaluations. More guidance in selecting correct checklists suiting the purpose of the quality check is therefore of utmost importance. Moreover, it appears that current checklists are lacking detailed disease-specific guidance resulting in models not correctly reflecting disease progression. Therefore, outcomes indicate that the problem of the wide variability of methodological choices is prevalent in some other disease areas too, regardless of the availability of quality checklists. More international collaboration should therefore be initiated in developing and publishing standardized and open source disease-specific reference models to overcome this problem.
    Expert Review of Pharmacoeconomics & Outcomes Research 08/2015; 15(4):675-85. DOI:10.1586/14737167.2015.1069185 · 1.67 Impact Factor
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    ABSTRACT: Patients with substantive bleeding usually require transfusion and/or (re-)operation. Red blood cell (RBC) transfusion is independently associated with a greater risk of infection, morbidity, increased hospital stay and mortality. ROTEM (ROTEM(®) Delta, TEM International GmbH, Munich, Germany; ), TEG (TEG(®) 5000 analyser, Haemonetics Corporation, Niles, IL, USA; ) and Sonoclot (Sonoclot(®) coagulation and platelet function analyser, Sienco Inc., Arvada, CO) are point-of-care viscoelastic (VE) devices that use thromboelastometry to test for haemostasis in whole blood. They have a number of proposed advantages over standard laboratory tests (SLTs): they provide a result much quicker, are able to identify what part of the clotting process is disrupted, and provide information on clot formation over time and fibrinolysis. This assessment aimed to assess the clinical effectiveness and cost-effectiveness of VE devices to assist with the diagnosis, management and monitoring of haemostasis disorders during and after cardiac surgery, trauma-induced coagulopathy and post-partum haemorrhage (PPH). Sixteen databases were searched to December 2013: MEDLINE (OvidSP), MEDLINE In-Process and Other Non-Indexed Citations and Daily Update (OvidSP), EMBASE (OvidSP), BIOSIS Previews (Web of Knowledge), Science Citation Index (SCI) (Web of Science), Conference Proceedings Citation Index (CPCI-S) (Web of Science), Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA) database, Latin American and Caribbean Health Sciences Literature (LILACS), International Network of Agencies for Health Technology Assessment (INAHTA), National Institute for Health Research (NIHR) HTA programme, Aggressive Research Intelligence Facility (ARIF), Medion, and the International Prospective Register of Systematic Reviews (PROSPERO). Randomised controlled trials (RCTs) were assessed for quality using the Cochrane Risk of Bias tool. Prediction studies were assessed using QUADAS-2. For RCTs, summary relative risks (RRs) were estimated using random-effects models. Continuous data were summarised narratively. For prediction studies, the odds ratio (OR) was selected as the primary effect estimate. The health-economic analysis considered the costs and quality-adjusted life-years of ROTEM, TEG and Sonoclot compared with SLTs in cardiac surgery and trauma patients. A decision tree was used to take into account short-term complications and longer-term side effects from transfusion. The model assumed a 1-year time horizon. Thirty-one studies (39 publications) were included in the clinical effectiveness review. Eleven RCTs (n = 1089) assessed VE devices in patients undergoing cardiac surgery; six assessed thromboelastography (TEG) and five assessed ROTEM. There was a significant reduction in RBC transfusion [RR 0.88, 95% confidence interval (CI) 0.80 to 0.96; six studies], platelet transfusion (RR 0.72, 95% CI 0.58 to 0.89; six studies) and fresh frozen plasma to transfusion (RR 0.47, 95% CI 0.35 to 0.65; five studies) in VE testing groups compared with control. There were no significant differences between groups in terms of other blood products transfused. Continuous data on blood product use supported these findings. Clinical outcomes did not differ significantly between groups. There were no apparent differences between ROTEM or TEG; none of the RCTs evaluated Sonoclot. There were no data on the clinical effectiveness of VE devices in trauma patients or women with PPH. VE testing was cost-saving and more effective than SLTs. For the cardiac surgery model, the cost-saving was £43 for ROTEM, £79 for TEG and £132 for Sonoclot. For the trauma population, the cost-savings owing to VE testing were more substantial, amounting to per-patient savings of £688 for ROTEM compared with SLTs, £721 for TEG, and £818 for Sonoclot. This finding was entirely dependent on material costs, which are slightly higher for ROTEM. VE testing remained cost-saving following various scenario analyses. VE testing is cost-saving and more effective than SLTs, in both patients undergoing cardiac surgery and trauma patients. However, there were no data on the clinical effectiveness of Sonoclot or of VE devices in trauma patients. This study is registered as PROSPERO CRD42013005623. The NIHR Health Technology Assessment programme.
