An overview of the time trade-off method: concept, foundation, and the evaluation of distorting factors in putting a value on health.

INTRODUCTION: Preference-based instruments measuring health status express the value of specific health states in a single number. One method used is time trade-off (TTO). Health-status values are key elements in calculating quality-adjusted life years (QALYs) and are pertinent for resource allocation. Since they are used in economic evaluations of healthcare, searching for a theoretical foundation of TTO in economics is justified. AREA COVERED: This paper provides an overview of TTO, including its relation to economic theory, and discusses biases and distortions, compiled from recent and older research. Inconsistencies between TTO and random utility theory were detected; The TTO is confounded by time preferences and by respondents' life expectancies. TTO is cognitively challenging, therefore guidance during the interviews is needed, producing interview effects. TTO does not measure one thing at a time, nor are the values independent of other states that are being valued in the same task. That is, TTO does not exhibit theoretical measurement properties such as unidimensionality and the invariance principle. EXPERT OPINION: We conclude that the TTO may be a pragmatic method of eliciting health state values, but the limitations in regard to measurement theory and practical elicitation problems makes it prone to inconsistencies and arbitrariness.

Consequences of restricted STI testing for young heterosexuals in the Netherlands on test costs and QALY losses.

BACKGROUND: Due to rising costs caused by increasing demand for sexually transmitted infection (STI) care, the Dutch government changed the funding of STI clinics. In 2015, a more restrictive testing policy was introduced with syphilis and HIV tests only on indication for younger, heterosexual clients. We evaluated intended savings and missed syphilis and/or HIV infections and explored efficiency of possible test policies. METHODS: Using surveillance data from 2011 to 2013 with extensive testing for all, we estimated effects of restrictive testing on test costs, number of infections missed, costs per Quality Adjusted Life Year (QALY) lost, and calculated the net monetary benefit from a government perspective. RESULTS: The 2015 policy led to estimated savings of €1.1 million, while missing approximately three HIV infections and seven syphilis infections annually. Savings were €435,000/QALY lost. If testing second-generation immigrants for syphilis and HIV, savings rose to €525,000/QALY lost. Offering an HIV test when diagnosed with chlamydia or gonorrhoea savings were €568,000/QALY lost. In a sensitivity analysis, the willingness-to-pay threshold had the highest impact on results. CONCLUSIONS: The 2015 testing policy resulted in a modest decline of detected HIV and syphilis infections, generating substantial savings. Syphilis and HIV tests for both first- and second-generation immigrants and an HIV test in case of positive chlamydia or gonorrhoea diagnosis could reduce missed infections in a cost-effective way.

The cost of Lyme borreliosis.

Background: Lyme borreliosis (LB) is the most frequently reported tick-borne infection in Europe and North America. The aim of this study was to estimate the cost-of-illness of LB in the Netherlands. We used available incidence estimates from 2010 for tick bite consultations and three symptomatic LB outcomes: erythema migrans (EM), disseminated LB and Lyme-related persisting symptoms. The cost was estimated using these incidences and the average cost per patient as derived from a patient questionnaire. We estimated the cost from a societal perspective, including healthcare cost, patient cost and production loss, using the friction cost method and a 4% annual discount rate. Tick bites and LB in 2010 led to a societal cost of €19.3 million (95% CI 15.6-23.4; 16.6 million population) for the Netherlands. Healthcare cost and production loss each constituted 48% of the total cost (€9.3 and €9.2 million/year), and patient cost 4% (€0.8 million/year). Of the total cost, 37% was related to disseminated LB, followed by 27% for persisting symptoms, 22% for tick bites and 14% for EM. Per outcome, for an individual case the mean cost of disseminated LB and Lyme-related persisting symptoms was both around €5700; for EM and GP consultations for tick bites this was €122 and €53. As an alternative to the friction cost method, the human capital method resulted in a total cost of €23.5 million/year. LB leads to a substantial societal cost. Further research should therefore focus on additional preventive interventions.

The whole story: a systematic review of economic evaluations of HPV vaccination including non-cervical HPV-associated diseases.

INTRODUCTION: Many economic evaluations of HPV vaccination have been published, but most have focused on the prevention of cervical disease as a primary health outcome. The cost-effectiveness of vaccination is likely to be underestimated if not all HPV-associated diseases are taken into account. In this review, we assess the influence of non-cervical HPV-associated diseases on the incremental cost-effectiveness ratio (ICER) of preadolescent HPV vaccination. Areas covered: We systematically searched the literature and identified 18 studies that included non-cervical diseases in the estimates of cost-effectiveness of HPV-vaccination. When taking other HPV-related diseases into account compared to not including such other diseases, the mean ICERs were 2.85 times more favorable for girls only vaccination and 3.89 times for gender neutral vaccination. Expert commentary: Including non-cervical diseases in economic evaluations of HPV vaccination programs makes it more likely that the ICER falls beneath accepted cost-effectiveness thresholds and therefore increases the scope for gender neutral vaccination.

