Objective

To estimate the lifetime cost utility of two antiretroviral regimens (once-daily atazanavir plus ritonavir [ATV+r] versus twice-daily lopinavir/ritonavir [LPV/r]) in Italian human immunodeficiency virus (HIV)-infected patients naïve to treatment.

Design

With this observational retrospective study we collected the clinical data of a cohort of HIV-infected patients receiving first-line treatment with LPV/r or ATV+r.

Methodology

A Markov microsimulation model including direct costs and health outcomes of first- and second-line highly active retroviral therapy was developed from a third-party (Italian National Healthcare Service) payer’s perspective. Health and monetary outcomes associated with the long-term use of ATV+r and LPV/r regimens were evaluated on the basis of eight health states, incidence of diarrhoea and hyperbilirubinemia, AIDS events, opportunistic infections, coronary heart disease events and, for the first time in an economic evaluation, chronic kidney disease (CKD) events. In order to account for possible deviations between real-life data and randomised controlled trial results, a second control arm (ATV+r 2) was created with differential transition probabilities taken from the literature.

Results

The average survival was 24.061 years for patients receiving LPV/r, 24.081 and 24.084 for those receiving ATV+r 1 and 2 respectively. The mean quality-adjusted life-years (QALYs) were higher for the patients receiving LPV/r than those receiving ATV+r (13.322 vs. 13.060 and 13.261 for ATV+r 1 and 2). The cost-utility values were 15,310.56 for LPV/r, 15,902.99 and 15,524.85 for ATV+r 1 and 2.

Conclusions

Using real-life data, the model produced significantly different results compared with other studies. With the innovative addition of an evaluation of CKD events, the model showed a cost-utility value advantage for twice-daily LPV/r over once-daily ATV+r, thus providing evidence for its continued use in the treatment of HIV.

Background

Infection with HPV 16 and 18, the major causative agents of cervical cancer, can be prevented through vaccination with a bivalent or quadrivalent vaccine. Both vaccines provide cross-protection against HPV-types not included in the vaccines. In particular, the bivalent vaccine provides additional protection against HPV 31, 33, and 45 and the quadrivalent vaccine against HPV31. The quadrivalent vaccine additionally protects against low-risk HPV type 6 and 11, responsible for most cases of genital warts. In this study, we made an analytical comparison of the two vaccines in terms of cost-effectiveness including the additional benefits of cross-protection and protection against genital warts in comparison with a screening-only strategy.

Methods

We used a Markov model, simulating the progression from HPV infection to cervical cancer or genital warts. The model was used to estimate the difference in future costs and health effects of both HPV-vaccines separately.

Results

In a cohort of 100,000 women, use of the bivalent or quadrivalent vaccine (both at 50% vaccination coverage) reduces the cervical cancer incidence by 221 and 207 cases, corresponding to ICERs of €17,600/QALY and €18,900/QALY, respectively. It was estimated that the quadrivalent vaccine additionally prevents 4390 cases of genital warts, reducing the ICER to €16,300/QALY. Assuming a comparable willingness to pay for cancer and genital warts prevention, the difference in ICERs could justify a slightly higher price (~7% per dose) in favor of the quadrivalent vaccine.

Conclusions

Clearly, HPV vaccination has been implemented for the prevention of cervical cancer. From this perspective, use of the bivalent HPV vaccine appears to be most effective and cost-effective. Including the benefits of prevention against genital warts, the ICER of the quadrivalent HPV vaccine was found to be slightly more favourable. However, current decision-making on the introduction of HPV is driven by the primary cervical cancer outcome. New vaccine tenders could consider the benefits of cross-protection and the benefits of genital warts, which requires more balanced decision-making.

Background

To update a cost-effectiveness analysis of rotavirus vaccination in the Netherlands previously published in 2011.

Methods

The rotavirus burden of disease and the indirect protection of older children and young adults (herd protection) were updated.

Results

When updated data was used, routine infant rotavirus vaccination in the Netherlands would potentially become an even more cost-effective strategy than previously estimated with the incremental cost per QALY at only €3,000-4,000. Break-even total vaccination costs were indicated at €92–122, depending on the applied threshold.

Conclusions

We concluded that the results on potentially favourable cost-effectiveness in the previous study remained valid, however, the new data suggested that previous results might represent an underestimation of the economic attractiveness of rotavirus vaccination.

