Practice efficiency and total cost of care with bispecifics and CAR-T in relapsed/refractory diffuse large B-cell lymphoma: an institutional perspective1.

Aim: Novel treatment options for relapsed/refractory diffuse large B-cell lymphoma include T-cell targeting therapies. Practice efficiency and cost are important for informed treatment decisions. Materials/methods: An institutional decision-maker cost model was developed for 6-month, 1-year and median cycles of treatment time horizons comparing practice efficiency and costs of epcoritamab vs glofitamab and axicabtagene ciloleucel (axi-cel). Results: Overall, epcoritamab required the shortest personnel and chair time, except over 1 year (second shortest chair time). Across all time horizons, epcoritamab was cost-saving vs axi-cel and had similar costs to glofitamab on a per-month basis. Conclusion: Epcoritamab reduced personnel and chair time. Additionally, epcoritamab was cost-saving vs axi-cel and had similar costs to glofitamab on a per-month basis.

There are new ways to treat diffuse large B-cell lymphoma, which is a type of cancer called lymphoma. When new treatments are available it is important to see if they take more or less time to give to patients and how much they cost versus other treatments. This study looked at three drugs used to treat diffuse large B-cell lymphoma, including epcoritamab, axi-cel and glofitamab. It estimated the time and cost with those treatments in patients who get them for 6 months, 1 year or for the most common length of time in the clinical trials. In most of the scenarios, epcoritamab had the least time needed for nurses or doctors and the least time needed for a patient to be in a chair in a clinic. When thinking about the cost per month, epcoritamab saved money versus axi-cel and was similar to glofitamab.

Comedication prescription patterns and potential for drug-drug interactions with antiretroviral therapy in people living with human immunodeficiency virus type 1 infection in Germany.

PURPOSE: Various first-line recommended antiretroviral therapy (ART) regimens have different drug-drug interaction (DDI)/contraindication profiles. The aim of this study was to estimate the rate of potential DDIs/contraindications of real-world prescribed non-ART comedication with first-line recommended ART in people living with HIV (PLHIV) in Germany. METHODS: A retrospective, cross-sectional cohort design was used to collect non-ART comedication prescription data from a representative sample of a German health insurance claims database. PLHIV who were prescribed ART during 2016 were included in the analysis. Patients were stratified by sex, age, comorbidities, and time on ART. Prescribed comedications were used to estimate potential DDIs/contraindications for each recommended first-line ART per patient based on criteria from www.hiv-druginteractions.org. RESULTS: Records from 2680 PLHIV were analyzed. Prescriptions for non-ART comedications were common (mean of seven per patient in the overall population, 10.2 in PLHIV aged 50 years and older). Antiretroviral regimens with the lowest proportion of patients with at least 1 potential DDI/contraindication were unboosted integrase inhibitor, non-tenofovir disoproxil fumarate-based regimens that included raltegravir + emtricitabine/tenofovir alafenamide fumarate (13%), dolutegravir + lamivudine (14%), dolutegravir/abacavir/lamivudine (14%), dolutegravir/emtricitabine/tenofovir alafenamide fumarate (15%), and bictegravir/emtricitabine/tenofovir alafenamide fumarate (19%). Boosted regimens and efavirenz-based regimens presented the highest potential for DDIs/contraindications. CONCLUSIONS: Comedication with potential DDIs/contraindications with ART is frequently prescribed among PLHIV in Germany. Potential risks for DDIs/contraindications vary by ART, with the lowest potential seen in unboosted integrase strand transfer inhibitor-based regimens, including raltegravir + emtricitabine/tenofovir alafenamide fumarate, followed by three dolutegravir-based regimens.

The present and future burden of previously treated advanced non-small cell lung cancer (NSCLC) by histology and line of therapy in France, Germany, Italy, and Spain: model-based predictions.

