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Introduction: Many states have mandated breast density notification and insurance coverage for additional screening; yet, the association between such legislation and stage of diagnosis for breast cancer is unclear. This study investigates this association and examines the differential impacts among different age and race/ethnicity subgroups., Methods: The Surveillance, Epidemiology, and End Results database was queried to identify patients with breast cancer aged 40-74 years diagnosed between 2005 and 2016. Using a difference-in-differences multinomial logistic model, the odds of being diagnosed at different stages of cancer relative to the localized stage depending on legislation and individual characteristics were examined. Analyses were conducted in 2020-2021., Results: The study included 689,641 cases. Overall, the impact of notification legislation was not significant, whereas insurance coverage legislation was associated with 6% lower odds (OR=0.94, 95% CI=0.91, 0.96) of being diagnosed at the regional stage. The association between insurance coverage legislation and stage of diagnosis was even stronger among women aged 40-49 years, with 11% lower odds (OR=0.89, 95% CI=0.82, 0.96) of being diagnosed at the regional stage and 12% lower odds (OR=0.88, 95% CI=0.81, 0.96) of being diagnosed at the distant stage. Hispanic women benefited from notification laws, with 11% lower odds (OR=0.89, 95% CI=0.82, 0.97) of being diagnosed at distant stage. Neither notification nor supplemental screening insurance coverage legislation showed a substantial impact on Black women., Conclusions: The findings imply that improving insurance coverage is more important than being notified overall. Raising awareness is important among Hispanic women; improving communication about dense breasts and access to screening might be more important than legislation among Black women., (Copyright © 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Aim: To estimate budget impact of adopting lesinurad as add-on to allopurinol for urate-lowering therapy in gout. Methods: A budget impact model was developed for a US payer perspective, using a Markov model to estimate costs, survival and discontinuation in a one-million-member health plan. The population included patients failing first-line gout therapy, followed for 5 years. Results: Incremental costs of adding lesinurad versus no lesinurad were US$241,907 and US$1,098,220 in first and fifth years, respectively. Cumulative 5-year incremental cost was US$3,633,440. Estimated incremental mean cost per treated patient with gout per year was US$112. The mean per-member per-month cost increased by US$0.06. Conclusion: Initiating lesinurad would result in an incremental per-member per-month cost of US$0.06 over 5 years.

Background: Necitumumab (Neci) was the first biologic approved by the FDA for use in combination with gemcitabine and cisplatin (Neci + GCis) in first-line treatment of metastatic squamous non-small cell lung cancer (msqNSCLC). The potential financial impact on a health plan of adding Neci + GCis to drug formularies may be important to value-based decision makers in the United States, given ever-tightening budget constraints., Objective: To estimate the budget impact of introducing Neci + GCis for first-line treatment of msqNSCLC from U.S. commercial and Medicare payer perspectives., Methods: The budget impact model estimates the costs of msqNSCLC before and after adoption of Neci + GCis in hypothetical U.S. commercial and Medicare health plans over a 3-year time horizon. The eligible patient population was estimated from U.S. epidemiology statistics. Clinical data were obtained from randomized clinical trials, U.S. prescribing information, and clinical guidelines. Market share projections were based on market research data. Cost data were obtained from online sources and published literature. The incremental aggregate annual health plan, per-patient-per-year (PPPY), and per-member-per-month (PMPM) costs were estimated in 2015 U.S. dollars. One-way sensitivity analyses were conducted to assess the effect of model parameters on results., Results: In a hypothetical 1,000,000-member commercial health plan with an estimated population of 30 msqNSCLC patients receiving first-line chemotherapy, the introduction of Neci + GCis at an initial market share of approximately 5% had an overall year 1 incremental budget impact of $88,394 ($3,177 PPPY, $0.007 PMPM), representing a 2.9% cost increase and reaching $304,079 ($10,397 PPPY, $0.025 PMPM) or a 7.4% cost increase at a market share of 14.7% in year 3. This increase in total costs was largely attributable to Neci drug costs and, in part, due to longer survival and treatment duration for patients treated with Neci+GCis. Overall, treatment costs increased by $81,812 (13.5%), and disease costs increased by $7,951 (0.4%), whereas adverse event costs decreased by $1,368 (0.5%) in year 1. From the Medicare perspective, the overall year 1 incremental budget impact was $438,056 ($0.037 PMPM, $3,112 PPPY), representing a 3.0% cost increase. The higher incremental budget in Medicare, compared with commercial plans, was due to higher msqNSCLC incidence in the older Medicare patients (154 vs. 30 patients, respectively). Results were most sensitive to Neci drug costs., Conclusions: Based on projected market shares, coverage for first-line therapy with Neci + GCis appeared to modestly affect overall U.S. health care budgets for msqNSCLC-related care. Given the small eligible patient population, the PMPM budgetary impact on a commercial health plan of reimbursing Neci + GCis in the first year was less than $0.01, rising with increased use of Neci + GCis to $0.025 in the third year. The real-world effect of Neci + GCis needs to be evaluated to validate this analysis; however, these findings may help policymakers in making coverage decisions for Neci + GCis., Disclosures: This study was funded by Eli Lilly and Company. Molife, Brown, Tawney, and Cuyun Carter are equity holders and employees of Eli Lilly and Company. Bly, Cinfio, and Klein are employees of Medical Decision Modeling, which received funding from Eli Lilly and Company to conduct this research and prepare this manuscript.