Background

Published economic assessments of rotavirus vaccination typically use modelling, mainly static Markov cohort models with birth cohorts followed up to the age of 5 years. Rotavirus vaccination has now been available for several years in some countries, and data have been collected to evaluate the real-world impact of vaccination on rotavirus hospitalisations. This study compared the economic impact of vaccination between model estimates and observed data on disease-specific hospitalisation reductions in a country for which both modelled and observed datasets exist (Belgium).

Methods

A previously published Markov cohort model estimated the impact of rotavirus vaccination on the number of rotavirus hospitalisations in children aged <5 years in Belgium using vaccine efficacy data from clinical development trials. Data on the number of rotavirus-positive gastroenteritis hospitalisations in children aged <5 years between 1 June 2004 and 31 May 2006 (pre-vaccination study period) or 1 June 2007 to 31 May 2010 (post-vaccination study period) were analysed from nine hospitals in Belgium and compared with the modelled estimates.

Results

The model predicted a smaller decrease in hospitalisations over time, mainly explained by two factors. First, the observed data indicated indirect vaccine protection in children too old or too young for vaccination. This herd effect is difficult to capture in static Markov cohort models and therefore was not included in the model. Second, the model included a ‘waning’ effect, i.e. reduced vaccine effectiveness over time. The observed data suggested this waning effect did not occur during that period, and so the model systematically underestimated vaccine effectiveness during the first 4 years after vaccine implementation.

Conclusions

Model predictions underestimated the direct medical economic value of rotavirus vaccination during the first 4 years of vaccination by approximately 10% when assessing hospitalisation rates as compared with observed data in Belgium.

Background

Despite the increase in cancer incidence in the last years in Serbia, no nation-wide, population-based cancer epidemiology data have been reported. In this study cancer incidence and mortality rates for Serbia are presented using nation-wide data from two population-based cancer registries. These rates are additionally compared to European and global cancer epidemiology estimates. Finally, predictions on Serbian cancer incidence and mortality rates are provided.

Methods

Cancer incidence and mortality was collected from the cancer registries of Central Serbia and Vojvodina from 1999 to 2009. Using age-specific regression models, we estimated time trends and predictions for cancer incidence and mortality for the following five years (2010–2014). The comparison of Serbian with European and global cancer incidence/mortality rates, adjusted to the world population (ASR-W) was performed using Serbian population-based data and estimates from GLOBOCAN 2008.

Results

Increasing trends in both overall cancer incidence and mortality rates were identified for Serbia. In men, lung cancer showed the highest incidence (ASR-W 2009: 70.8/100,000), followed by colorectal (ASR-W 2009: 39.9/100,000), prostate (ASR-W 2009: 29.1/100,000) and bladder cancer (ASR-W 2009: 16.2/100,000). Breast cancer was the most common form of cancer in women (ASR-W 2009: 70.8/100,000) followed by cervical (ASR-W 2009: 25.5/100,000), colorectal (ASR-W 2009: 21.1/100,000) and lung cancer (ASR-W 2009: 19.4/100,000). Prostate and colorectal cancers have been significantly increasing over the last years in men, while this was also observed for breast cancer incidence and lung cancer mortality in women. In 2008 Serbia had the highest mortality rate from breast cancer (ASR-W 2008: 22.7/100,000), among all European countries while incidence and mortality of cervical, lung and colorectal cancer were well above European estimates.

Conclusion

Cancer incidence and mortality in Serbia has been generally increasing over the past years. For a number of cancer sites, incidence and mortality is alarmingly higher than in the majority of European regions. For this increasing trend to be controlled, the management of risk factors that are present among the Serbian population is necessary. Additionally, prevention and early diagnosis are areas where significant improvements could still be made.

Background

The influenza vaccination rate in hospitals among health care workers in Europe remains low. As there is a lack of research about management factors we assessed factors reported by administrators of general hospitals that are associated with the influenza vaccine uptake among health care workers.

Methods

All 81 general hospitals in the Netherlands were approached to participate in a self-administered questionnaire study. The questionnaire was directed at the hospital administrators. The following factors were addressed: beliefs about the effectiveness of the influenza vaccine, whether the hospital had a written policy on influenza vaccination and how the hospital informed their staff about influenza vaccination. The questionnaire also included questions about mandatory vaccination, whether it was free of charge and how delivered as well as the vaccination campaign costs. The outcome of this one-season survey is the self-reported overall influenza vaccination rate of health care workers.

