The population-based prescription database IADB.nl: its development, usefulness in outcomes research and challenges.

Research databases with large numbers of prescriptions in observational settings can provide valuable information in addition to the initial randomized controlled trials. This paper reports on the development of prescription database IADB, formerly known as InterAction Database. IADB contains prescriptions from 54 community pharmacies in The Netherlands and covers a population of 500,000 people. Both the age distribution and the prevalence of drugs used are comparable to a large extent with the Dutch population. The representativeness of the population covered is examined by comparing population composition and drug use with data of the whole Dutch population. Enriching IADB with, among others, clinical parameters by linking to other databases is explored. A strong and unique aspect of IADB is the possibility to track patients over time, even when they receive their medication from different pharmacies. The authors conclude IADB is a useful tool for pharmacoepidemiological and pharmacoeconomic outcomes research.

[Peri-pregnancy folic acid supplementation must be improved]. / Foliumzuursuppletiebeleid bij zwangerschap werkt, maar moet beter.

The correct usage of folic acid (FA) supplements to prevent neural tube defects (NTDs) increased from 28% in 1996 to 50% in 2005 and remained stable until 2009. Recent data from national birth defect registries show a decrease of NTD prevalence from 13.2 (per 10,000) in 1997 to 8.3 in 2005 and stabilization up to 2009. It is estimated that between 2005 and 2009 FA supplementation prevented 583 NTD cases. The medical costs thus averted are € 75 M. If the correct usage of FA were to be increased to 70%, another 34 cases per year could be prevented. Part of the gain from continued prevention and other averted costs should be invested beforehand in the promotion of FA supplement usage.

Economic evaluation of anti-epileptic drug therapies with specific focus on teratogenic outcomes.

BACKGROUND: Anti-epileptic drugs are known to be teratogenic, yet many women do need to continue the anti-epileptic drug use during pregnancy. OBJECTIVES: To perform an economic evaluation of the anti-epileptic drug choice in young women who potentially wish to become pregnant. In particular, to estimate the impact of teratogenicity on the costs per quality adjusted life year (QALY). METHODS: A decision-tree model is used to calculate the costs per QALY, taking into account the malformation risk in offspring due to the exposure to carbamazepine, lamotrigine or valproic acid, based on the European birth cohort of 2007. Probabilistic sensitivity analyses were performed using Monte Carlo simulation. RESULTS: Valproic acid is dominated by carbamazepine after rank ordering on costs. The incremental cost-effectiveness of lamotrigine vs carbamazepine was estimated at €175,534 per QALY. Although valproic acid was dominated by carbamazepine in terms of costs and related effects, it is clinically relevant to compare lamotrigine with valproic acid. In particular, treatment options are dependent on several individual and clinical characteristics and these agents are therefore not always considered as interchangeable for all specified populations. The incremental cost-effectiveness for lamotrigine vs valproic acid was estimated at €13,370 per QALY. With assuming a willingness to pay threshold of €50,000 per QALY, results from the probabilistic analysis resulted in an acceptance level for lamotrigine vs carbamazepine and lamotrigine vs valproic acid of 4% and 99%, respectively. CONCLUSION: Based on epidemiological data it is advised to whenever possible avoid valproic acid during pregnancy. Both carbamazepine and lamotrigine are estimated to be cost-effective treatment options vs valproic acid if focused on teratogenicity.

Cost-effectiveness of a screening strategy for Q fever among pregnant women in risk areas: a clustered randomized controlled trial.

BACKGROUND: In The Netherlands the largest human Q fever outbreak ever reported in the literature is currently ongoing with more than 2300 notified cases in 2009. Pregnant women are particularly at risk as Q fever during pregnancy may cause maternal and obstetric complications. Since the majority of infected pregnant women are asymptomatic, a screening strategy might be of great value to reduce Q fever related complications. We designed a trial to assess the (cost-)effectiveness of a screening program for Q fever in pregnant women living in risks areas in The Netherlands. METHODS/DESIGN: We will conduct a clustered randomized controlled trial in which primary care midwife centres in Q fever risk areas are randomized to recruit pregnant women for either the control group or the intervention group. In both groups a blood sample is taken around 20 weeks postmenstrual age. In the intervention group, this sample is immediately analyzed by indirect immunofluorescence assay for detection of IgG and IgM antibodies using a sensitive cut-off level of 1:32. In case of an active Q fever infection, antibiotic treatment is recommended and serological follow up is performed. In the control group, serum is frozen for analysis after delivery. The primary endpoint is a maternal (chronic Q fever or reactivation) or obstetric complication (low birth weight, preterm delivery or fetal death) in Q fever positive women. Secondary aims pertain to the course of infection in pregnant women, diagnostic accuracy of laboratory tests used for screening, histo-pathological abnormalities of the placenta of Q fever positive women, side effects of therapy, and costs. The analysis will be according to the intention-to-screen principle, and cost-effectiveness analysis will be performed by comparing the direct and indirect costs between the intervention and control group. DISCUSSION: With this study we aim to provide insight into the balance of risks of undetected and detected Q fever during pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov, protocol record NL30340.042.09.

