Cost-effectiveness analysis of a multicentre randomized clinical trial comparing surgery with conservative management for recurrent and ongoing diverticulitis (DIRECT trial).

BACKGROUND: The results of the DIRECT trial, an RCT comparing conservative management with elective sigmoid resection in patients with recurrent diverticulitis or persistent complaints, showed that elective sigmoid resection leads to higher quality of life. The aim of this study is to determine the cost-effectiveness of surgical treatment at 1- and 5-year follow-up from a societal perspective. METHODS: Clinical effectiveness and resource use were derived from the DIRECT trial. The actual resource use and quality of life (EQ-5D-3L™ score) were documented prospectively per individual patient and analysed according to the intention-to-treat principle for up to 5 years after randomization. The main outcome was the incremental cost-effectiveness ratio (ICER), expressed as costs per quality-adjusted life-year (QALY). RESULTS: The study included 106 patients, of whom 50 were randomized to surgery and 56 to conservative treatment. At 1- and 5-year follow-up an incremental effect (QALY difference between groups) of 0·06 and 0·43 respectively was found, and an incremental cost (cost difference between groups) of €6957 and €2674 respectively, where surgery was more expensive than conservative treatment. This resulted in an ICER of €123 365 per additional QALY at 1-year follow-up, and €6275 at 5 years. At a threshold of €20 000 per QALY, operative treatment has 0 per cent probability of being cost-effective at 1-year follow-up, but a 95 per cent probability at 5 years. CONCLUSION: At 5-year follow-up, elective sigmoid resection in patients with recurring diverticulitis or persistent complaints was found to be cost-effective. Registration number: NTR1478 (www.trialregistrer.nl).

Long-term outcomes and cost effectiveness of high-dose dexamethasone for cardiac surgery: a randomised trial.

Prophylactic intra-operative administration of dexamethasone may improve short-term clinical outcomes in cardiac surgical patients. The purpose of this study was to evaluate long-term clinical outcomes and cost effectiveness of dexamethasone versus placebo. Patients included in the multicentre, randomised, double-blind, placebo-controlled DExamethasone for Cardiac Surgery (DECS) trial were followed up for 12 months after their cardiac surgical procedure. In the DECS trial, patients received a single intra-operative dose of dexamethasone 1 mg.kg-1 (n = 2239) or placebo (n = 2255). The effects on the incidence of major postoperative events were evaluated. Also, overall costs for the 12-month postoperative period, and cost effectiveness, were compared between groups. Of 4494 randomised patients, 4457 patients (99%) were followed up until 12 months after surgery. There was no difference in the incidence of major postoperative events, the relative risk (95%CI) being 0.86 (0.72-1.03); p = 0.1. Treatment with dexamethasone reduced costs per patient by £921 [€1084] (95%CI £-1672 to -137; p = 0.02), mainly through reduction of postoperative respiratory failure and duration of postoperative hospital stay. The probability of dexamethasone being cost effective compared with placebo was 97% at a threshold value of £17,000 [€20,000] per quality-adjusted life year. We conclude that intra-operative high-dose dexamethasone did not have an effect on major adverse events at 12 months after cardiac surgery, but was associated with a reduction in costs. Routine dexamethasone administration is expected to be cost effective at commonly accepted threshold levels for cost effectiveness.

Use of DALYs in economic analyses on interventions for infectious diseases: a systematic review.

A systematic literature review was performed on full economic evaluations of infectious disease interventions using disability-adjusted life years (DALY) as outcome measure. The search was limited to the period between 1994 and September 2011 and conducted in Medline, SciSearch and EMBASE databases. We included 154 studies, mostly targeting HIV/AIDS and malaria with most conducted for African countries (40%) and <10% in high-income countries. Third-payer perspective was applied in 29% of the studies, 25% used the societal perspective and 12% used both. Only 16% of the studies took indirect effects (i.e. herd immunity) of interventions into account. Intervention, direct healthcare and indirect non-healthcare costs were taken into account in respectively 100%, 81% and 36% of the studies. The majority of the studies followed the Global Burden of Disease method for DALY estimations, but most studies deviated from WHO cost-effectiveness guidelines. Better adherence to freely accessible guidelines will improve generalizability between full economic evaluations.

