Johan L Severens

Erasmus Universiteit Rotterdam, Rotterdam, South Holland, Netherlands

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Publications (256)879.67 Total impact

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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. · 2.56 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. · 4.03 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; · 6.18 Impact Factor
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    ABSTRACT: Objective To use contingent valuation (CV) to derive individual consumer values for both health and broader benefits of a public-health intervention directed at lifestyle behaviour change (LBC) and to examine the feasibility and validity of the method.Method Participants of a lifestyle intervention trial (n = 515) were invited to complete an online CV survey. Respondents (n = 312) expressed willingness to invest money and time for changes in life expectancy, health-related quality of life (HRQOL) and broader quality of life aspects. Internal validity was tested for by exploring associations between explanatory variables (i.e. income, paid work, experience and risk factors for cardiovascular diseases) and willingness to invest, and by examining ordering effects and respondents' sensitivity to the scope of the benefits.ResultsThe majority of respondents (94.3%) attached value to benefits of LBC, and 87.4% were willing to invest both money and time. Respondents were willing to invest more for improvements in HRQOL (€42/month; 3 h/week) and broader quality of life aspects (€40/month; 2.6 h/week) than for improvements in life expectancy (€24/month; 2 h/week). Protest answers were limited (3%) and findings regarding internal validity were mixed.Conclusion The importance of broader quality of life outcomes to consumers suggests that these outcomes are relevant to be considered in the decision making. Our research showed that CV is a feasible method to value both health and broader outcomes of LBC, but generalizability to other areas of public health still needs to be examined. Mixed evidence regarding internal validity pleads for caution to use CV as only the base for decision making.
    Health expectations: an international journal of public participation in health care and health policy 08/2014; · 1.80 Impact Factor
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    ABSTRACT: Management of rheumatoid arthritis (RA) is characterised by a sequence of disease-modifying antirheumatic drugs (DMARDs) and biological response modifiers (BRMs). In most of the Western countries, the drug sequences are determined based on disease activity and treatment history of the patients. A model for realistic patient outcomes should reflect the treatment pathways relevant for patients with specific characteristics.
    PharmacoEconomics 06/2014; · 2.86 Impact Factor
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    ABSTRACT: General recommendations for a reference case for economic studies in rheumatic diseases were published in 2002 in an initiative to improve the comparability of cost-effectiveness studies in the field. Since then, economic evaluations in osteoarthritis (OA) continue to show considerable heterogeneity in methodological approach.
    Seminars in arthritis and rheumatism. 06/2014;
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    ABSTRACT: Delayed diagnosis and treatment of Acute Myocardial Infarction (AMI) has a major adverse impact on prognosis in terms of both morbidity and mortality. Since conventional cardiac Troponin assays have a low sensitivity for diagnosing AMI in the first hours after myocardial necrosis, high-sensitive assays have been developed. The aim of this study was to assess the cost effectiveness of a high-sensitive Troponin T assay (hsTnT), alone or combined with the heart-type fatty acid-binding protein (H-FABP) assay in comparison with the conventional cardiac Troponin (cTnT) assay for the diagnosis of AMI in patients presenting to the hospital with chest pain.
