The cost and effectiveness of adherence‐improving interventions for antihypertensive and lipid‐lowering drugs*

Aims: Adherence to cardiovascular medications is poor. Accordingly, interventions have been proposed to improve adherence. However, as intervention‐associated costs are rarely considered in full, we sought to review the effectiveness and costs associated with different adherence‐improving interventions for cardiovascular disease therapies. Methods: We reviewed MEDLINE to update a prior review of interventions to improve adherence with antihypertensive and/or lipid‐lowering therapy covering January 1972 to June 2002, to add studies published from July 2002 to October 2007. Eligible studies evaluated ≥ 1 intervention compared with a control, used measures other than self‐report, reported significant improvement in adherence and followed patients for ≥ 6 months. Effectiveness was measured as relative improvement (RI), the ratio of adherence in the intervention group to the control group. Costs were calculated based on those reported in the analysis, if available or estimated based on resource use described. All costs were truncated to 6 months and adjusted to 2007 US$. Results: Of 755 new articles, five met all eligibility criteria. Combining with the prior review gave 23 interventions from 18 studies. RI in adherence ranged from 1.11 to 4.65. Six‐month intervention costs ranged from $10 to $142 per patient. Reminders had the lowest effectiveness (RI: 1.11–1.14), but were least costly ($10/6 months). Case management was most effective (RI: 1.23–4.65), but the most costly ($90–$130/6 months). Conclusions: Generally, we found a positive association between intervention costs and effectiveness. Therefore, consideration of intervention costs, along with the benefits afforded to adherence, may help guide the design and implementation of adherence‐improving programs.     

Genetic testing in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a cost‐effectiveness analysis

Summary. Background: The CYP2C19 genotype is a predictor of adverse cardiovascular events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) treated with clopidogrel. Objectives: We aimed to evaluate the cost‐effectiveness of a CYP2C19*2 genotype‐guided strategy of antiplatelet therapy in ACS patients undergoing PCI, compared with two ‘no testing’ strategies (empiric clopidogrel or prasugrel). Methods: We developed a Markov model to compare three strategies. The model captured adverse cardiovascular events and antiplatelet‐related complications. Costs were expressed in 2010 US dollars and estimated using diagnosis‐related group codes and Medicare reimbursement rates. The net wholesale price for prasugrel was estimated as $5.45 per day. A generic estimate for clopidogrel of $1.00 per day was used and genetic testing was assumed to cost $500. Results: Base case analyses demonstrated little difference between treatment strategies. The genetic testing‐guided strategy yielded the most QALYs and was the least costly. Over 15 months, total costs were $18 lower with a gain of 0.004 QALY in the genotype‐guided strategy compared with empiric clopidogrel, and $899 lower with a gain of 0.0005 QALY compared with empiric prasugrel. The strongest predictor of the preferred strategy was the relative risk of thrombotic events in carriers compared with wild‐type individuals treated with clopidogrel. Above a 47% increased risk, a genotype‐guided strategy was the dominant strategy. Above a clopidogrel cost of $3.96 per day, genetic testing was no longer dominant but remained cost‐effective. Conclusions: Among ACS patients undergoing PCI, a genotype‐guided strategy yields similar outcomes to empiric approaches to treatment, but is marginally less costly and more effective.     

Serum osteoprotegerin levels and long‐term prognosis in subjects with stable coronary artery disease

Summary. Background: Osteoprotegerin (OPG) is a secretory glycoprotein which belongs to the tumor necrosis factor receptor family. OPG immunoreactivity was demonstrated in normal blood vessels and in early atherosclerotic lesions. In a previous study, we showed that high serum OPG levels are associated with progression of coronary artery disease (CAD). Objectives: The present study was designed to assess the association between serum OPG level and long‐term prognosis in patients with stable coronary artery disease. Methods: We performed a prospective, observational cohort study in 225 subjects to examine whether serum OPG levels can predict cardiovascular mortality. The median OPG levels were 1.02 ng mL^?1 at baseline. Results: During the follow‐up (61 ± 25 months), 27 deaths occurred including 13 cardiovascular deaths. When the subjects were divided into three groups according to serum OPG level, the group with high serum OPG showed a higher risk for cardiovascular mortality. A Multivariate Cox proportional hazards model indicated that the higher risk of cardiovascular death in the high OPG level group remained significant (hazards ratio of 7.44, 95%CI 0.92–60.30, highest vs. lowest OPG tertile). In contrast, serum OPG levels were not associated with non‐cardiovascular mortality. Conclusions: Our data show that serum OPG levels are an independent predictor of cardiovascular mortality in patients with stable coronary artery disease.     