Results

In all, 79 of 81 hospitals that were approached were willing to participate and therefore received a questionnaire. Of these, 42 were returned (response rate 52%). Overall influenza vaccination rate among health care workers in our sample was 17.7% (95% confidence interval: 14.6% to 20.8%). Hospitals in which the administrators agreed with positive statements concerning the influenza vaccination had a slightly higher, but non-significant, vaccine uptake. There was a 9% higher vaccine uptake in hospitals that spent more than €1250,- on the vaccination campaign (24.0% versus 15.0%; 95% confidence interval from 0.7% to 17.3%).

Conclusions

Agreement with positive statements about management factors with regard to influenza vaccination were not associated with the uptake. More economic investments were related with a higher vaccine uptake; the reasons for this should be explored further.

Aim

Investigate the cost and effects of a single-pill versus two- or three pill first-line antiretroviral combinations in reducing viral load, increasing CD4 counts, and first-line failure rate associated with respective regimens at 6 and 12 months.

Methods

Patients on first-line TDF+3TC+EFV, TDF+FTC+EFV, Truvada®+EFV or Atripla® between 1996–2008 were identified and viral load and CD4 counts measured at baseline, six and twelve months respectively. Factors that independently predicted treatment failure at six and twelve months were derived using multivariate Cox's proportional hazard regression analyses. Use and cost of hospital services were calculated at six and twelve months respectively.

Results

All regimens reduced viral load to below the limit of detection and CD4 counts increased to similar levels at six and twelve months for all treatment regimens. No statistically significant differences were observed for rate of treatment failure at six and twelve months. People on Atripla® generated lower healthcare costs for non-AIDS patients at £5,340 (£5,254 to £5,426) per patient-semester and £9,821 (£9,719 to £9,924) per patient-year that was £1,344 (95%CI £1,222 to £1,465) less per patient-semester and £1,954 (95%CI £1,801 to £2,107) less per patient-year compared with Truvada®+EFV; healthcare costs for AIDS patients were similar across all regimens.

Conclusion

The single pill regimen is as effective as the two- and three-pill regimens of the same drugs, but if started as first-line induction therapy there would be a 20% savings on healthcare costs at six and 17% of costs at twelve months compared with Truvada®+EFV, that generated the next lowest costs.

Background

Diarrhoea is an important cause of death in the developing world, and rotavirus is the single most important cause of diarrhoea associated mortality. Two vaccines (Rotarix and RotaTeq) are available to prevent rotavirus disease. This analysis was undertaken to aid the decision in Kenya as to which vaccine to choose when introducing rotavirus vaccination.

Methods

Cost-effectiveness modelling, using national and sentinel surveillance data, and an impact assessment on the cold chain.

Results

The median estimated incidence of rotavirus disease in Kenya was 3015 outpatient visits, 279 hospitalisations and 65 deaths per 100,000 children under five years of age per year. Cumulated over the first five years of life vaccination was predicted to prevent 34% of the outpatient visits, 31% of the hospitalizations and 42% of the deaths. The estimated prevented costs accumulated over five years totalled US$1,782,761 (direct and indirect costs) with an associated 48,585 DALYs. From a societal perspective Rotarix had a cost-effectiveness ratio of US$142 per DALY (US$5 for the full course of two doses) and RotaTeq US$288 per DALY ($10.5 for the full course of three doses). RotaTeq will have a bigger impact on the cold chain compared to Rotarix.

Conclusion

Vaccination against rotavirus disease is cost-effective for Kenya irrespective of the vaccine. Of the two vaccines Rotarix was the preferred choice due to a better cost-effectiveness ratio, the presence of a vaccine vial monitor, the requirement of fewer doses and less storage space, and proven thermo-stability.

Background

Mutual health organizations (MHO) have been seen as a promising alternative to the fee-based funding model but scientific foundations to support their generalization are still limited. Very little is known about the extent of the impact of MHOs on health-seeking behaviours, quality and costs.

Methodology/Principal Findings

We present the results of an evaluation of the effects attributable to membership in an MHO in a rural region of Benin. Two prospective studies of users (parturients and hospitalized patients) were conducted on the territory of an inter-mutual consisting of 10 MHOs and as many healthcare centres (one, Ouessé, serving as a referral hospital) and one hospital (Papané). Members and non-members were matched (142 pairs of parturients and 109 triads of hospitalized patients) and multilevel multiple regression was used. Results show that member parturients went to healthcare centres sooner (p = 0.049) and were discharged more quickly after delivery (p = 0.001) than non-members. Length of stay in some cases was longer for hospitalized member parturients (+41%). Being a member did not shorten hospital stay, total length of episode of care, or time between appearance of symptoms and recourse to care. Regarding expenses, member parturients paid one-third less than non-members for a delivery. For hospitalized patients, the average savings for members was around $35 US. Total expenses incurred by patients hospitalized at Papané Hospital were higher than at Ouessé but the two hospitals’ relative advantages were comparable at −36% and −39%, respectively.