    BMC Cardiovascular Disorders 06/2014; 14(1):77. · 1.46 Impact Factor
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    ABSTRACT: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Some epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutations make tumours responsive to treatment with EGFR-TK inhibitors (EGFR-TKIs) but less responsive to treatment with standard chemotherapy. Patients with NSCLC are therefore tested for EGFR-TK tumour gene mutations to inform treatment decisions. There are a variety of tests available to detect these mutations. The different tests vary in the specific mutations that they attempt to detect, the amount of tumour cells needed for the test to work, the time that it takes to give a result, the error rate of the test, and the cost of the test. To compare the performance and cost-effectiveness of EGFR-TK mutation tests used to identify previously untreated adults with locally advanced or metastatic NSCLC, who may benefit from first-line treatment with TKIs. Twelve databases to August 2012 [including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations and Daily Update (OvidSP), EMBASE, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment database (HTA), Science Citation Index (SCI), Latin American and Caribbean Health Sciences Literature (LILACS), BIOSIS Previews, NIHR Health Technology Assessment programme, PROSPERO (International Prospective Register of Systematic Reviews)], research registers and conference proceedings. A web-based survey gathered data on technical performance of EGFR-TK mutation tests. Randomised controlled trials were assessed for methodological quality using the Cochrane risk of bias tool. Diagnostic accuracy studies were assessed using QUADAS-2. There were insufficient data for meta-analysis. For accuracy studies, we calculated sensitivity and specificity together with 95% confidence intervals (CIs). Survival data were summarised as hazard ratios and tumour response data as relative risks, with 95% CIs. The health-economic analysis considered the long-term costs and quality-adjusted life-years (QALYs) associated with different tests followed by treatment with either standard chemotherapy or a TKI. Direct sequencing was taken as the comparator. The de novo model consisted of a decision tree and a Markov model. The survey indicated no differences between tests in batch size, turnaround time, number of failed samples or cost. Six studies provided data on the accuracy of EGFR-TK mutation testing for predicting response to treatment with TKIs. Estimates of accuracy were similar across studies. Six analyses provided data on the clinical effectiveness of TKIs compared with standard chemotherapy. There were no clear differences in the treatment effects reported by different studies, regardless of which EGFR mutation test was used to select patients. Cost-effectiveness analysis using 'Evidence on comparative effectiveness available' and 'Linked evidence' approaches: Therascreen(®) EGFR polymerase chain reaction (PCR) Kit (Qiagen, Venlo, the Netherlands) was both less effective and less costly than direct sequencing of all exon 19-21 mutations at an incremental cost-effectiveness ratio of £32,167 (comparative) and £32,190 (linked) per QALY lost. 'Assumption of equal prognostic value' approach: the lowest total strategy cost was [commercial-in-confidence (CiC) information has been removed] [Sanger sequencing or Roche cobas EGFR Mutation Testing Kit(®) (Roche Molecular Systems, Inc., Branchburg, NJ, USA)] compared with (CiC information has been removed) for the most expensive strategy (fragment length analysis combined with pyrosequencing). The cost-effectiveness analysis assumed that the differences in outcomes between the results of the trials were solely attributable to the different mutation tests used to distinguish between patients; this assumption ignores other factors that might explain this variation. There was no strong evidence that any one EGFR mutation test had greater accuracy than any other test. Re-testing of stored samples from previous studies, where patient outcomes are already known, could be used to provide information on the relative effectiveness of TKIs and standard chemotherapy in patients with EGFR mutation-positive and mutation-negative tumours, where mutation status is determined using tests for which adequate data are currently unavailable. PROSPERO CRD42012002828. The National Institute for Health Research Health Technology Assessment programme.
    Health technology assessment (Winchester, England). 05/2014; 18(32):1-166.
  • Laura T Burgers, William K Redekop, Johan L Severens
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    ABSTRACT: Decision analytic modelling is essential in performing cost-effectiveness analyses (CEAs) of interventions in cardiovascular disease (CVD). However, modelling inherently poses challenges that need to be dealt with since models always represent a simplification of reality. The aim of this study was to identify and explore the challenges in modelling CVD interventions. A document analysis was performed of 40 model-based CEAs of CVD interventions published in high-impact journals. We analysed the systematically selected papers to identify challenges per type of intervention (test, non-drug, drug, disease management programme, and public health intervention), and a questionnaire was sent to the corresponding authors to obtain a more thorough overview. Ideas for possible solutions for the challenges were based on the papers, responses, modelling guidelines, and other sources. The systematic literature search identified 1,720 potentially relevant articles. Forty authors were identified after screening the most recent 294 papers. Besides the challenge of lack of data, the challenges encountered in the review suggest that it was difficult to obtain a sufficiently valid and accurate cost-effectiveness estimate, mainly due to lack of data or extrapolating from intermediate outcomes. Despite the low response rate of the questionnaire, it confirmed our results. This combination of a review and a survey showed examples of CVD modelling challenges found in studies published in high-impact journals. Modelling guidelines do not provide sufficient guidance in resolving all challenges. Some of the reported challenges are specific to the type of intervention and disease, while some are independent of intervention and disease.