Incidence of arterial cardiovascular events after venous thromboembolism: a systematic review and a meta‐analysis

Summary. Background: Whether patients with unprovoked venous thromboembolism (VTE) have a higher risk of arterial cardiovascular events than the general population and patients with provoked VTE is a matter of debate. Objective: To perform a systematic review and a meta‐analysis aimed at assessing the risk of arterial cardiovascular events in patients with unprovoked VTE as compared with both patients with provoked VTE and controls. Methods: A systematic search was performed. Studies reporting on (i) patients with confirmed VTE, (ii) a follow‐up of at least 6 months and (iii) the incidence of arterial cardiovascular events (acute myocardial infarction and ischemic stroke) were included in the systematic review. Those studies reporting separate incidences of cardiovascular events in patients with unprovoked and provoked VTE or patients with unprovoked VTE and controls were included in the incidence rate meta‐analysis. Results: Overall, 17 studies were included in the systematic review. The weighted mean incidence of arterial cardiovascular events was 0.46% [95% confidence interval (CI) 0.34–0.59] and 0.35% (95% CI 0.24–0.49) per patient‐year in patients with unprovoked and provoked VTE, respectively. Six studies were included in the meta‐analysis. The risk of arterial cardiovascular events appeared to be higher in patients with unprovoked VTE than in controls [incidence rate ratio (IRR) 1.87, 95% CI 1.32–2.65] and than in patients with provoked VTE (IRR 1.86, 95% CI 1.19–2.89). Conclusions: Patients with unprovoked VTE have a higher risk of arterial cardiovascular events than patients with provoked VTE over long‐term follow‐up.     

Comparison of the metabolic and economic consequences of long‐term treatment of schizophrenia using ziprasidone,olanzapine, quetiapine and risperidone in Canada: a cost‐effectiveness analysis

Rationale, aims and objectives Second‐generation antipsychotic agents have varying propensities to cause weight gain, elevated lipid levels and associated long‐term complications. This study evaluates the cost‐effectiveness of four second‐generation antipsychotic agents used in Canada for the treatment of schizophrenia (ziprasidone, olanzapine, quetiapine, risperidone) with a focus on their long‐term metabolic consequences. Method Using data from the Clinical Antipsychotic Trials of Intervention Effectiveness Study, a semi‐Markov model was developed to predict the incidence and associated costs of type 2 diabetes, cardiovascular complications (e.g. angina, myocardial infarction, stroke, cardiovascular disease death), and acute psychiatric hospitalizations in patients with chronic schizophrenia treated over 5 years. Incremental costs per quality‐adjusted life year (QALY) gained were calculated from the perspective of the Canadian provincial ministries of health. Scenario and probabilistic sensitivity analyses were performed. Results The total average cost of treatment with ziprasidone was $25 301 versus $28 563 with olanzapine, $26 233 with quetiapine and $21 831 with risperidone. Ziprasidone had the lowest predicted number of type 2 diabetes cases and cardiovascular disease events, and the highest QALY gains. Patients receiving quetiapine had the highest predicted number of hospitalizations. Ziprasidone was less costly and resulted in more QALYs compared with olanzapine and quetiapine. Compared with risperidone, ziprasidone was more costly and had higher QALYs, with an incremental cost per QALY gained of $218 060. Conclusion Compared with olanzapine and quetiapine, ziprasidone produced savings to the health care system. Although ziprasidone generated incremental expenditures versus risperidone, it resulted in more QALYs. Based on this analysis, ziprasidone treatment possesses cost and therapeutic advantages compared with olanzapine and quetiapine.     