Screen-and-treat strategies for albuminuria to prevent cardiovascular and renal disease: cost-effectiveness of nationwide and targeted interventions based on analysis of cohort data from the Netherlands.

BACKGROUND: Albuminuria is a marker for renal and cardiovascular (CV) risk, allowing early diagnosis of subjects with elevated renal and CV risk. OBJECTIVE: This study aimed to estimate the cost-effectiveness and budget impact of various population-based screen-and-treat scenarios for elevated albuminuria levels (ie, microalbuminuria) in the Netherlands. METHODS: A multistate transition Markov model was developed to simulate the natural course of albuminuria-based disease progression to dialysis and occurrence of CV events. Several population-based strategies directed at screening for elevated albuminuria were evaluated. These strategies depended on urinary albumin concentration (UAC), urinary albumin excretion (UAE), and age. Transition probabilities were derived from the observational community-based Prevention of Renal and Vascular End Stage Disease (PREVEND) cohort study. Health care costs (in year-2008 euros) and life-years gained were calculated over an 8-year period. In the base-case analysis, we analyzed screening for and treatment of microalbuminuria. Screening for microalbuminuria involved prescreening for UAC >or=20 mg/L, followed by a confirmation test for UAE >or=30 mg/d. Other options based on combinations of albuminuria for UAC prescreening (no prescreening, and >or=10, >or=20, >or=100, and >or=200 mg/L) and UAE confirmation test (>or=15, >or=30, and >or=300 mg/d) for treatment were investigated in scenario analyses. Furthermore, these various strategies based on UAC and UAE values were analyzed in different subgroups based on age (all ages, aged >or=50 years, and aged >or=60 years). RESULTS: The PREVEND study included 8592 Dutch residents aged 28 to 75 years at the time of initial screening. Among a hypothetical cohort of 1000 subjects identified and treated in the base-case analysis, it was estimated (based on PREVEND follow-up data) that, in the screening/treatment and no-screening scenarios, 76 versus 124 CV events occurred, 16 versus 27 CV deaths, and 3 versus 5 dialysis cases, respectively. The per-person difference in net costs for screening was calculated at euro926 (euro2003 vs euro1077), and prevention of CV deaths was estimated to gain 0.0421 discounted life-year per person. Correspondingly, the cost-effectiveness was estimated at euro22,000 per life-year gained. In the base-case analysis, probabilistic sensitivity analysis indicated that the likelihood of cost-effectiveness of a screen-and-treat strategy was 54%, 90%, and 95% for a maximum acceptable cost-effectiveness threshold of euro20,000, euro50,000, and euro80,000 per life-year gained, respectively. Higher albuminuria thresholds for screening and start of treatment further improved the cost-effectiveness but reduced the overall health gains achieved. Limiting screening to those subjects aged >or=50 and >or=60 years resulted in more favorable cost-effectiveness compared with population-based screening without age restriction. CONCLUSIONS: Our analyses suggest the potentially favorable cost-effectiveness of population-based screening for albuminuria in the general Dutch population. The results offer health care decision-makers new tools for considering actual implementation of such screening.

Results of a retrospective database analysis of drug utilization and costs for treatment of chronic hepatitis B virus infection in the northern Netherlands between 2000 and 2006.

