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2.  Cost-effectiveness of adult pneumococcal conjugate vaccination in the Netherlands 
The European Respiratory Journal  2015;46(5):1407-1416.
The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) demonstrated the efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) in preventing vaccine-type community-acquired pneumonia and vaccine-type invasive pneumococcal disease in elderly subjects. We examined the cost-effectiveness of PCV13 vaccination in the Netherlands.
Using a Markov-type model, incremental cost-effectiveness ratios (ICER) of PCV13 vaccination in different age- and risk-groups for pneumococcal disease were evaluated using a societal perspective. Estimates of quality-adjusted life-years (QALYs), costs, vaccine efficacy and epidemiological data were based on the CAPiTA study and other prospective studies. The base-case was PCV13 vaccination of adults aged 65–74 years compared to no vaccination, assuming no net indirect effects in base-case due to paediatric 10-valent pneumococcal conjugate vaccine use. Analyses for age- and risk-group specific vaccination strategies and for different levels of hypothetical herd effects from a paediatric PCV programme were also conducted.
The ICER for base-case was €8650 per QALY (95% CI 5750–17 100). Vaccination of high-risk individuals aged 65–74 years was cost-saving and extension to medium-risk individuals aged 65–74 years yielded an ICER of €2900. Further extension to include medium- and high-risk individuals aged ≥18 years yielded an ICER of €3100.
PCV13 vaccination is highly cost-effective in the Netherlands. The transferability of our results to other countries depends upon vaccination strategies already implemented in those countries.
Vaccinating the elderly with 13-valent pneumococcal conjugate vaccine is highly cost-effective
PMCID: PMC4750466  PMID: 26160871
4.  Exploring Outcomes to Consider in Economic Evaluations of Health Promotion Programs: What Broader Non-Health Outcomes Matter Most? 
Attention is increasing on the consideration of broader non-health outcomes in economic evaluations. It is unknown which non-health outcomes are valued as most relevant in the context of health promotion. The present study fills this gap by investigating the relative importance of non-health outcomes in a health promotion context.
We investigated the relative importance of ten non-health outcomes of health promotion programs not commonly captured in QALYs. Preferences were elicited from a sample of the Dutch general public (N = 549) by means of a ranking task. These preferences were analyzed using Borda scores and rank-ordered logit models.
The relative order of preference (from most to least important) was: self-confidence, insights into own (un)healthy behavior, perceived life control, knowledge about a certain health problem, social support, relaxation, better educational achievements, increased labor participation and work productivity, social participation, and a reduction in criminal behavior. The weight given to a particular non-health outcome was affected by the demographic variables age, gender, income, and education. Furthermore, in an open question, respondents mentioned a number of other relevant non-health outcomes, which we classified into outcomes relevant for the individual, the direct social environment, and for society as a whole.
The study provides valuable insights in the non-health outcomes that are considered as most important by the Dutch general population. Ideally, researchers should include the most important non-health outcomes in economic evaluations of health promotion.
Electronic supplementary material
The online version of this article (doi:10.1186/s12913-015-0908-y) contains supplementary material, which is available to authorized users.
PMCID: PMC4501101  PMID: 26169779
Non-health outcomes; health promotion; economic evaluation; general population preferences; the Netherlands
5.  Consistency between stated and revealed preferences: a discrete choice experiment and a behavioural experiment on vaccination behaviour compared 
Discrete Choice Experiments (DCEs) are increasingly used in studies in healthcare research but there is still little empirical evidence for the predictive value of these hypothetical situations in similar real life circumstances. The aim of this paper is to compare the stated preferences in a DCE and the accompanying questionnaire with the revealed preferences of young parents who have to decide whether to vaccinate their new born child against hepatitis B.
A DCE asking parents to decide in which scenario they would be more inclined to vaccinate their child against hepatitis B. The stated preference was estimated by comparing the per respondent utility of the most realistic scenario in which parents could choose to vaccinate their child against hepatitis B, with the utility of the opt-out, based on the mixed logit model from the DCE. This stated preference was compared with the actual behaviour of the parents concerning the vaccination of their new born child.
In 80% of the respondents the stated and revealed preferences corresponded. The positive predictive value is 85% but the negative predictive value is 26%.
The predictive value of the DCE in this study is satisfactory for predicting the positive choice but not for predicting the negative choice. However, the behaviour in this study is exceptional in the sense that most people chose to vaccinate. Future studies should focus on behaviours with a larger variance in the population.
Electronic supplementary material
The online version of this article (doi:10.1186/s12874-015-0010-5) contains supplementary material, which is available to authorized users.
PMCID: PMC4359569  PMID: 25887890
DCE; Predictive value; Stated preferences; Revealed preferences; Vaccination; Hepatitis B
6.  The impact of a healthy lifestyle on Disability-Adjusted Life Years: a prospective cohort study 
BMC Medicine  2015;13:39.
The association between single health behaviours and incidence of and premature mortality from major chronic diseases, including myocardial infarction, stroke, diabetes mellitus, and cancer, has been demonstrated thoroughly. However, the association of several healthy behaviours with Disability-Adjusted Life Years (DALYs), which is a measure for total health combining Years Lost due to Disability and the Years of Life Lost due to premature mortality, has not been studied yet.