Cost‐utility analysis of bevacizumab versus ranibizumab in neovascular age‐related macular degeneration using a Markov model

Objective To evaluate the cost‐effectiveness of intravitreal bevacizumab to ranibizumab in patients with neovascular age‐related macular degeneration (AMD). Methods A cost‐utility analysis using a Markov model was performed to evaluate incremental cost‐effectiveness ratio [ICER, $US per quality‐adjusted life year (QALY) gained] between bevacizumab and ranibizumab from a US payer perspective. Transition probabilities for ranibizumab and bevacizumab were extrapolated from published studies and local institutional data. Utility values, likewise, were obtained from another published study. Mortality rates were determined from the Centers for Disease Control 2003 Life Tables. Resource utilization and total direct costs were estimated using the Centers for Medicare and Medicaid Services and the Veterans Affairs Decision Support System. A hypothetical cohort of 1000 patients was simulated through the model for 20 years. Sensitivity analyses were performed using univariate and probabilistic sensitivity analysis (PSA) on all costs, transition probabilities and utility values. An acceptability curve was generated to illustrate the cost‐effectiveness probability of bevacizumab to ranibizumab with increasing willingness‐to‐pay (WTP). Results The cost‐effectiveness ratios (CER) for bevacizumab and ranibizumab were $1405 per QALY and $12 177 per QALY, respectively. The ICER for bevacizumab was dominant compared to ranibizumab. The base‐case CER was sensitive to drug costs of the study medications with a breakeven point of $44 for ranibizumab and $2666 for bevacizumab. PSA revealed a 95% probability of bevacizumab being more cost‐effective than ranibizumab at a WTP of $50 000 per QALY gained. Conclusion Based on a WTP defined at $50 000 per QALY gained, bevacizumab was cost‐effective versus ranibizumab 95% of the time because of lower acquisition costs and increased efficacy.     

A model for assessing the cost-effectiveness of atorvastatin and simvastatin in achieving Canadian low-density lipoprotein cholesterol targets

BACKGROUND: Elevated low-density lipoprotein cholesterol (LDL-C) is an important modifiable risk factor for cardiovascular (CV) disease. Statins differ in their LDL-C-lowering effects and acquisition costs. Atorvastatin and simvastatin are the 2 most commonly used statins in Canada. OBJECTIVE: This analysis compared the cost-effectiveness of atorvastatin and generic simvastatin in terms of annual drug cost per patient treated to Canadian LDL-C targets. It was conducted from the perspective of the Canadian provincial drug-reimbursement plans. METHODS: A hypothetical cohort of 1000 dyslipidemic patients was assigned baseline LDL-C serum concentrations and levels of risk for CV disease based on Canadian population data. Canadian data on statin dosing were combined with efficacy data from a published meta-analysis to determine the proportion of patients who would be expected to achieve LDL-C targets after treatment with atorvastatin or generic simvastatin. Statin acquisition costs were obtained from Ontario and Quebec and reported in 2005 Canadian dollars. The sensitivity of the model to changes in drug costs, effectiveness, and persistence with treatment was tested. RESULTS: The model predicted that more patients would reach the LDL-C target with atorvastatin than with simvastatin (73% vs 57%, respectively). The mean annual drug cost per patient treated to target was $54 higher with atorvastatin ($905 vs $851). The incremental cost-effectiveness ratio, measured as annual drug cost per additional patient treated to target with atorvastatin, was $1088. The model was sensitive to drug cost and effectiveness assumptions. Incorporating real-life rates of adherence into the model had no significant impact on the results. CONCLUSION: In this hypothetical cohort of dyslipidemic patients, treatment with atorvastatin would allow achievement of LDL-C targets in more patients than treatment with simvastatin, at an annual incremental cost of $1088 per additional patient treated to target.     