OBJECTIVES: The main aims of this work were to describe patterns of medication use in the treatment of chronic hepatitis B virus (HBV) infection in patients in the northern part of the Netherlands and to compare these practices with established guidelines. In addition, the duration of use and the costs of these treatments were investigated. METHODS: We selected subjects from the University of Groningen's IADB.nl database; by 2006, the database provided information about drug utilization from 55 community pharmacies in the northern Netherlands and included a population of 528,911 individuals, of which 49% were male. Eligible subjects had received >or=1 prescription for drugs used to treat chronic HBV infection (ie, lamivudine, pegylated interferon-alpha2a, pegylated interferon-alpha2b, adefovir, tenofovir, and entecavir) between the years 2000 and 2006. The annual prevalence and cumulative incidence of HBV treatment per 1000 people covered in the database were calculated and stratified by sex. Kaplan-Meier survival analysis was used to analyze the duration of use. Drug costs in the treatment were calculated for all patients or per patient, and by drugs used per subperiod (2000-2003 and 2004-2006). Treatments for hepatitis C virus and HIV were excluded from the analyses. RESULTS: From the database, we identified 59 patients (46 male, 13 female), aged 25 to 60 years, who received >or=1 prescription for a medication to treat chronic HBV infection between 2000 and 2006. The overall prevalence of people using chronic treatments for HBV was between 0.03 and 0.06 per 1000 during the years of the study. The cumulative incidence of treatment was approximately 0.01 per 1000 per year (ranging from a high of 0.021 in 2000 to a low of 0.009 in 2006). When stratified by sex, there were more male than female subjects who received medications for HBV. Lamivudine was the most commonly prescribed drug, followed by adefovir and pegylated interferon-alpha2b. In 2000 and 2001, lamivudine was the only medication prescribed for the treatment of chronic HBV. From 2002 to 2006, the prescription rate for lamivudine dropped from 90% to 61%. In contrast, the prescription rate for adefovir increased from 4% in 2003 to 36% in 2006. Pegylated interferon-alpha2b remained stable at 8% to 11% between 2002 and 2006. Twenty-five percent of patients had stopped HBV treatment by the end of 1 year. Fifty-five percent had stopped by 3 years. Seventy-seven percent of patients received their first HBV prescription from a medical specialist. Per patient, the cost of drug therapy was highest with adefovir. From 2004 to 2006, the cost of adefovir therapy accounted for 49% of total expenditures for the treatment of chronic HBV (equivalent to euro128,037; as of January 2010, euro1.00 = US $1.43). The second and third most expensive drugs were tenofovir and pegylated interferon-alpha2b (euro33,700 and euro33,250, respectively). Costs incurred per patient increased over the years of the study period. CONCLUSIONS: The overall prevalence and cumulative incidence of patients with treatments for chronic HBV were relatively low in the northern part of the Netherlands between 2000 and 2006. The prescribing and utilization patterns were in agreement with international and Dutch guidelines. Given the low numbers of prescriptions, the costs also remained relatively low.

Cost effectiveness of angiotensin receptor blocker monotherapy in patients with hypertension in the Netherlands: a comparative analysis using clinical trial and drug utilization data.

BACKGROUND AND OBJECTIVE: Health gains and related cost savings achieved by optimizing treatment in hypertensive patients is highly important. The aim of this study was to evaluate the costs and cost effectiveness of treatment with angiotensin II receptor antagonists (angiotensin II receptor blockers [ARBs]) in patients with essential hypertension and to compare within-trial with real-life dosing of ARBs. METHODS: Cost effectiveness was estimated based on a published clinical trial comparing the BP-lowering effects of olmesartan, losartan, valsartan, and irbesartan. BP lowering after 8 weeks of treatment was entered into the Framingham risk functions to estimate cardiovascular complications after 1 and 5 years, using an international health economics model that was adapted to the Netherlands. Dutch costs (2006 values) and complications derived from the model were discounted at 4% and 1.5%, respectively, and cost effectiveness was expressed in net costs per cardiovascular complication averted. In a drug-utilization study, pharmacy dispensing records were used to evaluate differences between within-trial and daily-practice dosing and related costs for treatment in the Netherlands. RESULTS: After 8 weeks, the trial-based analysis showed that treatment with olmesartan versus losartan, valsartan, and irbesartan resulted in a significantly larger decrease in BP (11.5 vs 8.2, 7.9 and 9.9 mmHg [p < 0.05], respectively) and consequently more complications averted. Cost effectiveness for olmesartan, losartan, valsartan, and irbesartan was estimated at euro39,100, euro77,100, euro70,700, and euro50,900 per cardiovascular complication averted, respectively. The incremental cost-effectiveness analysis indicated the most favorable cost-effectiveness outcome for olmesartan, with lower costs and less cardiovascular complications for olmesartan compared with the other three ARBs. The drug-utilization analysis showed that the dosing followed within clinical trials was not found in daily practice. On average, losartan, valsartan, and irbesartan were administered at doses above those used in clinical trials, whereas olmesartan was dosed lower than in clinical trials, resulting in relatively lower costs. CONCLUSION: Based on the exact trial data, olmesartan was estimated to be the most favorable option of the four ARBs based on within-trial decreases in BP levels after 8 weeks and in terms of cost-effectiveness for this particular Dutch setting. However, for definite conclusions to be drawn, this hypothesis-generating study requires confirmation from further prospective studies comparing ARBs based on comparable BP control and including hard endpoints.