A prospective cohort study was conducted among 33,066 healthy men and women aged 20 to 70 years recruited into the EPIC-NL study during 1993 to 1997. Participants’ smoking status, BMI, physical activity, and adherence to a Mediterranean-style diet (excluding alcohol) were investigated separately and combined into a simple health behaviour score ranging from 0 to 4. Participants were followed until the end of 2007 for occurrence of and mortality from the most important chronic diseases. The association between lifestyle (separate lifestyle factors and a simple health behaviour score) and DALYs were adjusted for relevant confounders.
After a median follow-up of 12.4 years, 6,647 disease incidences and 1,482 deaths were documented. Non-smoking, low BMI (BMI <25), being physically active, and adherence to a Mediterranean diet were all associated with a significantly lower disease burden. Persons adhering to all four healthy lifestyle characteristics lived a minimum of 2 years longer in good health (DALYs: −2.13; 95% CI: −2.65 to −1.62) than persons with none. Due to our non-extinct cohort, the total number of DALYs, and consequently the estimates, is underestimated. Therefore, true lifetime health benefits of a healthy lifestyle will be even larger.
Non-smoking, a low BMI, being physically active, and adherence to a Mediterranean diet were associated with a lower disease burden. Each additional healthy lifestyle factor contributed to a longer life in good health.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-015-0287-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4362634  PMID: 25858161
BMI; Disability-Adjusted Life Years (DALY); Disease burden; EPIC-NL; Lifestyle; Mediterranean diet; Physical activity; Smoking
7.  Association between Lifestyle Factors and Quality-Adjusted Life Years in the EPIC-NL Cohort 
PLoS ONE  2014;9(11):e111480.
The aim of our study was to relate four modifiable lifestyle factors (smoking status, body mass index, physical activity and diet) to health expectancy, using quality-adjusted life years (QALYs) in a prospective cohort study. Data of the prospective EPIC-NL study were used, including 33,066 healthy men and women aged 20–70 years at baseline (1993–7), followed until 31-12-2007 for occurrence of disease and death. Smoking status, body mass index, physical activity and adherence to a Mediterranean-style diet (excluding alcohol) were investigated separately and combined into a healthy lifestyle score, ranging from 0 to 4. QALYs were used as summary measure of healthy life expectancy, combining a person's life expectancy with a weight for quality of life when having a chronic disease. For lifestyle factors analyzed separately the number of years living longer in good health varied from 0.12 year to 0.84 year, after adjusting for covariates. A combination of the four lifestyle factors was positively associated with higher QALYs (P-trend <0.0001). A healthy lifestyle score of 4 compared to a score of 0 was associated with almost a 2 years longer life in good health (1.75 QALYs [95% CI 1.37, 2.14]).
PMCID: PMC4219750  PMID: 25369457
8.  The Effect of Including an Opt-Out Option in Discrete Choice Experiments 
PLoS ONE  2014;9(11):e111805.
to determine to what extent the inclusion of an opt-out option in a DCE may have an effect on choice behaviour and therefore might influence the attribute level estimates, the relative importance of the attributes and calculated trade-offs.
781 Dutch Type 2 Diabetes Mellitus patients completed a questionnaire containing nine choice tasks with an opt-out option and nice forced choice tasks. Mixed-logit models were used to estimate the relative importance of the five lifestyle program related attributes that were included. Willingness to pay (WTP) values were calculated and it was tested whether results differed between respondents who answered the choice tasks with an opt-out option in the first or second part of the questionnaire.
21.4% of the respondents always opted out. Respondents who were given the opt-out option in the first part of the questionnaire as well as lower educated respondents significantly more often opted out. For both the forced and unforced choice model, different attributes showed significant estimates, the relative importance of the attributes was equal. However, due to differences in relative importance weights, the WTP values for the PA schedule differed significantly between both datasets.
Results show differences in opting out based on the location of the opt-out option and respondents' educational level; this resulted in small differences between the forced and unforced choice model. Since respondents seem to learn from answering forced choice tasks, a dual response design might result in higher data quality compared to offering a direct opt-out option. Future research should empirically explore how choice sets should be presented to make them as easy and less complex as possible in order to reduce the proportion of respondents that opts-out due to choice task complexity. Moreover, future research should debrief respondents to examine the reasons for choosing the opt-out alternative.
PMCID: PMC4218820  PMID: 25365169
9.  The effect of out-of-pocket costs and financial rewards in a discrete choice experiment: an application to lifestyle programs 
BMC Public Health  2014;14:870.
Both out-of-pocket costs and financial rewards can be used to influence health related behavior. However, it is unclear which of these two has a larger effect on health related behavior. The aim of this study was to explore the possible difference in effect size between out-of-pocket costs and financial rewards on the willingness of diabetes mellitus type 2 (DM2) patients to participate in a lifestyle program.
A discrete choice experiment (DCE) questionnaire was sent to 767 DM2 patients in a geographically defined area (De Leidsche Rijn, Utrecht) in The Netherlands and completed by 206 of them. The questionnaire comprised of 18 choice tasks of which 9 contained a financial reward for lifestyle program completion, while the other 9 included out-of-pocket costs for program participation. In a second version of the questionnaire, the order of out-of-pocket cost and financial reward choice tasks was counterbalanced to reduce bias with respect to the position (first or second) of the two types of choice tasks. Panel-mixed-multinomial-logit models were used for data analysis.