Long‐term cost‐effectiveness of weight management in primary care

Background: As obesity prevalence and health‐care costs increase, Health Care providers must prevent and manage obesity cost‐effectively. Methods: Using the 2006 NICE obesity health economic model, a primary care weight management programme (Counterweight) was analysed, evaluating costs and outcomes associated with weight gain for three obesity‐related conditions (type 2 diabetes, coronary heart disease, colon cancer). Sensitivity analyses examined different scenarios of weight loss and background (untreated) weight gain. Results: Mean weight changes in Counterweight attenders was ?3 kg and ?2.3 kg at 12 and 24 months, both 4 kg below the expected 1 kg/year background weight gain. Counterweight delivery cost was £59.83 per patient entered. Even assuming drop‐outs/non‐attenders at 12 months (55%) lost no weight and gained at the background rate, Counterweight was ‘dominant’ (cost‐saving) under ‘base‐case scenario’, where 12‐month achieved weight loss was entirely regained over the next 2 years, returning to the expected background weight gain of 1 kg/year. Quality‐adjusted Life‐Year cost was £2017 where background weight gain was limited to 0.5 kg/year, and £2651 at 0.3 kg/year. Under a ‘best‐case scenario’, where weights of 12‐month‐attenders were assumed thereafter to rise at the background rate, 4 kg below non‐intervention trajectory (very close to the observed weight change), Counterweight remained ‘dominant’ with background weight gains 1 kg, 0.5 kg or 0.3 kg/year. Conclusion: Weight management for obesity in primary care is highly cost‐effective even considering only three clinical consequences. Reduced healthcare resources use could offset the total cost of providing the Counterweight Programme, as well as bringing multiple health and Quality of Life benefits.     

Evaluating cardiovascular mortality in type 2 diabetes patients: an analysis based on competing risks Markov chains and additive regression models

RATIONALE, AIMS AND OBJECTIVES: Type 2 diabetes represents a condition significantly associated with increased cardiovascular mortality. The aims of the study are: (i) to estimate the cumulative incidence function for cause-specific mortality using Cox and Aalen model; (ii) to describe how the prediction of cardiovascular or other causes mortality changes for patients with different pattern of covariates; (iii) to show if different statistical methods may give different results. METHODS: Cox and Aalen additive regression model through the Markov chain approach, are used to estimate the cause-specific hazard for cardiovascular or other causes mortality in a cohort of 2865 type 2 diabetic patients without insulin treatment. The models are compared in the estimation of the risk of death for patients of different severity. RESULTS: For younger patients with a better covariates profile, the Cumulative Incidence Function estimated by Cox and Aalen model was almost the same; for patients with the worst covariates profile, models gave different results: at the end of follow-up cardiovascular mortality rate estimated by Cox and Aalen model was 0.26 [95% confidence interval (CI) = 0.21-0.31] and 0.14 (95% CI = 0.09-0.18). CONCLUSIONS: Standard Cox and Aalen model capture the risk process for patients equally well with average profiles of co-morbidities. The Aalen model, in addition, is shown to be better at identifying cause-specific risk of death for patients with more severe clinical profiles. This result is relevant in the development of analytic tools for research and resource management within diabetes care.     

Comparison of associations of adherence to a Dietary Approaches to Stop Hypertension (DASH)‐style diet with risks of cardiovascular disease and venous thromboembolism

Summary. Background: Venous thromboembolism (VTE) and cardiovascular disease (CVD) share some risk factors, including obesity, but it is unclear how dietary patterns associated with reduced risk of CVD relate to risk of VTE. Objective: To compare the relationships of adherence to a Dietary Approaches to Stop Hypertension (DASH)‐style diet with the risks of CVD and VTE. Patients/Methods: We confirmed by medical record review 1094 incident cases of CVD and 675 incident VTEs during a mean follow‐up of 14.6 years in 34 827 initially healthy participants in the Women’s Health Study who completed at baseline a 133‐item food frequency questionnaire scored for adherence to a DASH diet. We compared estimated associations of dietary patterns with CVD and VTE from proportional hazards models in a competing risk framework. Results: Initial analyses adjusted for age, energy intake and randomized treatments showed 36–41% reduced hazards of CVD among women in the top two quintiles of DASH score relative to those in the bottom quintile (P_trend < 0.001). In multivariate analysis, women in the top two quintiles had 12–23% reduced hazards of CVD relative to women in the bottom quintile (P_trend = 0.04). Analyses restricted to coronary events showed more variable 10–33% reduced hazards in the top two quintiles (P_trend = 0.09). In contrast, higher DASH scores were unrelated to risk of VTE, with a 1% reduced hazard for the top vs. bottom quintile (P_trend = 0.95). Conclusion: An apparently strong association of adherence to the DASH diet with incidence of CVD was attenuated upon control for confounding variables. Adherence to the DASH diet was not associated with risk of VTE in women.     