Background and Objective: The first class of oral pharmacologic treatments for overactive bladder (OAB) are antimuscarinics that are associated with poor persistence, anticholinergic adverse events, and increased anticholinergic burden (ACB) with risk of cognitive impairment. Mirabegron, a β3-adrenoceptor agonist, is an oral treatment that does not contribute to ACB and has early evidence of improved persistence. The objective of the analysis was to assess the cost-effectiveness of mirabegron for OAB vs six antimuscarinics in the US., Methods: A Markov state-transition model assessed US commercial health-plan and Medicare Advantage perspectives over a 3-year time horizon in an OAB patient population. Transition probabilities between five micturition and five incontinence severity states were derived from a network meta-analysis of 44 trials of oral OAB treatments. Therapy beginning with an oral OAB agent could discontinue or switch to another oral agent and could be followed by tibial nerve stimulation, sacral neuromodulation, or onabotulinumtoxinA. The primary outcome was cost per quality-adjusted life year (QALY). Utilities were mapped from incontinence and micturition frequencies as well as demographics. Based on analysis of data from a large healthcare system, elevated ACB was associated with increased healthcare utilization and probability of cognitive impairment., Results: From both commercial and Medicare Advantage perspectives, mirabegron was the most clinically effective treatment, while oxybutynin was the least expensive. Tolterodine immediate release (IR) was also on the cost-effectiveness frontier. The analysis estimated costs per QALY of $59,690 and $66,347 for mirabegron from commercial health plan and Medicare Advantage perspectives, respectively, compared to tolterodine IR. Other antimuscarinics were dominated., Conclusions: This analysis estimated that mirabegron is a cost-effective treatment for OAB from US commercial health plan and Medicare Advantage perspectives, due to fewer projected adverse events and comorbidities, and data suggesting better persistence.