BACKGROUND: The burden of advanced non-small cell lung cancer (NSCLC) is not well understood, and the number of patients likely to receive treatment in Europe has not been quantified. The aim of this study was to forecast the annual number of patients with squamous and non-squamous advanced NSCLC likely to receive second and third lines of therapy (LOT) from 2016 to 2020 in France, Germany, Italy, and Spain. METHODS: A patient count model (PCM) was developed in Microsoft Excel to estimate the number of patients with refractory advanced NSCLC eligible to receive systemic treatment. Using historical population-based cancer registry data, segmented linear regression ("Joinpoint") was used to forecast age- and sex-stratified lung cancer incidence rates in each country through 2020. Yearly incident case count totals by country were apportioned according to NSCLC histology and stage at diagnosis. Country-specific treatment rates came from a recent medical chart review study, and early- to advanced-stage disease progression rates were estimated over a 10-year interval. A probabilistic sensitivity analysis (PSA) was performed to estimate variability in the patient counts. RESULTS: The combined number of squamous and non-squamous advanced NSCLC patients estimated to receive second and third LOT, respectively, in 2016 were France = 11,600 and 3500; Germany = 15,100 and 4900; Italy = 13,500 and 2500; Spain = 9400 and 2100. The forecasted numbers of patients receiving second and third LOT, respectively, in 2020 were France = 13,900 and 4200; Germany = 16,200 and 5200; Italy = 15,100 and 2600; Spain = 11,000 and 2500. CONCLUSIONS: Driven by growth in the incidence of NSCLC among women, the model forecasts an overall increase in the number of patients with advanced-stage squamous and non-squamous NSCLC likely to receive systemic treatment in the year 2020. The results highlight the significant burden of refractory advanced NSCLC and the need for more robust surveillance data to accurately quantify the burden of disease.

Cost per Patient Achieving Treatment Targets and Number Needed to Treat with Tirzepatide Versus Semaglutide 1 mg in Patients with Type 2 Diabetes in the United States.

INTRODUCTION: Achieving glycemic control can help reduce complications of type 2 diabetes (T2D). This study compared the pharmacy cost per responder and number needed to treat (NNT) of tirzepatide 5 mg, 10 mg, and 15 mg versus semaglutide 1 mg to achieve glycemic, weight loss, and composite treatment endpoints in patients with T2D in the United States. METHODS: The proportions of patients achieving glycemic, weight loss, and composite treatment endpoints were obtained from the phase 3 SURPASS-2 randomized clinical trial which compared tirzepatide 5 mg, 10 mg, and 15 mg to semaglutide 1 mg. Annual pharmacy costs were calculated using 2022 wholesale acquisition costs. Cost per responder and NNT were calculated along with 95% confidence intervals and tests for statistical significance (P ≤ 0.05). RESULTS: Tirzepatide had a lower cost per responder to achieve glycated hemoglobin A1c (HbA1c) endpoints of ≤ 6.5% (10 mg and 15 mg doses) and < 5.7% (all doses) and weight loss endpoints of ≥ 5% (10 mg and 15 mg doses), ≥ 10% (all doses), and ≥ 15% (all doses). The cost per responder to achieve HbA1c < 7% (all doses of tirzepatide) and ≤ 6.5% (5 mg tirzepatide) were not statistically significantly different between tirzepatide and semaglutide 1 mg. The cost per patient to achieve the composite endpoints (HbA1c < 7.0%, ≤ 6.5%, or < 5.7%/weight loss ≥ 10%/no hypoglycemia) was statistically significantly lower for all doses of tirzepatide than for semaglutide 1 mg. The NNTs for all doses of tirzepatide were statistically significantly lower than that for semaglutide 1 mg to achieve all individual and composite endpoints, with the exception of the 5 mg dose for HbA1c < 7.0% and HbA1c ≤ 6.5%, where tirzepatide had numerically lower NNTs that were not statistically significant. CONCLUSION: Tirzepatide is a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) that may offer the potential to achieve stringent glycemic goals, weight loss targets, and composite treatment goals at a lower cost per responder compared to semaglutide 1 mg among people with T2D.

Economic and humanistic consequences of preventable bladder tumor recurrences in nonmuscle invasive bladder cancer cases.