Increasing out-of-pocket costs were associated with a decreasing willingness to participate in a lifestyle program and, contrary to our expectations, increasing financial rewards were also associated with a decreasing willingness to participate in a lifestyle program. In addition, this willingness to participate changed to the same extent for both increasing out-of-pocket costs and increasing financial rewards.
As expected, increasing out-of-pocket costs may prevent people from deciding to participate in a lifestyle program. However, offering a financial reward to persuade people to participate in a lifestyle program, may result in decreasing willingness to participate in a lifestyle program as well.
PMCID: PMC4153916  PMID: 25151503
Out-of-pocket costs; Financial rewards; Lifestyle programs; Discrete choice experiment; Willingness to participate; Diabetes mellitus type 2
10.  Design of the INTEGRATE study: effectiveness and cost-effectiveness of a cardiometabolic risk assessment and treatment program integrated in primary care 
BMC Family Practice  2014;15:90.
The increasing prevalence of cardiometabolic disease (CMD) in combination with an ageing population is a major public health problem. Early detection and management of individuals at risk for CMD is required to prevent future health problems with associated costs. General practice is the optimal health care setting to accomplish this goal. Prevention programs for identification and treatment of patients with an increased risk for CMD in primary care have been proven feasible. However, the effectiveness and cost-effectiveness have yet to be demonstrated. The ‘Personalized Prevention Approach for CardioMetabolic Risk’ (PPA CMR) is such a prevention program. The objective of the INTEGRATE study is to investigate the effectiveness and cost-effectiveness of PPA CMR, as well as to establish determinants for participation and compliance.
The INTEGRATE study is designed as a stepped-wedge randomized controlled trial with a waiting list control group. In approximately 40 general practices, all enlisted patients without CMD aged 45–70 years, are invited to participate in PPA CMR. After an online risk estimation, patients with a score above risk threshold are invited to the GP for additional measurements, detailed risk profiling and tailored treatment of risk factors through medication and/or lifestyle counseling. At baseline and after twelve months of follow-up lifestyle, health and work status of all participants are established with online questionnaires. Additionally after twelve months, we will determine health care utilization, costs of PPA CMR and compliance. Primary endpoints are the number of newly detected patients with CMD and changes in individual risk factors between the intervention and waiting list control group. Medical data will be extracted from the GPs’ electronic medical records. In order to assess factors related to participation, we will send questionnaires to non-participants and assess characteristics of participating practices. For all participants, additional demographic characteristics will be available through Statistics Netherlands.
The INTEGRATE study will provide insight into the effectiveness and cost-effectiveness of PPA CMR as well as determinants for participation and compliance, which represents essential information to guide further large-scale implementation of primary prevention programs for CMD.
Trial registration number
NTR4277, The Netherlands National Trial Register, 26-11-2013.
PMCID: PMC4022539  PMID: 24884779
Cardiometabolic disease; Prevention; (Primary) screening; Non-participation; Primary care; Family practice; Effectiveness; Economic evaluation; RCT
11.  Rationale and design of the costs, health status and outcomes in community-acquired pneumonia (CHO-CAP) study in elderly persons hospitalized with CAP 
BMC Infectious Diseases  2013;13:597.
Vaccine effectiveness is usually determined in randomized controlled trials (RCT) and if effective, additional information, e.g. on cost-effectiveness, is required to allow evidence-based decision making. A prerequisite for proper health economic modelling is the availability of good quality data on health care resources use, health outcomes and quality-of-life (QoL) data. The “Collecting health outcomes and economic data on hospitalized Community Acquired Pneumonia (CHO-CAP) – a prospective cohort study” is executed alongside the Community Acquired Pneumonia Immunization Trial with Adults (CAPiTA trial) to capture health outcomes and economic data of elderly hospitalized with CAP and matched controls without CAP.
CAPiTA is a placebo-controlled double-blind RCT evaluating the effectiveness of a 13-valent conjugated pneumococcal vaccine in preventing vaccine-type pneumococcal CAP in 84,496 elderly in the Netherlands. Participants of CAPiTA, who consented and provided information on health status (EQ-5D) and socio-demographic background at the time of vaccination, constitute the source population of CHO-CAP and are eligible for the nested matched cohort study. CHO-CAP patients hospitalized with CAP form the “diseased” cohort and the “non-diseased” cohort consists of unaffected persons (i.e. no CAP). Observations in the diseased cohort and in matched controls from the non-diseased cohort are used to determine excess costs and QoL changes attributable to CAP.
Based on an estimated 2,000 CAPiTA participants being hospitalized with CAP and an assumed CHO-CAP participation rate of 30% of all CAPiTA participants (±25,000), 600 CAP episodes are expected among CHO-CAP participants (the “diseased” cohort). For each patient with CAP, two non-diseased CHO-CAP subjects will be selected from the CHO-CAP cohort, with matching for age, gender and EQ-5D baseline-score. Data on healthcare and non-healthcare resources use, quality-of-life (using EQ-5D and SF-36 questionnaires) and selected health outcomes will be collected at 0, 1, 6 and 12 months after hospitalization for CAP.
The CHO-CAP study was approved by the Central Committee on Research involving Human Subjects in the Netherlands.