Background: Oral pharmacological treatment for overactive bladder (OAB) consists of antimuscarinics and the beta-3 adrenergic agonist mirabegron. Antimuscarinic adverse events (AEs) such as dry mouth, constipation, and blurry vision can result in frequent treatment discontinuation rates, leaving part of the OAB population untreated. Antimuscarinics also contribute to a patient's anticholinergic cognitive burden (ACB), so the Beers Criteria recommends cautious use of antimuscarinics in elderly patients who take multiple anticholinergic medications or have cognitive impairment. Since mirabegron does not affect the cholinergic pathways, it is unlikely to contribute to a patient's ACB., Objective: To estimate the health care costs associated with the pharmacological treatment of OAB with mirabegron and antimuscarinics from U.S. commercial payer and Medicare Advantage perspectives, using a budget impact model., Methods: For this budget impact model, 2 analyses were performed. The primary analysis estimated the budgetary impact of increasing the use of mirabegron in a closed patient cohort treated with oral pharmacological treatments. The secondary analysis modeled the economic impact in an open cohort by allowing untreated patients to begin treatment with mirabegron after potential contraindication, intolerance, or lack of effectiveness of antimuscarinics. The analyses were performed over a 3-year time horizon. The economic impact of increased mirabegron use was quantified using direct medical costs, including prescription costs and health resource utilization (HRU) costs. Costs of comorbidities included pharmacy and medical costs of treating OAB-related urinary tract infections (UTI), skin rashes, and depression. An analysis of a large single-site integrated health network database was commissioned to quantify ACB-related HRU in terms of the increases in yearly outpatient and emergency department visits. Based on this analysis, the model associated each unit increase in ACB score with increased HRU and probability of mild cognitive impairment. Clinical outcomes of increased use of mirabegron were presented as the number of AEs and comorbidity episodes that could be avoided. One-way sensitivity analyses were performed to quantify the expected budget impact over the range of uncertainty for the key input variables., Results: Primary analysis calculated the impact of increasing the use of mirabegron from 4.5% to 5.3%, 7.1%, and 9.4% in years 1, 2, and 3, respectively, among oral pharmacological OAB treatments that included generic and branded antimuscarinics: oxybutynin, tolterodine, trospium, darifenacin, fesoterodine, and solifenacin. For a 1 million-member U.S. commercial payer plan, the total prescription costs increased, and the total medical costs decreased during the 3-year time horizon, yielding increases of $0.005, $0.016, and $0.031 from current per member per month (PMPM) costs and $0.90, $2.92, and $5.53 from current per treated member per month (PTMPM) costs, an average of less than 2% of current OAB treatment costs. For the Medicare Advantage plan, the resulting incremental PMPM costs were $0.010, $0.034, and $0.065, and the incremental PTMPM costs were $0.93, $3.04, and $5.76; all were less than 4% of the current cost. The secondary analysis estimated the budgetary effects of reducing the untreated population by 1% annually by initiating treatment with mirabegron. For a commercial payer, this resulted in PMPM cost increases of $0.156, $0.311, and $0.467 from the current value, while the incremental PTMPM cost increased by $6.17, $11.67, and $16.61. For the Medicare Advantage plan, the incremental increases in PMPM costs were $0.277, $0.553, and $0.830, and in PTMPM costs were $6.42, $12.15, and $17.29. Clinically, treating more OAB patients resulted in fewer OAB-related comorbidities from both health plan perspectives, since most events associated with nontreatment could be avoided. In the Medicare Advantage population of the secondary analysis, the total numbers of avoided events were predicted as 452 UTIs, 2,598 depression diagnoses, and 3,020 skin rashes during the time horizon of the model., Conclusions: Mirabegron addresses an unmet need for therapy for certain OAB patients, for whom antimuscarinics are not recommended because of a risk of cognitive impairment and who are intolerant to the anticholinergic AEs. Using mirabegron involves moderate additional economic cost to a commercial or Medicare Advantage health plan for which medical cost savings can offset a substantial part of increased pharmacy costs., Disclosures: Funding for this study was provided by Astellas. Perk, Wielage, T. Klein, and R. Klein are employed by Medical Decision Modeling, a contract research company that was paid to perform the described outcomes research and build the model contained in this study. Campbell and Perkins are employed by the Regenstrief Institute, which conducted a database analysis for this research. Campbell reports consultancy fees from Astellas, as well as pending grants from Merck, Sharpe, and Dohme Corp. Posta, Yuran, and Ng are employed by Astellas Pharma Global Development, the developer of mirabegron. Study concept and design were contributed by Perk, Wielage, R. Klein, and Ng. Campbell, T. Klein, and Perkins took the lead in data collection, assisted by Perk, Wielage, and Ng. Data interpretation was performed by Posta and Yuran, along with Perk, Wielage, R. Klein, Ng, Campbell, and Perkins. The manuscript was written by Perk and R. Klein, along with Wielage, T. Klein, Posta, Yuran, and Ng, and revised by all the authors.

Background: The cost of cancer care is increasing, and tools are needed to understand the economic impact of new drugs on the hospital pharmacy budget., Objective: To develop an interactive budget impact model (BIM) through a collaborative effort of industry, academia, and modeling experts to evaluate the use of a new agent in non-small cell lung cancer (NSCLC); this BIM included an institutional module specific to the needs of practices that purchase medications for use in institutional settings., Methods: Treatment regimens, doses, duration of therapy, toxicity, and cost data are from published sources. All input data may be modified to match the local population. Outputs include cost of care, reimbursement, and margin overall and by treatment regimen., Results: The base case assumes 20 NSCLC patients progressing after initial therapy (3 receiving ramucirumab+docetaxel, 2 bevacizumab+erlotinib, 3 docetaxel, 6 erlotinib, and 6 pemetrexed), wholesale acquisition cost (WAC) purchase price, and reimbursement at WAC+4.3%. The model estimated the total cost and reimbursement for the institutional oncology pharmacy to be $699,413 and $729,487, respectively, resulting in a margin of $30,075 (difference due to rounding) for the year for regimens utilized in the treatment of NSCLC in the post-progression setting. Results will vary depending on the input data., Conclusions: There is an increasing need for institutional pharmacies to plan ahead and anticipate the impact of new drugs on their oncology budgets. This interactive Excel-based institutional BIM may provide evidence-based support for pharmacy decision making.