    07/2015; 19(58):1-228. DOI:10.3310/hta19580
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    ABSTRACT: - There is increasing discussion in the Netherlands about the introduction of a threshold value for the costs per extra year of life when reimbursing costs of new drugs. - The Medicines Committee ('Commissie Geneesmiddelen'), a division of the Netherlands National Healthcare Institute ('Zorginstituut Nederland'), advises on reimbursement of costs of new drugs. - This advice is based upon the determination of therapeutic value of the drug and the results of economic evaluations.- Mathematical models that predict future costs and effectiveness are often used in economic evaluations; these models can vary greatly in transparency and quality due to author assumptions.- Standardisation of cost-effectiveness models is one solution to overcome the unwanted variation in quality.- Discussions about the introduction of a threshold value can only be meaningful if all involved are adequately informed, and by high quality in cost-effectiveness research and, particularly, economic evaluations.- Collaboration and discussion between medical specialists, patients or patient organisations, health economists and policy makers, both in development of methods and in standardisation, are essential to improve the quality of decision making.
    Nederlands tijdschrift voor geneeskunde 06/2015; 159:A7728.
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    Olena Mandrik · Saskia Knies · Johan L Severens
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    ABSTRACT: An economic value calculation was performed to estimate the lifetime net present value of in vitro fertilization (IVF) in Ukraine, Belarus, and Kazakhstan. Net lifetime tax revenues were used to represent governmental benefits accruing from a hypothetical cohort of an IVF population born in 2009 using the methodology of generational accounting. Governmental expenses related to this population included social benefits, education and health care, unemployment support, and pensions. Where available, country-specific data referencing official sources were applied. The average health care cost needed to achieve one additional birth from the governmental perspective varied from $2,599 in Ukraine to $5,509 in Belarus. The net present value from the population born using IVF was positive in all countries: for Ukraine ($9,839), Belarus ($21,702), and Kazakhstan ($2,295). The break-even costs of drugs and supplies per IVF procedure is expected to be $3,870, $8,530, and $1,780, respectively. Probabilistic sensitivity analyses based on 5,000 simulations show that the average net present value per person remains positive: $1,894±$7,619, $27,925±$12,407, and $17,229±$24,637 in Ukraine, Belarus, and Kazakhstan, respectively. Financing IVF may represent a good investment in terms of governmental financial returns, even in lower-income countries with state-financed health care systems such as Ukraine, Belarus, and Kazakhstan.