With an expected 600 CAP episodes this study will be one of the biggest prospectively studied cohorts of hospitalized elderly with CAP with regard to resources use and Qol data. Strengths of this study further include collection of out-of-pocket costs of patients and productivity losses of both patients and their caregivers and the follow-up period of up to one year post-discharge. This study is therefore expected to add more in-depth knowledge on the short and longer term outcomes of pneumonia in elderly.
Trial registration, NCT00812084.
PMCID: PMC3880048  PMID: 24354588
Community-acquired pneumonia; Quality-of-life; Healthcare resources use; Non-healthcare resources use; Societal costs
12.  Type 2 diabetes patients’ preferences and willingness to pay for lifestyle programs: a discrete choice experiment 
BMC Public Health  2013;13:1099.
Participation rates of lifestyle programs among type 2 diabetes mellitus (T2DM) patients are less than optimal around the globe. Whereas research shows notable delays in the development of the disease among lifestyle program participants. Very little is known about the relative importance of barriers for participation as well as the willingness of T2DM patients to pay for participation in such programs. The aim of this study was to identify the preferences of T2DM patients with regard to lifestyle programs and to calculate participants’ willingness to pay (WTP) as well as to estimate the potential participation rates of lifestyle programs.
A Discrete Choice Experiment (DCE) questionnaire assessing five different lifestyle program attributes was distributed among 1250 Dutch adults aged 35–65 years with T2DM, 391 questionnaires (31%) were returned and included in the analysis. The relative importance of the program attributes (i.e., meal plan, physical activity (PA) schedule, consultation structure, expected program outcome and out-of-pocket costs) was determined using panel-mixed logit models. Based on the retrieved attribute estimates, patients’ WTP and potential participation rates were determined.
The out-of-pocket costs (β = −0.75, P < .001), consultation structure (β = −0.46, P < .001) and expected outcome (β = 0.72, P < .001) were the most important factors for respondents when deciding whether to participate in a lifestyle program. Respondents were willing to pay €128 per year for individual instead of group consultation and €97 per year for 10 kilograms anticipated weight loss. Potential participation rates for different lifestyle-program scenarios ranged between 48.5% and 62.4%.
When deciding whether to participate in a lifestyle program, T2DM patients are mostly driven by low levels of out-of-pocket costs. Thereafter, they prefer individual consultation and high levels of anticipated outcomes with respect to weight loss.
PMCID: PMC3909291  PMID: 24289831
Discrete choice experiment; Preferences; Diabetes mellitus type 2; Lifestyle program; Participation rate; Willingness to participate; Willingness to pay
13.  Development of Methodology for Disability-Adjusted Life Years (DALYs) Calculation Based on Real-Life Data 
PLoS ONE  2013;8(9):e74294.
Disability-Adjusted Life Years (DALYs) have the advantage that effects on total health instead of on a specific disease incidence or mortality can be estimated. Our aim was to address several methodological points related to the computation of DALYs at an individual level in a follow-up study.
DALYs were computed for 33,507 men and women aged 20–70 years when participating in the EPIC-NL study in 1993–7. DALYs are the sum of the Years Lost due to Disability (YLD) and the Years of Life Lost (YLL) due to premature mortality. Premature mortality was defined as death before the estimated date of individual Life Expectancy (LE). Different methods to compute LE were compared as well as the effect of different follow-up periods using a two-part model estimating the effect of smoking status on health as an example.
During a mean follow-up of 12.4 years, there were 69,245 DALYs due to years lived with a disease or premature death. Current-smokers had lost 1.28 healthy years of their life (1.28 DALYs 95%CI 1.10; 1.46) compared to never-smokers. The outcome varied depending on the method used for estimating LE, completeness of disease and mortality ascertainment and notably the percentage of extinction (duration of follow-up) of the cohort.
We conclude that the use of DALYs in a cohort study is an appropriate way to assess total disease burden in relation to a determinant. The outcome is sensitive to the LE calculation method and the follow-up duration of the cohort.
PMCID: PMC3779209  PMID: 24073206
14.  Effects of Population Based Screening for Chlamydia Infections in The Netherlands Limited by Declining Participation Rates 
PLoS ONE  2013;8(3):e58674.
A large trial to investigate the effectiveness of population based screening for chlamydia infections was conducted in the Netherlands in 2008–2012. The trial was register based and consisted of four rounds of screening of women and men in the age groups 16–29 years in three regions in the Netherlands. Data were collected on participation rates and positivity rates per round. A modeling study was conducted to project screening effects for various screening strategies into the future.
Methods and Findings
We used a stochastic network simulation model incorporating partnership formation and dissolution, aging and a sexual life course perspective. Trends in baseline rates of chlamydia testing and treatment were used to describe the epidemiological situation before the start of the screening program. Data on participation rates was used to describe screening uptake in rural and urban areas. Simulations were used to project the effectiveness of screening on chlamydia prevalence for a time period of 10 years. In addition, we tested alternative screening strategies, such as including only women, targeting different age groups, and biennial screening. Screening reduced prevalence by about 1% in the first two screening rounds and leveled off after that. Extrapolating observed participation rates into the future indicated very low participation in the long run. Alternative strategies only marginally changed the effectiveness of screening. Higher participation rates as originally foreseen in the program would have succeeded in reducing chlamydia prevalence to very low levels in the long run.