Background: Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare, paraneoplastic syndrome characterized by bilateral painless visual loss and proliferation of choroidal melanocytes in association with an underlying systemic malignancy. We report a case of bilateral diffuse uveal melanocytic proliferation associated with an underlying gynecological malignancy that also features the infrequent finding of an iris mass lesion, using multimodal imaging including ultra-widefield imaging, spectral domain and swept-source optical coherence tomography., Case Presentation: A 59-year-old white female with a prior history of gynecological malignancy in remission presented with progressive bilateral visual loss over several weeks. The patient was noted to have a focal iris mass lesion in her right eye. Ultra-widefield color fundus photography showed a characteristic bilateral 'giraffe pattern' of pigmentary changes extending into the periphery as well as multiple discrete deeply pigmented lesions. Ultra-widefield autofluorescence was useful for visualizing the full extent of involvement. Indocyanine green angiography helped to demarcate the discrete pigmented choroidal lesions. Swept-source OCT clearly delineated the alternating zones of retinal pigment epithelium (RPE) thickening and RPE loss, as well as the prominent choroidal infiltration and thickening., Conclusions: BDUMP is an important diagnosis to consider in the presence of multiple discrete melanocytic choroidal lesions, diffuse choroidal thickening, characteristic RPE changes, iris mass lesions and exudative retinal detachment. Ultra-widefield imaging may demonstrate more extensive lesions than that detected on clinical examination or standard field imaging. Imaging with SS-OCT shows choroidal and RPE characteristics that correlate well with known histopathology of this entity.

Tissue engineering of osteochondral grafts may offer a cell-based alternative to native allografts, which are in short supply. Previous studies promote the fabrication of grafts consisting of a viable cell-seeded hydrogel integrated atop a porous, bone-like metal. Advantages of the manufacturing process have led to the evaluation of porous titanium as the bone-like base material. Here, porous titanium was shown to support the growth of cartilage to produce native levels of Young's modulus, using a clinically relevant cell source. Mechanical and biochemical properties were similar or higher for the osteochondral constructs compared to chondral-only controls. Further investigation into the mechanical influence of the base on the composite material suggests that underlying pores may decrease interstitial fluid pressurization and applied strains, which may be overcome by alterations to the base structure. Future studies aim to optimize titanium-based tissue engineered osteochondral constructs to best match the structural architecture and strength of native grafts., Statement of Significance: The studies described in this manuscript follow up on previous studies from our lab pertaining to the fabrication of osteochondral grafts that consist of a bone-like porous metal and a chondrocyte-seeded hydrogel. Here, tissue engineered osteochondral grafts were cultured to native stiffness using adult chondrocytes, a clinically relevant cell source, and a porous titanium base, a material currently used in clinical implants. This porous titanium is manufactured via selective laser melting, offering the advantages of precise control over shape, pore size, and orientation. Additionally, this manuscript describes the mechanical influence of the porous base, which may have applicability to porous bases derived from other materials., (Copyright © 2015. Published by Elsevier Ltd.)

Objective: To assess the cost effectiveness of duloxetine compared to other oral postacetaminophen treatments for osteoarthritis (OA) from a Quebec societal perspective., Methods: A cost-utility analysis was performed enhancing the Markov model from the 2008 OA guidelines of the National Institute for Health and Clinical Excellence (NICE). The NICE model was extended to include opioid and antidepressant comparators, adding titration, discontinuation, and relevant adverse events (AEs). Comparators included duloxetine, celecoxib, diclofenac, naproxen, hydromorphone, and oxycodone extended release (oxycodone). AEs included gastrointestinal and cardiovascular events associated with nonsteroidal antiinflammatory drugs (NSAIDs), as well as fracture, opioid abuse, and constipation, among others. Costs and incremental cost-effectiveness ratios (ICERs) were estimated in 2011 Canadian dollars. The base case modeled a cohort of 55-year-old patients with OA for a 12-month period of treatment, followed by treatment from a basket of post-discontinuation oral therapies until death. Sensitivity analyses (one-way and probabilistic) were conducted., Results: Overall, naproxen was the least expensive treatment, whereas oxycodone was the most expensive. Duloxetine accumulated the highest number of quality-adjusted life years (QALYs), with an ICER of $36,291 per QALY versus celecoxib. Duloxetine was dominant over opioids. In subgroup analyses, ICERs for duloxetine versus celecoxib were $15,619 and $20,463 for patients at high risk of NSAID-related AEs and patients ages >65 years, respectively., Conclusion: Duloxetine was cost effective for a cohort of 55-year-old patients with OA, and more so in older patients and those with greater AE risks.