The burden of Lyme borreliosis expressed in disability-adjusted life years.

BACKGROUND: Lyme borreliosis (LB) is the most commonly reported tick-borne infection in Europe and North America. In the last 15 years a 3-fold increase was observed in general practitioner consultations for LB in the Netherlands. To support prioritization of prevention and control efforts for LB, we estimated its burden expressed in Disability-Adjusted Life Years (DALYs). METHODS: We used available incidence estimates for three LB outcomes: (i) erythema migrans (EM), (ii) disseminated LB and (iii) Lyme-related persisting symptoms. To generate DALYs, disability weights and duration per outcome were derived using a patient questionnaire including health-related quality of life as measured by the EQ-5D. RESULTS: We estimated the total LB burden for the Netherlands in 2010 at 10.55 DALYs per 100,000 population (95% CI: 8.80-12.43); i.e. 0.60 DALYs for EM, 0.86 DALYs for disseminated LB and 9.09 DALYs for Lyme-related persisting symptoms. Per patient this was 0.005 DALYs for EM, 0.113 for disseminated LB and 1.661 DALYs for a patient with Lyme-related persisting symptoms. In a sensitivity analysis the total LB burden ranged from 7.58 to 16.93 DALYs per 100,000 population. CONCLUSIONS: LB causes a substantial disease burden in the Netherlands. The vast majority of this burden is caused by patients with Lyme-related persisting symptoms. EM and disseminated Lyme have a more modest impact. Further research should focus on the mechanisms that trigger development of these persisting symptoms that patients and their physicians attribute to LB.

[Cost-effectiveness of addiction care]. / De kosteneffectiviteit van interventies gericht op verslaving aan alcohol en drugs.

BACKGROUND: A large number of interventions are available for the treatment of addiction. Professionals need to know about the effectiveness and cost-effectiveness of interventions so they can prioritise appropriate interventions for the treatment of addiction. AIM: To provide an overview of the scientific literature on the cost-effectiveness of addiction treatment for alcohol- and drug-abusers. METHOD: We searched the databases Medline and Centre for Reviews and Dissemination. To be relevant for our study, articles had to focus on interventions in the health-care setting, have a Western context and have a health-related outcome measure such as quality adjusted life years (QALY). Twenty-nine studies met our inclusion criteria: 15 for alcohol and 14 for drugs. RESULTS: The studies on alcohol addiction related mainly to brief interventions. They proved to be cost-saving or had a favourable incremental cost-effectiveness ratio (ICER), remaining below the threshold of € 20,000 per QALY. The studies on drug addiction all involved pharmacotherapeutic interventions. In the case of 10 out of 14 interventions, the ICER was less than € 20,000 per QALY. CONCLUSION: Almost all of the interventions studied were cost-saving or cost-effective. Many studies consider only health-care costs. Additional research, for instance using a social cost-benefit analysis, could provide more details about the costs of addiction and about the impact that an intervention could have in these/the costs.

Effectiveness and cost-effectiveness of 3-monthly versus 6-monthly monitoring of well-controlled type 2 diabetes patients: a pragmatic randomised controlled patient-preference equivalence trial in primary care (EFFIMODI study).