Conclusion/Significance

These results confirm mutual health organizations’ capacity to protect households financially, even if benefits for the poor have not been clearly determined. The search for scientific evidence should continue, to understand their impacts with regard to services obtained by their members.

Stratified Medicine (SM) has the potential to target patient populations who will most benefit from a therapy while reducing unnecessary health interventions associated with side effects. The link between clinical biomarkers/diagnostics and therapies provides new opportunities for value creation to strengthen the value proposition to pricing and reimbursement (P&R) authorities. However, the introduction of SM challenges current reimbursement schemes in many EU countries and the US as different P&R policies have been adopted for drugs and diagnostics. Also, there is a lack of a consistent process for value assessment of more complex diagnostics in these markets. New, innovative approaches and more flexible P&R systems are needed to reflect the added value of diagnostic tests and to stimulate investments in new technologies. Yet, the framework for access of diagnostic-based therapies still requires further development while setting the right incentives and appropriate align stakeholders interests when realizing long-term patient benefits. This article addresses the reimbursement challenges of SM approaches in several EU countries and the US outlining some options to overcome existing reimbursement barriers for stratified medicine.

Background

To analyse the cost-effectiveness of traditional disease-modifying anti-rheumatic drugs (tDMARDs) compared to biological therapies from the perspective of Chinese society.

Methodology/Principal Findings

A mathematical model was developed by incorporating the clinical trial data and Chinese unit costs and treatment sequences from a lifetime perspective. Hypothetical cohorts with moderate to severe RA were simulated. The primary outcome measure–quality-adjusted life years (QALYs)–was derived from disease severity (HAQ scores). Primary analysis included drug costs, monitoring costs, and other costs. Probabilistic and one-way sensitivity analyses were performed. Treatment sequences that included TNF antagonists and rituximab produced a greater number of QALYs than tDMARDs alone or TNF antagonists plus DMARDs. In comparison with tDMARDs, the incremental cost-effectiveness ratios (ICERs) for etanercept, infliximab, and adalimumab without rituximab were $77,357.7, $26,562.4 and $57,838.4 per QALY and $66,422.9, $28,780.6 and $50,937.6 per QALY, for etanercept, infliximab, and adalimumab with rituximab. No biotherapy was cost-effective under the willingness to pay threshold when the threshold was 3 times the per capita GDP of China. When 3 times the per capita GDP of Shanghai used as the threshold, infliximab and rituximab could yield nearly 90% cost-effective simulations in probabilistic sensitivity analysis.

Conclusions/Significance

tDMARD was the most cost-effective option in the Chinese healthcare setting. In some relatively developed regions in China, infliximab and rituximab may be a favorable cost-effective alternative for moderate to severe RA.

Objective

Intravenous iron is widely used to treat iron deficiency in day-care units. Ferric carboxymaltose (FCM) allows administration of larger iron doses than iron sucrose (IS) in each infusion (1000 mg vs. 200 mg). As FCM reduces the number of infusions required but is more expensive, we performed a cost-minimization analysis to compare the cost impact of the two drugs.

Materials and Methods

The number of infusions and the iron dose of 111 consecutive patients who received intravenous iron at a gastrointestinal diseases day-care unit from 8/2007 to 7/2008 were retrospectively obtained. Costs of intravenous iron drugs were obtained from the Spanish regulatory agencies. The accounting department of the Hospital determined hospital direct and indirect costs for outpatient iron infusion. Non-hospital direct costs were calculated on the basis of patient interviews. In the pharmacoeconomic model, base case mean costs per patient were calculated for administering 1000 mg of iron per infusion using FCM or 200 mg using IS. Sensitivity analysis and Monte Carlo simulation were performed.

Results

Under baseline assumptions, the estimated cost of iron infusion per patient and year was €304 for IS and €274 for FCM, a difference of €30 in favour of FCM. Adding non-hospital direct costs to the model increased the difference to €67 (€354 for IS vs. €287 for FCM). A Monte Carlo simulation taking into account non-hospital direct costs favoured the use of FCM in 97% of simulations.

Conclusion

In this pharmacoeconomic analysis, FCM infusion reduced the costs of iron infusion at a gastrointestinal day-care unit.