    PharmacoEconomics 04/2014; · 2.86 Impact Factor
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    ABSTRACT: In the current study, we propose an approach for selection of a model that is transferable to a specific decision-making context (in this case, the Netherlands), using the case of rheumatoid arthritis (RA). The objectives of this study were (a) to perform a systematic literature review to identify existing health economic evaluation models for economic evaluation of disease-modifying antirheumatic drugs (DMARDs) in RA; and (b) to test the appropriateness of a stepwise model-selection process. First, we searched Medline and Embase to identify relevant studies in the English language, published between 1 January 2002 and 31 August 2012. From the included studies, all unique models were identified. Second, we applied a multi-step approach to model selection. Models that did not meet all minimal methodological and structural requirements based on the Outcome Measures in Rheumatology (OMERACT) criteria were excluded. Next, models were assessed on the basis of their fit when transferred to the Dutch health care setting. The criteria for model fit were transferability factors, as published by Welte et al., after exclusion of those that were deemed transferable by simple adaptation. Finally, the remaining models underwent a general quality check using the Philips checklist. Models showing good fit and high quality were considered to be transferable to the Dutch health care setting, using simple adaptation. The systematic literature search identified 498 articles, which included 33 unique health economic evaluation models. Only six models passed the minimal methodological and structural requirements. Two of these models had an imperfect transferability fit to the Dutch health care setting, according to the Welte method. The remaining four models were, according to the Philips method, of good quality and were expected to be transferable by a simple adaptation. This study introduces a stepwise approach for selecting health economic evaluation models that are transferable by a simple adaptation. The approach seems feasible and can be applied in various therapeutic areas, provided that the minimal methodological and structural requirements are defined accordingly. Availability of health economic evaluation models coupled with structured model selection could improve the efficiency, quality and comparability of health economic research.
    PharmacoEconomics 02/2014; · 2.86 Impact Factor
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    ABSTRACT: Asymptomatic Peripheral Arterial Disease (PAD) is associated with greater risk of acute cardiovascular events. This study aims to determine the cost-effectiveness of one time only PAD screening using Ankle Brachial Index (ABI) test and subsequent anti platelet preventive treatment (low dose aspirin or clopidogrel) in individuals at high risk for acute cardiovascular events compared to no screening and no treatment using decision analytic modelling. A probabilistic Markov model was developed to evaluate the life time cost-effectiveness of the strategy of selective PAD screening and consequent preventive treatment compared to no screening and no preventive treatment. The analysis was conducted from the Dutch societal perspective and to address decision uncertainty, probabilistic sensitivity analysis was performed. Results were based on average values of 1000 Monte Carlo simulations and using discount rates of 1.5 % and 4 % for effects and costs respectively. One way sensitivity analyses were performed to identify the two most influential model parameters affecting model outputs. Then, a two way sensitivity analysis was conducted for combinations of values tested for these two most influential parameters. For the PAD screening strategy, life years and quality adjusted life years gained were 21.79 and 15.66 respectively at a lifetime cost of 26,548 Euros. Compared to no screening and treatment (20.69 life years, 15.58 Quality Adjusted Life Years, 28,052 Euros), these results indicate that PAD screening and treatment is a dominant strategy. The cost effectiveness acceptability curves show 88 % probability of PAD screening being cost effective at the Willingness To Pay (WTP) threshold of 40000 Euros. In a scenario analysis using clopidogrel as an alternative anti-platelet drug, PAD screening strategy remained dominant. This decision analysis suggests that targeted ABI screening and consequent secondary prevention of cardiovascular events using low dose aspirin or clopidogrel in the identified patients is a cost-effective strategy. Implementation of targeted PAD screening and subsequent treatment in primary care practices and in public health programs is likely to improve the societal health and to save health care costs by reducing catastrophic cardiovascular events.