AIM: To investigate effectiveness and cost-effectiveness of 6-monthly monitoring compared with 3-monthly monitoring of well-controlled type 2 diabetes patients in primary care. METHODS: A pragmatic randomised controlled patient-preference equivalence trial was performed. From April 2009 to August 2010, 2215 patients from 233 general practitioners across the Netherlands were included. Patients were eligible if between 40- and 80-years-old, diagnosed with type 2 diabetes for more than a year, treated by their general practitioner, not on insulin treatment and well-controlled during the last year (HbA1c ≤ 58 mmol/mol, systolic blood pressure ≤ 145 mmHg and total cholesterol ≤ 5.2 mmol/l). Patients without a strong preference for their monitoring frequency were randomised to 3-monthly or 6-monthly monitoring. Follow-up was 18 months. The primary outcome is the percentage of patients remaining under: HbA1c ≤ 58 mmol/mol, systolic blood pressure ≤ 145 mmHg and total cholesterol ≤ 5.2 mmol/l. Equivalence was assumed if the two-sided 95% confidence interval (CI) was between -5 and 5%. Cost-effectiveness was determined using a cost-minimisation analysis. RESULTS: In the 3-monthly group 69.5% remained under good cardiometabolic control, versus 69.8% in the 6-monthly group (difference: 0.3%; 95%CI: -6.2-6.7%). All secondary outcomes were equivalent for 3-monthly and 6-monthly monitoring, except the systolic blood pressure target, physical activity and antihypertensive drug use. Six-monthly monitoring was €387 (£333) cheaper per patient compared to 3-monthly monitoring during the study period. CONCLUSIONS: Patients with good cardiometabolic control and without preference for their monitoring frequency can visit the primary care physician less often. The cost-savings can be considerable.

Comparing Discrete Choice Experiment with Swing Weighting to Estimate Attribute Relative Importance: A Case Study in Lung Cancer Patient Preferences.

INTRODUCTION: Discrete choice experiments (DCE) are commonly used to elicit patient preferences and to determine the relative importance of attributes but can be complex and costly to administer. Simpler methods that measure relative importance exist, such as swing weighting with direct rating (SW-DR), but there is little empirical evidence comparing the two. This study aimed to directly compare attribute relative importance rankings and weights elicited using a DCE and SW-DR. METHODS: A total of 307 patients with non-small-cell lung cancer in Italy and Belgium completed an online survey assessing preferences for cancer treatment using DCE and SW-DR. The relative importance of the attributes was determined using a random parameter logit model for the DCE and rank order centroid method (ROC) for SW-DR. Differences in relative importance ranking and weights between the methods were assessed using Cohen's weighted kappa and Dirichlet regression. Feedback on ease of understanding and answering the 2 tasks was also collected. RESULTS: Most respondents (>65%) found both tasks (very) easy to understand and answer. The same attribute, survival, was ranked most important irrespective of the methods applied. The overall ranking of the attributes on an aggregate level differed significantly between DCE and SW-ROC (P < 0.01). Greater differences in attribute weights between attributes were reported in DCE compared with SW-DR (P < 0.01). Agreement between the individual-level attribute ranking across methods was moderate (weighted Kappa 0.53-0.55). CONCLUSION: Significant differences in attribute importance between DCE and SW-DR were found. Respondents reported both methods being relatively easy to understand and answer. Further studies confirming these findings are warranted. Such studies will help to provide accurate guidance for methods selection when studying relative attribute importance across a wide array of preference-relevant decisions. HIGHLIGHTS: Both DCEs and SW tasks can be used to determine attribute relative importance rankings and weights; however, little evidence exists empirically comparing these methods in terms of outcomes or respondent usability.Most respondents found the DCE and SW tasks very easy or easy to understand and answer.A direct comparison of DCE and SW found significant differences in attribute importance rankings and weights as well as a greater spread in the DCE-derived attribute relative importance weights.

Cost-effectiveness of targeted screening for hepatitis C in The Netherlands.