Background

The Dutch Human Papillomavirus (HPV) catch-up vaccination program in 2009 appeared less successful than expected. We aimed to identify the most important determinants of refusing the vaccination.

Methods

Two thousand parents of girls born in 1996 targeted for HPV vaccination received an invitation letter to participate in a questionnaire study. Two study groups were defined: the first group consisted of parents of girls who had accepted the vaccine and already received the first dose of HPV vaccination. The second group consisted of parents whose daughters were not vaccinated. The questionnaire consisted of a broad spectrum of possible determinants that were revealed after literature search and discussions with the stakeholders.

Results

Four hundred sixty nine questionnaires (24%) were returned, 307 (31%) from those who accepted and 162 (16%) from those who declined the vaccine. The decision not to accept the vaccine was largely determined by: (i) perception that the information provided by the government about the vaccine was limited or biased (OR 13.27); (ii) limited trust, that the government would stop the vaccination program if there were serious side effects (OR 9.95); (iii) lack of knowledge about the effectiveness of the vaccine (OR 7.67); (iv) concerns about the side effects of the vaccine (OR 4.94); (v) lack of conviction that HPV can be extremely harmful (OR 3.78); (vi) perception that the government is strongly influenced by vaccine producers (OR 3.54); and (vii) religious convictions (OR 2.18).

Conclusions

This study revealed several determinants for HPV vaccination uptake after implementation of the HPV vaccine for adolescent girls. These determinants should be taken into consideration in order to successfully implement HPV vaccination into National Immunization Programs.

Background

Mutuelles is a community-based health insurance program, established since 1999 by the Government of Rwanda as a key component of the national health strategy on providing universal health care. The objective of the study was to evaluate the impact of Mutuelles on achieving universal coverage of medical services and financial risk protection in its first eight years of implementation.

Methods and Findings

We conducted a quantitative impact evaluation of Mutuelles between 2000 and 2008 using nationally-representative surveys. At the national and provincial levels, we traced the evolution of Mutuelles coverage and its impact on child and maternal care coverage from 2000 to 2008, as well as household catastrophic health payments from 2000 to 2006. At the individual level, we investigated the impact of Mutuelles' coverage on enrollees' medical care utilization using logistic regression. We focused on three target populations: the general population, under-five children, and women with delivery. At the household level, we used logistic regression to study the relationship between Mutuelles coverage and the probability of incurring catastrophic health spending. The main limitation was that due to insufficient data, we are not able to study the impact of Mutuelles on health outcomes, such as child and maternal mortalities, directly.

The findings show that Mutuelles improved medical care utilization and protected households from catastrophic health spending. Among Mutuelles enrollees, those in the poorest expenditure quintile had a significantly lower rate of utilization and higher rate of catastrophic health spending. The findings are robust to various estimation methods and datasets.

Conclusions

Rwanda's experience suggests that community-based health insurance schemes can be effective tools for achieving universal health coverage even in the poorest settings. We suggest a future study on how eliminating Mutuelles copayments for the poorest will improve their healthcare utilization, lower their catastrophic health spending, and affect the finances of health care providers.

Background

Varicella and herpes zoster are both caused by varicella zoster virus (VZV) infection or reactivation and may lead to complications associated with a (severe) societal burden. Because the epidemiology of VZV-related diseases in the Netherlands remains largely unknown or incomplete, the main objective of this study was to study the primary care incidence, associated complications and health care resource use.

Methods

We investigated the incidence of VZV complications in the Dutch general practitioner (GP) practices and pharmacies in a retrospective population-based cohort study (2004–2008) based on longitudinal GP data including free text fields, hospital referral and discharge letters from approximately 165,000 patients.

Results

The average annual incidence of varicella GP-consultations was 51.5 per 10,000 (95% CI 44.4-58.7) overall; 465.5 per 10,000 for 0–1 year-olds; 610.8 per 10,000 for 1–4 year-olds; 153.5 per 10,000 for 5–9 year-olds; 8,3 per 10,000 for >10 year olds. When only ICPC coded diagnoses were analyzed the incidence was 27% lower. The proportion of complications among varicella patients was 34.9%. Most frequently complications were upper respiratory tract infections. Almost half of the varicella patients received medication. The referral rate based on GP consultations was 1.7%. The average annual incidence of herpes zoster GP-consultations was 47.5 per 10,000 (95% CI 40.6-54.4). The incidence increased with age; 32.8 per 10,000 for <60 year-olds; 93.1 per 10,000 for 60–64 year-olds and 113.2 per 10,000 for >65 year olds. When estimating herpes zoster incidence only on ICPC coded information, the incidence was 28% lower. The complication rate of herpes zoster was 32.9%. Post herpetic neuralgia was seen most often. Of patients diagnosed with herpes zoster 67.8% received medication. The referral rate based on GP consultations was 3.5%.