Background: Cost-effectiveness analyses (CEAs) have been performed for oral non-disease-altering osteoarthritis (OA) treatments for well over a decade. During that period the methods for performing these analyses have evolved as pharmacoeconomic methods have advanced, new treatments have been introduced, and the knowledge of associated adverse events (AEs) has improved., Objective: The objective of this systematic review was to trace the development of CEAs for oral non-disease-altering treatments in OA., Methods: A systematic search for CEAs of OA oral treatments was performed of the English-language medical literature using the following databases: PubMed, EMBASE, MEDLINE In-Process, EconLit, and Cochrane. Key requirements for inclusion were that the population described patients with OA or arthritis and that the analysis reported at least one incremental cost-effectiveness ratio. Each identified publication was assessed for inclusion. Thirteen characteristics and all AEs appearing in each included CEA were extracted and organized. Reference lists from these CEAs were also searched. A chronology of key CEAs in the field was compiled, noting the characteristics that advanced the state of the art in modeling oral OA treatments., Results: Thirty publications of 28 CEAs were identified and evaluated. Developments in CEAs included an expanded set of comparators that broadened from non-steroidal anti-inflammatory drugs (NSAIDs) only to NSAIDs plus gastroprotective agents, cyclooxygenase-2 inhibitors, and opioids. In turn, AEs expanded from gastrointestinal (GI) events to also include cardiovascular (CV) and neurological events. Efficacy, which initially was presumed to be equivalent for all treatments, evolved to treatment-specific efficacies. Decision-tree analyses were generally replaced by Markov models or, occasionally, stochastic or discrete event simulation. Finally, outcomes have progressed from GI-centric measures to also include quality-adjusted life-years., Conclusion: Methods used by CEAs of oral non-disease-altering OA treatments have evolved in response to changing treatments with different safety profiles and efficacies as well as technical advances in the application of decision science to health care.

Objectives: To identify the problem of separating statistical noise from treatment effects in health outcomes modeling and analysis. To demonstrate the implementation of one technique, common random numbers (CRNs), and to illustrate the value of CRNs to assess costs and outcomes under uncertainty., Methods: A microsimulation model was designed to evaluate osteoporosis treatment, estimating cost and utility measures for patient cohorts at high risk of osteoporosis-related fractures. Incremental cost-effectiveness ratios (ICERs) were estimated using a full implementation of CRNs, a partial implementation of CRNs, and no CRNs. A modification to traditional probabilistic sensitivity analysis (PSA) was used to determine how variance reduction can impact a decision maker's view of treatment efficacy and costs., Results: The full use of CRNs provided a 93.6 percent reduction in variance compared to simulations not using the technique. The use of partial CRNs provided a 5.6 percent reduction. The PSA results using full CRNs demonstrated a substantially tighter range of cost-benefit outcomes for teriparatide usage than the cost-benefits generated without the technique., Conclusions: CRNs provide substantial variance reduction for cost-effectiveness studies. By reducing variability not associated with the treatment being evaluated, CRNs provide a better understanding of treatment effects and risks., (© Health Research and Educational Trust.)