Association between allopurinol and mortality in heart failure patients: a long‐term follow‐up study

Aims: The aim of the study was to explore the long‐term effect of allopurinol on mortality and cardiovascular hospitalisations in heart failure (HF) patients. Methods: This is a population‐based cohort study using a record‐linkage database in Tayside, Scotland. A total of 4785 HF patients (4260 non‐users, 267 incident users and 258 prevalent users) were studied between 1993 and 2002. Results: Compared with non‐users, low‐dose users in the incident group had a significant increased risk of all‐cause mortality, cardiovascular mortality and cardiovascular recurrence (adjusted HR, 1.60, 95%CI 1.26–2.03; 1.70, 1.29–2.23 and 1.44, 1.01–2.07). For the prevalent users, the adjusted HR were 1.27, 0.98–1.64; 1.43, 1.07–1.90 and 1.27, 0.91–1.76 respectively. There was no increased risk of outcome for high‐dose users when compared with non‐users (adjusted HR, 1.18, 0.84–1.66; 1.14, 0.76–1.71 and 1.36, 0.88–2.10 for the incident users, and 0.86, 0.64–1.15; 0.90, 0.64–1.26; and 1.27, 0.93–1.74 for the prevalent users respectively). High‐dose allopurinol was associated with reduced risk of all‐course mortality for prevalent users when compared with low‐dose (adjusted HR 0.65, 95%CI 0.42–0.99). Conclusions: The prevalent high‐dose allopurinol use had a lower risk of mortality than the prevalent low‐dose use suggesting that allopurinol may be of benefit in HF patients.     

Increased risk of pulmonary embolism among patients with hyperthyroidism: a 5‐year follow‐up study

Summary Background: Although studies have indicated that hyperthyroidism is associated with hypercoagulability, most such studies have focused only on examining the incidence of venous thrombosis. As far as we know, no study has attempted to explore the risk of pulmonary embolism (PE) among patients with hyperthyroidism. Objective: Using a nationwide population‐based dataset, this study was aimed at estimating the risk of PE among hyperthyroidism patients during a 5‐year period, as compared with non‐hyperthyroidism patients during the same period. Methods: Data sourced from the Taiwan Longitudinal Health Insurance Database were analyzed. The study included 8903 patients with hyperthyroidism as a study cohort and 44 515 randomly selected patients without hyperthyroidism as a comparison cohort. Stratified Cox proportional hazard regressions were used to compute the 5‐year PE‐free survival rate between these two cohorts. Results: Of the total of 53 418 patients, 41 patients (0.08%) were identified as having PE during the follow‐up period, 14 from the study cohort (0.16% of the hyperthyroidism patients) and 27 comparison patients (0.06% of patients from the comparison cohort). After adjustment for geographic region, monthly income, hypertension, diabetes, hyperlipidemia, peripheral vascular disease, coronary heart disease, cancer, recent surgery, recent fracture, pregnancy and the use of anticoagulants, the risk of having PE during the 5‐year follow‐up period was 2.31 times greater (95% confidence interval 1.20–4.45, P = 0.012) for patients with hyperthyroidism than for patients in the comparison cohort. Conclusion: We found an increased risk of PE in patients with hyperthyroidism. Clinicians should be aware of this increased risk.     

Cost-Effectiveness of Multitarget Stool DNA Testing vs Colonoscopy or Fecal Immunochemical Testing for Colorectal Cancer Screening in Alaska Native People