Decreasing participation rates over time profoundly impact the effectiveness of population based screening for chlamydia infections. Using data from several consecutive rounds of screening in a simulation model enabled us to assess the future effectiveness of screening on prevalence. If participation rates cannot be kept at a sufficient level, the effectiveness of screening on prevalence will remain limited.
PMCID: PMC3604006  PMID: 23527005
15.  The polypill in the primary prevention of cardiovascular disease: cost-effectiveness in the Dutch population 
BMJ Open  2011;1(2):e000363.
The aim of the present study was to estimate the cost-effectiveness of the polypill in the primary prevention of cardiovascular disease.
A health economic modelling study.
Primary healthcare in the Netherlands.
Simulated individuals from the general Dutch population, aged 45–75 years.
Opportunistic screening followed by prescription of the polypill to eligible individuals. Eligibility was defined as having a minimum 10-year risk of cardiovascular death as assessed with the Systematic Coronary Risk Evaluation function of alternatively 5%, 7.5% or 10%. Different versions of the polypill were considered, depending on composition: (1) the Indian polycap, with three different types of blood pressure-lowering drugs, a statin and aspirin; (2) as (1) but without aspirin and (3) as (2) but with a double statin dose. In addition, a scenario of (targeted) separate antihypertensive and/or statin medication was simulated.
Primary outcome measures
Cases of acute myocardial infarction or stroke prevented, quality-adjusted life years (QALYs) gained and the costs per QALY gained. All interventions were compared with usual care.
All scenarios were cost-effective with an incremental cost-effectiveness ratio between €7900 and 12 300 per QALY compared with usual care. Most health gains were achieved with the polypill without aspirin and containing a double dose of statins. With a 10-year risk of 7.5% as the threshold, this pill would prevent approximately 3.5% of all cardiovascular events.
Opportunistic screening based on global cardiovascular risk assessment followed by polypill prescription to those with increased risk offers a cost-effective strategy. Most health gain is achieved by the polypill without aspirin and a double statin dose.
Article summary
Article focus
Cardiovascular diseases continue to be still a major, partly preventable, cause of illness and death.
A polypill that lowers by targeting several risk factors simultaneously is in line with the concept that the aim in primary prevention should be to bring down ‘global’ cardiovascular risk.
The aim of this study was to estimate the potential cost-effectiveness of polypill prescription after opportunistic screening.
Key messages
The results of this study suggest that opportunistic screening and offering a polypill to people with a minimum 10-year risk of cardiovascular mortality of alternatively 5%, 7.5% or 10% is a cost-effective strategy.
A polypill without aspirin but with a double dose of simvastatin leads to most health gains at all risk thresholds considered. At a 10-year risk of cardiovascular death of ≥7.5%, such a strategy would lead to an estimated decrease in the incidence of myocardial infarction and stroke of about 3.5%, at a cost of €8900 per quality-adjusted life year.
Opportunistic screening of the population of ≥40 years to select individuals with a mild to moderately increased risk for cardiovascular diseases, followed by polypill prescription would prevent approximately 3.5% of all cardiovascular events.
Strengths and limitations of this study
Strong point of the study is that different compositions of the polypill have been modelled. Also, realistic estimates for adherence and compliance have been used.
As only preliminary results of a phase II clinical trial on efficacy of the polypill were available, we had to apply mathematical modelling to estimate cost-effectiveness. This provides insight into the range of health benefits that can be expected. Pending results with regard to established clinical endpoints from large-scale phase III trials, the results of this study should not be taken as a precise estimate of the cost-effectiveness of the polypill.
PMCID: PMC3278482  PMID: 22189351
16.  Willingness to participate in a lifestyle intervention program of patients with type 2 diabetes mellitus: a conjoint analysis 
Several studies suggest that lifestyle interventions can be effective for people with, or at risk for, diabetes. The participation in lifestyle interventions is generally low. Financial incentives may encourage participation in lifestyle intervention programs.
The main aim of this exploratory analysis is to study empirically potential effects of financial incentives on diabetes patients’ willingness to participate in lifestyle interventions. One financial incentive is negative (“copayment”) and the other incentive is positive (“bonus”). The key part of this research is to contrast both incentives. The second aim is to investigate the factors that influence participation in a lifestyle intervention program.
Conjoint analysis techniques were used to empirically identify factors that influence willingness to participate in a lifestyle intervention. For this purpose diabetic patients received a questionnaire with descriptions of various forms of hypothetical lifestyle interventions. They were asked if they would be willing to participate in these hypothetical programs.
In total, 174 observations were rated by 46 respondents. Analysis showed that money was an important factor independently associated with respondents’ willingness to participate. Receiving a bonus seemed to be associated with a higher willingness to participate, but having to pay was negatively associated with participation in the lifestyle intervention.
Conjoint analysis results suggest that financial considerations may influence willingness to participate in lifestyle intervention programs. Financial disincentives in the form of copayments might discourage participation. Although the positive impact of bonuses is smaller than the negative impact of copayments, bonuses could still be used to encourage willingness to participate.
PMCID: PMC3218115  PMID: 22114468
incentives; bonus; copayment; conjoint analysis; willingness to participate
17.  Differences in quality of life of hemodialysis patients between dialysis centers 
Quality of Life Research  2011;21(2):299-307.