    ClinicoEconomics and Outcomes Research 06/2015; 7:347—356. DOI:10.2147/CEOR.S79513
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    ABSTRACT: The study aimed to determine the room for improvement of a perfect cerebrospinal fluid (CSF) biomarker and the societal incremental net monetary benefit of CSF in subjects with mild cognitive impairment (MCI) assuming a hypothetical disease-modifying Alzheimer's disease (AD) treatment. A decision model compared current practice to a perfect biomarker and to two strategies positioning CSF as add-on test when current practice concluded the presence or absence of AD. The simulated MCI population was aged on average 68.3% and 49% had AD. The room for improvement by the perfect CSF test was 0.39 quality adjusted life years, €33,622 ($43,372) savings, 2.0 potential beneficial treatment years, and 1.3-year delay in dementia conversion. The results indicated more potential benefit from a biomarker positioned to verify subjects who are not expected to have AD (i.e., to prevent undertreatment) rather than to verify subjects expected to have AD (prevent overtreatment). Sensitivity analyses explored different CSF positions. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 06/2015; 11(8). DOI:10.1016/j.jalz.2015.02.009 · 12.41 Impact Factor
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    ABSTRACT: Early diagnosis of acute myocardial infarction (AMI) can ensure quick and effective treatment but only 20% of adults with emergency admissions for chest pain have an AMI. High-sensitivity cardiac troponin (hs-cTn) assays may allow rapid rule-out of AMI and avoidance of unnecessary hospital admissions and anxiety. Objective To assess the clinical effectiveness and cost-effectiveness of hs-cTn assays for the early (within 4 hours of presentation) rule-out of AMI in adults with acute chest pain. Methods Sixteen databases, including MEDLINE and EMBASE, research registers and conference proceedings, were searched to October 2013. Study quality was assessed using QUADAS-2. The bivariate model was used to estimate summary sensitivity and specificity for meta-analyses involving four or more studies, otherwise random-effects logistic regression was used. The health-economic analysis considered the long-term costs and quality-adjusted life-years (QALYs) associated with different troponin (Tn) testing methods. The de novo model consisted of a decision tree and Markov model. A lifetime time horizon (60 years) was used. Results Eighteen studies were included in the clinical effectiveness review. The optimum strategy, based on the Roche assay, used a limit of blank (LoB) threshold in a presentation sample to rule out AMI [negative likelihood ratio (LR–) 0.10, 95% confidence interval (CI) 0.05 to 0.18]. Patients testing positive could then have a further test at 2 hours; a result above the 99th centile on either sample and a delta (Δ) of ≥ 20% has some potential for ruling in an AMI [positive likelihood ratio (LR+) 8.42, 95% CI 6.11 to 11.60], whereas a result below the 99th centile on both samples and a Δ of
    06/2015; 19(44):1-234. DOI:10.3310/hta19440
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    Ties Hoomans · Johan L Severens
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    ABSTRACT: Economic evaluations can inform decisions about the efficiency and allocation of resources to implementation strategies¿strategies explicitly designed to inform care providers and patients about the best available research evidence and to enhance its use in their practices. These strategies are increasingly popular in health care, especially in light of growing concerns about quality of care and limits on resources. But such concerns have hardly motivated health authorities and other decision-makers to spend on some form of economic evaluation in their assessments of implementation strategies. This editorial addresses the importance of economic evaluation in the context of implementation science¿particularly, how these analyses can be most efficiently incorporated into decision-making processes about implementation strategies.
    Implementation Science 12/2014; 9(1):168. DOI:10.1186/s13012-014-0168-y · 4.12 Impact Factor
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    ABSTRACT: Currently, no country-specific metastatic breast cancer (MBC) observational costing data are available for the Netherlands and Belgium. Our aim is to describe country-specific resource use and costs of human epidermal receptor 2 (HER-2)-positive MBC in the Netherlands and Belgium, making use of real-world data.The eligibility period for patient selection was from April 2004 to April 2010. Inclusion and retrospective data collection begins at the time of first diagnosis of HER-2-positive MBC during the eligibility period and ends 24 months post-index diagnosis of MBC or at patient death.We identified 88 eligible patients in the Netherlands and 44 patients in Belgium. The total costs of medical treatment and other resource use utilisation per patient was €48 301 in the Netherlands and €37 431 in Belgium. Majority of costs was related to the use of trastuzumab in both countries, which was 50% of the total costs in the Netherlands and 56% in Belgium respectively.Our study provides estimates of resource use and costs for HER-2-positive MBC in the Netherlands and Belgium. We noticed various differences in resource use patterns between both countries demonstrating caution is needed when transferring cost estimates between countries.