ObjectiveTo estimate the cost-effectiveness of multitarget stool DNA testing (MT-sDNA) compared with colonoscopy and fecal immunochemical testing (FIT) for Alaska Native adults.Patients and MethodsA Markov model was used to evaluate the 3 screening test effects over 40 years. Outcomes included colorectal cancer (CRC) incidence and mortality, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). The study incorporated updated evidence on screening test performance and adherence and was conducted from December 15, 2016, through November 6, 2019.ResultsWith perfect adherence, CRC incidence was reduced by 52% (95% CI, 46% to 56%) using colonoscopy, 61% (95% CI, 57% to 64%) using annual FIT, and 66% (95% CI, 63% to 68%) using MT-sDNA. Compared with no screening, perfect adherence screening extends life by 0.15, 0.17, and 0.19 QALYs per person with colonoscopy, FIT, and MT-sDNA, respectively. Colonoscopy is the most expensive strategy: approximately $110 million more than MT-sDNA and $127 million more than FIT. With imperfect adherence (best case), MT-sDNA resulted in 0.12 QALYs per person vs 0.05 and 0.06 QALYs per person by FIT and colonoscopy, respectively. Probabilistic sensitivity analyses supported the base-case analysis. Under varied adherence scenarios, MT-sDNA either dominates or is cost-effective (ICERs, $1740-$75,868 per QALY saved) compared with FIT and colonoscopy.ConclusionEach strategy reduced costs and increased QALYs compared with no screening. Screening by MT-sDNA results in the largest QALY savings. In Markov model analysis, screening by MT-sDNA in the Alaska Native population was cost-effective compared with screening by colonoscopy and FIT for a wide range of adherence scenarios.     

Analytical decision model for sample size and effectiveness projections for use in planning a population‐based randomized controlled trial of colorectal cancer screening

Rationale, aims and objectives Population‐based randomized controlled trials (RCTs) often involve enormous costs and long‐term follow‐up to evaluate primary end points. Analytical decision‐simulated model for sample size and effectiveness projections based on primary and surrogate end points are necessary before planning a population‐based RCT. Method Based on the study design similar to two previous RCTs, transition rates were estimated using a five‐state natural history model [normal, preclinical detection phase (PCDP) Dukes' A/B, PCDP Dukes' C/D, Clinical Dukes' A/B and Clinical Dukes' C/D]. The Markov cycle tree was assigned transition parameters, variables related to screening and survival rate that simulated results of 10‐year follow‐up in the absence of screening for a hypothetical cohort aged 45–74 years. The corresponding screened arm was to simulate the results after the introduction of population‐based screening for colorectal cancer with fecal occult blood test with stop screen design. Results The natural course of mean sojourn time for five‐state Markov model were estimated as 2.75 years for preclinical Dukes' A/B and 1.38 years for preclinical Dukes' C/D. The expected reductions in mortality and Dukes' C/D were 13% (95% confidence intervals: 7–19%) and 26% (95% confidence intervals: 20–32%), respectively, given a 70% acceptance rate and a 90% colonoscopy referral rate. Sample sizes required were 86 150 and 65 592 subjects for the primary end point and the surrogate end point, respectively, given an incidence rate up to 0.0020 per year. Conclusions The sample sizes required for primary and surrogate end points and the projection of effectiveness of fecal occult blood test for colorectal cancer screening were developed. Both are very important to plan a population‐based RCT.     

Family history of myocardial infarction is an independent risk factor for venous thromboembolism: the Tromsø study

Summary. Background: Recent studies indicate that arterial cardiovascular diseases and venous thromboembolism (VTE) share common risk factors. A family history of myocardial infarction (MI) is a strong and independent risk factor for future MI. Objectives: The purpose of the present study was to determine the impact of cardiovascular risk factors, including family history of MI, on the incidence of VTE in a prospective, population‐based study. Patients and methods: Traditional cardiovascular risk factors and family history of MI were registered in 21 330 subjects, aged 25–96 years, enrolled in the Tromsø study in 1994–95. First‐lifetime VTE events during follow‐up were registered up to 1 September 2007. Results: There were 327 VTE events (1.40 per 1000 person‐years), 138 (42%) unprovoked, during a mean of 10.9 years of follow‐up. In age‐ and gender‐adjusted analysis, age [hazard ratio (HR) per decade, 1.97; 95% confidence interval (CI), 1.82–2.12], gender (men vs. women; HR, 1.25; 95% CI, 1.01–1.55), body mass index (BMI; HR per 3 kg m^?2, 1.21; 95% CI, 1.13–1.31), and family history of MI (HR, 1.31; 95% CI, 1.04–1.65) were significantly associated with VTE. Family history of MI remained a significant risk factor for total VTE (HR, 1.27; 95% CI, 1.01–1.60) and unprovoked VTE (HR, 1.46; 95% CI, 1.03–2.07) in multivariable analysis. Blood pressure, total cholesterol, HDL‐cholesterol, triglycerides, and smoking were not independently associated with total VTE. Conclusions: Family history of MI is a risk factor for both MI and VTE, and provides further evidence of a link between venous and arterial thrombosis.     