PURPOSE: Perioperative intravesical chemotherapy following transurethral resection of bladder tumor has been underused despite level 1 evidence supporting its performance. The primary objective of this study was to estimate the economic and humanistic consequences associated with preventable recurrences in patients initially diagnosed with nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Using population based estimates of nonmuscle invasive bladder cancer incidence, a 2-year model was developed to estimate the number of preventable recurrences in eligible patients untreated with perioperative intravesical chemotherapy. Therapy utilization rates were obtained from a retrospective database analysis and a chart review study of 1,010 patients with nonmuscle invasive bladder cancer. Recurrence rates of nonmuscle invasive bladder cancer were obtained from a randomized clinical trial comparing transurethral resection of bladder tumor with or without perioperative mitomycin C. Costs were estimated using prevailing Medicare reimbursement rates. Quality adjusted life-year estimates and disutilities for complications were obtained from the literature. RESULTS: The model estimated that 7,827 bladder recurrences could be avoided if all patients received immediate intravesical chemotherapy. It estimated an economic savings of $3,847 per avoidable recurrence, resulting in an aggregate savings of $30.1 million. The model also estimated that 1,025 quality adjusted life-years are lost every 2 years due to preventable recurrences, resulting in 0.13 quality adjusted life-years (48 quality adjusted days) lost per avoidable recurrence. This translates into 0.02 quality adjusted life-years (8.1 quality adjusted days) lost per patient not receiving immediate intravesical chemotherapy. CONCLUSIONS: Greater use of immediate intravesical chemotherapy in the United States has the potential to substantially decrease the economic and humanistic burdens of nonmuscle invasive bladder cancer.

How patient cost-sharing trends affect adherence and outcomes: a literature review.

OBJECTIVE: We sought to assess the relationship between patient cost sharing; medication adherence; and clinical, utilization, and economic outcomes. METHODOLOGY: We conducted a literature review of articles and abstracts published from January 1974 to May 2008. Articles were identified using PubMed, Ovid, medline, Web of Science, and Google Scholar databases. The following terms were used in the search: adherence, compliance, copay, cost sharing, costs, noncompliance, outcomes, hospitalization, utilization, economics, income, and persistence. RESULTS: We identified and included 160 articles in the review. Although the types of interventions, measures, and populations studied varied widely, we were able to identify relatively clear relationships between cost sharing, adherence, and outcomes. Of the articles that evaluated the relationship between changes in cost sharing and adherence, 85% showed that an increasing patient share of medication costs was significantly associated with a decrease in adherence. For articles that investigated the relationship between adherence and outcomes, the majority noted that increased adherence was associated with a statistically significant improvement in outcomes. CONCLUSION: Increasing patient cost sharing was associated with declines in medication adherence, which in turn was associated with poorer health outcomes.

Number Needed to Treat and Number Needed to Harm analysis of the zuranolone phase 2 clinical trial results in major depressive disorder.

BACKGROUND: Zuranolone (SAGE-217) is a novel, investigational positive allosteric modulator of GABAA receptors being investigated in major depressive disorder (MDD). This analysis of phase 2 data quantified the benefit and risk of zuranolone (30mg) versus placebo and antidepressants in terms of number needed to treat (NNT) and number needed to harm (NNH). METHODS: Rates of response, remission, and all-cause discontinuation for zuranolone and 11 antidepressant comparators were obtained from the zuranolone phase 2 clinical study (N=89) and a published network meta-analysis, respectively. An indirect treatment comparison was conducted using the Bucher method to compare zuranolone to standard-of-care. RESULTS: Zuranolone demonstrated greater benefit compared to placebo on Day 3 (NNT range for response=4-5, NNT for remission=10) and at Day 15 (NNT=3 for response and remission). Compared to SSRIs and SNRIs, zuranolone at Day 15 showed improved treatment response (NNT=4 [95% CI = 3; 16] and 5 [95% CI = 3; 25], respectively) and remission (NNT=4 [95% CI = 2; 13] and 4 [95% CI = 2; 18], respectively). This was accompanied by a reduction in all-cause discontinuation, with negative NNH values (-57 and -28), respectively. LIMITATIONS: Variations in study design across the included trials may limit the generalizability of results. CONCLUSIONS: With a small positive NNT as early as Day 3 indicating robust benefit and a negative NNH indicating reduced harm, this analysis based on a phase 2 study suggests that patients with MDD may benefit from the benefit-to-risk profile of zuranolone.

Cost-effectiveness of coronary CT angiography versus myocardial perfusion SPECT for evaluation of patients with chest pain and no known coronary artery disease.