Economic Costs of Measles Outbreak in the Netherlands, 2013-2014.

In 2013 and 2014, the Netherlands experienced a measles outbreak in orthodox Protestant communities with low measles-mumps-rubella vaccination coverage. Assessing total outbreak costs is needed for public health outbreak preparedness and control. Total costs of this outbreak were an estimated $4.7 million.

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.

[More efficient testing policy at STI clinics]. / Doelmatiger testbeleid van soa-poliklinieken GGD.

OBJECTIVE: To assess the efficiency of the testing policy change in 2012 in sexually transmitted infection (STI) outpatient clinics: persons who attend the clinic and are aged < 25 years without other risk factors are initially tested only for chlamydia, and only in the event of a positive test result will they be tested for other STIs. Other possible changes in the STI testing policy were explored. DESIGN: Explorative study. METHOD: To test the new policy, data from STI outpatient clinics from 2011 were used for the risk group "young people under 25 years of age without other STI risks". Other groups who visited STI outpatient clinic were selected from the data from the STI outpatient clinics from 2012. Test cost savings and missed STIs were calculated if STI outpatient clinic attendees from these risk groups first received only a chlamydia or a combination test (chlamydia and gonorrhoea). Test cost savings were divided by the number of missed STIs as a measure of efficiency. RESULTS: The policy change led to an annual test cost saving of € 1.1 million but missed 31 gonorrhoea infections (€ 36,200 at the cost of one missed gonorrhoea infection). Using a combination test for chlamydia and gonorrhoea in heterosexual individuals visiting the clinic aged < 25 years and not from a STI-endemic country could lead to test costs savings of € 3.8 million. Savings at the cost of one missed STI would be about € 350,000; 4 HIV and 7 syphilis infections would have been missed. CONCLUSION: The national policy change has led to a substantial reduction in test costs. The policy measure would be even more efficient if a combination test for chlamydia and gonorrhoea were applied. Testing using a combination test in all heterosexual individuals who attend the clinic and are aged < 25 years and not from an STI-endemic country would lead to additional savings.

Cost-effectiveness of targeted vaccination to protect new-borns against pertussis: comparing neonatal, maternal, and cocooning vaccination strategies.

Pertussis (whooping cough) is a severe infectious disease in infants less than 6 months old. Mass vaccination programmes have been unable to halt transmission effectively. Strategies to protect new-borns against infection include vaccination of the neonate or the mother directly after birth (cocooning), or the mother during pregnancy (maternal). Here we investigate the cost-effectiveness of these three strategies in the Netherlands. Costs for health care utilization and productivity losses, as well as impact on quality of life were calculated for a 10-year vaccination programme, assuming that vaccine-induced immunity lasts 5 years. Cocooning was the most attractive option from a cost-effectiveness viewpoint (€89,000/QALY). However, both cocooning and maternal vaccination would reduce the disease burden in infants and mothers vaccinated (about 17-20 QALY/year). Specifically, with a persistent epidemic as seen in 2012, there is need for reconsidering the vaccination schedules against pertussis in order to increase protection of the vulnerable new-borns.

Modelling the impact of chlamydia screening on the transmission of HIV among men who have sex with men.

BACKGROUND: Recent studies have found high prevalences of asymptomatic rectal chlamydia among HIV-infected men who have sex with men (MSM). Chlamydia could increase the infectivity of HIV and the susceptibility to HIV infection. We investigate the role of chlamydia in the spread of HIV among MSM and the possible impact of routine chlamydia screening among HIV-infected MSM at HIV treatment centres on the incidence of chlamydia and HIV in the overall MSM population. METHODS: A mathematical model was developed to describe the transmission of HIV and chlamydia among MSM. Parameters relating to sexual behaviour were estimated from data from the Amsterdam Cohort Study among MSM. Uncertainty analysis was carried out for model parameters without confident estimates. The effects of different screening strategies for chlamydia were investigated. RESULTS: Among all new HIV infections in MSM, 15% can be attributed to chlamydia infection. Introduction of routine chlamydia screening every six months among HIV-infected MSM during regular HIV consultations can reduce the incidence of both infections among MSM: after 10 years, the relative percentage reduction in chlamydia incidence would be 15% and in HIV incidence 4%, compared to the current situation. Chlamydia screening is more effective in reducing HIV incidence with more frequent screening and with higher participation of the most risky MSM in the screening program. CONCLUSIONS: Chlamydia infection could contribute to the transmission of HIV among MSM. Preventive measures reducing chlamydia prevalence, such as routine chlamydia screening of HIV-infected MSM, can result in a decline in the incidence of chlamydia and HIV.