On account of the serious complications of hepatitis C virus (HCV) infection and the improved treatment possibilities, the need to improve HCV awareness and case-finding is increasingly recognized. To optimize a future national campaign with this objective, three pilot campaigns were executed in three regions in The Netherlands. One campaign was aimed at the general population, a second (similar) campaign was extended with a support programme for primary care and a third campaign was specifically aimed at hard-drug users. Data from the pilot campaigns were used to build a mathematical model to estimate the incremental cost-effectiveness ratio of the different campaigns. The campaign aimed at the general public without support for primary care did not improve case-finding and was therefore not cost-effective. The similar campaign accompanied by additional support for primary care and the campaign aimed at hard-drug users emerged as cost-effective interventions for identification of HCV carriers.

If you were a policymaker, which treatment would you disinvest? A participatory value evaluation on public preferences for active disinvestment of health care interventions in the Netherlands.

INTRODUCTION: Currently, it is not known what attributes of health care interventions citizens consider important in disinvestment decision-making (i.e. decisions to discontinue reimbursement). Therefore, this study aims to investigate the preferences of citizens of the Netherlands toward the relative importance of attributes of health care interventions in the context of disinvestment. METHODS: A participatory value evaluation (PVE) was conducted in April and May 2020. In this PVE, 1143 Dutch citizens were asked to save at least €100 million by selecting health care interventions for disinvestment from a list of eight unlabeled health care interventions, described solely with attributes. A portfolio choice model was used to analyze participants' choices. RESULTS: Participants preferred to disinvest health care interventions resulting in smaller gains in quality of life and life expectancy that are provided to older patient groups. Portfolios (i.e. combinations of health care interventions) resulting in smaller savings were preferred for disinvestment over portfolios with larger savings. CONCLUSION: The disinvestment of health care interventions resulting in smaller health gains and that are targeted at older patient groups is likely to receive most public support. By incorporating this information in the selection of candidate interventions for disinvestment and the communication on disinvestment decisions, policymakers may increase public support for disinvestment.

Societal views in the Netherlands on active disinvestment of publicly funded healthcare interventions.

OBJECTIVES: To obtain public support for the active disinvestment (i.e. policy decision to stop reimbursement) of healthcare interventions, it is important to have insight in what the public thinks about disinvestment and which considerations they find relevant in this context. Currently, evidence on relevant considerations in the disinvestment context is limited. Therefore, this study aimed to explore the societal views in the Netherlands on the active disinvestment of healthcare interventions and obtain insight into the considerations that are relevant for those holding the different views. METHODS: A Q-methodology study was conducted among a purposively selected sample of citizens (n = 43). Data were collected in June and July 2019. Participants individually ranked a set of 43 statements broadly covering the issues that participants could consider relevant in the disinvestment context, from 'least agree' to 'most agree'. Qualitative feedback on the statement ranking was collected from each participant using a questionnaire. Principal component analysis followed by oblimin rotation was used to identify clusters of participants with similar statement rankings. These clusters/factors were interpreted as distinct viewpoints using the factor arrays and qualitative questionnaire responses of participants. RESULTS: Four viewpoints were identified. People holding viewpoint I believe that reimbursement of necessary healthcare should be maintained, irrespective of its costs. People holding viewpoint II agree with viewpoint I, although they believe that necessity should be objectively determined. People holding viewpoint III think that unnecessary, ineffective and inefficient healthcare should be disinvested. People holding viewpoint IV, consider it most important that disinvestment decision-making processes are transparent and consistent. CONCLUSION: Insight in the distinct viewpoints identified in this study contributes to a better understanding of why it has been considered difficult to obtain public support for disinvestment of healthcare interventions, and can help policymakers to change their approach to disinvestment to increase public support.

Impact of preventive screening and lifestyle interventions in women with a history of preeclampsia: A micro-simulation study.

