A Test-and-Not-Treat Strategy for Onchocerciasis Elimination in Loa loa-coendemic Areas: Cost Analysis of a Pilot in the Soa Health District, Cameroon.

BACKGROUND: Severe adverse events after treatment with ivermectin in individuals with high levels of Loa loa microfilariae in the blood preclude onchocerciasis elimination through community-directed treatment with ivermectin (CDTI) in Central Africa. We measured the cost of a community-based pilot using a test-and-not-treat (TaNT) strategy in the Soa health district in Cameroon. METHODS: Based on actual expenditures, we empirically estimated the economic cost of the Soa TaNT campaign, including financial costs and opportunity costs that will likely be borne by control programs and stakeholders in the future. In addition to the empirical analyses, we estimated base-case, less intensive, and more intensive resource use scenarios to explore how costs might differ if TaNT were implemented programmatically. RESULTS: The total costs of US$283 938 divided by total population, people tested, and people treated with 42% coverage were US$4.0, US$9.2, and US$9.5, respectively. In programmatic implementation, these costs (base-case estimates with less and more intensive scenarios) could be US$2.2 ($1.9-$3.6), US$5.2 ($4.5-$8.3), and US$5.4 ($4.6-$8.6), respectively. CONCLUSIONS: TaNT clearly provides a safe strategy for large-scale ivermectin treatment and overcomes a major obstacle to the elimination of onchocerciasis in areas coendemic for Loa loa. Although it is more expensive than standard CDTI, costs vary depending on the setting, the implementation choices made by the institutions involved, and the community participation rate. Research on the required duration of TaNT is needed to improve the affordability assessment, and more experience is needed to understand how to implement TaNT optimally.

Exploring the Cost-Effectiveness of Mechanical Thrombectomy Beyond 6 Hours Following Advanced Imaging in the United Kingdom.

Background and Purpose- In the United Kingdom, mechanical thrombectomy (MT) for acute ischemic stroke patients assessed beyond 6 hours from symptom onset will be commissioned up to 12 hours provided that advanced imaging (AdvImg) demonstrates salvageable brain tissue. While the accuracy of AdvImg differs across technologies, evidence is limited regarding the proportion of patients who would benefit from late MT. We compared the cost-effectiveness of 2 care pathways: (1) MT within and beyond 6 hours based on AdvImg selection versus (2) MT only within 6 hours based on conventional imaging selection. The impact of varying AdvImg accuracy and prior probability for acute ischemic stroke patients to benefit from late MT was assessed. Methods- A decision tree and a Markov trace were developed. A hypothetical United Kingdom cohort of suspected stroke patients aged 71 years with first event was modeled. Costs, health outcomes, and probabilities were obtained from the literature. Outcomes included costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. Probabilistic sensitivity analyses were performed. Various scenarios with prior probabilities of 10%, 20%, and 30%, respectively, for acute ischemic stroke patients to benefit from late MT, and with perfect accuracy, 80% sensitivity, and 70% specificity of AdvImg were studied. Results- Incremental cost-effectiveness ratios resulting from our deterministic analyses varied from $8199 (£6164) to $49 515 (£37 229) per QALY gained. AdvImg accuracy impacted the incremental cost-effectiveness ratio only when its specificity decreased. Over lifetime horizons, all scenarios including late MT improved QALYs and LYs. Depending on the scenario, the probabilistic sensitivity analyses showed probabilities varying between 46% and 93% for the late MT pathway to be cost-effective at a willingness to pay threshold of $39 900 (£30 000) per QALY. Conclusions- Late MT based on AdvImg selection may be good value for money. However, additional data regarding the implementation of AdvImg and prior probability to benefit from late MT are needed before its cost-effectiveness can be fully assessed.

Socioeconomic benefit to individuals of achieving 2020 targets for four neglected tropical diseases controlled/eliminated by innovative and intensified disease management: Human African trypanosomiasis, leprosy, visceral leishmaniasis, Chagas disease.