Background: Duloxetine has recently been approved in the USA for chronic musculoskeletal pain, including osteoarthritis and chronic low back pain. The cost effectiveness of duloxetine in osteoarthritis has not previously been assessed. Duloxetine is targeted as post first-line (after acetaminophen) treatment of moderate to severe pain., Objective: The objective of this study was to estimate the cost effectiveness of duloxetine in the treatment of osteoarthritis from a US private payer perspective compared with other post first-line oral treatments, including nonsteroidal anti-inflammatory drugs (NSAIDs), and both strong and weak opioids., Methods: A cost-utility analysis was performed using a discrete-state, time-dependent semi-Markov model based on the National Institute for Health and Clinical Excellence (NICE) model documented in its 2008 osteoarthritis guidelines. The model was extended for opioids by adding titration, discontinuation and additional adverse events (AEs). A life-long time horizon was adopted to capture the full consequences of NSAID-induced AEs. Fourteen health states comprised the structure of the model: treatment without persistent AE, six during-AE states, six post-AE states and death. Treatment-specific utilities were calculated using the transfer-to-utility method and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores from a meta-analysis of osteoarthritis clinical trials of 12 weeks and longer. Costs for 2011 were estimated using Red Book, The Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project database, the literature and, sparingly, expert opinion. One-way and probabilistic sensitivity analyses were undertaken, as well as subgroup analyses of patients over 65 years old and a population at greater risk of NSAID-related AEs., Results: In the base case the model estimated naproxen to be the lowest total-cost treatment, tapentadol the highest cost, and duloxetine the most effective after considering AEs. Duloxetine accumulated 0.027 discounted quality-adjusted life-years (QALYs) more than naproxen and 0.013 more than oxycodone. Celecoxib was dominated by naproxen, tramadol was subject to extended dominance, and strong opioids were dominated by duloxetine. The model estimated an incremental cost-effectiveness ratio (ICER) of US$47,678 per QALY for duloxetine versus naproxen. One-way sensitivity analysis identified the probabilities of NSAID-related cardiovascular AEs as the inputs to which the ICER was most sensitive when duloxetine was compared with an NSAID. When compared with a strong opioid, duloxetine dominated the opioid under nearly all sensitivity analysis scenarios. When compared with tramadol, the ICER was most sensitive to the costs of duloxetine and tramadol. In subgroup analysis, the cost per QALY for duloxetine versus naproxen fell to US$24,125 for patients over 65 years and to US$18,472 for a population at high risk of cardiovascular and gastrointestinal AEs., Conclusion: The model estimated that duloxetine was potentially cost effective in the base-case population and more cost effective for subgroups over 65 years or at high risk of NSAID-related AEs. In sensitivity analysis, duloxetine dominated all strong opioids in nearly all scenarios.

The objective of this study was to quantify the direct medical resources used and the corresponding burden of disease in the treatment of patients with schizophrenia. Because low-frequency administration (LFA) of risperidone guarantees adherence during treatment intervals and offers fewer opportunities to discontinue, adherence and persistence were assumed to improve, thereby reducing relapses of major symptoms.A decision tree model including Markov processes with monthly cycles and a five-year maximum timeframe was constructed. Costs were adapted from the literature and discounted at a 3% annual rate. The population is a demographically homogeneous cohort of patients with schizophrenia, differentiated by initial disease severity (mildly ill, moderately ill, and severely ill). Treatment parameters are estimated using published information for once-daily risperidone standard oral therapy (RIS-SOT) and once-monthly risperidone long-acting injection (RIS-LAI) with LFA therapy characteristics derived from observed study trends. One-year and five-year results are expressed as discounted direct medical costs and mean number of relapses per patient (inpatient, outpatient, total) and are estimated for LFA therapies given at three, six, and nine month intervals.The one-year results show that LFA therapy every 3 months (LFA-3) ($6,088) is less costly than either RIS-SOT ($10,721) or RIS-LAI ($9,450) with similar trends in the 5-year results. Moreover, the model predicts that LFA-3 vs. RIS-SOT vs. RIS LAI therapy will reduce costly inpatient relapses (0.16 vs. 0.51 vs. 0.41). Extending the interval to six (LFA-6) and nine (LFA-9) months resulted in further reductions in relapse and costs.Limitations include the fact that LFA therapeutic options are hypothetical and do not yet exist and limited applicability to compare one antipsychotic agent versus another as only risperidone therapy is evaluated. However, study results have quantified the potential health state improvements and potential direct medical cost savings achievable with the development and use of LFA medication delivery technologies.

Background: This paper presents the model and results to evaluate the use of teriparatide as a first-line treatment of severe postmenopausal osteoporosis (PMO) and glucocorticoid-induced osteoporosis (GIOP). The study's objective was to determine if teriparatide is cost effective against oral bisphosphonates for two large and high risk cohorts., Methods: A computer simulation model was created to model treatment, osteoporosis related fractures, and the remaining life of PMO and GIOP patients. Natural mortality and additional mortality from osteoporosis related fractures were included in the model. Costs for treatment with both teriparatide and oral bisphosphonates were included. Drug efficacy was modeled as a reduction to the relative fracture risk for subsequent osteoporosis related fractures. Patient health utilities associated with age, gender, and osteoporosis related fractures were included in the model. Patient costs and utilities were summarized and incremental cost-effectiveness ratios (ICERs) for teriparatide versus oral bisphosphonates and teriparatide versus no treatment were estimated.For each of the PMO and GIOP populations, two cohorts differentiated by fracture history were simulated. The first contained patients with both a historical vertebral fracture and an incident vertebral fracture. The second contained patients with only an incident vertebral fracture. The PMO cohorts simulated had an initial Bone Mineral Density (BMD) T-Score of -3.0. The GIOP cohorts simulated had an initial BMD T-Score of -2.5., Results: The ICERs for teriparatide versus bisphosphonate use for the one and two fracture PMO cohorts were €36,995 per QALY and €19,371 per QALY. The ICERs for teriparatide versus bisphosphonate use for the one and two fracture GIOP cohorts were €20,826 per QALY and €15,155 per QALY, respectively., Conclusions: The selection of teriparatide versus oral bisphosphonates as a first-line treatment for the high risk PMO and GIOP cohorts evaluated is justified at a cost per QALY threshold of €50,000.