PURPOSE: To evaluate the cost-effectiveness of diagnostic strategies for individuals with chest pain without known coronary artery disease (CAD) in the Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography-eligible population. MATERIALS AND METHODS: A decision analysis was performed in which the following were compared: coronary computed tomographic (CT) angiography followed by invasive coronary angiography for positive or equivocal findings (coronary CT angiography only), coronary CT angiography followed by invasive coronary angiography for positive findings and myocardial perfusion single photon emission computed tomography (SPECT) for equivocal findings (coronary CT angiography first), myocardial perfusion SPECT followed by invasive coronary angiography for positive/equivocal findings (myocardial perfusion SPECT only), myocardial perfusion SPECT followed by invasive coronary angiography for positive findings and coronary CT angiography for equivocal findings (myocardial perfusion SPECT first), and invasive coronary angiography. Analyses were conducted from the payer perspective for a near-term diagnostic period and a long-term lifetime period. The base case was a 55-year-old man with 30% risk of obstructive CAD. RESULTS: By using the base case for near-term cost per correct diagnosis, a coronary CT angiography-first strategy was the least expensive, followed by coronary CT angiography only (incremental cost-effectiveness ratio [ICER] = $17516). For long-term cost-effectiveness, a coronary CT angiography-only strategy demonstrated a favorable ICER of $20429 per quality-adjusted life-year (QALY) relative to the least expensive coronary CT angiography-first strategy. Both myocardial perfusion SPECT-only and myocardial perfusion SPECT-first strategies were more costly and less effective than either coronary CT angiographic strategy. Long-term results were sensitive to coronary CT angiographic sensitivity, myocardial perfusion SPECT sensitivity, and CAD prevalence. Coronary CT angiography-first and coronary CT angiography-only strategies remained dominant up to a baseline coronary CT angiography test cost of $1100 and 80% CAD prevalence. CONCLUSION: With a $20000 threshold level for cost per correct diagnosis and $50000 per QALY, a coronary CT angiography-only approach is the most cost-effective diagnostic strategy for evaluation of patients who have stable chest pain without known CAD with intermediate CAD prevalence. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090349/-/DC1.

Budget Impact of Enzalutamide for Nonmetastatic Castration-Resistant Prostate Cancer.

BACKGROUND: Prostate cancer is the most common cancer and second-leading cause of cancer death among men in the United States. Prostate cancer poses a large economic burden, which increases with progression from localized to metastatic disease. Newly approved treatments for non-metastatic castration-resistant prostate cancer (nmCRPC) delay disease progression and reduce the risk of metastatic disease. Quantifying the potential budget impact of these new treatments is of interest to health care decision makers. OBJECTIVE: To estimate the budget impact of enzalutamide for the treatment of patients with nmCRPC in the United States over a 3-year time horizon. METHODS: An Excel-based model was developed to estimate the budget impact to a U.S. health plan of enzalutamide, a second-generation antiandrogen, as an add-on to androgen deprivation therapy (ADT) for the treatment of high-risk nmCRPC patients (prostate-specific antigen doubling time of ≤ 10 months). Comparators include apalutamide + ADT, bicalutamide + ADT, and ADT only. The analysis includes treatment costs for nmCRPC and for treatment after progression to metastatic castration-resistant prostate cancer (mCRPC). The treated population size was estimated from epidemiological data and literature. Dosing, duration of therapy, and adverse event rates were based on package inserts and pivotal studies. RED BOOK, Centers for Medicare & Medicaid Services fee schedules, and literature were used to obtain costs of drugs, adverse events, and health care visits. Market shares were estimated for each comparator before and after enzalutamide adoption. A 1-way sensitivity analysis was performed to quantify the impact of parameter uncertainty. RESULTS: In a hypothetical 1-million-member plan with 3% annual growth, it was estimated that there would be approximately 19 eligible incident nmCRPC patients in year 1, increasing to 20 eligible incident patients in year 3. With an assumed market share of approximately 6% for enzalutamide in year 1, the budget impact would be $106,074 ($0.009 per member per month [PMPM]). With a 26% enzalutamide share in year 3, the budget impact would be $632,729 ($0.048 PMPM). Cumulative budget impact to the health plan over 3 years is estimated to be $1,082,095 ($0.028 PMPM). The increased cost of the treatment regimen is partly offset by reduced postprogression costs. CONCLUSIONS: Treatment of nmCRPC patients with enzalutamide has a modest budget impact that is partly offset by delaying progression to mCRPC. DISCLOSURES: This research was sponsored by Astellas Pharma and Pfizer, the codevelopers of enzalutamide. All authors contributed to the development of the manuscript and maintained control over the final content. Schultz is employed by Astellas Pharma and owns stock in Gilead Sciences and Shire. O'Day and Sugarman are employees of Xcenda, which received consultancy fees from Astellas Pharma. Ramaswamy is employed by Pfizer. A synopsis of the current study was presented in poster format at the AMCP Managed Care & Specialty Pharmacy Annual Meeting 2019, in San Diego, CA, on March 25-28, 2019.