Monitoring of the folic acid supplementation program in the Netherlands.

In November of 1993, the Dutch government recommended daily folic acid supplementation of 0.4 or 0.5 mg for all women planning pregnancy, starting 4 weeks before conception until 8 weeks after. In 1995, a one-time mass media campaign was conducted, and due to this campaign, the use of folic acid in this recommended period increased from 4.8% in 1995 to 21% in 1996. Subsequently, no structural strategies were undertaken until 2003, and at that time, 22% of lower-educated women used folic acid in the recommended period. The prevalence of neural tube defects (NTD) decreased from 11.44/10,000 before the official recommendations to 6.52/10,000 thereafter. Currently, community pharmacies proactively approach women before their first pregnancy on the subject of folic acid supplementation. This is done by means of a sticker placed on packages of oral contraceptives with the text "Child wish?*". "Ask for information about folic acid in your pharmacy," and a brochure (leaflet) containing detailed information about folic acid. (*"Child wish" refers to women who plan to become pregnant.) Data from an explorative, comparative study strongly suggest that this intervention is effective. Sustainable education programs through which women are informed repeatedly to take folic acid supplements during the periconceptional period are urgently needed.

Cost-utility of repeated screening for Chlamydia trachomatis.

OBJECTIVE: To estimate the cost-effectiveness of repeated screening for chlamydia trachomatis at various time intervals compared to one-off screening of Dutch young adults. METHODS: We used a dynamic model to fully take the spread of the disease over time in the population into account, with data being used gathered within the context of a recently performed pilot study in The Netherlands. The screening frequencies analyzed were: every year, every 2 years, every 5 years, and every 10 years. The strategies were compared in terms of incremental cost-effectiveness, expressed as the net costs per quality-adjusted life-year (QALY). RESULTS: For all interval strategies, with the exception of screening every year, incremental cost-effectiveness stays below the informal Dutch threshold of euro20,000 per QALY. CONCLUSION: From a health-economic point of view, for the Dutch situation, we estimated screening every 2 years as the optimal strategy among the options investigated.

Economic evaluation of folic acid food fortification in The Netherlands.

BACKGROUND: Folic acid intake before and during pregnancy reduces neural tube defects (NTD). Therefore, several countries have enriched bulk food with folic acid resulting in a 26-48% decrease in the prevalence of NTDs. In 2000, the Dutch Health Council advised against folic acid enrichment based on literature research; yet formal cost-effectiveness information was absent. We designed our study to estimate cost-effectiveness of folic acid food fortification in the Netherlands. METHOD: Prevalence of NTD at birth, life-time costs of care, and folic acid fortification costs were estimated using Dutch registrations, Dutch guidelines for costing, (inter)national literature and expert opinions. Both net cost per discounted life year gained and net cost per discounted quality adjusted life year (QALY) gained were estimated for the base case and sensitivity analyses. RESULTS: In the base case and most sensitivity analyses, folic acid enrichment was estimated to be cost-saving. Bulk food fortification with folic acid remains cost-effective as long as enrichment costs do not exceed euro5.5 million (threshold at euro20 000 per QALY). CONCLUSION: Our model suggests that folic acid fortification of bulk food to prevent cases of NTD in newborns might be a cost-saving intervention in the Netherlands. Additionally, besides the evidence that folic acid reduces the number of NTDs, there are indications that folic acid is associated with the prevention of other birth defects, cardiovascular diseases and cancer. Our model did not yet include these possibly beneficial effects.