Assessing the value of atomoxetine in treating children and adolescents with ADHD in the UK

Background: Economic evaluation of healthcare technologies is becoming increasingly relevant, enabling decision makers to assess and compare treatments within the context of costs and outcomes. Moreover, it is increasingly important for clinicians and prescribers to have some understanding of economic evaluation. For attention‐deficit/hyperactivity disorder (ADHD), economic evaluations have largely focused on pharmacotherapy, and results indicate that such treatments are cost‐effective compared with other interventions. Aims: This review provides an overview of ADHD, its consequences and pharmacotherapy; describes the principles of health economic analysis, health‐related quality of life (HRQL) and a cost‐effectiveness model of atomoxetine for ADHD treatment; and outlines guidance from the National Institute for Health and Clinical Excellence on ADHD pharmacotherapy. Methods: The cost‐effectiveness of atomoxetine for children with ADHD in the UK was compared with treatment alternatives using an economic model with Markov processes. The model evaluated atomoxetine in five patient subgroups according to treatment history and comorbidities precluding stimulants. Incremental cost per quality‐adjusted life‐year (QALY) was calculated and compared between treatment algorithms. The Markov process incorporated 18 health states, representing a range of outcomes across the treatments. Utility values were derived from a survey of 83 parents of children with ADHD, and treatment efficacy and safety were based on a review of controlled clinical trials and literature, and validated by international experts. Costs and outcomes were estimated using Monte Carlo simulation over 1‐year. Results: Atomoxetine was a cost‐effective treatment across the whole ADHD population, with incremental cost‐effectiveness ratios ranging from £11,500 to £15,900 per QALY, compared with alternative pharmacotherapies, which are within UK and rest of Europe acceptability limits. Higher utility values achieved treating ADHD with atomoxetine, compensate for the relatively higher acquisition cost compared with stimulants. Conclusions: Atomoxetine is cost‐effective and may have advantages over stimulants, including benefits to HRQL and no abuse liability and is the only treatment in the UK licensed for continued treatment into adulthood in adolescents who have shown a response from treatment.     

Clinical outcomes after peripheral blood stem cell donation by related donors: a Dutch single‐center cohort study

BACKGROUND: Relatives donating peripheral blood stem cells (PBSCs) may be accepted for donation on less strict criteria than unrelated donors. We evaluated the occurrence of adverse events during procedure and follow‐up, with a special focus on donors who would have been deferred as unrelated donors. STUDY DESIGN AND METHODS: All 268 related PBSC donors at our center (1996‐2006) were included. Data were retrospectively collected from medical reports and standard follow‐up. Health questionnaires were sent from 2007. Medical outcomes of donors, deferrable or eligible according to international criteria for unrelated donation, were compared. RESULTS: Forty donors (15%) would have been deferred for unrelated donation. Short‐term adverse events occurred in 2% of procedures. Questionnaires were returned by 162 (60%) donors on average 7.5 years after donation, bringing total person‐years of follow‐up to 1278 (177 in deferrable donors). Nine malignancies and 14 cardiovascular events were reported. The incidence rate of cardiovascular events in eligible donors was 6.5 (95% confidence interval [CI], 2.5‐12.3) per 1000 person‐years compared to 44.9 (95% CI, 17.4‐85.2) in deferrable donors; incidence rates of malignancies were 4.6 (1.4‐9.6) and 24.0 (6.0‐53.9) per 1000 person‐years, respectively, in eligible and deferrable donors. All incidence rates were within the range of age‐ and sex‐matched general population. No autoimmune disorders were reported. CONCLUSION: In both the eligible and the deferrable related donors treated with granulocyte–colony‐stimulating factor there are few short‐term and long‐term problems. The occurrence of post‐PBSC cardiovascular events and malignant disease in related donors appears to be within the range of the general population.