BACKGROUND: The control or elimination of neglected tropical diseases (NTDs) has targets defined by the WHO for 2020, reinforced by the 2012 London Declaration. We estimated the economic impact to individuals of meeting these targets for human African trypanosomiasis, leprosy, visceral leishmaniasis and Chagas disease, NTDs controlled or eliminated by innovative and intensified disease management (IDM). METHODS: A systematic literature review identified information on productivity loss and out-of-pocket payments (OPPs) related to these NTDs, which were combined with projections of the number of people suffering from each NTD, country and year for 2011-2020 and 2021-2030. The ideal scenario in which the WHO's 2020 targets are met was compared with a counterfactual scenario that assumed the situation of 1990 stayed unaltered. Economic benefit equaled the difference between the two scenarios. Values are reported in 2005 US$, purchasing power parity-adjusted, discounted at 3% per annum from 2010. Probabilistic sensitivity analyses were used to quantify the degree of uncertainty around the base-case impact estimate. RESULTS: The total global productivity gained for the four IDM-NTDs was I$ 23.1 (I$ 15.9 -I$ 34.0) billion in 2011-2020 and I$ 35.9 (I$ 25.0 -I$ 51.9) billion in 2021-2030 (2.5th and 97.5th percentiles in brackets), corresponding to US$ 10.7 billion (US$ 7.4 -US$ 15.7) and US$ 16.6 billion (US$ 11.6 -US$ 24.0). Reduction in OPPs was I$ 14 billion (US$ 6.7 billion) and I$ 18 billion (US$ 10.4 billion) for the same periods. CONCLUSIONS: We faced important limitations to our work, such as finding no OPPs for leprosy. We had to combine limited data from various sources, heterogeneous background, and of variable quality. Nevertheless, based on conservative assumptions and subsequent uncertainty analyses, we estimate that the benefits of achieving the targets are considerable. Under plausible scenarios, the economic benefits far exceed the necessary investments by endemic country governments and their development partners. Given the higher frequency of NTDs among the poorest households, these investments represent good value for money in the effort to improve well-being, distribute the world's prosperity more equitably and reduce inequity.

Potential therapeutic and economic value of risk-stratified treatment as initial treatment of multiple myeloma in Europe.

Biomarkers associated with prognosis in multiple myeloma (MM) can be used to stratify patients into risk categories. An attractive alternative to uniform treatment (UT), risk-stratified treatment (RST) is proposed where high-risk patients receive bortezomib-based regimens while standard-risk patients receive alternative less costly regimens. An early Markov-type decision analytic model evaluated the potential therapeutic and economic value of different RST strategies compared with UT in MM patients in key European countries. Results suggest RST strategies were both cheaper and more effective than UT across all countries, with the molecular marker-only strategy RST-SKY92 producing maximum health gains (0.031-0.039 QALYs). The conclusions remained consistent in the univariate sensitivity analyses. These findings should encourage stakeholders to support the adoption of RST approaches in MM.

The Socioeconomic Benefit to Individuals of Achieving the 2020 Targets for Five Preventive Chemotherapy Neglected Tropical Diseases.

BACKGROUND: Lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminths (STH) and trachoma represent the five most prevalent neglected tropical diseases (NTDs). They can be controlled or eliminated by means of safe and cost-effective interventions delivered through programs of Mass Drug Administration (MDA)-also named Preventive Chemotherapy (PCT). The WHO defined targets for NTD control/elimination by 2020, reinforced by the 2012 London Declaration, which, if achieved, would result in dramatic health gains. We estimated the potential economic benefit of achieving these targets, focusing specifically on productivity and out-of-pocket payments. METHODS: Productivity loss was calculated by combining disease frequency with productivity loss from the disease, from the perspective of affected individuals. Productivity gain was calculated by deducting the total loss expected in the target achievement scenario from the loss in a counterfactual scenario where it was assumed the pre-intervention situation in 1990 regarding NTDs would continue unabated until 2030. Economic benefits from out-of-pocket payments (OPPs) were calculated similarly. Benefits are reported in 2005 US$ (purchasing power parity-adjusted and discounted at 3% per annum from 2010). Sensitivity analyses were used to assess the influence of changes in input parameters. RESULTS: The economic benefit from productivity gain was estimated to be I$251 billion in 2011-2020 and I$313 billion in 2021-2030, considerably greater than the total OPPs averted of I$0.72 billion and I$0.96 billion in the same periods. The net benefit is expected to be US$ 27.4 and US$ 42.8 for every dollar invested during the same periods. Impact varies between NTDs and regions, since it is determined by disease prevalence and extent of disease-related productivity loss. CONCLUSION: Achieving the PCT-NTD targets for 2020 will yield significant economic benefits to affected individuals. Despite large uncertainty, these benefits far exceed the investment required by governments and their development partners within all reasonable scenarios. Given the concentration of the NTDs among the poorest households, these investments represent good value for money in efforts to share the world's prosperity and reduce inequity.