Background: Advances in screening and treatment are needed to mitigate increasing prevalence of dementia due to Alzheimer's disease (DAT). Current proposals to revise Alzheimer's disease (AD) diagnostic criteria incorporate diagnostic biomarkers. Such revisions would allow identification of persons with AD pathology before the onset of dementia. The population-level impact of screening for preclinical AD and treating with a disease-modifying agent is important when evaluating new biomarkers and medications., Methods: A published computer simulation model assigned AD-related event times, such that delays in disease progression due to therapy effectiveness can be estimated for a preclinical AD cohort. Attributes such as screening sensitivity/specificity, treatment efficacy, age at first screening, and rescreening intervals were varied. Outcomes included incident mild cognitive impairment (MCI-AD), incident DAT, and number of patients recommended for treatment., Results: One-time screening at age 65 years, 50% efficacy, and literature-based proxy persistence rates yielded 12.4% incidence of MCI-AD and 0.9% decrease in DAT incidence from base case of no screening/treatment. Modest reductions in incident MCI-AD and DAT were observed with more sensitive testing. Reducing specificity yielded greater reductions in MCI-AD and DAT cases, albeit by treating more patients. Probabilistic sensitivity analysis predicted that for a cohort of patients aged 65 years, the number that needed to be treated to avoid one AD case was 11.6 (range: 5.7-104)., Conclusion: The reduction in MCI-AD and DAT depends on initial screening age, screening frequency, and specificity. When considering population-level impact of screening-treatment, the effect of these parameters on incidence would need to be weighed against the number of individuals screened and treated., (Copyright © 2012 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Objective: To compare, from the perspective of third-party payers in the United States health care system, the cost-effectiveness of olanzapine long-acting injection (LAI, depot) with alternative antipsychotic agents including risperidone-LAI, paliperidone-LAI, haloperidol-LAI, and oral olanzapine, in the treatment of patients with schizophrenia who have been non-adherent or partially adherent with oral antipsychotics., Research Design and Methods: A 1-year micro-simulation economic decision model was developed to simulate the dynamics of usual care of patients with schizophrenia who continue, discontinue, switch, or restart their medication. The model uses a range of clinical and cost parameters including adherence levels, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment discontinuation rates by reason, treatment-emergent adverse events, suicide, health care resource utilization, and direct health care costs. Published medical literature and a clinical expert panel were used to develop baseline model assumptions., Outcome Measures: Key model outputs include annual total direct cost (US$) per treatment and incremental cost-effectiveness values per additional QALY gained., Results: Model results found that the olanzapine-LAI treatment strategy was more effective (greater QALYs) and less costly than risperidone-LAI, paliperidone-LAI, and haloperidol-LAI. In addition, olanzapine-LAI was both more effective and more costly, with an estimated incremental cost/QALY of $26,824 compared to oral olanzapine. The base-case and multiple sensitivity analyses found olanzapine-LAI to remain within acceptable cost-effective ranges (<$50,000) in terms of incremental cost/QALY gained., Conclusions: This micro-simulation model finds the olanzapine-LAI treatment strategy to result in better effectiveness and to be a cost-effective alternative compared to oral olanzapine and the LAI formulations of risperidone, paliperidone, and haloperidol in the treatment of non-adherent and partially adherent patients with schizophrenia in the United States. A key limitation is the assumption how LAI therapies compare to oral counterparts due to sparse head-to-head data. Further research is needed to verify baseline assumptions.

Background: Alzheimer's Disease (AD) affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development., Methods: A time-to-event (TTE) simulation provided estimates of screening asymptomatic patients in the general population age > or =55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death., Results: The base case results indicated increased AD free years (AD-FYs) through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years) the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90)., Conclusions: This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials.

