The Budget Impact of Including Necitumumab on the Formulary for First-Line Treatment of Metastatic Squamous Non-Small Cell Lung Cancer: U.S. Commercial Payer and Medicare Perspectives.

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.

Budget impact of adding lesinurad for second-line treatment of gout: a US health plan perspective.

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.

Multimodal imaging of bilateral diffuse uveal melanocytic proliferation associated with an iris mass lesion.

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.

Enhancing the Budget Impact Model for Institutional Use: A Tool with Practical Applications for the Hospital Oncology Pharmacy.

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.

Using common random numbers in health care cost-effectiveness simulation modeling.

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.

Screening and treatment for Alzheimer's disease: predicting population-level outcomes.

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.

Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model.

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.

Prevalence of respiratory syncytial virus (RSV) risk factors and cost implications of immunoprophylaxis to infants 32 to 35 weeks gestation for health plans in the United States.

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.

Cost-effectiveness analysis of variceal ligation vs. beta-blockers for primary prevention of variceal bleeding.

Although both beta-blockade (BB) and endoscopic variceal ligation (EVL) are used for primary prevention of variceal bleeding (VB) in patients with cirrhosis with moderate to large esophageal varices (EVs), the more cost-effective option is uncertain. We created a Markov decision model to compare BB and EVL in such patients, examining both cost-effectiveness (cost per life year [LY]) and cost-utility (cost per quality-adjusted life year [QALY]). Outcomes included cost per LY, cost per QALY, proportions of persons with VB, TIPS, and all-cause mortality. EVL and BB were compared using the incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR). When considering only LYs, initial EVL exceeds the benchmark of 50,000 dollars/LY, with an ICER of 98,407 dollars. However, when quality of life (QoL) is considered, EVL is cost-effective compared to BB (ICUR of 25,548 dollars/QALY). In sensitivity analysis, EVL is cost-effective if the yearly risk of EV bleeding is > or = 0.26 (base case 0.15), the relative risk of bleeding on BB is > or = 0.69 (base case 0.58), or if the relative risk of bleeding with EVL is < 0.27 (base case 0.35). The ICUR favored EVL unless the relative risk of bleeding on BB is < 0.46, the relative risk of bleeding with EVL is > 0.46, or the time horizon is < or = 24 months. Whether EVL is "cost-effective" relative to BB therapy for primary prevention of EV bleeding depends on whether LYs or QALYs are considered. If only LYs are considered, then EVL is not cost-effective compared to BB therapy; however, if QoL is considered, then EVL is cost-effective.

Cost-effectiveness of tamsulosin, doxazosin, and terazosin in the treatment of benign prostatic hyperplasia.

OBJECTIVE: To evaluate the cost-effectiveness of tamsulosin, doxazosin, or terazosin as initial treatments for moderate benign prostatic hyperplasia (BPH) over a 3-year time horizon from a health-system-payer perspective. METHODS: A decision-analytic model is used to project the course of treatment at 6-month intervals over 3 years following initiation of therapy with tamsulosin, doxazosin, or terazosin. Treatment failure is defined as failure to attain and maintain a 25% improvement in the American Urological Association (AUA) symptom score from baseline. In the model, finasteride is added for patients who fail on their initial therapy and, in the event of finasteride treatment failure, patients progress to transurethral resection of the prostate (TURP) and, if needed, a second TURP. The ranges of values for treatment failure rates and clinical event cost parameters used in the decision model are derived from the literature. Only direct medical costs related to BPH and its treatment are included. Since 2 comparators are available generically (doxazosin and terazosin) drug acquisition costs are defined by the list prices at Drugstore.com. All costs are discounted by 3% per year. Effectiveness is measured as successful medical treatment without surgery over 3 years. RESULTS: For base-case model parameters, discounted BPH-related total direct medical costs over 3 years are 4084 dollars, 4323 dollars, and 4695 dollars for generic terazosin, generic doxazosin, and tamsulosin, respectively. The model estimates a medical treatment success rate (no TURP) at 3 years of 72.3% for tamsulosin, compared with 68.2% for both terazosin and doxazosin. The incremental cost for tamsulosin versus terazosin is 610 dollars over 3 years, which yields an incremental cost-effectiveness ratio of 14,609 dollars per success. Generic doxazosin is dominated (higher cost but equal effectiveness compared with terazosin). Higher rates of twice-daily (or 2 units per day) dosing are associated with higher incremental cost-effectiveness ratios. The decision-model results also are sensitive to the estimated costs of TURP and hypotensive adverse events. CONCLUSION: As an initial medical therapy for moderate BPH, tamsulosin is more effective than generic terazosin or doxazosin, with an incremental cost of about 203 dollars per year (or about 17 dollars per month) over 3 years.