Hemodialysis patients undergo frequent and long visits to the clinic to receive adequate dialysis treatment, medical guidance, and support. This may affect health-related quality of life (HRQOL). Although HRQOL is a very important management aspect in hemodialysis patients, there is a paucity of information on the differences in HRQOL between centers. We set out to assess the differences in HRQOL of hemodialysis patients between dialysis centers and explore which modifiable center characteristics could explain possible differences.
This cross-sectional study evaluated 570 hemodialysis patients from 24 Dutch dialysis centers. HRQOL was measured with the Kidney Disease Quality Of Life-Short Form (KDQOL-SF).
After adjustment for differences in case-mix, three HRQOL domains differed between dialysis centers: the physical composite score (PCS, P = 0.01), quality of social interaction (P = 0.04), and dialysis staff encouragement (P = 0.001). These center differences had a range of 11–21 points on a scale of 0–100, depending on the domain. Two center characteristics showed a clinical relevant relation with patients’ HRQOL: dieticians’ fulltime-equivalent and the type of dialysis center.
This study showed that clinical relevant differences exist between dialysis centers in multiple HRQOL domains. This is especially remarkable as hemodialysis is a highly standardized therapy.
PMCID: PMC3276757  PMID: 21633878
Quality of life; Center differences; Hemodialysis; Dialysis staff encouragement
18.  Cost-Effectiveness of Preoperative Screening and Eradication of Staphylococcus aureus Carriage 
PLoS ONE  2011;6(5):e14815.
Preoperative screening for nasal S. aureus carriage, followed by eradication treatment of identified carriers with nasal mupirocine ointment and chlorhexidine soap was highly effective in preventing deep-seated S. aureus infections. It is unknown how cost-effectiveness of this intervention is affected by suboptimal S. aureus screening. We determined cost-effectiveness of different preoperative S. aureus screening regimes.
We compared different screening scenarios (ranging from treating all patients without screening to treating only identified S. aureus carriers) to the base case scenario without any screening and treatment. Screening and treatment costs as well as costs and mortality due to deep-seated S. aureus infection were derived from hospital databases and prospectively collected data, respectively.
As compared to the base case scenario, all scenarios are associated with improved health care outcomes at reduced costs. Treating all patients without screening is most cost-beneficial, saving €7339 per life year gained, as compared to €3330 when only identified carriers are treated. In sensitivity analysis, outcomes are susceptible to the sensitivity of the screening test and the efficacy of treatment. Reductions in these parameters would reduce the cost-effectiveness of scenarios in which treatment is based on screening. When only identified S. aureus carriers are treated costs of screening should be less than €6.23 to become the dominant strategy.
Preoperative screening and eradication of S. aureus carriage to prevent deep-seated S. aureus infections saves both life years and medical costs at the same time, although treating all patients without screening is the dominant strategy, resulting in most health gains and largest savings.
PMCID: PMC3102653  PMID: 21637333
19.  Effectiveness and cost-effectiveness of an injury prevention programme for adult male amateur soccer players: design of a cluster-randomised controlled trial 
Injury Prevention  2010;17(1):e2.
Background and aims
Approximately 16% of all sports injuries in the Netherlands are caused by outdoor soccer. A cluster-randomised controlled trial has been designed to investigate the effectiveness and cost-effectiveness of an injury prevention programme (‘The11’) for male amateur soccer players. The injury prevention programme The11, developed with the support of the World Football Association FIFA, aims to reduce the impact of intrinsic injury risk factors in soccer.
Teams playing at first-class amateur level in two districts in the Netherlands are participating in the study. Teams in the intervention group were instructed to apply The11 during each practice session throughout the 2009–10 season. All participants of the control group continued their practice sessions as usual. All soccer-related injuries and related costs for each team were systematically reported online by a member of the medical staff. Player exposure to practice sessions and matches was reported weekly by the coaches. Also the use of The11 during the season after the intervention season will be monitored.
Our hypothesis is that integrating the The11 exercises in the warm-up for each practice session is effective in terms of injury incidence, injury severity, healthcare use, and its associated costs and/or absenteeism. Prevention of soccer injuries is expected to be beneficial to adult soccer players, soccer clubs, the Royal Dutch Football Association (KNVB), health insurance companies and society.
PMCID: PMC3063459  PMID: 21177664
Soccer; injuries; prevention; effectiveness; cost-effectiveness; economics; methods; program; sports
20.  DIRECT trial. Diverticulitis recurrences or continuing symptoms: Operative versus conservative Treatment. A MULTICENTER RANDOMISED CLINICAL TRIAL 
BMC Surgery  2010;10:25.
Persisting abdominal complaints are common after an episode of diverticulitis treated conservatively. Furthermore, some patients develop frequent recurrences. These two groups of patients suffer greatly from their disease, as shown by impaired health related quality of life and increased costs due to multiple specialist consultations, pain medication and productivity losses.
Both conservative and operative management of patients with persisting abdominal complaints after an episode of diverticulitis and/or frequently recurring diverticulitis are applied. However, direct comparison by a randomised controlled trial is necessary to determine which is superior in relieving symptoms, optimising health related quality of life, minimising costs and preventing diverticulitis recurrences against acceptable morbidity and mortality associated with surgery or the occurrence of a complicated recurrence after conservative management.