Evaluating the Presence of Cognitive Biases in Health Care Decision Making: A Survey of U.S. Formulary Decision Makers.

BACKGROUND: Behavioral economics is a field of economics that draws on insights from psychology to understand and identify patterns of decision making. Cognitive biases are psychological tendencies to process information in predictable patterns that result in deviations from rational decision making. Previous research has not evaluated the influence of cognitive biases on decision making in a managed care setting. OBJECTIVE: To assess the presence of cognitive biases in formulary decision making. METHODS: An online survey was conducted with a panel of U.S. pharmacy and medical directors who worked at managed care organizations and served on pharmacy and therapeutics committees. Survey questions assessed 4 cognitive biases: relative versus absolute framing effect, risk aversion, zero-risk bias, and delay discounting. Simulated data were presented in various scenarios related to adverse event profiles, drug safety and efficacy, and drug pricing for new hypothetical oncology products. Survey questions prompted participants to select a preferred drug based on the information provided. Survey answers were analyzed to identify decision patterns that could be explained by the cognitive biases. Likelihood of bias was analyzed via chi-square tests for framing effect, risk aversion, and zero-risk bias. The delay discounting section used a published algorithm to characterize discounting patterns. RESULTS: A total of 35 pharmacy directors and 19 medical directors completed the survey. In the framing effect section, 80% of participants selected the suboptimal choice in the relative risk frame, compared with 38.9% in the absolute risk frame (P < 0.0001). When assessing risk aversion, 42.6% and 61.1% of participants displayed risk aversion in the cost- and efficacy-based scenarios, respectively, but these were not statistically significant (P = 0.27 and P = 0.10, respectively). In the zero-risk bias section, results from each scenario diverged. In the first zero-risk bias scenario, 90.7% of participants selected the drug with zero risk (P < 0.001), but in the second scenario, only 32.1% chose the zero-risk option (P < 0.01). In the section assessing delay discounting, 54% of survey participants favored a larger delayed rebate over a smaller immediate discount. A shallow delay discounting curve was produced, which indicated participants discounted delayed rewards to a minimal degree. CONCLUSIONS: Pharmacy and medical directors, like other decision makers, appear to be susceptible to some cognitive biases. Directors demonstrated a tendency to underestimate risks when they were presented in relative risk terms but made more accurate appraisals when information was presented in absolute risk terms. Delay discounting also may be applicable to directors when choosing immediate discounts over delayed rebates. However, directors neither displayed a statistically significant bias for risk aversion when assessing scenarios related to drug pricing or clinical efficacy nor were there significant conclusions for zero-risk biases. Further research with larger samples using real-world health care decisions is necessary to validate these findings. DISCLOSURES: This research was funded by Xcenda. Mezzio, Nguyen, and O'Day are employees of Xcenda. Kiselica was employed by Xcenda at the time the study was conducted. The authors have nothing to disclose. A portion of the preliminary data was presented as posters at the 2017 AMCP Managed Care & Specialty Pharmacy Annual Meeting; March 27-30, 2017; in Denver, CO, and the 2017 International Society for Pharmacoeconomics and Outcomes Research 22nd Annual International Meeting; May 20-24, 2017; in Boston, MA.

Cost analysis of plasma-derived factor VIII/von Willebrand factor versus recombinant factor VIII for treatment of previously untreated patients with severe hemophilia A in the United States.