The strength of acrylic bone cement cured under thumb pressure.

In this investigation, the static tensile strength of bone cement was quantified after mixing it in an open bowl or in a commercially available vacuum mixer and molding it under pressures consistent with values obtained by finger/digital application, as it is used in surgery. Pressure, held for a brief time span on cement in its lower viscosity state, has been demonstrated to increase penetration of the cement into bone. Clinically, bone cement is pressurized by digital pressure, specialized instruments, or by implant design. Specimens were cured under constant pressures of up to 100kPa, which is in the range reported for thumb pressurization of plugged proximal femurs and instrumented pressurization of acetabular sockets. The results showed that application of constant pressure during the polymerization of open bowl mixed bone cement significantly improved its mechanical properties. Application of 100kPa constant pressure to the open bowl mixed bone cement while it cured increased its ultimate strength to a value similar to vacuum mixed cement. Curing under pressure showed no significant effect on the tensile properties of vacuum mixed cement. Curing under pressure did not significantly reduce the size of the largest pores in the tensile specimens.

Measuring the hemodynamic response to primary pharmacoprophylaxis of variceal bleeding: a cost-effectiveness analysis.

OBJECTIVES: The hemodynamic response to ss-blockers alone or with nitrates is highly predictive of efficacy in prevention of variceal bleeding. Hemodynamic monitoring (HDM) requires catheterization of the hepatic vein and measurement of the hepatic venous pressure gradient, the difference between wedged and free hepatic venous pressure. The aim of this study was to compare HDM with no HDM in patients considered for primary pharmacoprophylaxis of esophageal variceal bleeding. METHODS: A decision model was constructed to compare HDM with no HDM in cirrhotic patients with moderate to large esophageal varices. Patients intolerant to beta-blocker therapy would undergo endoscopic variceal ligation; those with an inadequate hemodynamic response (HDR) to beta-blocker therapy could have nitrates added before ligation was considered. Variceal bleeding was treated with ligation, with transjugular intrahepatic portosystemic shunt (TIPS) reserved for refractory bleeding. Probabilities of treatment responses as well as risks of bleeding and mortality were based on published literature. Only direct costs were considered during the 5-yr time horizon. Outcomes were cost in United States dollars, survival length in life-years, and proportions of patients who experienced variceal bleeding, TIPS insertion, and mortality from any cause. RESULTS: In the base case analysis, HDM was either cost-saving ($2,523 US dollars /life-year gained) or cost-effective (incremental cost-effectiveness ratio of $5,200 US dollars/life-year saved) compared with no HDM, depending on whether nitrates were added to beta-blocker therapy. HDM reduced variceal bleeding by nearly 60% and had a small effect on all-cause mortality. In the sensitivity analysis, HDM was sensitive to the time horizon, as it was not cost-effective for a time horizon of <22 months and was not cost-saving before 49 months. The cost-effectiveness of HDM was not sensitive to reasonable variation in the probability of HDR to beta-blocker therapy, risk of bleeding, risk reduction with pharmacotherapy, or to the costs of HDM, bleeding, ligation, or TIPS. Probabilistic sensitivity analysis indicated that HDM was more effective and less costly 100% and 57% of the time, respectively. CONCLUSIONS: Compared with the current standard of no HDM, measuring the hemodynamic response of primary pharmacoprophylaxis substantially reduces the number of bleeding episodes and is cost-effective or cost-saving over a wide range of sensitivity analyses. A randomized trial of HDM is needed to verify its efficacy in clinical practice.