BACKGROUND: Preeclampsia is a female-specific risk factor for the development of future cardiovascular disease. Whether early preventive cardiovascular disease risk screenings combined with risk-based lifestyle interventions in women with previous preeclampsia are beneficial and cost-effective is unknown. METHODS: A micro-simulation model was developed to assess the life-long impact of preventive cardiovascular screening strategies initiated after women experienced preeclampsia during pregnancy. Screening was started at the age of 30 or 40 years and repeated every five years. Data (initial and follow-up) from women with a history of preeclampsia was used to calculate 10-year cardiovascular disease risk estimates according to Framingham Risk Score. An absolute risk threshold of 2% was evaluated for treatment selection, i.e. lifestyle interventions (e.g. increasing physical activity). Screening benefits were assessed in terms of costs and quality-adjusted-life-years, and incremental cost-effectiveness ratios compared with no screening. RESULTS: Expected health outcomes for no screening are 27.35 quality-adjusted-life-years and increase to 27.43 quality-adjusted-life-years (screening at 30 years with 2% threshold). The expected costs for no screening are €9426 and around €13,881 for screening at 30 years (for a 2% threshold). Preventive screening at 40 years with a 2% threshold has the most favourable incremental cost-effectiveness ratio, i.e. €34,996/quality-adjusted-life-year, compared with other screening scenarios and no screening. CONCLUSIONS: Early cardiovascular disease risk screening followed by risk-based lifestyle interventions may lead to small long-term health benefits in women with a history of preeclampsia. However, the cost-effectiveness of a lifelong cardiovascular prevention programme starting early after preeclampsia with risk-based lifestyle advice alone is relatively unfavourable. A combination of risk-based lifestyle advice plus medical therapy may be more beneficial.

Cost-effectiveness of additional hepatitis B virus nucleic acid testing of individual donations or minipools of six donations in the Netherlands.

BACKGROUND: To further reduce the risk of hepatitis B virus (HBV) transmission by blood transfusion, nucleic acid testing (NAT) can be employed. The aim of this study is to estimate the incremental cost-effectiveness ratio (ICER) in the Netherlands of employing a triplex NAT assay aimed at HBV nucleic acid detection in individual donations (ID-NAT) or in minipools of 6 donations (MP-6-NAT), compared to a triplex NAT assay in minipools of 24 donations (MP-24-NAT). STUDY DESIGN AND METHODS: A mathematical model was made of the whole transfusion chain from donors to recipients of blood in the Netherlands. The annual number of avoided HBV transmissions was estimated with the window-period incidence model. The natural history of a HBV infection in recipients is described by a Markov model. RESULTS: The ICER of adding HBV MP-6-NAT or HBV ID-NAT in the Netherlands is Euro303,218 (95% confidence interval [CI], Euro233,001-Euro408,388) and Euro518,995 (95% CI, Euro399,359-Euro699,120) per quality-adjusted life-year, respectively. The ICER strongly correlates with the age of transfusion recipients. CONCLUSION: The cost-effectiveness of additional HBV NAT is limited by the limited loss of life caused by HBV transmission. Despite a higher effectiveness, HBV ID-NAT is less cost-effective than MP-6-NAT due to higher costs. A future equivalent participation of immigrants from HBV-endemic countries in the donor base renders HBV NAT only slightly more cost-effective.

Interpretation of CVD risk predictions in clinical practice: Mission impossible?

BACKGROUND: Cardiovascular disease (CVD) risk prediction models are often used to identify individuals at high risk of CVD events. Providing preventive treatment to these individuals may then reduce the CVD burden at population level. However, different prediction models may predict different (sets of) CVD outcomes which may lead to variation in selection of high risk individuals. Here, it is investigated if the use of different prediction models may actually lead to different treatment recommendations in clinical practice. METHOD: The exact definition of and the event types included in the predicted outcomes of four widely used CVD risk prediction models (ATP-III, Framingham (FRS), Pooled Cohort Equations (PCE) and SCORE) was determined according to ICD-10 codes. The models were applied to a Dutch population cohort (n = 18,137) to predict the 10-year CVD risks. Finally, treatment recommendations, based on predicted risks and the treatment threshold associated with each model, were investigated and compared across models. RESULTS: Due to the different definitions of predicted outcomes, the predicted risks varied widely, with an average 10-year CVD risk of 1.2% (ATP), 5.2% (FRS), 1.9% (PCE), and 0.7% (SCORE). Given the variation in predicted risks and recommended treatment thresholds, preventive drugs would be prescribed for 0.2%, 14.9%, 4.4%, and 2.0% of all individuals when using ATP, FRS, PCE and SCORE, respectively. CONCLUSION: Widely used CVD prediction models vary substantially regarding their outcomes and associated absolute risk estimates. Consequently, absolute predicted 10-year risks from different prediction models cannot be compared directly. Furthermore, treatment decisions often depend on which prediction model is applied and its recommended risk threshold, introducing unwanted practice variation into risk-based preventive strategies for CVD.