    BMC Public Health 01/2014; 14(1):89. · 2.08 Impact Factor
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    ABSTRACT: Background. The introduction of innovative non-invasive screening tests (e.g. tests based on stool and blood samples or both) may be a solution to increase colorectal cancer (CRC) screening uptake. However, preferences for these non-invasive screening tests have not been investigated in great detail yet. The purpose of this article therefore is to elicit individuals' preferences for different non-invasive screening tests in a Dutch screening campaign context. Material and methods. We investigate preferences by means of a labeled discrete choice experiment. Data of 815 individuals, aged 55-75 years, are used in the analysis. Results. Multinomial logit model analysis showed that the combi-test is generally preferred over the blood-test and the (currently available) stool-test. Furthermore, besides the large effect of screening test type, there are significant differences in preference depending on participants' socio-demographic background. Finally, the analysis showed a significant positive effect on screening test choice for the attributes sensitivity, risk reduction, and level of evidence and a non-significant effect for the attribute unnecessary follow-up test. Conclusion. Introducing new non-invasive screening tests that are based on a combination of stool and blood samples (or blood sample only) has the potential to increase CRC screening participation compared to the current standard stool-based test.
    Acta oncologica (Stockholm, Sweden) 01/2014; · 2.27 Impact Factor
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    ABSTRACT: Objectives Many national colorectal cancer screening campaigns have a similar structure. First, individuals are invited to take a noninvasive screening test, and, second, in the case of a positive screening test result, they are advised to undergo a more invasive follow-up test. The objective of this study was to investigate how much individuals’ participation decision in noninvasive screening is affected by the presence or absence of detailed information about invasive follow-up testing and how this effect varies over screening tests. Methods We used a labeled discrete choice experiment of three noninvasive colorectal cancer screening types with two versions that did or did not present respondents with detailed information about the possible invasive follow-up test (i.e., colonoscopy) and its procedure. We used data from 631 Dutch respondents aged 55 to 75 years. Each respondent received only one of the two versions (N = 310 for the invasive follow-up test information specification version, and N = 321 for the no-information specification version). Results Mixed logit model results show that detailed information about the invasive follow-up test negatively affects screening participation decisions. This effect can be explained mainly by a decrease in choice shares for the most preferred screening test (a combined stool and blood sample test). Choice share simulations based on the discrete choice experiment indicated that presenting invasive follow-up test information decreases screening participation by 4.79%. Conclusions Detailed information about the invasive follow-up test has a negative effect on individuals’ screening participation decisions in noninvasive colorectal cancer screening campaigns. This result poses new challenges for policymakers who aim not only to increase uptake but also to provide full disclosure to potential screening participants.
    Value in Health 01/2014; · 2.19 Impact Factor
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    ABSTRACT: To investigate the long-term health and economic consequences of direct treatment initiation in ocular hypertension patients. A cost-effectiveness analysis with a societal perspective and a lifelong horizon was performed. The primary outcomes were the incremental quality-adjusted life years (QALYs) and costs of direct pressure-lowering treatment for ocular hypertension, compared to a strategy where treatment is postponed until conversion to glaucoma has been observed. We used a decision analytic model based on individual patient simulation to forecast disease progression and treatment decisions in both strategies in a representative heterogeneous patient population and in 18 patient subgroups stratified by initial intraocular pressure and additional risk factors for conversion. The incremental discounted health gain of direct treatment was 0.27 QALYs, whereas the incremental discounted costs were -€ 649 during an average lifetime of 26 years. In the simulations of patient subgroups, the model outcomes moved towards higher health gains and lower incremental costs with increasing risk of conversion in the patient population. The incremental cost-effectiveness ratio of direct treatment ranged from € 15,425 per QALY gained in the lowest-risk subgroup to dominance in the highest-risk subgroup. Probabilistic sensitivity analysis indicated that uncertainty surrounding the model input parameters did not affect the conclusions. Direct, early, pressure-lowering treatment is a dominant cost-effective treatment strategy over a strategy to start the same treatment approach later, after glaucoma has occurred for patients with ocular hypertension. Its implementation and consequences should be discussed with ophthalmologists and individual patients.