Long-acting methylphenidate-OROS in youths with attention-deficit hyperactivity disorder suboptimally controlled with immediate-release methylphenidate: a study of cost effectiveness in The Netherlands.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is the most common mental health disorder in youths. Stimulants are the drugs of first choice in the treatment of ADHD. It has been suggested that full costs associated with the treatment of ADHD may be reduced by once-daily administration regimens of stimulants. OBJECTIVES: To estimate the cost effectiveness of treatment with long-acting methylphenidate osmotic release oral system (OROS) [Concerta] for youths with ADHD for whom treatment with immediate-release (IR) methylphenidate is suboptimal. STUDY DESIGN: We developed a Markov model to obtain an incremental cost-effectiveness ratio (ICER). The analysis covered 10 years, with a Markov cycle of 1 day. Costs (in 2005 euros ) included medication, consultations and treatment interventions, and additional costs for attending special education. Quality-adjusted life-years (QALYs) were used as the effectiveness measure. Outcome probabilities were taken from the medical literature and an expert panel of five child psychiatrists and paediatricians. Univariate sensitivity analyses were performed to assess the robustness of the base-case estimate. Multivariate sensitivity analysis was used to estimate a worst- and best-case ICER. RESULTS: The ICER of methylphenidate-OROS treatment in youths with ADHD for whom treatment with IR methylphenidate is suboptimal was euro 2004 per QALY. Total costs after 10 years were euro 15,739 for the IR methylphenidate pathway and euro 16,015 for the methylphenidate-OROS pathway. In the univariate sensitivity analysis, the ICER was sensitive to changes in resource use and the probability of stopping stimulant treatment in favour of IR methylphenidate. An ICER of 0 was reached with a 6.2% price reduction of methylphenidate-OROS. CONCLUSION: Methylphenidate-OROS is a cost-effective treatment for youths with ADHD for whom treatment with IR methylphenidate is suboptimal. Higher medication costs of methylphenidate-OROS were compensated for by savings on resource use, yielding similar 10-year costs compared with treatment with IR methylphenidate. Our analysis is sensitive to both clinical parameters and (differences in) resource utilization and costs between the groups modelled, warranting further research within clinical trials and observational databases, and into the full scope of costs.

Cost effectiveness of itraconazole in the prophylaxis of invasive fungal infections.

BACKGROUND: Invasive fungal infections in neutropenic patients treated for haematological malignancies are associated with a high mortality rate and, therefore, require early treatment. As the diagnosis of invasive fungal infections is difficult, effective antifungal prophylaxis is desirable. So far, fluconazole has been the most commonly used. OBJECTIVE: To assess the cost effectiveness of itraconazole compared with both fluconazole and no prophylaxis for the prevention of invasive fungal infections in haematological patients, mean age 51 years, in Germany and The Netherlands. STUDY DESIGN: We designed a probabilistic decision model to fully incorporate the uncertainty associated with the risk estimates of acquiring an invasive fungal infection. These risk estimates were extracted from two meta-analyses, evaluating the effectiveness of fluconazole and itraconazole and no prophylaxis. The perspective of the analysis was that of the healthcare sector; only medical costs were taken into account. All costs were reported in euro, year 2004 values.Cost effectiveness was expressed as net costs per invasive fungal infection averted. No discounting was performed, as the model followed patients during their neutropenic period, which was assumed to be less than 1 year. RESULTS: According to our probabilistic decision model, the monetary benefits of averted healthcare exceed the costs of itraconazole prophylaxis under baseline assumptions (95% CI: from cost-saving to euro 5000 per invasive fungal infection averted). Compared with fluconazole, itraconazole is estimated to be both more effective and more economically favourable, with a probability of almost 98%. CONCLUSIONS: In specific groups of neutropenic patients treated for haematological malignancies, itraconazole prophylaxis could potentially reduce overall healthcare expenditure, without harming effectiveness, in settings where fluconazole is common practice in the prophylaxis of invasive fungal infections.

Pharmacoeconomics of angiotensin II antagonists in type 2 diabetic patients with nephropathy: implications for decision making.