We, therefore, constructed a randomised clinical trial comparing these two treatment strategies.
The DIRECT trial is a multicenter randomised clinical trial. Patients (18-75 years) presenting themselves with persisting abdominal complaints after an episode of diverticulitis and/or three or more recurrences within 2 years will be included and randomised. Patients randomised for conservative treatment are treated according to the current daily practice (antibiotics, analgetics and/or expectant management). Patients randomised for elective resection will undergo an elective resection of the affected colon segment. Preferably, a laparoscopic approach is used.
The primary outcome is health related quality of life measured by the Gastro-intestinal Quality of Life Index, Short-Form 36, EQ-5D and a visual analogue scale for pain quantification. Secondary endpoints are morbidity, mortality and total costs. The total follow-up will be three years.
Considering the high incidence and the multicenter design of this study, it may be assumed that the number of patients needed for this study (n = 214), may be gathered within one and a half year.
Depending on the expertise and available equipment, we prefer to perform a laparoscopic resection on patients randomised for elective surgery. Should this be impossible, an open technique may be used as this also reflects the current situation.
Trial Registration
(Trial register number: NTR1478)
PMCID: PMC2928179  PMID: 20691040
21.  Quantifying Cost-Effectiveness of Controlling Nosocomial Spread of Antibiotic-Resistant Bacteria: The Case of MRSA 
PLoS ONE  2010;5(7):e11562.
The costs and benefits of controlling nosocomial spread of antibiotic-resistant bacteria are unknown.
We developed a mathematical algorithm to determine cost-effectiveness of infection control programs and explored the dynamical interactions between different epidemiological variables and cost-effectiveness. The algorithm includes occurrence of nosocomial infections, attributable mortality, costs and efficacy of infection control and how antibiotic-resistant bacteria affect total number of infections: do infections with antibiotic-resistant bacteria replace infections caused by susceptible bacteria (replacement scenario) or occur in addition to them (addition scenario). Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was used for illustration using observational data on S. aureus bacteremia (SAB) in our hospital (n = 189 between 2001–2004, all being methicillin-susceptible S. aureus [MSSA]).
In the replacement scenario, the costs per life year gained range from € 45,912 to € 6590 for attributable mortality rates ranging from 10% to 50%. Using € 20,000 per life year gained as a threshold, completely preventing MRSA would be cost-effective in the replacement scenario if attributable mortality of MRSA is ≥21%. In the addition scenario, infection control would be cost saving along the entire range of estimates for attributable mortality.
Cost-effectiveness of controlling antibiotic-resistant bacteria is highly sensitive to the interaction between infections caused by resistant and susceptible bacteria (addition or replacement) and attributable mortality. In our setting, controlling MRSA would be cost saving for the addition scenario but would not be cost-effective in the replacement scenario if attributable mortality would be <21%.
PMCID: PMC2905392  PMID: 20661278
22.  The scope of costs in alcohol studies: Cost-of-illness studies differ from economic evaluations 
Alcohol abuse results in problems on various levels in society. In terms of health, alcohol abuse is not only an important risk factor for chronic disease, but it is also related to injuries. Social harms which can be related to drinking include interpersonal problems, work problems, violent and other crimes. The scope of societal costs related to alcohol abuse in principle should be the same for both economic evaluations and cost-of-illness studies. In general, economic evaluations report a small part of all societal costs. To determine the cost- effectiveness of an intervention it is necessary that all costs and benefits are included. The purpose of this study is to describe and quantify the difference in societal costs incorporated in economic evaluations and cost-of-illness studies on alcohol abuse.
To investigate the economic costs attributable to alcohol in cost-of-illness studies we used the results of a recent systematic review (June 2009). We performed a PubMed search to identify economic evaluations on alcohol interventions. Only economic evaluations in which two or more interventions were compared from a societal perspective were included. The proportion of health care costs and the proportion of societal costs were estimated in both type of studies.
The proportion of healthcare costs in cost-of-illness studies was 17% and the proportion of societal costs 83%. In economic evaluations, the proportion of healthcare costs was 57%, and the proportion of societal costs was 43%.
The costs included in economic evaluations performed from a societal perspective do not correspond with those included in cost-of-illness studies. Economic evaluations on alcohol abuse underreport true societal cost of alcohol abuse. When considering implementation of alcohol abuse interventions, policy makers should take into account that economic evaluations from the societal perspective might underestimate the total effects and costs of interventions.
PMCID: PMC2907313  PMID: 20602804
23.  Physical Activity during Cancer Treatment (PACT) Study: design of a randomised clinical trial 
BMC Cancer  2010;10:272.
Fatigue is a major problem of cancer patients. Thirty percent of cancer survivors report serious fatigue three years after finishing treatment. There is evidence that physical exercise during cancer treatment reduces fatigue. This may also lead to an improvement of quality of life. Such findings may result in a decrease of healthcare related expenditures and societal costs due to sick leave. However, no studies are known that investigated these hypotheses. Therefore, the primary aim of our study is to assess the effect of exercise during cancer treatment on reducing complaints of fatigue and on reducing health service utilisation and sick leave.
