Cost-effectiveness of tipranavir versus comparator protease inhibitor regimens in HIV infected patients previously exposed to antiretroviral therapy in the Netherlands.

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 euro167,200 compared to euro145,400 for the CPI/r regimen. This results in an incremental cost of euro21,800 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 euro41,600 per LYG and euro42,500 per QALY. CONCLUSION: We estimated the iCER for TPV/r compared to CPI/r at approximately euro40,000 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.

Combination vaccine against invasive meningococcal B and pneumococcal infections: potential epidemiological and economic impact in the Netherlands.

BACKGROUND: Streptococcus pneumoniae and Neisseria meningitidis group B are among the main causes of invasive bacterial meningitis infections in infants. Worldwide, these diseases lead to significant mortality, morbidity and costs. The societal impact is especially severe since the majority of cases occur in very young infants. A combination vaccine consisting of 9-valent conjugated pneumococcal and meningococcal B components is currently being developed. The aim of this study was to estimate the potential impact and cost effectiveness from the societal perspective of vaccinating infants in The Netherlands with this combination pneumococcal and meningococcal B vaccine versus no vaccination. METHODS: A Markov cycle model was developed using epidemiological and healthcare resource use data from 1996 to 2001. This model was used to project the annual costs, benefits and health gains associated with vaccinating all newborns. The base year for the costing was 2003 and all costs and health effects were discounted at 4%. The results of the analysis are expressed in costs per QALY and both probabilistic and univariate sensitivity analyses were used to identify the robustness of the results. RESULTS: Annually, an average of 755 cases of invasive pneumococcal and meningococcal B infection occurred in infants aged 0-10 years in The Netherlands. Introduction of the combination vaccine would prevent 201 cases of meningococcal B meningitis and 165 cases of invasive pneumococcal disease per year. Additionally, 3410 cases of pneumococcal pneumonia and 46,350 cases of otitis media would be prevented. Vaccination would save 35 lives per year and prevent 71 cases of severe sequelae. This translates into 860 life-years gained, or 1128 QALYs gained. Alongside these health gains, vaccination would prevent euro 17,681,370 of direct medical and indirect costs attributable to meningococcal and pneumococcal infections in The Netherlands. Depending on vaccine price, cost effectiveness varied from euro 3160 (vaccine price per dose euro 20) to euro 32,170 (vaccine price euro 60 per dose) per QALY. Base-case cost effectiveness (vaccine price euro 40) was euro 17,700 per QALY. The model was most sensitive to changes in incidence, vaccine price and duration of protective efficacy. CONCLUSION: Our results suggest that the introduction of a combination meningococcal B and pneumococcal vaccine into the Dutch infant vaccination programme is potentially cost effective compared with no vaccination.

Adherence of pharmacoeconomic studies to national guidelines in the Netherlands.

OBJECTIVE: This study examines the adherence of Dutch pharmacoeconomic studies to the national guidelines of conducting a pharmacoeconomic evaluation. METHODS: Dutch guidelines for pharmacoeconomic research were issued in 1999. All Dutch pharmacoeconomic studies that were published in English during 2000-2002 were selected for our review. Two reviewers examined each study for relevance and compared each study with the nine methodological guidelines selected. RESULTS: It was found that 29 studies satisfied the inclusion criteria. The societal perspective was taken in 13 out of the 29 studies (45%), an adequate time period of analysis was chosen in 21 (72%), effectiveness was explicitly differentiated from efficacy in 17 (59%), an incremental analysis was performed in 23 (79%), costs, benefits and health gains were discounted in 24 (83%), effectiveness was expressed in LYGs or QALYs in 16 (55%), reference prices were used in 8 (28%), subgroup analysis was presented in 13 (45%) and sensitivity analysis was included in 26 (90%). CONCLUSIONS: In this review we found that the adherence of studies to some of the Dutch guidelines for pharmacoeconomic studies is fair. However, major improvements are required with respect to the adoption of the societal perspective, presentation of adequate subgroup analyses and application of reference prices.

Drug costs developments after patent expiry of enalapril, fluoxetine and ranitidine: a study conducted for the Netherlands.

BACKGROUND: In order to increase price competition, government regulations focus on controlling drug costs. Drug costs after patent expiry are an area of particular interest because the substitution of branded medication with generics represents an opportunity for lowering drug costs. However, drug costs may not decrease after patent expiry, because of a lack of price competition and different national pricing systems. AIM: The aim of this study was to investigate the trends in the use of generics after patent expiry for enalapril, fluoxetine and ranitidine and the subsequent changes, if any, in the costs of these medications. METHODS: A drug-utilisation study was performed using data from a large sample of Dutch pharmacies. Both volumes (measured as defined daily doses [DDD] per 1000 population) as well as drug costs (calculated per DDD) prior to and after patent expiry were calculated. Costs per DDD were compared using trend-line analysis. In addition, the relative market shares of the different trade channels (branded, parallel imported and generic) were compared before and after patent expiry. RESULTS: The costs per DDD decreased for all three drugs and, as expected, these costs decrease more rapidly after patent expiry. Significant differences in the trend lines were found for enalapril and fluoxetine. CONCLUSIONS: Despite relatively high reimbursement prices for generics in the Netherlands, this example from the Dutch pharmaceutical market demonstrates the benefit of generic substitution for containing pharmaceutical costs, which contrasts with concerns raised by the Dutch government.

Towards a healthier discount procedure.