Conclusions

For varicella the highest incidence of GP-consultations was found in 1–4 year-olds, for herpes zoster in the >65 years olds. The occurrence of complications was not age-dependent but varies per complication. When estimating incidence of VZV-related diseases in primary care, based on diagnostic codes only, one should be aware of a gross underestimation of the incidence. Our analysis may have important implications for the outcomes of upcoming cost-effectiveness analyses on VZV vaccination.

Rationale: Isoniazid preventive therapy is effective in reducing the risk of tuberculosis (TB) in persons living with HIV (PLWH); however, screening must exclude TB disease before initiating therapy. Symptom screening alone may be insufficient to exclude TB disease in PLWH because some PLWH with TB disease have no symptoms. The addition of chest radiography (CXR) may improve disease detection.

Objectives: The objective of the present analysis was to compare the costs and effects of the addition of CXR to the symptom screening process against the costs and effects of symptom screening alone.

Methods: Using data from Botswana, a decision analytic model was used to compare a “Symptom only” policy against a “Symptom+CXR” policy. The outcomes of interest were cost, death, and isoniazid- and multidrug-resistant TB in a hypothetical cohort of 10,000 PLWH.

Measurements and Main Results: The Symptom+CXR policy prevented 16 isoniazid- and 0.3 multidrug-resistant TB cases; however, because of attrition from the screening process, there were 98 excess cases of TB, 15 excess deaths, and an additional cost of U.S. $127,100. The Symptom+CXR policy reduced deaths only if attrition was close to zero; however, to eliminate attrition the cost would be U.S. $2.8 million per death averted. These findings did not change in best- and worst-case scenario analyses.

Conclusions: In Botswana, a policy with symptom screening only preceding isoniazid-preventive therapy initiation prevents more TB and TB-related deaths, and uses fewer resources, than a policy that uses both CXR and symptom screening.

Background

This study aims to critically review available cost-effectiveness models for rotavirus vaccination, compare their designs using a standardized approach and compare similarities and differences in cost-effectiveness outcomes using a uniform set of input parameters.

Methods

We identified various models used to estimate the cost-effectiveness of rotavirus vaccination. From these, results using a standardized dataset for four regions in the world could be obtained for three specific applications.

Results

Despite differences in the approaches and individual constituting elements including costs, QALYs Quality Adjusted Life Years and deaths, cost-effectiveness results of the models were quite similar. Differences between the models on the individual components of cost-effectiveness could be related to some specific features of the respective models. Sensitivity analysis revealed that cost-effectiveness of rotavirus vaccination is highly sensitive to vaccine prices, rotavirus-associated mortality and discount rates, in particular that for QALYs.

Conclusions

The comparative approach followed here is helpful in understanding the various models selected and will thus benefit (low-income) countries in designing their own cost-effectiveness analyses using new or adapted existing models. Potential users of the models in low and middle income countries need to consider results from existing studies and reviews. There will be a need for contextualization including the use of country specific data inputs. However, given that the underlying biological and epidemiological mechanisms do not change between countries, users are likely to be able to adapt existing model designs rather than developing completely new approaches. Also, the communication established between the individual researchers involved in the three models is helpful in the further development of these individual models. Therefore, we recommend that this kind of comparative study be extended to other areas of vaccination and even other infectious disease interventions.

Background

Each year rotavirus gastroenteritis results in thousands of paediatric hospitalisations and primary care visits in the Netherlands. While two vaccines against rotavirus are registered, routine immunisation of infants has not yet been implemented. Existing cost-effectiveness studies showed inconsistent results for these vaccines because of lack of consensus on the impact. We aimed to investigate which factors had a major impact on cost-effectiveness and were primarily responsible for the large differences in previously estimated cost-effectiveness ratios.

Methods

Based on updated data on health outcomes and cost estimates, we re-assessed the cost-effectiveness of routine paediatric rotavirus vaccination within the National Immunization Program for the Netherlands. Two consensus meetings were organised with national and international experts in the field to achieve consensus and resolve potential controversies.