THE EARLY BIRD CATCHES THE WORM: EARLY COST-EFFECTIVENESS ANALYSIS OF NEW MEDICAL TESTS.

OBJECTIVES: There is little specific guidance on performing an early cost-effectiveness analysis (CEA) of medical tests. We developed a framework with general steps and applied it to two cases. METHODS: Step 1 is to narrow down the scope of analysis by defining the test's application, target population, outcome measures, and investigating current test strategies and test strategies if the new test were available. Step 2 is to collect evidence on the current test strategy. Step 3 is to develop a conceptual model of the current and new test strategies. Step 4 is to conduct the early-CEA by evaluating the potential (cost-)effectiveness of the new test in clinical practice. Step 5 involves a decision about the further development of the test. RESULTS: The first case illustrated the impact of varying the test performance on the headroom (maximum possible price) of an add-on test for patients with an intermediate-risk of having rheumatoid arthritis. Analyses showed that the headroom is particularly dependent on test performance. The second case estimated the minimum performance of a confirmatory imaging test to predict individual stroke risk. Different combinations of sensitivity and specificity were found to be cost-effective; if these combinations are attainable, the medical test developer can feel more confident about the value of further development of the test. CONCLUSIONS: A well-designed early-CEA methodology can improve the ability to develop (cost-)effective medical tests in an efficient manner. Early-CEAs should continuously integrate insights and evidence that arise through feedback, which may convince developers to return to earlier steps.

Cost-effectiveness of open versus endovascular repair of abdominal aortic aneurysm.

BACKGROUND: Patients with a large unruptured abdominal aortic aneurysm with a diameter >5.0 cm are treated with open surgical repair (OSR) or endovascular aneurysm repair (EVAR). Because many studies have assessed the cost-effectiveness of these treatments with conflicting results, this systematic review examined published cost-effectiveness analyses of elective EVAR vs OSR in patients with abdominal aortic aneurysm. METHODS: A systematic search strategy using three databases was conducted to find all relevant studies. Characteristics extracted from these studies included study characteristics (eg, age of the population), input parameters (eg, costs of the EVAR procedure), general results, and sensitivity analyses. The quality of each study was assessed using the Drummond checklist. RESULTS: The search identified 1141 potentially relevant studies, of which 13 studies met inclusion criteria. Most studies found that EVAR was more expensive and more effective than OSR. However, most studies concluded that the health gained from EVAR did not offset the higher total costs, leading to an unacceptably high incremental cost-effectiveness ratio. EVAR was considered more cost-effective in patient groups with a high surgical risk. The quality of most studies was judged as reasonably good. CONCLUSIONS: Overall, published cost-effectiveness analyses of EVAR do not provide a clear answer about whether elective EVAR is a cost-effective solution because the incremental cost-effectiveness ratio varies considerably among the studies. This answer can best be provided through a cost-effectiveness analysis of EVAR that incorporates more recent technologic advances and the improved experience that clinicians have with EVAR.

Clinical Practice Variation Needs to be Considered in Cost-Effectiveness Analyses: A Case Study of Patients with a Recent Transient Ischemic Attack or Minor Ischemic Stroke.

BACKGROUND AND OBJECTIVE: The cost-effectiveness of clinical interventions is often assessed using current care as the comparator, with national guidelines as a proxy. However, this comparison is inadequate when clinical practice differs from guidelines, or when clinical practice differs between hospitals. We examined the degree of variation in the way patients with a recent transient ischemic attack (TIA) or minor ischemic stroke are assessed and used the results to illustrate the importance of investigating possible clinical practice variation, and the need to perform hospital-level cost-effectiveness analyses (CEAs) when variation exists. METHODS: Semi-structured interviews were conducted with 16 vascular neurologists in hospitals throughout the Netherlands. Questions were asked about the use of initial and confirmatory diagnostic imaging tests to assess carotid stenosis in patients with a recent TIA or minor ischemic stroke, criteria to perform confirmatory tests, and criteria for treatment. We also performed hospital-level CEAs to illustrate the consequences of the observed diagnostic strategies in which the diagnostic test costs, sensitivity and specified were varied according to the local hospital conditions. RESULTS: 56 % (9/16) of the emergency units and 63 % (10/16) of the outpatient clinics use the initial and confirmatory diagnostic tests to assess carotid stenosis in accordance with the national guidelines. Of the hospitals studied, only one uses the recommended criteria for use of a confirmatory test, 38 % (6/16) follow the guidelines for treatment. The most cost-effective diagnostic test strategy differs between hospitals. CONCLUSIONS: If important practice variation exists, hospital-level CEAs should be performed. These CEAs should include an assessment of the feasibility and costs of switching to a different strategy.

Hospital costs of ischemic stroke and TIA in the Netherlands.

OBJECTIVES: There have been no ischemic stroke costing studies since major improvements were implemented in stroke care. We therefore determined hospital resource use and costs of ischemic stroke and TIA in the Netherlands for 2012. METHODS: We conducted a retrospective cost analysis using individual patient data from a national diagnosis-related group registry. We analyzed 4 subgroups: inpatient ischemic stroke, inpatient TIA, outpatient ischemic stroke, and outpatient TIA. Costs of carotid endarterectomy and costs of an extra follow-up visit were also estimated. Unit costs were based on reference prices from the Dutch Healthcare Insurance Board and tariffs provided by the Dutch Healthcare Authority. Linear regression analysis was used to examine the association between hospital costs and various patient and hospital characteristics. RESULTS: A total of 35,903 ischemic stroke and 21,653 TIA patients were included. Inpatient costs were €5,328 ($6,845) for ischemic stroke and €2,470 ($3,173) for TIA. Outpatient costs were €495 ($636) for ischemic stroke and €587 ($754) for TIA. Costs of carotid endarterectomy were €6,836 ($8,783). Costs of inpatient days were the largest contributor to hospital costs. Age, hospital type, and region were strongly associated with hospital costs. CONCLUSIONS: Hospital costs are higher for inpatients and ischemic strokes compared with outpatients and TIAs, with length of stay (LOS) the most important contributor. LOS and hospital costs have substantially declined over the last 10 years, possibly due to improved hospital stroke care and efficient integrated stroke services.

Economic evaluation of a pharmacogenetic dosing algorithm for coumarin anticoagulants in The Netherlands.

AIM: To investigate the cost-effectiveness of a pharmacogenetic dosing algorithm versus a clinical dosing algorithm for coumarin anticoagulants in The Netherlands. MATERIALS & METHODS: A decision-analytic Markov model was used to analyze the cost-effectiveness of pharmacogenetic dosing of phenprocoumon and acenocoumarol versus clinical dosing. RESULTS: Pharmacogenetic dosing increased costs by €33 and quality-adjusted life-years (QALYs) by 0.001. The incremental cost-effectiveness ratios were €28,349 and €24,427 per QALY gained for phenprocoumon and acenocoumarol, respectively. At a willingness-to-pay threshold of €20,000 per QALY, the pharmacogenetic dosing algorithm was not likely to be cost effective compared with the clinical dosing algorithm. CONCLUSION: Pharmacogenetic dosing improves health only slightly when compared with clinical dosing. However, availability of low-cost genotyping would make it a cost-effective option.

Experience with outcomes research into the real-world effectiveness of novel therapies in Dutch daily practice from the context of conditional reimbursement.

Policymakers more often request outcomes research for expensive therapies to help resolve uncertainty of their health benefits and budget impact at reimbursement. Given the limitations of observational data, we assessed its usefulness in evaluating clinical outcomes for bortezomib in advanced multiple myeloma patients. Data were retrospectively collected from patients included in the pivotal Assessment of Proteasome Inhibition for Extending Remissions trial (APEX; n=333) and two groups of daily practice patients treated with bortezomib following progression from upfront therapy (n=201): real-world patients treated as of May 2009 (RW-1; n=72) and June 2012 (RW-2; n=129). Prognosis, treatment, and effectiveness were compared. Outcomes research was useful for policymakers for addressing to whom and how bortezomib was administered in daily practice. It was limited however in generating robust evidence on real-world safety and effectiveness. The quality of real-world evidence on effectiveness was low due to missing data in patient charts, existing treatment variation and the dynamics in care during the novel drug's initial market uptake period. Policymakers requesting real-world evidence on clinical outcomes for reimbursement decisions should be aware of these limitations and advised to carefully consider beforehand the type of evidence that best addresses their needs for the re-assessment phase.

Cost effectiveness of new oral anticoagulants for stroke prevention in patients with atrial fibrillation in two different European healthcare settings.

OBJECTIVES: Our objectives were to investigate the cost effectiveness of apixaban, rivaroxaban, and dabigatran compared with coumarin derivatives for stroke prevention in patients with atrial fibrillation in a country with specialized anticoagulation clinics (the Netherlands) and in a country without these clinics (the UK). METHODS: A decision-analytic Markov model was used to analyse the cost effectiveness of apixaban, rivaroxaban, and dabigatran compared with coumarin derivatives in the Netherlands and the UK over a lifetime horizon. RESULTS: In the Netherlands, the use of rivaroxaban, apixaban, or dabigatran increased health by 0.166, 0.365, and 0.374 quality-adjusted life-years (QALYs) compared with coumarin derivatives, but also increased costs by 5,681, 4,754, and 5,465, respectively. The incremental cost-effectiveness ratios (ICERs) were 34,248, 13,024, and 14,626 per QALY gained. In the UK, health was increased by 0.302, 0.455, and 0.461 QALYs, and the incremental costs were similar for all three new oral anticoagulants (5,118-5,217). The ICERs varied from 11,172 to 16,949 per QALY gained. In the Netherlands, apixaban had the highest chance (37 %) of being cost effective at a threshold of 20,000; in the UK, this chance was 41 % for dabigatran. The quality of care, reflected in time in therapeutic range, had an important influence on the ICER. CONCLUSIONS: Apixaban, rivaroxaban, and dabigatran are cost-effective alternatives to coumarin derivatives in the UK, while in the Netherlands, only apixaban and dabigatran could be considered cost effective. The cost effectiveness of the new oral anticoagulants is largely dependent on the setting and quality of local anticoagulant care facilities.

Challenges in modelling the cost effectiveness of various interventions for cardiovascular disease.

OBJECTIVES: Decision analytic modelling is essential in performing cost-effectiveness analyses (CEAs) of interventions in cardiovascular disease (CVD). However, modelling inherently poses challenges that need to be dealt with since models always represent a simplification of reality. The aim of this study was to identify and explore the challenges in modelling CVD interventions. METHODS: A document analysis was performed of 40 model-based CEAs of CVD interventions published in high-impact journals. We analysed the systematically selected papers to identify challenges per type of intervention (test, non-drug, drug, disease management programme, and public health intervention), and a questionnaire was sent to the corresponding authors to obtain a more thorough overview. Ideas for possible solutions for the challenges were based on the papers, responses, modelling guidelines, and other sources. RESULTS: The systematic literature search identified 1,720 potentially relevant articles. Forty authors were identified after screening the most recent 294 papers. Besides the challenge of lack of data, the challenges encountered in the review suggest that it was difficult to obtain a sufficiently valid and accurate cost-effectiveness estimate, mainly due to lack of data or extrapolating from intermediate outcomes. Despite the low response rate of the questionnaire, it confirmed our results. CONCLUSIONS: This combination of a review and a survey showed examples of CVD modelling challenges found in studies published in high-impact journals. Modelling guidelines do not provide sufficient guidance in resolving all challenges. Some of the reported challenges are specific to the type of intervention and disease, while some are independent of intervention and disease.

Step-by-step guideline for disease-specific costing studies in low- and middle-income countries: a mixed methodology.

BACKGROUND: Disease-specific costing studies can be used as input into cost-effectiveness analyses and provide important information for efficient resource allocation. However, limited data availability and limited expertise constrain such studies in low- and middle-income countries (LMICs). OBJECTIVE: To describe a step-by-step guideline for conducting disease-specific costing studies in LMICs where data availability is limited and to illustrate how the guideline was applied in a costing study of cardiovascular disease prevention care in rural Nigeria. DESIGN: The step-by-step guideline provides practical recommendations on methods and data requirements for six sequential steps: 1) definition of the study perspective, 2) characterization of the unit of analysis, 3) identification of cost items, 4) measurement of cost items, 5) valuation of cost items, and 6) uncertainty analyses.Please provide the significance of asterisk given in table body. RESULTS: We discuss the necessary tradeoffs between the accuracy of estimates and data availability constraints at each step and illustrate how a mixed methodology of accurate bottom-up micro-costing and more feasible approaches can be used to make optimal use of all available data. An illustrative example from Nigeria is provided. CONCLUSIONS: An innovative, user-friendly guideline for disease-specific costing in LMICs is presented, using a mixed methodology to account for limited data availability. The illustrative example showed that the step-by-step guideline can be used by healthcare professionals in LMICs to conduct feasible and accurate disease-specific cost analyses.

Policymaker, please consider your needs carefully: does outcomes research in relapsed or refractory multiple myeloma reduce policymaker uncertainty regarding value for money of bortezomib?

INTRODUCTION: Dutch policy regulations require outcomes research for the assessment of appropriate drug use and cost-effectiveness after 4 years of temporary reimbursement. We investigated whether outcomes research reduced policymaker uncertainty regarding the question whether the costs are worth public funding. METHODS: Our cohort study included 139 patients with relapsed/refractory multiple myeloma who were treated outside of a clinical study; 72 received bortezomib and 67 did not receive bortezomib. Detailed data were retrospectively collected from medical records in 38% of Dutch hospitals. RESULTS: All patients received second-line treatment; 65%, 40%, and 14%, received three, four, or five or more lines of therapy. Neither a specific treatment sequence nor an appropriate comparator could be identified because of large variation in regimes. Kaplan-Meier curves showed an increased overall survival (mean [median] 29.5 [33.2] vs. 28.0 [21.6] months) for patients treated with bortezomib (Wilcoxon P = 0.01). Total mean costs were €81,626 (range €17,793-€229,783) and €52,760 (range €748-€179,571) for patients receiving bortezomib and patients not receiving bortezomib, respectively. Patients treated with bortezomib, however, were not comparable to other patients despite attempts to correct for confounding. Therefore, it was impossible to develop a feasible model to obtain a valid incremental cost-effectiveness estimate. CONCLUSIONS: It was possible to develop evidence on bortezomib's use, effects, and costs in everyday practice. Much uncertainty, however, remained regarding its cost-effectiveness. Policymakers should carefully consider whether outcomes research sufficiently decreases uncertainty or whether other options (e.g., finance- and/or outcomes-based risk-sharing arrangements) are more appropriate to ensure sufficient value for money of expensive drugs.

Impaired health-related quality of life in acute myeloid leukemia survivors: a single-center study.

OBJECTIVES: The purpose of this study was to assess the impact of acute myeloid leukemia (AML) and its treatment on health-related quality of life (HRQOL) by comparing the HRQOL of AML survivors with the HRQOL in the general population. METHODS: Two HRQOL questionnaires (EQ-5D and QLQ-C30) were sent to patients diagnosed with AML between 1999 and 2011 at a single academic hospital and still alive in 2012. HRQOL in AML survivors was compared with general population reference values. Multivariate analysis was used to identify factors associated with HRQOL in AML survivors. RESULTS: Questionnaires were returned by 92 of the 103 patients (89%). AML survivors reported significantly worse functioning, more fatigue, pain, dyspnea, appetite loss, and financial difficulties and lower EQ-VAS scores than the general population (P < 0.05). Impaired HRQOL in AML survivors was mainly found in survivors without a paid job. Other factors associated with a poor HRQOL were allogeneic hematopoietic stem cell transplantation and the absence of social support. CONCLUSION: This single-center study showed that the HRQOL in AML survivors is worse than the HRQOL in the general population. HRQOL in these patients can be improved by adequately treating and preventing fatigue, pain, dyspnea, and appetite loss.

Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon.

Coumarin derivatives, such as warfarin, acenocoumarol and phenprocoumon are frequently prescribed oral anticoagulants to treat and prevent thromboembolism. Because there is a large inter-individual and intra-individual variability in dose-response and a small therapeutic window, treatment with coumarin derivatives is challenging. Certain polymorphisms in CYP2C9 and VKORC1 are associated with lower dose requirements and a higher risk of bleeding. In this review we describe the use of different coumarin derivatives, pharmacokinetic characteristics of these drugs and differences amongst the coumarins. We also describe the current clinical challenges and the role of pharmacogenetic factors. These genetic factors are used to develop dosing algorithms and can be used to predict the right coumarin dose. The effectiveness of this new dosing strategy is currently being investigated in clinical trials.

The Drug Reimbursement Decision-Making System in Iran.

BACKGROUND: Previous studies of health policies in Iran have not focused exclusively on the drug reimbursement process. OBJECTIVE: The aim of this study was to describe the entire drug reimbursement process and the stakeholders, and discuss issues faced by policymakers. METHODS: Review of documents describing the administrative rules and directives of stakeholders, supplemented by published statistics and interviews with experts and policymakers. RESULTS: Iran has a systematic process for the assessment, appraisal, and judgment of drug reimbursements. The two most important organizations in this process are the Food and Drug Organization, which considers clinical effectiveness, safety, and economic issues, and the Supreme Council of Health Insurance, which considers various criteria, including budget impact and cost-effectiveness. Ultimately, the Iranian Cabinet approves a drug and recommends its use to all health insurance organizations. Reimbursed drugs account for about 53.5% of all available drugs and 77.3% of drug expenditures. Despite its strengths, the system faces various issues, including conflicting stakeholder aims, lengthy decision-making duration, limited access to decision-making details, and rigidity in the assessment process. CONCLUSIONS: The Iranian drug reimbursement system uses decision-making criteria and a structured approach similar to those in other countries. Important shortcomings in the system include out-of-pocket contributions due to lengthy decision making, lack of transparency, and conflicting interests among stakeholders. Iranian policymakers should consider a number of ways to remedy these problems, such as case studies of individual drugs and closer examination of experiences in other countries.

Stratified patient-centered care in type 2 diabetes: a cluster-randomized, controlled clinical trial of effectiveness and cost-effectiveness.

OBJECTIVE: Diabetes treatment should be effective and cost-effective. HbA1c-associated complications are costly. Would patient-centered care be more (cost-) effective if it was targeted to patients within specific HbA1c ranges? RESEARCH DESIGN AND METHODS: This prospective, cluster-randomized, controlled trial involved 13 hospitals (clusters) in the Netherlands and 506 patients with type 2 diabetes randomized to patient-centered (n=237) or usual care (controls) (n=269). Primary outcomes were change in HbA1c and quality-adjusted life years (QALYs); costs and incremental costs (USD) after 1 year were secondary outcomes. We applied nonparametric bootstrapping and probabilistic modeling over a lifetime using a validated Dutch model. The baseline HbA1c strata were <7.0% (53 mmol/mol), 7.0-8.5%, and >8.5% (69 mmol/mol). RESULTS: Patient-centered care was most effective and cost-effective in those with baseline HbA1c>8.5% (69 mmol/mol). After 1 year, the HbA1c reduction was 0.83% (95% CI 0.81-0.84%) (6.7 mmol/mol [6.5-6.8]), and the incremental cost-effectiveness ratio (ICER) was 261 USD (235-288) per QALY. Over a lifetime, 0.54 QALYs (0.30-0.78) were gained at a cost of 3,482 USD (2,706-4,258); ICER 6,443 USD/QALY (3,199-9,686). For baseline HbA1c 7.0-8.5% (53-69 mmol/mol), 0.24 QALY (0.07-0.41) was gained at a cost of 4,731 USD (4,259-5,205); ICER 20,086 USD (5,979-34,193). Care was not cost-effective for patients at a baseline HbA1c<7.0% (53 mmol/mol). CONCLUSIONS: Patient-centered care is more valuable when targeted to patients with HbA1c>8.5% (69 mmol/mol), confirming clinical intuition. The findings support treatment in those with baseline HbA1c 7-8.5% (53-69 mmol/mol) and demonstrate little to no benefit among those with HbA1c<7% (53 mmol/mol). Further studies should assess different HbA1c strata and additional risk profiles to account for heterogeneity among patients.

Cost-effectiveness of pharmacogenetic-guided dosing of phenprocoumon in atrial fibrillation.

AIM: To investigate the cost-effectiveness of pharmacogenetic-guided phenprocoumon dosing versus standard anticoagulation care in Dutch patients with atrial fibrillation. MATERIALS & METHODS: Using a decision-analytic Markov model, cost-effectiveness of pharmacogenetic-guided therapy versus standard care was estimated. RESULTS: Compared with standard care, the pharmacogenetic-guided dosing strategy increased quality-adjusted life-years (QALYs) only very slightly and increased costs by €15. The incremental cost-effectiveness ratio was €2658 per QALY gained. In sensitivity analyses, the cost of genotyping had the largest influence on the cost-effectiveness ratio. In a probabilistic sensitivity analysis, the incremental costs of genotype-guided dosing were less than €20,000 per QALY gained in 75.6% of the simulations. CONCLUSION: Pharmacogenetic-guided dosing of phenprocoumon has the potential to increase health slightly and may be able to achieve this in a cost-effective way. Owing to the many uncertainties it is too early to conclude whether or not patients starting phenprocoumon should be genotyped.