Sexually transmitted infections screening at HIV treatment centers for MSM can be cost-effective.

OBJECTIVE: To estimate the cost-effectiveness of anorectal chlamydia screening among men who have sex with men (MSM) in care at HIV treatment centers. DESIGN: Transmission model combined with economic analysis over a 20-year period. SETTING AND PARTICIPANTS: MSM in care at HIV treatment centers. INTERVENTION: Once-yearly or twice-yearly screening for anorectal chlamydia among MSM in care at HIV treatment centers. MAIN OUTCOME MEASURES: Averted HIV and chlamydia infections; discounted quality-adjusted life-years and costs; incremental cost-effectiveness ratio (ICER). RESULTS: Costs will be saved by routine chlamydia screening of MSM in care at HIV treatment centers if these patients seek little or no screening elsewhere. Nonroutine screening is considerably more expensive than routine screening offered within a scheduled visit. Adding once-yearly chlamydia screening for MSM in care at HIV treatment centers is cost saving when 30% or fewer of those men seek once-yearly screening elsewhere (1.5 to 8.1 million euro saved). Twice-yearly routine screening at HIV treatment centers is cost-effective only when routine screening takes place without additional nonroutine screening (1.9 million euro saved). CONCLUSIONS: Adding annual chlamydia screening to the HIV consultation will be cost saving as long as only a limited proportion of men are nonroutinely screened. The ICER was most sensitive to the percentage of MSM that continue to be screened elsewhere.

Cost effectiveness of vaccination against pandemic influenza in European countries: mathematical modelling analysis.

OBJECTIVE: To investigate whether a single optimal vaccination strategy exists across countries to deal with a future influenza pandemic by comparing the cost effectiveness of different strategies in various pandemic scenarios for three European countries. DESIGN: Economic and epidemic modelling study. SETTINGS: General populations in Germany, the Netherlands, and the United Kingdom. DATA SOURCES: Country specific patterns of social contact and demographic data. MODEL: An age structured susceptible-exposed-infected-recovered transmission model that describes how an influenza A virus will spread in the populations of Germany, the Netherlands, and the United Kingdom. INTERVENTIONS: Comparison of four vaccination strategies: no vaccination, blanket vaccination, vaccination of elderly people (≥ 65 years), and vaccination of high transmitters (5-19 years). The four strategies were evaluated for scenarios in which a vaccine became available early or at the peak of the pandemic, and in which either everyone was initially susceptible or older age groups had pre-existing immunity. MAIN OUTCOME MEASURE: Cost per quality adjusted life years (QALYs) gained. RESULTS: All vaccination strategies were cost effective (incremental cost per QALY gained, comparing intervention with non-intervention). In scenarios where the vaccine became available at the peak of the pandemic and there was pre-existing immunity among elderly people the incremental cost effectiveness ratios for vaccinating high transmitters were €7325 (£5815; $10,470) per QALY gained for Germany, €10,216 per QALY gained for the Netherlands, and €7280 per QALY gained for the United Kingdom. The most cost effective strategy not only differed across the pandemic scenarios but also between countries. Specifically, when the vaccine was available early in the pandemic and there was no pre-existing immunity, in Germany it would be most cost effective to vaccinate elderly people ( €940 per QALY gained), whereas it would be most cost effective to vaccinate high transmitters in both the Netherlands (€525 per QALY gained) and the United Kingdom (€163 per QALY gained). This difference in optimal strategies was due to differences in the demographic characteristics of the countries: Germany has a significantly higher proportion of elderly people compared with the Netherlands and the United Kingdom. CONCLUSIONS: No single vaccination strategy was most cost effective across countries. With aging populations, pre-existing immunity in particular could be of crucial importance for the cost effectiveness of options to mitigate a future influenza pandemic.

Investment in antiviral drugs: a real options approach.

Real options analysis is a promising approach to model investment under uncertainty. We employ this approach to value stockpiling of antiviral drugs as a precautionary measure against a possible influenza pandemic. Modifications of the real options approach to include risk attitude and deviations from expected utility are presented. We show that risk aversion counteracts the tendency to delay investment for this case of precautionary investment, which is in contrast to earlier applications of risk aversion to real options analysis. Moreover, we provide a numerical example using real world data and discuss the implications of real options analysis for health policy. Suggestions for further extensions of the model and a comparison with the expected value of information analysis are put forward.