Results

It was estimated that rotavirus vaccination in the Netherlands could avert 34,214 cases of rotavirus gastroenteritis in children aged less than 5 years. Notably, 2,779 hospitalisations were averted of which 315 were extensions of existing hospital stays due to nosocomial rotavirus infection. With a threshold varying from 20K€ - 50K€ per QALY and according to the base-case scenario, the full vaccination costs per child leading to cost-effectiveness was €57.76 -€77.71. Results were sensitive to the inclusion of potential vaccine induced herd protection, QALY losses and number of deaths associated with rotavirus gastroenteritis.

Conclusions

Our economic analysis indicates that inclusion of rotavirus vaccination in the Dutch National Immunization Program might be cost-effective depending on the cost of the vaccine and the impact of rotavirus gastroenteritis on children's quality of life.

Background

As in other societies, pharmaceutical expenditures in the Netherlands are rising every year. As a consequence, needs for cost control are often expressed. One possible solution for cost control could come through increasing generic substitution by pharmacists. We aim to analyse the extent and nature of substitution in recent years and estimate the likelihood of generic or branded substitution in Dutch pharmacies in relation to various characteristics.

Methods

We utilized a linked prescription dataset originating from a general practitioner (GP) and a pharmacy database, both from the northern Netherlands. We selected specific drugs of interest, containing about 55,000 prescriptions from 15 different classes. We used a crossed generalized linear mixed model to estimate the effects that certain patient and pharmacy characteristics as well as timing have on the likelihood that a prescription will eventually be substituted by the pharmacist.

Results

Generic substitution occurred at 25% of the branded prescriptions. Generic substitution was more likely to occur earlier in time after patent expiry and to patients that were older and more experienced in their drug use. Individually owned pharmacies had a lower probability of generic substitution compared to chain pharmacies. Oppositely, branded substitution occurred in 10% of generic prescriptions and was positively related to the patients' experience in branded use. Individually owned pharmacies were more likely to substitute a generic drug to a branded compared to other pharmacies. Antidepressant and PPI prescriptions were less prone to generic and more prone to branded substitution.

Conclusion

Analysis of prescription substitution by the pharmacist revealed strong relations between substitution and patient experience on drug use, pharmacy status and timing. These findings can be utilised to design further strategies to enhance generic substitution.

Background

Screening at hospital admission for carriage of methicillin-resistant Staphylococcus aureus (MRSA) has been proposed as a strategy to reduce nosocomial infections. The objective of this study was to determine the long-term costs and health benefits of selective and universal screening for MRSA at hospital admission, using both PCR-based and chromogenic media-based tests in various settings.

Methodology/Principal Findings

A simulation model of MRSA transmission was used to determine costs and effects over 15 years from a US healthcare perspective. We compared admission screening together with isolation of identified carriers against a baseline policy without screening or isolation. Strategies included selective screening of high risk patients or universal admission screening, with PCR-based or chromogenic media-based tests, in medium (5%) or high nosocomial prevalence (15%) settings. The costs of screening and isolation per averted MRSA infection were lowest using selective chromogenic-based screening in high and medium prevalence settings, at $4,100 and $10,300, respectively. Replacing the chromogenic-based test with a PCR-based test costs $13,000 and $36,200 per additional infection averted, and subsequent extension to universal screening with PCR would cost $131,000 and $232,700 per additional infection averted, in high and medium prevalence settings respectively. Assuming $17,645 benefit per infection averted, the most cost-saving strategies in high and medium prevalence settings were selective screening with PCR and selective screening with chromogenic, respectively.

Conclusions/Significance

Admission screening costs $4,100–$21,200 per infection averted, depending on strategy and setting. Including financial benefits from averted infections, screening could well be cost saving.

Background

Despite widespread immunization programs, a clear increase in pertussis incidence is apparent in many developed countries during the last decades. Consequently, additional immunization strategies are considered to reduce the burden of disease. The aim of this study is to design an individual-based stochastic dynamic framework to model pertussis transmission in the population in order to predict the epidemiologic and economic consequences of the implementation of universal booster vaccination programs. Using this framework, we estimate the cost-effectiveness of universal adolescent pertussis booster vaccination at the age of 12 years in the Netherlands.