Angiotensin II receptor antagonists (angiotensin II receptor blockers; ARBs) are a class of antihypertensive drugs that are generally considered comparable to ACE inhibitors in the prevention of heart and kidney failure. However, these two classes of agents do interfere in different stages of the renin-angiotensin system. In patients with type 2 diabetes mellitus, advantages for ARBs over conventional (non-ACE inhibitor) therapy on progression from micro- to macroalbuminuria and overt nephropathy and end-stage renal disease have been shown in clinical trials. In patients with type 2 diabetes and end-stage renal disease, the need for dialysis and/or transplantation results in the use of major healthcare resources. This paper reviews the available economic evidence on treatment with ARBs in type 2 diabetic patients with advanced renal disease.Within-trial analytic and Markov model economic evaluations of the RENAAL (Reduction of Endpoint in Non-insulin dependent diabetes mellitus with Angiotensin II Antagonist Losartan), IDNT (Irbesartan Diabetic Nephropathy Trial) and IRMA (IRbesartan in type 2 diabetes with MicroAlbuminuria)-2 studies suggest that treatment with ARBs in patients with type 2 diabetes with overt or incipient nephropathy confers health gains and net cost savings compared with conventional (non-ACE inhibitor) therapy. For reimbursement and reference pricing decisions, there is a need for a head-to-head comparison of an ACE inhibitor with ARBs to model all possible costs and effects of ACE inhibitors and ARBs. This will result in a proper pharmacoeconomic outcome, where both types of drugs can be compared for healthcare decisions.

Cost-effectiveness of screening for albuminuria with subsequent fosinopril treatment to prevent cardiovascular events: A pharmacoeconomic analysis linked to the prevention of renal and vascular endstage disease (PREVEND) study and the prevention of renal and vascular endstage disease intervention trial (PREVEND IT).

OBJECTIVE: This study estimated the cost-effectiveness,from the Dutch health care perspective, of screening for albuminuria in the general Dutch population to prevent cardiovascular events (CVEs) with subsequent angiotensin-converting enzyme inhibitor treatment, using data from the Prevention of REnal and Vascular ENdstage Disease Intervention Trial (PREVEND IT). METHODS: PREVEND IT was a single-center, double-blind, randomized, placebo-controlled trial with a 2 x 2 factorial design within the larger observational Prevention of REnal and Vascular ENdstage Disease (PREVEND) study. The PREVEND IT study was conducted to assess the effects of fosinopril 20 mg and pravastatin 40 mg on CVEs in subjects with specific inclusion criteria: urinary albumin excretion (UAE) rate in the range from 15 to 300 mg/d, blood pressure <160/100 mm Hg, and plasma cholesterol level <8.0 mmol/L. Cost-effectiveness estimates for the Dutch population were expressed in euros (2002; 1 euro = US 1.01 dollars) as net costs per life-year gained (LYG) in the baseline and sensitivity (stochastic) analyses. RESULTS: Data were assessed for 864 subjects, with a mean (SD) follow-up of 46 (7) months. CVEs occurred in 45 (5.2%) subjects. Subjects who received fosinopril had a 40% lower incidence of CVEs than subjects in the placebo group (3.9% vs 6.5%, respectively; P = NS). The cost-effectiveness of screening for albumnuria was determined to be euro 16,700/LYG for the study population. Stochastic analysis indicated that the probability of the cost-effectiveness being below the suggested Dutch threshold of euro 20,000/LYG was 59% in the baseline analysis. The probability of cost-effectiveness below euro 20,000/LYG would increase to 91% if only subjects with UAE >50 mg/d were treated with fosinopril. Limiting the screening to subjects aged >50 years and >60 years also improved cost-effectiveness. CONCLUSIONS: The results of our study suggest that screening the general Dutch population for albuminuria and subsequently treating those found positive with fosinopril may be cost-effective compared with no screening and adopting the Dutch health care perspective. However, confirmation from larger multicenter trials is needed.

Antidepressant prevalence for youths: a multi-national comparison.