Most national guidelines for pharmacoeconomic research prescribe discounting, mostly of money and health against the same rate. There is much debate on whether this is adequate. Two theoretical arguments, the consistency argument of Weinstein and Stason, and the paralyzing paradox of Keeler and Cretin, are mostly responsible for the current standards. However, more recently, several authors have indicated that the basis to claim the necessity of using similar discount rates is rather weak, both practically and theoretically. In terms of finding a new theoretical basis on which to base discount rates for money and, in particular, health, Van Hout has made an important suggestion arguing that the discount rate for health could be based on the expected growth in life expectancy and the diminishing marginal utility related to such additional health. Similarly, Gravelle and Smith argue that if the value of health grows over time, discount rates that are used for costs cannot directly be applied to effects, but should be adjusted downwards.

Valuing prevention through economic evaluation: some considerations regarding the choice of discount model for health effects with focus on infectious diseases.

In cost-effectiveness analysis, the valuing of costs and health effects over time remains a controversial issue. The debate mostly focuses on whether the discount rates for health and money should be equal and which discounting model and time preferences are most appropriate. In this paper we add to the debate by arguing that the assessment of effectiveness of a preventive intervention may influence the choice of the discounting procedure for health. Health effects in cost-effectiveness analysis are commonly expressed in life-years gained, QALYs gained or lives saved. These denominators are only indirect and partial measures of the effects of a preventive intervention. The actual effect of the intervention is a reduction of the risk of mortality and morbidity in a given period of time. This risk reduction will not always coincide with the moment at which the impact on (quality-adjusted) life-years gained is made (i.e. at risk exposure), for example when preventing chronic disease with an asymptomatic stage. In this paper we show that truly acknowledging the origin of health benefits could have implications for the discounting procedure. We present a discounting model that adequately focuses on the reduction of risk. This model recognises the potential interpretation of risk reduction for infection as an economic good to be acquired with associated mortality reductions as later indirect effects. This implies that our suggested discounting model focuses on the moment(s) of risk reduction. A numerical example illustrates our approach. We discuss the associated potential implications for public health policy and discuss how the effects of the intervention can be additionally corrected for societal preferences.

Epidemiologic impact and cost-effectiveness of universal infant vaccination with a 7-valent conjugated pneumococcal vaccine in the Netherlands.

BACKGROUND: Streptococcus pneumoniae is one of the main causes of bacterial meningitis, bacteremia, pneumonia, and otitis media in the Netherlands. These diseases lead to substantial mortality, morbidity, and costs. The societal impact is especially severe because most cases occur in very young infants. OBJECTIVE: The aim of this study was to estimate the epidemiological impact and cost-effectiveness of universal infant vaccination with a 7-valent conjugated pneumococcal vaccine in the Netherlands. METHODS: Decision analysis was performed using epidemiological data and data on health care resource use from 1996 to 2001. A model was used to project the impact of pneumococcal vaccination on the incidence of pneumococcal infections in infants and children from birth to age 10 years. Costs, benefits, and health gains were estimated, and cost-effectiveness was calculated. All analyses were performed from a societal perspective. RESULTS: On average, 339 cases per year of invasive pneumococcal infection occurred in infants and children from birth to age 10 years in the Netherlands from 1996 to 2001. The model predicted that introduction of the 7-valent conjugated pneumococcal vaccine would prevent 48 cases of bacterial meningitis and 88 cases of pneumococcal bacteremia per year, as well as 42,695 cases of pneumococcal otitis media and 3411 cases of invasive pneumococcal pneumonia. The model also predicted that vaccination would save 13 lives per year and prevent 31 cases of lifelong sequelae, rendering 382 discounted quality-adjusted life-years (QALYs) gained or 329 discounted life-years gained per year. Considering these health gains, vaccination would prevent Euro 9,453,600 of direct and indirect medical costs of meningococcal and pneumococcal infections in the Netherlands, including acute medical care, management of sequelae, and lost time at work. With a vaccine price of Euro 40 per dose, the base-case cost-effectiveness ratio would be Euro 71,250 per QALY. The model was sensitive to changes in incidence of infections, vaccine effectiveness, and vaccine price. CONCLUSIONS: Our analytic model predicted that universal pneumococcal vaccination of infants in the Netherlands could prevent a large number of pneumococcal infections and considerably reduce related mortality and morbidity. However, the baseline cost-effectiveness ratio of such a vaccination program would be relatively unfavorable compared with other interventions implemented in the Netherlands.

Routine HIV screening of sexually transmitted disease clinic attenders has favourable cost-effectiveness ratio in low HIV prevalence settings.

HIV screening for attenders of clinics for sexually transmitted disease (STD) may identify individuals with high-risk sexual behaviour and avert HIV infections in partners. Extending our previous analysis in AIDS, we performed an economic evaluation of HIV screening of STD-clinic attenders in Rotterdam, the Netherlands. The results, at euro 2987 per life-year gained, display a favourable economic profile. Routine HIV screening in STD clinics should be considered as a highly cost-effective prevention measure even in countries with a low HIV prevalence.

The use of modeling in the economic evaluation of vaccines.

As a consequence of the increased role of pharmacoeconomics in policy-making, economic evaluations are performed at more and more early stages in the development of a therapeutic. This implies the development of models to assess the future impact of an intervention and to account for the level of uncertainty in the associated parameters. This also applies for economic evaluations of vaccines, where not only progression of disease and associated costs are important, but the transmission of the causing agent in the target population also has to be modelled. In this review, we provide an overview of the models that have been used in recent publications on the pharmacoeconomics of vaccines and go deeper into some of the methodological issues associated with the use of models in the economic evaluation of vaccines.