    Acta ophthalmologica 12/2013; · 2.44 Impact Factor
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    ABSTRACT: Structural uncertainty relates to differences in model structure and parameterization. For many published health economic analyses in oncology, substantial differences in model structure exist, leading to differences in analysis outcomes and potentially impacting decision-making processes. The objectives of this analysis were (1) to identify differences in model structure and parameterization for cost-effectiveness analyses (CEAs) comparing tamoxifen and anastrazole for adjuvant breast cancer (ABC) treatment; and (2) to quantify the impact of these differences on analysis outcome metrics. The analysis consisted of four steps: (1) review of the literature for identification of eligible CEAs; (2) definition and implementation of a base model structure, which included the core structural components for all identified CEAs; (3) definition and implementation of changes or additions in the base model structure or parameterization; and (4) quantification of the impact of changes in model structure or parameterizations on the analysis outcome metrics life-years gained (LYG), incremental costs (IC) and the incremental cost-effectiveness ratio (ICER). Eleven CEA analyses comparing anastrazole and tamoxifen as ABC treatment were identified. The base model consisted of the following health states: (1) on treatment; (2) off treatment; (3) local recurrence; (4) metastatic disease; (5) death due to breast cancer; and (6) death due to other causes. The base model estimates of anastrazole versus tamoxifen for the LYG, IC and ICER were 0.263 years, 3,647 and 13,868/LYG, respectively. In the published models that were evaluated, differences in model structure included the addition of different recurrence health states, and associated transition rates were identified. Differences in parameterization were related to the incidences of recurrence, local recurrence to metastatic disease, and metastatic disease to death. The separate impact of these model components on the LYG ranged from 0.207 to 0.356 years, while incremental costs ranged from 3,490 to 3,714 and ICERs ranged from 9,804/LYG to 17,966/LYG. When we re-analyzed the published CEAs in our framework by including their respective model properties, the LYG ranged from 0.207 to 0.383 years, IC ranged from 3,556 to 3,731 and ICERs ranged from 9,683/LYG to 17,570/LYG. Differences in model structure and parameterization lead to substantial differences in analysis outcome metrics. This analysis supports the need for more guidance regarding structural uncertainty and the use of standardized disease-specific models for health economic analyses of adjuvant endocrine breast cancer therapies. The developed approach in the current analysis could potentially serve as a template for further evaluations of structural uncertainty and development of disease-specific models.
    PharmacoEconomics 11/2013; · 2.86 Impact Factor
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    ABSTRACT: Lower extremity artery disease (LEAD) is a sign of wide spread atherosclerosis also affecting coronary, cerebral and renal arteries and is associated with increased risk of cardiovascular events. Many economic evaluations have been published for LEAD due to its clinical, social and economic importance. The aim of this systematic review was to assess modelling methods used in published economic evaluations in the field of LEAD. Our review appraised and compared the general characteristics, model structure and methodological quality of published models. Electronic databases MEDLINE and EMBASE were searched until February 2013 via OVID interface. Cochrane database of systematic reviews, Health Technology Assessment database hosted by National Institute for Health research and National Health Services Economic Evaluation Database (NHSEED) were also searched. The methodological quality of the included studies was assessed by using the Philips' checklist. Sixteen model-based economic evaluations were identified and included. Eleven models compared therapeutic health technologies; three models compared diagnostic tests and two models compared a combination of diagnostic and therapeutic options for LEAD. Results of this systematic review revealed an acceptable to low methodological quality of the included studies. Methodological diversity and insufficient information posed a challenge for valid comparison of the included studies. In conclusion, there is a need for transparent, methodologically comparable and scientifically credible model-based economic evaluations in the field of LEAD. Future modelling studies should include clinically and economically important cardiovascular outcomes to reflect the wider impact of LEAD on individual patients and on the society.
    Thrombosis and Haemostasis 10/2013; 111(1). · 5.76 Impact Factor
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    ABSTRACT: Many children stand to benefit from being asthma-free for life with primary (i.e., prenatally started) prevention addressing one environmental exposure in a unifaceted (UF) approach or at least two in a multifaceted (MF) approach. We assessed the cost-effectiveness of primary prevention programmes for Dutch children in a decision-analytic framework. A decision-analytic tree model analysing healthcare costs and asthma cases prevented was developed to compare usual care (UC) with two UF and three MF programmes on the primary prevention of asthma amongst children. Programmes were evaluated through incremental cost-effectiveness ratios and net monetary benefits. Decision and parameter uncertainty were subjected to value-of-information analyses. The current UC and one of three MF programmes dominated the other alternatives. The MF programme was more costly but also more effective than UC at an incremental cost-effectiveness ratio of 8,209.20/additional asthma case prevented. The value of perfect information to reduce uncertainty was 291.6M at its lowest. Most of the uncertainty in the cost-effectiveness threshold was attributable to the probability and cost estimates for low-risk children. This study supports the feasibility of a structured programme that simultaneously addresses exposure to house dust mites, pet dander, environmental tobacco, and breast-feeding as a cost-effective alternative to UC in the primary prevention of asthma amongst children.