Background: During the period of this study, the American Academy of Pediatrics (AAP) 2006 guidelines recommended respiratory syncytial virus (RSV) prophylaxis for infants 32 to 35 weeks gestation age (wGA) with two or more of five risk factors (RFs). New recommendations have recently been published in 2009. The cost implications of expanding this list of RFs to include other evidence-based RFs like passive smoke exposure (PSE), crowded living conditions (CLCs), and young chronological age (YCA) are unclear., Methods: We estimated the prevalence of RSV RFs in a US sample of infants 32 to 35 wGA referred for prophylaxis from nine specialty pharmacy providers during the 2007-2008 season. We estimated the percent eligible for RSV prophylaxis under various potential RF coverage policies. Using a budget impact model, we calculated the per-member-per-month (PMPM) cost for each policy in 2007 USD for a hypothetical one million member plan., Results: Infants 32 to 35 wGA represented 0.08% of the plan. Approximately 20.2% of these infants met at least two or more of five AAP RFs. Expanding this list to include one additional RF of PSE, CLC, or YCA increased the percent of infants potentially prophylaxed to 29.9%, 23.9%, and 47%, respectively. Adding all three RFs to the list (two or more of eight) increased the percent of infants potentially prophylaxed to 55.6%, and increased payer costs by 9 cents PMPM., Conclusion: Expanding the AAP RF criteria to include PSE, CLC, and YCA would identify more 32 to 35 wGA infants at high risk for severe RSV disease at an acceptable budget impact.

Background: Schizophrenia is often a persistent and costly illness that requires continued treatment with antipsychotics. Differences among antipsychotics on efficacy, safety, tolerability, adherence, and cost have cost-effectiveness implications for treating schizophrenia. This study compares the cost-effectiveness of oral olanzapine, oral risperidone (at generic cost, primary comparator), quetiapine, ziprasidone, and aripiprazole in the treatment of patients with schizophrenia from the perspective of third-party payers in the U.S. health care system., Methods: A 1-year microsimulation economic decision model, with quarterly cycles, was developed to simulate the dynamic nature of usual care of schizophrenia patients who switch, continue, discontinue, and restart their medications. The model captures clinical and cost parameters including adherence levels, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment discontinuation by reason, treatment-emergent adverse events, suicide, health care resource utilization, and direct medical care costs. Published medical literature and a clinical expert panel were used to develop baseline model assumptions. Key model outcomes included mean annual total direct cost per treatment, cost per stable patient, and incremental cost-effectiveness values per QALY gained., Results: The results of the microsimulation model indicated that olanzapine had the lowest mean annual direct health care cost ($8,544) followed by generic risperidone ($9,080). In addition, olanzapine resulted in more QALYs than risperidone (0.733 vs. 0.719). The base case and multiple sensitivity analyses found olanzapine to be the dominant choice in terms of incremental cost-effectiveness per QALY gained., Conclusion: The utilization of olanzapine is predicted in this model to result in better clinical outcomes and lower total direct health care costs compared to generic risperidone, quetiapine, ziprasidone, and aripiprazole. Olanzapine may, therefore, be a cost-effective therapeutic option for patients with schizophrenia.

Objective: To determine the optimal first-line tocolytic agent for treatment of premature labor., Methods: We performed a quantitative analysis of randomized controlled trials of tocolysis, extracting data on maternal and neonatal outcomes, and pooling rates for each outcome across trials by treatment. Outcomes were delay of delivery for 48 hours, 7 days, and until 37 weeks; adverse effects causing discontinuation of therapy; absence of respiratory distress syndrome; and neonatal survival. We used weighted proportions from a random-effects meta-analysis in a decision model to determine the optimal first-line tocolytic therapy. Sensitivity analysis was performed using the standard errors of the weighted proportions., Results: Fifty-eight studies satisfied the inclusion criteria. A random-effects meta-analysis showed that all tocolytic agents were superior to placebo or control groups at delaying delivery both for at least 48 hours (53% for placebo compared with 75-93% for tocolytics) and 7 days (39% for placebo compared with 61-78% for tocolytics). No statistically significant differences were found for the other outcomes, including the neonatal outcomes of respiratory distress and neonatal survival. The decision model demonstrated that prostaglandin inhibitors provided the best combination of tolerance and delayed delivery. In a hypothetical cohort of 1,000 women receiving prostaglandin inhibitors, only 80 would deliver within 48 hours, compared with 182 for the next-best treatment., Conclusion: Although all current tocolytic agents were superior to no treatment at delaying delivery for both 48 hours and 7 days, prostaglandin inhibitors were superior to the other agents and may be considered the optimal first-line agent before 32 weeks of gestation to delay delivery.