Dynamic versus static models in cost-effectiveness analyses of anti-viral drug therapy to mitigate an influenza pandemic.

Conventional (static) models used in health economics implicitly assume that the probability of disease exposure is constant over time and unaffected by interventions. For transmissible infectious diseases this is not realistic and another class of models is required, so-called dynamic models. This study aims to examine the differences between one dynamic and one static model, estimating the effects of therapeutic treatment with antiviral (AV) drugs during an influenza pandemic in the Netherlands. Specifically, we focus on the sensitivity of the cost-effectiveness ratios to model choice, to the assumed drug coverage, and to the value of several epidemiological factors. Therapeutic use of AV-drugs is cost-effective compared with non-intervention, irrespective of which model approach is chosen. The findings further show that: (1) the cost-effectiveness ratio according to the static model is insensitive to the size of a pandemic, whereas the ratio according to the dynamic model increases with the size of a pandemic; (2) according to the dynamic model, the cost per infection and the life-years gained per treatment are not constant but depend on the proportion of cases that are treated; and (3) the age-specific clinical attack rates affect the sensitivity of cost-effectiveness ratio to model choice.

Mitigation of pandemic influenza: review of cost-effectiveness studies.

We conducted a review of economic evaluations of pandemic influenza control measures. In the studies found, we detected various interventions being investigated: antiviral stockpiling and treatment, prophylaxis, vaccination, school closure and restricting international travel. Cost-effectiveness varied but often showed potentials for the favorable economic profiles of these measures. Both static and dynamic models were used. We conclude that the choice of an appropriate model - in particular, a dynamic model - is crucial to arrive at valid cost-effectiveness ratios. Yet, of the economic evaluations considered here, only a few were based on dynamic modeling. We recommend that further research is directed toward linking dynamic epidemiological models for pandemic spread with economic outcomes by considering the full impacts on national economies, including direct, indirect, medical and nonmedical costs.

Investment decisions in influenza pandemic contingency planning: cost-effectiveness of stockpiling antiviral drugs.

BACKGROUND: The threat of an influenza pandemic has led to stockpiling of antiviral drugs in order to mitigate a plausible outbreak. If the stockpile would be used in relation to the recent pandemic alert, an investment decision about renewing the stock for a possible subsequent pandemic is essential. The decision should include cost-effectiveness considerations. METHODS: We constructed a cost-effectiveness analysis in the Dutch context, explicitly including risk of an outbreak. Outcomes from a dynamic transmission model, comparing an intervention with a non-intervention scenario, were input in our health economic calculations. RESULTS: Stockpiling was cost-effective from the health-care perspective if the actual risk is 37% for 30 years. If less than 60% of the population would take the antiviral drugs or the attack rate is about 50%, the investment would not be cost-effective from this perspective. CONCLUSION: Risk perception, realistic coverage among population and size of a pandemic are crucial parameters and highly decisive for the investment decision.

Economic analysis of pertussis illness in the Dutch population: implications for current and future vaccination strategies.

To reduce pertussis disease burden new vaccination strategies are considered in many countries. Since not only health benefits, but also economical aspects play a role when introducing new vaccinations, we estimated medical costs of pertussis in the Netherlands. Besides, we retrospectively performed a cost-utility analysis of the preschool booster introduced in 2001. Our results show that annual costs for pertussis are still considerable (approximately c.1.77 million for a population of 16 million). Although infants represented only 5% of cases, they accounted for 50% of the total costs. Hence, the economic burden of pertussis is largely determined by costs per infant case (c.1490) and only to a limited degree by costs per patient in other age-groups (circa c.75). Despite a substantial reduction in the number of cases, the preschool booster was not considered cost-effective. The effectiveness of universal adolescent or adult booster strategies -- to prevent pertussis in infants -- should also be considered from an economical point of view before being implemented.

Optimal allocation of pandemic influenza vaccine depends on age, risk and timing.

The limited production capacity for vaccines raises the question what the best strategy is for allocating the vaccine to mitigate an influenza pandemic. We developed an age-structured model for spread of an influenza pandemic and validated it against observations from the Asian flu pandemic. Two strategies were evaluated: vaccination can be implemented at the start of the influenza pandemic, or vaccination will be implemented near the peak of it. Our results suggest prioritizing individuals with a high-risk of complications if a vaccine becomes available during a pandemic. If available at the start, vaccinating school children might be considered since this results in slightly lower expected number of deaths.