OBJECTIVE: To compare antidepressant prevalence data in youths across three western European countries (Denmark, Germany, and the Netherlands) with US regional data in terms of age and gender and to show proportional subclass antidepressant (ATD) use. METHOD: A population-based analysis of administrative claims data for the year 2000 was undertaken in 0 to 19-year-old enrollees who were part of the insured populations from four countries having a total of from 72,570 to 480,680 members. RESULTS: ATD medication utilization in the US dataset (1.63%) exceeded that of three Western European countries (prevalence ranged from 0.11 to 0.54%) by at least 3-fold. There were major variations in the use of subclasses: tricyclic antidepressants (TCAs) predominated in Germany while selective serotonin reuptake inhibitors (SSRIs) predominated in the US, Denmark and the Netherlands. CONCLUSIONS: Cross-national variations should be further explored to understand the factors related to these differences and how prevalence differences relate to effectiveness and safety. Community-based cohorts should be followed to establish outcomes in the usual practice setting.

Systematic screening for Chlamydia trachomatis: estimating cost-effectiveness using dynamic modeling and Dutch data.

OBJECTIVE: To estimate the cost-effectiveness of a systematic one-off Chlamydia trachomatis (CT) screening program including partner treatment for Dutch young adults. METHODS: Data on infection prevalence, participation rates, and sexual behavior were obtained from a large pilot study conducted in The Netherlands. Opposite to almost all previous economic evaluations of CT screening, we developed a dynamic Susceptible-Infected-Susceptible (SIS) model to estimate the impact of the screening program on the incidence and prevalence of CT in the population. SIS models are widely used in epidemiology of infectious diseases, for modeling the transmission dynamics over time. Subsequently, a predictive decision model was used to calculate the complications averted by the screening program. Cost-effectiveness was expressed as the net costs per major outcome averted (MOA) and was estimated in the baseline analysis and in sensitivity analysis. RESULTS: The overall prevalence decreased from 1.79% to 1.05% as a result of the screening program directed at both men and women. The program costs were mainly offset by the averted costs, although not fully. Resulting net costs per MOA were 373 euro sin the baseline analysis. Sensitivity analysis showed that partner treatment and sending a reminder are important aspects improving cost-effectiveness. Additionally, restricting the screening to women only was estimated to save costs. CONCLUSIONS: Our cost-effectiveness analysis shows that the Dutch society has net to pay for the prevention of CT-complications through screening young men and women. One could argue although that 373 euros per MOA presents a reasonable cost. A screening program consisting of screening women only should always be adopted from a pharmacoeconomic point of view. Our dynamic approach appreciates better the specific characteristics of an infectious disease, such as CT.

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.

Identifying parents in pharmacy data: a tool for the continuous monitoring of drug exposure to unborn children.

OBJECTIVE: This study aimed to develop and validate a method for retrospectively identifying parents in pharmacy data during pregnancy. STUDY DESIGN AND SETTING: The principle of the method was to select all children 0-2 years in pharmacy records, and to consider men/women 15-50 years older with the same address as fathers/mothers. RESULTS: Applying this method to the records of all 4 pharmacies in 1 town (33,000 inhabitants) resulted in identification of 807 fathers and 765 mothers, corresponding with 68.5% of all fathers, and 64.9% of all mothers from the town. Additionally, the method was applied to one selected pharmacy, resulting in 151 fathers and 170 mothers. Validation criterions, evaluated by pharmacy employees and GPs, disproved one of these fathers (0.7% of all identified fathers) and one mother (0.6%). CONCLUSION: We conclude that automatic retrospective identification of parents in pharmacy data is feasible in a valid way. The main limitation is that not all parents were found, possibly resulting in selection bias.

Pharmacoeconomic aspects of losartan treatment to delay progression of renal disease in patients with Type 2 diabetes.

There is growing evidence from clinical trials that losartan (Cozaar, Merck & Co., Inc.) and other angiotensin (A)-II-receptor antagonists have beneficial effects on the progression of renal disease among Type 2 diabetic patients beyond the benefits derived from the effect of blood-pressure lowering alone [corrected]. Comparators used is the studies were not angiotensin-converting enzyme-inhibitors but typically conventional hypertensive therapy plus placebo, placebo alone and in one case, amlodipine. These trials have reported reductions in progression to end stage renal disease (ESRD) (losartan and irbesartan) and to nephropathy (irbesartan). An important pharmacoeconomic question is whether potential cost-savings on reduced progression to ESRD and nephropathy outweigh the extra costs of A-II-antagonist treatment. This paper will review the published economic studies for A-II-receptor antagonists and their pharmacoeconomic implications. In particular, potential pharmacoeconomic implications and related methodological aspects of the recent RENAAL trial for losartan are considered.