The Physical Activity during Cancer Treatment study is a multicentre randomised controlled trial in 150 breast and 150 colon cancer patients undergoing cancer treatment. Participants will be randomised to an exercise or a control group. In addition to the usual care, the exercise group will participate in an 18-week supervised group exercise programme. The control group will be asked to maintain their habitual physical activity pattern. Study endpoints will be assessed after 18 weeks (short term) and after 9 months (long term). Validated questionnaires will be used. Primary outcome: fatigue (Multidimensional Fatigue Inventory and Fatigue Quality List) and cost-effectiveness, health service utilisation and sick leave. Secondary outcome: health related quality of life (European Organisation Research and Treatment of Cancer-Quality of Life questionnaire-C30, Short Form 36 healthy survey), impact on functioning and autonomy (Impact on functioning and autonomy questionnaire), anxiety and depression (Hospital Anxiety and Depression Scale), physical fitness (aerobic peak capacity, muscle strength), body composition and cognitive-behavioural aspects. To register health service utilisation and sick leave, participants will keep diaries including the EuroQuol-5D. Physical activity level will be measured using the Short Questionnaire to Assess Health-Enhancing Physical Activity and will be monitored with an exercise log and a pedometer.
This study investigates the (cost)-effectiveness of exercise during adjuvant treatment of patients with breast or colon cancer. If early physical exercise proves to be (cost) effective, establishing standardised physical exercise programmes during cancer treatment will be planned.
Trial registration
Current Controlled trials ISRCTN43801571, Dutch Trial Register NTR2138
PMCID: PMC2927992  PMID: 20534147
24.  Early recognition of heart failure in patients with diabetes type 2 in primary care. A prospective diagnostic efficiency study. (UHFO-DM2) 
BMC Public Health  2009;9:479.
We hypothesize that the prevalence of unknown heart failure in diabetic patients aged 60 years and over is relatively high (15% or more) and that a cost-effective strategy can be developed to detect heart failure in these patients. The strategy is expected to include some signs and symptoms (such as dyspnoea, orthopnoea, pulmonary crepitations and laterally displaced apical beat), natriuretic peptide measurements (Amino-terminal B-type natriuretic peptide) and possibly electrocardiography. In a subset of patients straightforward echocardiography may show to be cost-effective. With information from our study the detection of previously unknown heart failure in diabetic patients could be improved and enable the physician to initiate beneficial morbidity and mortality reducing heart failure treatment more timely.
Primary objectives
- To assess the prevalence of (previously unrecognised) heart failure in primary care patients with diabetes type 2.
- To establish the most cost-effective diagnostic strategy to detect unrecognised heart failure in these patients.
Secondary objectives
- To assess the impact of heart failure, and the combination of a new diagnosis with accordingly treatment in patients with diabetes type 2 on health status.
Design: A prospective diagnostic efficiency study.
Patient population: Patients aged 60 years and older with diabetes type 2 from primary care, enlisted with the diabetes service of the Diagnostic Center in Etten-Leur (SHL)
All participants will be investigated at the cardiology out-patient department of the regional hospital (Oosterschelde Hospital in Goes, Zeeland, the Netherlands) during a single 1.5 hour standardised diagnostic assessment, including history taking, physical examination, electrocardiography, echocardiography, blood tests, and Health status questionnaires. Patients will be asked if we can contact them afterwards for follow-up and for repeating the questionnaires after three and 12 months.
Main study parameters/endpoints: Prevalence (with exact 95% confidence intervals) of (previously unrecognised) heart failure (systolic and 'isolated' diastolic) and the diagnostic value of signs and symptoms, NT-proBNP, electrocardiography and a combination of these items. The cost-effectiveness of different diagnostic strategies. Impact of heart failure and the combination of a new diagnosis with accordingly treatment on health status.
Trial registration
CCMO register NL2271704108
PMCID: PMC2804618  PMID: 20025758
25.  The cost-effectiveness of increasing alcohol taxes: a modelling study 
BMC Medicine  2008;6:36.
Excessive alcohol use increases risks of chronic diseases such as coronary heart disease and several types of cancer, with associated losses of quality of life and life-years. Alcohol taxes can be considered as a public health instrument as they are known to be able to decrease alcohol consumption. In this paper, we estimate the cost-effectiveness of an alcohol tax increase for the entire Dutch population from a health-care perspective focusing on health benefits and health-care costs in alcohol users.
The chronic disease model of the National Institute for Public Health and the Environment was used to extrapolate from decreased alcohol consumption due to tax increases to effects on health-care costs, life-years gained and quality-adjusted life-years gained, A Dutch scenario in which tax increases for beer are planned, and a Swedish scenario representing one of the highest alcohol taxes in Europe, were compared with current practice in the Netherlands. To estimate cost-effectiveness ratios, yearly differences in model outcomes between intervention and current practice scenarios were discounted and added over the time horizon of 100 years to find net present values for incremental life-years gained, quality-adjusted life-years gained, and health-care costs.
In the Swedish scenario, many more quality-adjusted life-years were gained than in the Dutch scenario, but both scenarios had almost equal incremental cost-effectiveness ratios: €5100 per quality-adjusted life-year and €5300 per quality-adjusted life-year, respectively.
Focusing on health-care costs and health consequences for drinkers, an alcohol tax increase is a cost-effective policy instrument.
PMCID: PMC2637894  PMID: 19040717

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