    European Journal of Cancer Care 12/2014; 24(3). DOI:10.1111/ecc.12266 · 1.56 Impact Factor
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    ABSTRACT: Patients with large abdominal aortic aneurysms (AAAs) are usually offered reparative treatment given the high mortality risk. There is uncertainty about how to treat juxtarenal AAAs (JRAAAs) or thoracoabdominal aortic aneurysms (TAAAs). Endovascular repair of an abdominal aortic aneurysm (EVAR) is often seen as safer and easier than open surgical repair (OSR). However, endovascular treatment of JRAAAs or TAAAs requires specially manufactured stent grafts, with openings to allow blood to reach branches of the aorta. Commissioners are receiving increasing requests for fenestrated EVAR (fEVAR) and branched EVAR (bEVAR), but it is unclear whether or not the extra cost of fEVAR or bEVAR is justified by advantages for patients. To assess the clinical effectiveness, safety and cost-effectiveness of fEVAR and bEVAR in comparison with conventional treatment (i.e. no surgery) or OSR for two populations: JRAAAs and TAAAs. Resources were searched from inception to October 2013, including MEDLINE (OvidSP), EMBASE (OvidSP) and the Cochrane Central Register of Controlled Trials (Wiley) and, additionally, for cost-effectiveness, NHS Economic Evaluation Database (NHS EED; Wiley) and EconLit (EBSCOhost). Conference abstracts were also searched. Studies were included based on an intervention of either fEVAR or bEVAR and a comparator of either OSR or no surgery. For clinical effectiveness, observational studies were excluded only if they were not comparative, i.e. explicitly selected on the basis of prognosis. For clinical effectiveness, searches retrieved 5253 records before deduplication. Owing to overlap between the databases, 1985 duplicate records were removed. Of the remaining 3268 records, based on titles and abstracts, 3244 records were excluded, leaving 24 publications to be ordered. All 24 studies were excluded as none of them satisfied the inclusion criteria. Sixteen studies were excluded on study design, six on intervention and two on comparator. Five out of 16 studies excluded on study design reported a comparison. However, all of the studies acknowledged that they had groups that were not comparable at baseline given that they had selectively assigned younger, fitter patients to OSR. Therefore, these studies were considered 'non-comparative'. For cost-effectiveness, searches identified 104 references before deduplication. Owing to overlap between the databases, 34 duplicate records were removed. Of the remaining 70 records, seven were included for the full assessment based on initial screening. After a full-text review, no studies were included. Because of the lack of clinical effectiveness evidence and difficulty in estimating costs given the rapidly changing and variable technology, a cost-effectiveness analysis (CEA) was not performed. Instead a detailed description of modelling methods was provided. Despite a thorough search, no studies could be found that met the inclusion criteria. All studies that compared either fEVAR or bEVAR with either OSR or no surgery explicitly selected patients based on prognosis, i.e. essentially the populations for each comparator were not the same. Despite not being able to conduct a CEA, we have provided detailed methods for the conduct if data becomes available. We recommend at least one clinical trial to provide an unbiased estimate of effect for fEVAR/bEVAR compared with OSR or no surgery. This trial should also collect data for a CEA. This study is registered as PROSPERO CRD42013006051. The National Institute for Health Research Health Technology Assessment programme.