    The European Journal of Health Economics 10/2013; · 2.10 Impact Factor
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    ABSTRACT: Premature birth is defined as birth of before 37 completed weeks' gestation. Not all pregnant women showing symptoms of preterm labour will go on to deliver before 37 weeks' gestation. Hence, addition of fetal fibronectin (fFN) testing to the diagnostic workup of women with suspected preterm labour may help to identify those women who do not require active management, and thus avoid unnecessary interventions, hospitalisations and associated costs. To assess the clinical effectiveness and cost-effectiveness of rapid fFN testing in predicting preterm birth (PTB) in symptomatic women. Bibliographic databases (including EMBASE, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials) were searched from 2000 to September/November 2011. Trial registers were also searched. Systematic review methods followed published guidance; we assessed clinical effectiveness and updated a previous systematic review of test accuracy. Risk of bias was assessed using the Cochrane tool (randomised controlled trials; RCTs) and a modification of QUADAS-2 (diagnostic test accuracy studies; DTAs). Summary risk ratios or weighted mean difference were calculated using random-effects models. Summary sensitivity and specificity used a bivariate summary receiver operating characteristic model. Heterogeneity was investigated using subgroup and sensitivity analyses. Health economic analysis focused on cost consequences. The time horizon was hospital admission for observation. A main structural assumption was that, compared with usual care, fFN testing doesn't increase adverse events or negative pregnancy outcomes. Five RCTs and 15 new DTAs were identified. No RCT reported significant effects of fFN testing on maternal or neonatal outcomes. One study reported a subgroup analysis of women with negative fFN test observed > 6 hours, which showed a reduction in length of hospital stay where results were known to clinicians. Combining data from new studies and the previous systematic review, the pooled estimates of sensitivity and specificity were: 76.7% and 82.7% for delivery within 7-10 days of testing; 69.1% and 84.4% for delivery < 34 weeks' gestation; and 60.8% and 82.3% for delivery < 37 weeks' gestation. Estimates were similar across all subgroups sensitivity analyses. The base-case cost analysis resulted in a cost saving of £23.87 for fFN testing compared with usual care. The fFN testing was cost-neutral at an approximate cost of £45. Probabilistic sensitivity analysis gave an incremental cost (saving) of -£25.59 (97.5% confidence interval -£304.96 to £240.06), indicating substantial uncertainty. Sensitivity analyses indicated that admission rate had the largest impact on results. Fetal fibronectin testing has moderate accuracy for predicting PTB. The main potential role is likely to be reducing health-care resource usage by identifying women not requiring intervention. Evidence from RCTs suggests that fFN does not increase adverse outcomes and may reduce resource use. The base-case analysis showed a modest cost difference in favour of fFN testing, which is largely dependent on whether or not fFN testing reduces hospital admission. Currently, there are no high-quality studies and the existing trials were generally underpowered. Hence, there is a need for high-quality adequately powered trials using appropriate study designs to confirm the findings presented. PROSPERO 2011:CRD42011001468. Available from The National Institute for Health Research Health Technology Assessment programme.
    Health technology assessment (Winchester, England). 09/2013; 17(40):1-138.