[Cost-effectiveness of prevention: opportunities for public health policy in the Netherlands]. / Kosteneffectiviteit van preventie: kansen voor het Nederlandse volksgezondheidsbeleid.

OBJECTIVE: To gain insight into the cost-effectiveness of new preventive interventions. DESIGN: Systematic review and interviews. METHOD: Based on literature search, a search of the project database of ZonMw and interviews with experts, the National Institute for Public Health and the Environment drew up a long list of preventive interventions that are potentially cost-effective but are not yet systematically carried out in the Netherlands. From this long list, 21 interventions were selected for each of which, at least 3 economic evaluations were available that indicate favourable cost-effectiveness (< Euro 20,000,--per QALY gained). RESULTS: The majority of the interventions concerned vaccination and screening programmes (7 and 5 respectively). Only a small minority concerned health promotion or health protection (1 respectively 3). There was strong evidence that 5 interventions were both cost-effective, and feasible. These were: screening for Chlamydia, screening for diabetic retinopathy in type 2 diabetes, screening for neonatal group beta streptococcal infections through a combination strategy, prevention of recurrent myocardial infarction through heart habilitation, and prevention of head injuries by wearing of bicycle helmets by children. CONCLUSION: Before implementation of preventive interventions, it is necessary to investigate whether these interventions are also cost-effective in the Dutch context.

The design of a Social Cost-Benefit Analysis of preventive interventions for toxoplasmosis: An example of the One Health approach.

Toxoplasma gondii infections cause a large disease burden in the Netherlands, with an estimated health loss of 1,900 Disability Adjusted Life Years and a cost-of-illness estimated at €44 million annually. Infections in humans occur via exposure to oocysts in the environment and after eating undercooked meat containing tissue cysts, leading to asymptomatic or mild symptoms, but potentially leading to the development of ocular toxoplasmosis. Infection in pregnant women can lead to stillbirth and disorders in newborns. At present, prevention is only targeted at pregnant women. Cat vaccination, freezing of meat destined for undercooked consumption and enhancing biosecurity in pig husbandries are possible interventions to prevent toxoplasmosis. As these interventions bear costs for sectors in society that differ from those profiting from the benefits, we perform a social cost-benefit analysis (SCBA). In an SCBA, costs and benefits of societal domains affected by the interventions are identified, making explicit which stakeholder pays and who benefits. Using an epidemiological model, we consider transmission of T. gondii after vaccination of all owned cats or cats at livestock farms. To identify relevant high-risk meat products that will be eaten undercooked, a quantitative microbial risk assessment model developed to attribute predicted T. gondii infections to specific meat products will be used. In addition, we evaluate serological monitoring of pigs at slaughter followed by an audit and tailor made advice for farmers in case positive results were found. The benefits will be modelled stochastically as reduction in DALYs and monetized in Euro's following reference prices for DALYs. If the balance of total costs and benefits is positive, this will lend support to implementation of these preventive interventions at the societal level. Ultimately, the SCBA will provide guidance to policy makers on the most optimal intervention measures to reduce the disease burden of T. gondii in the Netherlands.