    Health technology assessment (Winchester, England) 12/2014; 18(70):1-66. DOI:10.3310/hta18700 · 5.03 Impact Factor
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    Saskia Knies · Annelies Boonen · Johan L Severens
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    ABSTRACT: The question of how to value lost productivity in economic evaluations has been subject of debate in the past twenty years. According to the Washington panel, lost productivity influences health-related quality of life and should thus be considered a health effect instead of a cost to avoid double counting. Current empirical evidence on the inclusion of income loss when valuing health states is not decisive. We examined the relationship between three aspects of lost productivity (work-status, absenteeism and presenteeism) and patient or social valuation of health-related quality of life (HRQoL). Cross-sectional survey data were collected from a total of 830 respondents with a rheumatic disorder from four West-European countries. Health-related quality of life was expressed in either the European societal utility using EQ-5D-3L or the patient valuation using EQ-VAS. The impact of work-status (four categories), absenteeism (absent from paid work during the past three months), and presenteeism (QQ method) on EQ-5D utilities and VAS scores was examined in linear regression analyses taking into account demographic characteristics and disease severity (duration, pain and restriction). The relationship between work-status, absenteeism or presenteeism and HRQoL was stronger for patient valuation than societal valuation. Compared to work-status and presenteeism the relationship between absenteeism and HRQoL was even less explicit. However, results for all measures of lost productivity are only marginally significant and negligible compared to the influence of disease-related restrictions. This survey study in patients with a rheumatic disorder in four European countries, does not fully support the Washington panel's claim that lost productivity is a significantly related with HRQoL, and this is even more apparent for absenteeism than for work-status and presenteeism. For West-European countries, there is no reason, to include absenteeism in the QALY. Findings need to be confirmed in other disease areas.
    Cost Effectiveness and Resource Allocation 11/2014; 12(7):24. DOI:10.1186/1478-7547-12-24 · 0.87 Impact Factor
  • Value in Health 11/2014; 17(7):A490. DOI:10.1016/j.jval.2014.08.1444 · 3.28 Impact Factor
  • Value in Health 11/2014; 17(7):A550. DOI:10.1016/j.jval.2014.08.1791 · 3.28 Impact Factor
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    ABSTRACT: Background In the absence of a gold standard, a panel of experts can be invited to assign a reference diagnosis for use in research. Available literature offers limited guidance on assembling and working with an expert panel for this purpose. We aimed to develop a protocol for an expert panel consensus diagnosis and evaluated its applicability in a pilot project.Methods An adjusted Delphi method was used, which started with the assessment of clinical vignettes by 3 experts individually, followed by a consensus discussion meeting to solve diagnostic discrepancies. A panel facilitator ensured that all experts were able to express their views, and encouraged the use of argumentation to arrive at a specific diagnosis, until consensus was reached by all experts. Eleven vignettes of patients suspected of having a primary neurodegenerative disease were presented to the experts. Clinical information was provided stepwise and included medical history, neurological, physical and cognitive function, brain MRI scan, and follow-up assessments over 2 years. After the consensus discussion meeting, the procedure was evaluated by the experts.ResultsThe average degree of consensus for the reference diagnosis increased from 52% after individual assessment of the vignettes to 94% after the consensus discussion meeting. Average confidence in the diagnosis after individual assessment was 85%. This did not increase after the consensus discussion meeting. The process evaluation led to several recommendations for improvement of the protocol.ConclusionA protocol for attaining a reference diagnosis based on expert panel consensus was shown feasible in research practice.
    BMC Neurology 10/2014; 14(1):190. DOI:10.1186/PREACCEPT-1702688938102976 · 2.04 Impact Factor
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    ABSTRACT: Bowel cancer is the third most common cancer in the UK. Most bowel cancers are initially treated with surgery, but around 17% spread to the liver. When this happens, sometimes the liver tumour can be treated surgically, or chemotherapy may be used to shrink the tumour to make surgery possible. Kirsten rat sarcoma viral oncogene (KRAS) mutations make some tumours less responsive to treatment with biological therapies such as cetuximab. There are a variety of tests available to detect these mutations. These vary in the specific mutations that they detect, the amount of mutation they detect, the amount of tumour cells needed, the time to give a result, the error rate and cost.