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    ABSTRACT: The objective of this study was to review methodological quality of economic evaluations of lifestyle behavior change interventions (LBCIs) and to examine how they address methodological challenges for public health economic evaluation identified in the literature. Pubmed and the NHS economic evaluation database were searched for published studies in six key areas for behavior change: smoking, physical activity, dietary behavior, (illegal) drug use, alcohol use and sexual behavior. From included studies (n = 142), we extracted data on general study characteristics, characteristics of the LBCIs, methodological quality and handling of methodological challenges. Economic evaluation evidence for LBCIs showed a number of weaknesses: methods, study design and characteristics of evaluated interventions were not well reported; methodological quality showed several shortcomings and progress with addressing methodological challenges remained limited. Based on the findings of this review we propose an agenda for improving future evidence to support decision-making. Recommendations for practice include improving reporting of essential study details and increasing adherence with good practice standards. Recommendations for research methods focus on mapping out complex causal pathways for modeling, developing measures to capture broader domains of wellbeing and community outcomes, testing methods for considering equity, identifying relevant non-health sector costs and advancing methods for evidence synthesis.
    Journal of Public Health 08/2013; · 2.06 Impact Factor
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    ABSTRACT: Background: Empirical models of the natural history of Alzheimer's disease (AD) may help to evaluate new interventions for AD. Objective: We aimed to estimate AD-free survival time in people with mild cognitive impairment (MCI) and decline of cognitive and physical function in AD cases. Methods: Within the Kungsholmen project, 153 incident MCI and 323 incident AD cases (international criteria) were identified during 9 years of follow-up in a cognitively healthy cohort of elderly people aged ≥75 at baseline (n = 1,082). Global cognitive function was assessed with the Mini-Mental State Examination (MMSE), and daily life function was evaluated with the Katz index of activities of daily living (ADL) at each follow-up examination. Data were analyzed using parametric survival analysis and mixed effect models. Results: Median AD-free survival time of 153 participants with incident MCI was 3.5 years. Among 323 incident AD cases, the cognitive decline was 1.84 MMSE points per year, which was significantly associated with age. Physical functioning declined by 0.38 ADL points per year and was significantly associated with age, education, and MMSE, but not with gender. Conclusion: Elderly people with MCI may develop AD in approximately 3.5 years. Both cognitive and physical function may decline gradually after AD onset. The empirical models can be used to evaluate long-term disease progression of new interventions for AD.
    Journal of Alzheimer's disease: JAD 07/2013; · 4.17 Impact Factor

Publication Stats

3k Citations
879.67 Total Impact Points


  • 2010–2014
    • Erasmus Universiteit Rotterdam
      • • Institute for Medical Technology Assessment (iMTA)
      • • Institute of Health Policy & Management (iBMG)
      Rotterdam, South Holland, Netherlands
    • Karolinska Institutet
      Solna, Stockholm, Sweden
  • 2013
    • Netherlands Cancer Institute
      Amsterdamo, North Holland, Netherlands
    • Universiteit Utrecht
      • Department of Pharmaceutical Sciences
      Utrecht, Utrecht, Netherlands
  • 2002–2013
    • Maastricht University
      • • Department of Health Services Research
      • • GROW School for Oncology & Developmental Biology
      • • Department of General Practice
      • • Interne Geneeskunde
      Maastricht, Provincie Limburg, Netherlands
  • 1997–2013
    • Radboud University Nijmegen
      • • Department of Health Evidence
      • • Department of Radiology
      • • Expert Centre Chronic Fatigue
      • • Institute of Otorhinolaryngology
      • • Department of Gastroenterology and Hepatology
      Nijmegen, Provincie Gelderland, Netherlands
  • 2010–2012
    • University of Chicago
      • • Section of Hospital Medicine
      • • Department of Medicine
      Chicago, IL, United States
  • 2005–2012
    • Maastricht Universitair Medisch Centrum
      • Central Diagnostic Laboratory
      Maestricht, Limburg, Netherlands
  • 2011
    • Karolinska University Hospital
      Tukholma, Stockholm, Sweden
  • 2009
    • Cardiff University
      • Department of Primary Care and Public Health
      Cardiff, Wales, United Kingdom
    • University of Leipzig
      Leipzig, Saxony, Germany
    • The University of York
      • Centre for Health Economics
      York, ENG, United Kingdom
  • 2007
    • University of Zurich
      Zürich, Zurich, Switzerland
    • Bronovo Hospital
      's-Gravenhage, South Holland, Netherlands
  • 2000–2003
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands