Real-World Financial and Clinical Impact of Diagnostic-Driven and Empirical-Treatment Strategies in High-Risk Immunocompromised Patients with Suspected Aspergillus Infection in the United Kingdom.

A diagnostic-driven (DD) treatment strategy has proven successful for treating invasive fungal infections (IFIs) caused by Aspergillus. However, uptake of this treatment strategy is not fully embraced. This study compares the economic and clinical impact of DD and empirical-treatment (ET) strategies used within hospitals. Methods: a decision-analytic model was developed to compare costs and clinical outcomes associated with ET or a DD strategy of identifying infections caused by Aspergillus via galactomannan-antigen testing or Aspergillus polymerase chain reaction (PCR) in neutropenic patients with unexplained fever. Patients were treated prophylactically with antifungal treatments as seen in United Kingdom (UK) hospitals. The IFI incidence, response, mortality, resource use, and adverse events were obtained from meta-analyses and other clinical studies. Analyses were performed from the U.K. hospital perspective, and costs were obtained from standard costing sources. Although diagnostic-testing costs increased, total cost and length of stay were reduced by £1,121 and 1.54 days when treating via a DD strategy. Intensive care and general ward days accounted for > 40% of total costs and > 58% of the cost reduction came from reduced antifungal costs. Treating with a DD strategy reduced the number of patients being treated with antifungal agents while survival was increased. Thus, a DD strategy was cost savings (-£136,787 cost per death avoided) compared with an ET strategy. Conclusion: this study suggests that incorporating a DD strategy as the preferred treatment protocol may be a cost-saving and clinically improved treatment strategy for managing neutropenic patients with unexplained fever. IMPORTANCE Patients at risk of invasive fungal infections (IFIs), such as Aspergillus spp., tend to be immunocompromised and usually take several medications which may generate many side effects. Prescribing is further complicated by comorbidities, drug interactions and challenges accessing diagnostics. Therefore, adding another agent may be neither straightforward nor the best option for these types of patients. A diagnostic-driven (DD) treatment strategy has proven successful for treating IFIs. However, uptake of this treatment strategy is not fully embraced in clinical practice perhaps because this strategy is thought to be more costly and/or to result in higher mortality relative to treating empirically. We developed a decision-analytic model to examine the impact of these 2 strategies on costs and health outcomes. This study indicates that incorporating a DD strategy as the preferred treatment protocol may be a cost-saving and clinically improved treatment strategy for managing neutropenic patients with unexplained fever.

Health and Economic Impact of Routine Pediatric Pneumococcal Immunization Programs in Canada: A Retrospective Analysis.

OBJECTIVE: A model was developed to estimate the historical impact (including total societal health and economic benefit) of pneumococcal conjugate vaccine (PCV) programs in the overall Canadian population between 2005 and 2015, inclusively. METHODS: Historical incidence of invasive pneumococcal disease (IPD), pneumonia, and acute otitis media (AOM) were obtained from epidemiologic databases supplemented with published and unpublished data. Two scenarios were considered: (1) the observed historical incidence from 2005 to 2015 in the setting of PCV use; (2) a hypothetical scenario in which we estimated the number of disease cases assuming no PCV use. Disease cases averted as a result of PCV programs were calculated by subtracting the number of observed historical cases from the number of estimated cases expected in the absence of PCV use. RESULTS: PCV programs were estimated to have saved 6631 lives and averted 14,990 IPD cases, 735,700 pneumonia episodes, and 3,697,993 AOM episodes. Positive clinical outcomes resulted in total cost savings of CAD $1.76 billion over 11 years. Vaccination costs were offset by the direct medical cost savings from fewer cases of IPD, pneumonia, and AOM. CONCLUSIONS: Canadian PCV programs have provided significant health benefits and resulted in a substantial value for money. Net savings achieved over the reviewed period would have provided funding for $1.76 billion in other health care costs or public health initiatives. These findings highlight the importance of considering the total value of a vaccination program, rather than vaccine acquisition costs only, when assessing the value of immunization programs.

Cost-effectiveness analysis of umeclidinium/vilanterol for the management of patients with moderate to very severe COPD using an economic model.

BACKGROUND: Bronchodilators such as long-acting muscarinic antagonists (LAMAs) and long-acting ß2-agonists (LABAs) are central to the pharmacological management of COPD. Dual bronchodilation with umeclidinium/vilanterol (UMEC/VI; 62.5/25 µg) is a novel LAMA/LABA combination approved for maintenance treatment for patients with COPD. OBJECTIVE: The objective of this study was to assess the cost-effectiveness of maintenance treatment with UMEC/VI compared with tiotropium (TIO) 18 µg, open dual LAMA + LABA treatment, or no long-acting bronchodilator treatment in patients with moderate to very severe COPD. METHODS: A Markov model was developed to estimate the costs and outcomes associated with UMEC/VI treatment in patients with moderate to very severe COPD (GSK study number: HO-13-13411). Clinical efficacy, costs, utilities, and mortality obtained from the published literature were used as the model inputs. Costs are presented in US dollars based on 2015 prices. The model outputs are total costs, drug costs, other medical costs, number of COPD exacerbations, and quality-adjusted life-years (QALYs). Costs and outcomes were discounted at a 3% annual rate. Incremental cost-effectiveness ratios were calculated. One-way and probabilistic sensitivity analyses were conducted to assess the effects of changing parameters on the uncertainty of the results. RESULTS: UMEC/VI treatment for moderate to very severe COPD was associated with lower lifetime medical costs ($82,344) compared with TIO ($88,822), open dual LAMA + LABA treatment ($114,442), and no long-acting bronchodilator ($86,751). Fewer exacerbations were predicted to occur with UMEC/VI treatment compared with no long-acting bronchodilator treatment. UMEC/VI provided an 0.11 and 0.25 increase in QALYs compared with TIO and no long-acting bronchodilator treatment, and as such, dominated these cost-effectiveness analyses. Sensitivity analyses confirmed that the results were robust. CONCLUSION: The results from this model suggest that UMEC/VI treatment would be dominant compared with TIO and no long-acting bronchodilator treatment, and less costly than open dual LAMA + LABA treatment in patients with moderate to very severe COPD.

Cost-effectiveness of Maintaining Daily Intake of Oat ß-Glucan for Coronary Heart Disease Primary Prevention.

PURPOSE: Oat ß-glucan reduces cholesterol levels and thus reduces the risk for coronary heart disease (CHD). However, its economic impact has not been well studied. We examined the economic impact of daily intake of ≥3 g of oat ß-glucan in primary prevention of CHD in patients receiving statins or no pharmacologic treatment. METHODS: A decision model was developed to compare costs and outcomes associated with lowering cholesterol levels with no pharmacologic treatment and normal diet, no pharmacologic treatment plus ≥3 g/d of oat ß-glucan, and statin therapy plus ≥3 g/d of oat ß-glucan. The population comprised men 45, 55, or 65 years of age with no history of cardiovascular disease and a 10-year risk for CHD of 5%, 7.5%, or 10%. Clinical efficacy data were gathered from meta-analyses; safety data, costs, and utilities were gathered from published literature. Cost per quality-adjusted life years and number of first events were reported. FINDINGS: Maintaining ≥3 g/d of ß-glucan may be cost-effective in men aged 45, 55, and 65 years with 10-year CHD risks of 5.0%, 7.5%, and 10.0% taking no pharmacologic treatment or on statins. It may also reduce first events of myocardial infarction and CHD death. Results are sensitive to oat ß-glucan cost but insensitive to changes in other parameters. Maintaining ≥3 g of oat ß-glucan daily remains cost-effective within plausible range of values. IMPLICATIONS: ß-glucan may be cost-effective for preventing CHD events in middle-aged men with no history of cardiovascular events whose 10-year CHD risk is ≥5%. Maintaining daily ß-glucan intake may have considerable impact on first events.

Economic analysis of empiric versus diagnostic-driven strategies for immunocompromised patients with suspected fungal infections in the People's Republic of China.

Invasive fungal infections (IFIs) require rapid diagnosis and treatment. A decision-analytic model was used to estimate total costs and survival associated with a diagnostic-driven (DD) or an empiric treatment approach in neutropenic patients with hematological malignancies receiving chemotherapy or autologous/allogeneic stem cell transplants in Shanghai, Beijing, Chengdu, and Guangzhou, the People's Republic of China. Treatment initiation for the empiric approach occurred after clinical suspicion of an IFI; treatment initiation for the DD approach occurred after clinical suspicion and a positive IFI diagnostic test result. Model inputs were obtained from the literature; treatment patterns and resource use were based on clinical opinion. Total costs were lower for the DD versus the empiric approach in Shanghai (¥3,232 vs ¥4,331), Beijing (¥3,894 vs ¥4,864), Chengdu, (¥4,632 vs ¥5,795), and Guangzhou (¥8,489 vs ¥9,795). Antifungal administration was lower using the DD (5.7%) than empiric (9.8%) approach, with similar survival rates. Results from one-way and probabilistic sensitivity analyses were most sensitive to changes in diagnostic test sensitivity and IFI incidence; the DD approach dominated the empiric approach in 88% of scenarios. These results suggest that a DD compared to an empiric treatment approach in the People's Republic of China may be cost saving, with similar overall survival in immunocompromised patients with suspected IFIs.

Economic Impact of Alvimopan Considering Varying Definitions of Postoperative Ileus.

BACKGROUND: Prolonged postoperative ileus (POI) is the predominant cause of extended hospitalization after bowel resection surgery. Alvimopan accelerates gastrointestinal recovery, potentially reducing health care costs. We examined the value of alvimopan in reducing prolonged POI and length of stay for patients undergoing abdominal surgery using different definitions of POI. STUDY DESIGN: We developed a decision analytic model to examine costs and outcomes associated with postoperative treatment with either an accelerated care pathway (ACP) only or alvimopan+ACP. To represent an overall perspective for alvimopan, data from four phase 3 bowel resection trials and one phase 4 radical cystectomy trial were used to populate the model with 3 different definitions of POI. The period analyzed included start of surgery to 7 days post discharge. Costs were obtained from standard US costing sources and are reported in 2015 US dollars. Due to variations in published definitions of POI, alternative definitions based on adverse event reports, NG tube insertion, and time to food toleration were examined. RESULTS: The combined clinical trial data included 1,003 ACP and 1,013 alvimopan+ACP patients. When POI was reported as an adverse event, the incidence of POI was significantly lower with alvimopan+ACP (n = 70 [7%]) vs ACP alone (n = 148 [15%]; p < 0.0001). Time to discharge order written was shorter for patients with POI who were treated with alvimopan+ACP than with ACP (202 ± 115 hours vs 266 ± 138 hours; p < 0.0001). As a result, costs were $731 lower with alvimopan+ACP ($17,835) vs ACP ($18,566). Alternative definitions of POI produced similar results. CONCLUSIONS: The addition of alvimopan to existing treatment pathways for patients undergoing abdominal surgery can reduce overall hospital costs.

Comparative evaluation of patients newly initiating first-generation versus second-generation tyrosine kinase inhibitors for chronic myeloid leukemia and medication adherence, health services utilization, and healthcare costs.

BACKGROUND: Chronic myeloid leukemia (CML) treatment guidelines recommend first-line therapy with either first- or second-generation tyrosine kinase inhibitors (1GTKI, 2GTKI), but do not specify which generation should be used first. OBJECTIVE: To examine the association between initiation of 2GTKI versus 1GTKI and medication adherence, health services utilization, and healthcare costs. METHOD: This was a retrospective cohort study utilizing administrative claims data from a single health plan within the US of commercial and Medicare patients newly initiating 1GTKI or 2GTKI therapy for CML between June 2010 and December 2011. Multivariate logistic regression was used to investigate the association between TKI therapy and adherence, defined as proportion of days covered ≥0.85. Multivariate logistic regression and generalized linear models examined the association between TKI and health services utilization and direct healthcare costs (plan and patient paid) during the 12 month follow-up period. RESULTS: Among the 368 patients included, there was no difference in adherence between patients initiating a 2GTKI compared to a 1GTKI (odds ratio = 0.88, 95% confidence interval [CI] 0.55-1.40). Initiating a 2GTKI was associated with increased outpatient visits (incidence rate ratio [IRR] = 1.12, 95% CI 1.06-1.20); however, there were no statistically significant differences in emergency room visits or inpatient visits between the treatment groups. Total costs were 1.3 times higher for 2GTKI initiators versus 1GTKI initiators ($86,509 versus $66,443; p = 0.001), with a significant difference in TKI pharmacy costs. CONCLUSIONS: Although there were no differences in adherence, hospitalizations, or emergency room visits among patients initiating a second- versus first-generation TKI, total all-cause costs and outpatient visits were higher for 2GTKI initiators. With the impending release of generic imatinib, these comparative data will become germane in the selection of a first-line TKI therapy. Because this study used claims from a single health plan, it may not be generalizable to the general population.

Treatment Interruption and Regimen Change in Firstgeneration versus Second-generation Tyrosine Kinase Inhibitors used as First-line Therapy for Chronic Myeloid Leukemia.

Background: Research has shown that treatment interruptions are associated with worse failure-free survival in chronic myeloid leukemia (CML); however they are commonly used in clinical trials to manage adverse events. Objectives: This study assessed the comparative rates of treatment interruption and regimen change between patients initiating first-line therapy with a first-generation tyrosine kinase inhibitor (1GTKI) imatinib versus second-generation TKI (2GTKI), dasatinib or nilotinib, for the treatment of CML in clinical practice. Methods: This was a retrospective cohort study using the Humana Research Database. Patients with CML who were between the ages of 18 and 89 and newly initiated 1GTKI or 2GTKI therapy between June 1, 2010 and December 31, 2011 were included. Treatment interruption and regimen change were compared using multivariable Cox proportional hazard regression models. Treatment interruption was defined as a gap in any TKI pharmacy claim that was longer than an allowable refill gap plus days' supply from the previous TKI medication claim. Regimen change was defined as 1) a prescription claim for a different TKI therapy, or 2) increase in dose for the same medication. Results: 368 patients met the inclusion criteria: 1GTKI n=237, 2GTKI n=131. Patients initiating therapy with a 2GTKI had a 48% higher risk of treatment interruption versus patients initiating therapy with a 1GTKI (hazard ratio=1.48, 95% confidence interval 1.08-2.02). The time to treatment interruption was significantly longer in patients initiating therapy with a 1GTKI. Approximately 19% of patients had a regimen change, but there were no differences in rates of regimen changes between the two generations. Conclusions: In this study from a large single health plan population, treatment interruptions were more common among patients initiating therapy with a 2GTKI, yet regimen change rates did not vary by generation of TKI. Future research should assess reasons for treatment interruption and investigate these associations in other populations.

Model-based cost-effectiveness analyses for prostate cancer chemoprevention : a review and summary of challenges.

BACKGROUND AND PURPOSE: Decision-analytic modelling is often used to examine the economics associated with using a specific treatment. As a result, it is important to understand structural and methodological approaches used in published decision-analytic models for examining the cost effectiveness of 5α-reductase inhibitors (5ARIs) for prostate cancer (PCa) chemoprevention. This understanding allows us to provide recommendations for using decision modelling in future economic evaluations of chemoprevention for PCa. METHODS: A review of the published literature was performed using MEDLINE and the Cochrane Library to identify studies involving mathematical decision models that evaluated 5ARIs for PCa chemoprevention. Published articles were reviewed and key modelling components were extracted and summarized. Recommendations for developing future decision models to examine the economic consequences of PCa chemoprevention were presented. RESULTS: We identified seven published models of PCa chemoprevention. All the models identified used a Markov framework with time horizons ranging from 4 years to lifetime. Due to the wide range of patient risk groups examined, PCa risk data were taken from the Surveillance, Epidemiology, and End Results (SEER) and other databases or estimates published in relevant clinical trials. Treatment effects included change in the incidence of high- and low-grade PCa and impacts on benign prostate hyperplasia. Adverse events were considered to affect compliance, discontinuation and quality of life. Quality-of-life impacts were similar among studies. Examination of modelling parameter sensitivities was comprehensive. CONCLUSIONS: Published models have examined the cost effectiveness of PCa chemoprevention; however, limitations exist. Decision models should take into account the full PCa clinical pathway when compiling health states. The time horizon should be long enough to consider the full benefit of chemoprevention while allowing actual time receiving the drug to occur from the start of the model until a man's life expectancy is less than 10 years. Baseline PCa risk should be specific to the population of concern. Models should examine the impact on both low- and high-grade tumours and account for the impact of 5ARIs on benign prostatic hyperplasia. Because chemoprevention has an upfront effect, the structure of the model should be constructed so that the downstream effect of avoiding or delaying recurrence can be considered. Adverse events due to chemoprevention should be considered through compliance, discontinuation or quality-of-life impact, and understanding the impact of avoiding PCa and benign prostatic hyperplasia events are important model properties.

Economic impact of using additional diagnostic tests to better select patients with stroke for intravenous thrombolysis in the United Kingdom.

BACKGROUND: Eligibility for thrombolysis as an acute stroke treatment is determined through the use of unenhanced noncontrast computed tomography (CT), time since stroke onset, and patient history. Assessing penumbral patterns, which can be examined only through the use of diagnostic technologies such as magnetic resonance imaging (MRI) and perfusion CT (CTP), may be able to better select patients for thrombolysis. However, trade-offs in terms of administration time and cost may affect the value of using these diagnostic studies. OBJECTIVE: We examined the trade-offs among patient selection via usual care with CT, usual care plus MRI using diffusion-weighted and perfusion imaging, and usual care plus CTP for their effect on costs and outcomes when diagnosing stroke and selecting candidates for thrombolysis in the United Kingdom. METHODS: A decision-analytic model was developed. Efficacy and utilities were obtained from published studies. Costs were obtained from standard UK costing sources and were supplemented with data from the published literature. Outcomes included a favorable outcome (modified Rankin Scale score <2), costs, life-years, quality-adjusted life-years, and incremental cost-effectiveness ratios. RESULTS: Compared with usual care selection, adding CTP or MRI to better select patients for thrombolysis reduced the number of patients receiving thrombolysis by 9 and 14.6 per 1000 patients treated, respectively, while improving favorable outcome (19.2 and 17.6 per 1000 patients treated, respectively). In both scenarios, costs were decreased slightly. Both CTP and MRI selection were cost saving (more efficacious and less costly) compared with unenhanced CT selection; CTP selection was found to dominate MRI selection. CONCLUSIONS: Adding diagnostic tests such as CTP and MRI to select UK patients for thrombolysis may be a good value for the money and may improve patient outcomes. If a preferred diagnostic test had to be chosen based on economic value, CTP might be the best compromise between unenhanced CT selection and MRI selection.

Cost-effectiveness of 2 + 1 dosing of 13-valent and 10-valent pneumococcal conjugate vaccines in Canada.

BACKGROUND: Thirteen-valent pneumococcal conjugate vaccine (PCV13) and 10-valent pneumococcal conjugate vaccine (PCV10) are two recently approved vaccines for the active immunization against Streptococcus pneumoniae causing invasive pneumococcal disease in infants and children. PCV13 offers broader protection against Streptococcus pneumoniae; however, PCV10 offers potential protection against non-typeable Haemophilus influenza (NTHi). We examined public health and economic impacts of a PCV10 and PCV13 pediatric national immunization programs (NIPs) in Canada. METHODS: A decision-analytic model was developed to examine the costs and outcomes associated with PCV10 and PCV13 pediatric NIPs. The model followed individuals over the remainder of their lifetime. Recent disease incidence, serotype coverage, population data, percent vaccinated, costs, and utilities were obtained from the published literature. Direct and indirect effects were derived from 7-valent pneumococcal vaccine. Additional direct effect of 4% was attributed to PCV10 for moderate to severe acute otitis media to account for potential NTHi benefit. Annual number of disease cases and costs (2010 Canadian dollars) were presented. RESULTS: In Canada, PCV13 was estimated to prevent more cases of disease (49,340 when considering both direct and indirect effects and 7,466 when considering direct effects only) than PCV10. This translated to population gains of 258 to 13,828 more quality-adjusted life-years when vaccinating with PCV13 versus PCV10. Annual direct medical costs (including the cost of vaccination) were estimated to be reduced by $5.7 million to $132.8 million when vaccinating with PCV13. Thus, PCV13 dominated PCV10, and sensitivity analyses showed PCV13 to always be dominant or cost-effective versus PCV10. CONCLUSIONS: Considering the epidemiology of pneumococcal disease in Canada, PCV13 is shown to be a cost-saving immunization program because it provides substantial public health and economic benefits relative to PCV10.

Spillover adherence effects of fixed-dose combination HIV therapy.

The impact of fixed-dose combination (FDC) products on adherence to other, non-fixed regimen components has not been examined. We compared adherence to a third antiretroviral (ART) component among patients receiving a nucleoside reverse transcriptase inhibitor (NRTI) backbone consisting of the FDC Epzicom(®), GlaxoSmithKline Inc, Research Triangle Park, NC (abacavir sulfate 600 mg + lamivudine 300 mg; FDC group) versus NRTI combinations taken as two separate pills (NRTI Combo group) using data from a national sample of 30 health plans covering approximately 38 million lives from 1997 to 2005. Adherence was measured as the medication possession ratio (MPR). Multivariate logistic regression compared treatment groups based on the likelihood of achieving ≥95% adherence, with sensitivity analyses using alternative thresholds. MPR was assessed as a continuous variable using multivariate linear regression. Covariates included age, gender, insurance payer type, year of study drug initiation, presence of mental health and substance abuse disorders, and third agent class. The study sample consisted of 650 FDC and 1947 NRTI Combo patients. Unadjusted mean adherence to the third agent was higher in the FDC group than the NRTI Combo group (0.92 vs 0.85; P < 0.0001). In regression analyses, FDC patients were 48% and 39% more likely to achieve 95% and 90% third agent adherence, respectively (P ≤ 0.03). None of the other MPR specifications achieved comparable results. Among managed care patients, use of an FDC appears to substantially improve adherence to a third regimen component and thus the likelihood of achieving the accepted standard for adherence to HIV therapy of 95%.

Cost-effectiveness of 13-valent pneumococcal conjugate vaccine: Germany, Greece, and The Netherlands.

BACKGROUND: Seven-valent pneumococcal conjugate vaccine (PCV7) had profound public-health impacts and is considered cost-effective and potentially cost saving. Two new PCVs have been launched, a 10-valent vaccine (PCV10) and a 13-valent vaccine (PCV13). We examined public-health and economic impacts of PCV pediatric national immunization programs (NIPs) in Germany, Greece, and the Netherlands. METHODS: A decision-analytic model was developed to estimate the impact of PCV13, PCV7, and 10-valent pneumococcal conjugate vaccine (PCV10) on invasive pneumococcal disease (IPD), pneumonia (PNE), and acute otitis media (AOM). Using epidemiological data, we calculated the cases of IPD, PNE, and AOM, using country-specific incidence, serotype coverage, disease sequelae, mortality, vaccine effectiveness, indirect effects, costs, and utilities. Direct effects for PCV13- and PCV10-covered serotypes were assumed similar to PCV7. PCV13 was assumed to confer an indirect effect, while PCV10 was not. Assumptions were tested in sensitivity analyses. RESULTS: In a NIP, PCV13 was estimated to eliminate 31.7%, 46.4%, and 33.8% of IPD in Germany, Greece, and the Netherlands, respectively. Compared with PCV7 and PCV10, PCV13 was found to be cost-effective or cost saving in all cases when PCV13 indirect effects were included. CONCLUSIONS: Pediatric NIPs with PCV13 in Europe are expected to have dramatic public-health impacts and be cost-effective or cost saving.

Cost effectiveness of chemoprevention for prostate cancer with dutasteride in a high-risk population based on results from the REDUCE clinical trial.

BACKGROUND: The REDUCE trial examined whether chemoprevention with the dual 5-alpha reductase inhibitor, dutasteride, reduced risk of prostate cancer (PCa) detection on biopsy. OBJECTIVE: We examined the cost effectiveness of dutasteride compared with placebo in preventing PCa in men at increased risk as seen in REDUCE, from a US payer perspective. METHODS: A Markov model was developed to compare costs and outcomes of chemoprevention with dutasteride 0.5 mg/day or placebo with usual care in men aged 50-75 years, with serum prostate-specific antigen (PSA) of 2.5-10 ng/mL (men aged <60 years) or 3.0-10 ng/mL (men aged ≥60 years), and with a single negative prostate biopsy in the prior 6 months. The model simulated the REDUCE cohort annually through different health states over 4-, 10-year and lifetime time horizons. Risks of PCa for men receiving placebo and dutasteride were obtained from REDUCE. Rates of acute urinary retention events and benign prostate hyperplasia-related surgeries also came from REDUCE. Costs and utilities were obtained from published literature. All costs are reported in $US, year 2009 values. RESULTS: The model indicated that, over 10 years, dutasteride patients would experience fewer PCas (251 vs 312 per 1000 patients) at increased cost ($US15 341 vs $US12 316) than placebo patients. Although life-years were not substantially affected, the model calculated an increase in QALYs of 0.14 for dutasteride patients. Chemoprevention with dutasteride appeared to be cost effective, with an incremental cost per QALY of $US21 781 and cost per PCa avoided of $US50 254. The 4-year and lifetime incremental costs per QALY were $US18 409 and $US22 498, respectively. CONCLUSIONS: Despite increased cost due to taking a drug for prevention, dutasteride 0.5 mg/day may be cost effective in men at increased risk for PCa.

Cost-utility of aspirin and proton pump inhibitors for primary prevention.

BACKGROUND: Aspirin reduces myocardial infarction but increases gastrointestinal tract (GI) bleeding. Proton pump inhibitors (PPIs) may reduce upper GI bleeding. We estimate the cost-utility of aspirin treatment with or without a PPI for coronary heart disease (CHD) prevention among men at different risks for CHD and GI bleeding. METHODS: We updated a Markov model to compare costs and outcomes of low-dose aspirin plus PPI (omeprazole, 20 mg/d), low-dose aspirin alone, or no treatment for CHD prevention. We performed lifetime analyses in men with different risks for cardiovascular events and GI bleeding. Aspirin reduced nonfatal myocardial infarction by 30%, increased total stroke by 6%, and increased GI bleeding risk 2-fold. Adding a PPI reduced upper GI bleeding by 80%. Annual aspirin cost was $13.99; the generic PPI cost was $200.00. RESULTS: In 45-year-old men with a 10-year CHD risk of 10% and 0.8 per 1000 annual GI bleeding risk, aspirin ($17,571 and 18.67 quality-adjusted life-years [QALYs]) was more effective and less costly than no treatment ($18,483 and 18.44 QALYs). Compared with aspirin alone, aspirin plus PPI ($21,037 and 18.68 QALYs) had an incremental cost per QALY of $447,077. Results were similar in 55- and 65-year-old men. The incremental cost per QALY of adding a PPI was less than $50,000 per QALY at annual GI bleeding probabilities greater than 4 to 6 per 1000. CONCLUSIONS: Treatment with aspirin for CHD prevention is less costly and more effective than no treatment in men older than 45 years with greater than 10-year, 10% CHD risks. Adding a PPI is not cost-effective for men with average GI bleeding risk but may be cost-effective for selected men at increased risk for GI bleeding.

Economic efficiency of genetic screening to inform the use of abacavir sulfate in the treatment of HIV.

BACKGROUND: Abacavir sulfate (abacavir) is associated with a hypersensitivity reaction (HSR) that affects 5-8% of patients. While serious complications are rare, failure to identify it, or abacavir re-challenge following HSR, can be fatal. Genetic screening for HLA-B*5701 can identify patients who are likely to experience an HSR and reduces the incidence of the reaction. OBJECTIVE: We assessed the intrinsic and practical value, from the US healthcare system perspective, of prospective HLA-B*5701 screening among a population of antiretroviral-naive patients without elevated risk factors for cardiovascular disease, plasma HIV RNA >100,000 copies/mL, or pre-existing renal insufficiency. METHODS: Two approaches were used to evaluate the costs and benefits of prospective screening. First, the efficiency of HLA-B*5701 screening compared with no screening prior to abacavir initiation (intrinsic value of screening) was evaluated using a 60-day decision-tree model. Next, the practical value of screening was assessed using a lifetime discrete-event simulation model that compared HLA-B*5701 screening prior to abacavir use versus initiation with a tenofovir-containing regimen. Screening-effectiveness parameters were taken from an open-label trial that incorporated screening prior to abacavir initiation and other published studies. Treatment efficacy was derived from clinical trials. Modelling assumptions, costs ($US, year 2007 values) and other parameters were derived from published sources, primary data analysis and expert opinion. Multiple one-way sensitivity and scenario analyses were performed to assess parameter uncertainty. The primary outcome measure for the short-term screening versus no screening analysis was cost per patient. For the long-term analysis, outcomes were presented as QALYs. Costs and effects were discounted at 3% per year. RESULTS: Over the first 60 days of treatment, prospective screening prior to abacavir initiation cost an additional $US17 per patient and avoided 537 HSRs per 10,000 patients. The per-patient cost of screening was sensitive to the cost of the genetic test, HSR costs and screening performance. In the lifetime model, screening-informed abacavir use was more effective and less costly than initiation with a tenofovir-containing regimen in the base case and in sensitivity analyses. CONCLUSIONS: Our results suggest that prospective HLA-B*5701 screening prior to abacavir initiation produces cost savings and should become a standard component of HIV care.

Cost effectiveness of 5-alpha reductase inhibitors for the prevention of prostate cancer in multiple patient populations.

BACKGROUND: Although 5-alpha reductase inhibitors (5ARIs) have demonstrated that they reduce the risk of prostate cancer (PCa), they have not demonstrated cost effectiveness in the patient populations in which they have been examined. OBJECTIVE: A decision-analytic model was created to explore economic benefits from a third-party payer perspective of the use of 5ARIs in preventing PCa in men with different risk factors for developing the disease. METHODS: A Markov model was developed to simulate a cohort of men annually through health states (e.g. healthy male, benign prostatic hyperplasia [BPH], PCa, PCa recurrence) over a man's lifetime. Men with risk factors were treated with a 5ARI and compared with patients given no chemoprevention. Men from the general population were examined along with higher-risk men who had been referred to a PCa centre. Baseline risk was estimated via published risk data, risk factor analyses and risk equations. Clinical efficacy, morality, costs and utilities were obtained from published literature. Outcomes of the model included number of prostate cancers, incremental costs, incremental QALYs, incremental cost per QALY and number needed to treat. Along with sensitivity and scenario analyses, a validation of outcomes was performed. All costs were valued in $US, year 2009 values. Costs were discounted at 3% per annum. RESULTS: Men receiving 5ARIs benefited through a reduction in the number of PCas. Assuming a cost-effectiveness threshold of $US50 000 per QALY, chemoprevention with 5ARIs was cost effective ($US37 900 per QALY) in men from the general population who were aged 50 years with elevated prostate-specific antigen (PSA), and who were aged 50 years with PCa family history and elevated PSA ($US31 065 per QALY). Chemoprevention with 5ARIs was not cost effective in men aged 50 years with no additional risk factors, men aged 50 years with abnormal digital rectal examinations (DREs), and men aged 50 years with a family history ($US86 511, $US85 577 and $US84 950 per QALY, respectively). In higher-risk men, chemoprevention could be expected to be cost effective ($US18 490 to $US11 816 per QALY, depending on risk scenario). Results were sensitive to changes in utilities, assumed PCa risk reduction with 5ARIs, and patient age. CONCLUSION: When considering common risk factors associated with PCa, prevention with 5ARIs is expected to be cost effective in 50-year-old men with elevated PSA. As a man's risk increases, the cost effectiveness of 5ARI chemoprevention improves.