    Health technology assessment (Winchester, England) 10/2014; 18(62):1-132. DOI:10.3310/hta18620 · 5.03 Impact Factor
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    ABSTRACT: Backgroud The 2012 European guidelines recommend statins for intermediate-risk individuals with elevated cholesterol levels. Improved discrimination of intermediate-risk individuals is needed to prevent both cardiovascular disease (CVD) and statin side-effects (e.g. myopathy) efficiently since only 3-15 in every 100 individuals actually experience a cardiovascular event in the next 10 years. We estimated the potential cost-effectiveness of a hypothetical test which helps to determine which individuals will benefit from statins. Methods and Results Prognosis of different age- and gender-specific cohorts with an intermediate risk was simulated with a Markov model to estimate the potential costs and quality-adjusted life-years for four strategies: treat all with statins, treat none with statins, treat according to the European guidelines, or use a test to select individuals for statin treatment. The test-first strategy dominated the other strategies if the hypothetical test was 100% accurate and cost no more than €237. This strategy and the treat-all strategy were equally effective but the test generated lower costs by reducing statin usage and side-effects. The treat-none strategy was the least effective strategy. Threshold analyses show that the test must be highly accurate (especially sensitive) and inexpensive to be the most cost-effective strategy, since myopathy has a negligible impact on cost-effectiveness and statin costs are low. Conclusion Use of a highly accurate prognostic test could reduce overall CVD risk, frequency of drug side-effects and lifetime costs. However, no additional test would add usefully to risk prediction over SCORE when it does not satisfy the costs and accuracy requirements.
    International Journal of Cardiology 09/2014; 176(3). DOI:10.1016/j.ijcard.2014.08.134 · 4.04 Impact Factor
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    ABSTRACT: Aim: The objective of this study was to explore the cost-effectiveness of D-dimer biomarker and the societal value (headroom) of a hypothetical perfect biomarker for risk assessment and subsequent treatment stratification of prophylactic treatment for peripheral arterial disease (PAD). Patients & methods: Decision analytic modeling. Results: Use of the D-dimer biomarker to prescribe oral anticoagulants in the high-risk subset of patients is a cost-effective healthcare intervention. The headroom (societal willingness to pay multiplied by incremental quality-adjusted life years) available for the hypothetical perfect biomarker amounted to €83,877. Conclusion: D-dimer-based PAD risk assessment and treatment tailoring is cost effective. Identification of high-risk PAD patients and prescription of oral anticoagulants could potentially save substantial costs and improve chances of survival for high-risk PAD patients. However, further research of risk stratifying biomarkers test accuracy is needed to support and strengthen the results of this modeling study.
    Biomarkers in Medicine 08/2014; 8(8-8):989-999. DOI:10.2217/bmm.14.45 · 2.65 Impact Factor

Publication Stats

5k Citations
1,076.07 Total Impact Points


  • 2010–2015
    • Erasmus Universiteit Rotterdam
      • • Institute of Health Policy & Management (iBMG)
      • • Institute for Medical Technology Assessment (iMTA)
      Rotterdam, South Holland, Netherlands
  • 2013
    • Utrecht University
      • Department of Pharmaceutical Sciences
      Utrecht, Utrecht, Netherlands
  • 2002–2013
    • Maastricht University
      • • CAPHRI School for Public Health and Primary Care
      • • Faculty of Health, Medicine and Life Sciences
      Maestricht, Limburg, Netherlands
  • 2005–2010
    • Maastricht Universitair Medisch Centrum
      • Central Diagnostic Laboratory
      Maestricht, Limburg, Netherlands
  • 2009
    • University of Leipzig
      Leipzig, Saxony, Germany
  • 2008
    • Maastro Clinic
      Maestricht, Limburg, Netherlands
  • 2007
    • University of Zurich
      Zürich, Zurich, Switzerland
  • 2000–2003
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
  • 1997–2000
    • Radboud University Nijmegen
      • Department of Gastroenterology and Hepatology
      Nymegen, Gelderland, Netherlands