Methods/Principal Findings

We designed a discrete event simulation (DES) model to predict the epidemiological and economic consequences of implementing universal adolescent booster vaccination. We used national age-specific notification data over the period 1996–2000—corrected for underreporting—to calibrate the model assuming a steady state situation. Subsequently, booster vaccination was introduced. Input parameters of the model were derived from literature, national data sources (e.g. costing data, incidence and hospitalization data) and expert opinions. As there is no consensus on the duration of immunity acquired by natural infection, we considered two scenarios for this duration of protection (i.e. 8 and 15 years). In both scenarios, total pertussis incidence decreased as a result of adolescent vaccination. From a societal perspective, the cost-effectiveness was estimated at €4418/QALY (range: 3205–6364 € per QALY) and €6371/QALY (range: 4139–9549 € per QALY) for the 8- and 15-year protection scenarios, respectively. Sensitivity analyses revealed that the outcomes are most sensitive to the quality of life weights used for pertussis disease.

Conclusions/Significance

To our knowledge we designed the first individual-based dynamic framework to model pertussis transmission in the population. This study indicates that adolescent pertussis vaccination is likely to be a cost-effective intervention for The Netherlands. The model is suited to investigate further pertussis booster vaccination strategies.

Introduction

We estimated the cost effectiveness of concomitant proton pump inhibitors (PPIs) in relation to the occurrence of non-steroidal anti-inflammatory drug (NSAID) ulcer complications.

Methods

This study was linked to a nested case-control study. Patients with NSAID ulcer complications were compared with matched controls. Only direct medical costs were reported. For the calculation of the incremental cost effectiveness ratio we extrapolated the data to 1,000 patients using concomitant PPIs and 1,000 patients not using PPIs for 1 year. Sensitivity analysis was performed by 'worst case' and 'best case' scenarios in which the 95% confidence interval (CI) of the odds ratio (OR) and the 95% CI of the cost estimate of a NSAID ulcer complication were varied. Costs of PPIs was varied separately.

Results

In all, 104 incident cases and 284 matched controls were identified from a cohort of 51,903 NSAID users with 10,402 NSAID exposition years. Use of PPIs was associated with an adjusted OR of 0.33 (95% CI 0.17 to 0.67; p = 0.002) for NSAID ulcer complications. In the extrapolation the estimated number of NSAID ulcer complications was 13.8 for non-PPI users and 3.6 for PPI users. The incremental total costs were € 50,094 higher for concomitant PPIs use. The incremental cost effectiveness ratio was € 4,907 per NSAID ulcer complication prevented when using the least costly PPIs.

Conclusions

Concomitant use of PPIs for the prevention of NSAID ulcer complications costs € 4,907 per NSAID ulcer complication prevented when using the least costly PPIs. The price of PPIs highly influenced the robustness of the results.

Background

This study compares the costs and effects of a regimen with ritonavir-boosted tipranavir (TPV/r) to a physician-selected genotypically-defined standard-of-care comparator protease inhibitor regimen boosted with ritonavir (CPI/r) in HIV infected patients that were previously exposed to antiretroviral therapy in the Netherlands.

Methods

We compared the projected lifetime costs and effects of two theoretical groups of 1000 patients, one receiving a standard of care regimen with TPV/r as a component and the other receiving a standard of care regimen with CPI/r. A 3-stage Markov model was formulated to represent three different consecutive HAART regimens. The model uses 12 health states based on viral load and CD4+ count to simulate disease progression. The transition probabilities for the Markov model were derived from a United States cohort of treatment experienced HIV patients. Furthermore, the study design was based on 48-week data from the RESIST-2 clinical trial and local Dutch costing data. Cost and health effects were discounted at 4% and 1.5% respectively according to the Dutch guideline. The analysis was conducted from the Dutch healthcare perspective using 2006 unit cost prices.

Results

Our model projects an accumulated discounted cost to the Dutch healthcare system per patient receiving the TPV/r regimen of €167,200 compared to €145,400 for the CPI/r regimen. This results in an incremental cost of €21,800 per patient. The accumulated discounted effect is 7.43 life years or 6.31 quality adjusted life years (QALYs) per patient receiving TPV/r, compared to 6.91 life years or 5.80 QALYs per patient receiving CPI/r. This translates into an incremental effect of TPV/r over CPI/r of 0.52 life years gained (LYG) or 0.51 QALYs gained. The corresponding incremental cost effectiveness ratios (iCERs) are €41,600 per LYG and €42,500 per QALY.

Conclusion

We estimated the iCER for TPV/r compared to CPI/r at approximately €40,000 in treatment experienced HIV-1 infected patients in the Netherlands. This ratio may well be in range of what is acceptable and warrants reimbursement for new drug treatments in the Netherlands, in particular in therapeutic areas as end-stage oncology and HIV and other last-resort health-care interventions.

The decision of the National Institute for Health and Clinical Excellence to abandon differential discounting of future health is a step backwards and could change funding decisions

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.