BACKGROUND: Inhibitor development to factor VIII (FVIII) hemophilia therapy results in increased complications and substantial economic costs. The SIPPET study, the first randomized controlled trial to compare the immunogenicity of plasma-derived FVIII (pdFVIII)/von Willebrand factor (VWF) and recombinant-DNA-derived FVIII (rFVIII), demonstrated higher inhibitor rates in previously untreated patients (PUPs) treated with rFVIII than in PUPs treated with pdFVIII/VWF. OBJECTIVE: To quantify the economic impact of treating PUPs with pdFVIII/VWF vs rFVIII. METHODS: An Excel-based clinical and economic model was developed from a US healthcare payer perspective and run over a 5-year period. The analysis utilized a cohort approach to model patient treatment and outcomes over a monthly cycle to quantify differences in costs of FVIII, bypassing agents, and hospitalizations for serious bleeds. Rates of high-titer inhibitor development were obtained from the SIPPET study. Patients developing high-titer inhibitors were treated with immune tolerance induction (ITI). Patients who developed low-titer inhibitors and those who did not develop inhibitors continued their usual FVIII treatment. Patients who were successfully treated with ITI returned to FVIII treatment, while unsuccessfully treated patients received bypassing agents. Total costs per treated patient were estimated and a one-way sensitivity analysis was conducted to quantify the impact of parameter uncertainty on the model outcomes. RESULTS: Total cumulative costs per patient over 5 years were $834,621 for pdFVIII/VWF patients and $1,237,163 for rFVIII patients, representing a total saving of $402,542 per patient over the 5-year period, for an average annual saving of $80,508 per patient. CONCLUSIONS: Based on data from the SIPPET study, this analysis found that initiating FVIII treatment in severe hemophilia A PUPs with pdFVIII/VWF has the potential to offer substantial cost savings to healthcare payers, amounting to a one-third reduction in costs.

Cost-effectiveness of diagnostic evaluation strategies for individuals with stable chest pain syndrome and suspected coronary artery disease.

PURPOSE: To determine lifetime cost-effectiveness of diagnostic evaluation strategies for individuals with stable chest pain and suspected coronary artery disease (CAD). METHODS: Exercise treadmill testing (ETT), stress echocardiography (SE), myocardial perfusion scintigraphy (MPS), coronary computed tomographic angiography (CCTA), and invasive coronary angiography (ICA) were assessed alone, or in succession to each other. RESULTS: Initial ETT followed by imaging wherein ETT was equivocal or unable to be performed appeared more cost-effective than any strategy employing initial testing by imaging. CONCLUSION: As pre-test likelihood of CAD varies, different modalities including SE, CCTA, and MPS result in improved costs and enhanced effectiveness.

Cost-Effectiveness Analysis of Iodine-123 Meta-Iodobenzylguanidine Imaging for Screening Heart Failure Patients Eligible for an Implantable Cardioverter Defibrillator in the USA.

BACKGROUND: Many guideline-eligible heart failure (HF) patients do not receive a survival benefit from implantable cardioverter defibrillators (ICDs). Improved risk stratification may help to reduce costs and improve the cost effectiveness of ICDs. OBJECTIVE: To estimate the potential outcomes, costs, and cost effectiveness of using iodine-123 meta-iodobenzylguanidine (I-mIBG) to screen HF patients eligible for an ICD. METHODS: A decision-analytic model was developed to compare screening with I-mIBG imaging and no screening over 2-year and 10-year time horizons from a US payer perspective. Data on I-mIBG imaging and risk stratification were obtained from the ADMIRE-HF/HFX (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) trial. Data on ICD effectiveness for prevention of sudden cardiac death (SCD) were obtained from a meta-analysis. Costs of ICDs and costs of generator and lead procedures were obtained from the Agency for Healthcare Research and Quality National Inpatient Sample. Age-specific mortality was modeled using US life tables and data from the ACT (Advancements in ICD Therapy) Registry on risks of SCD and non-SCD mortality. Sensitivity analyses were conducted. RESULTS: In the analysis, screening with I-mIBG imaging was associated with a reduction in ICD utilization of 21 %, resulting in a number needed to screen to prevent 1 ICD implantation of 5. Screening reduced the costs per patient by US$5500 and US$13,431 (in 2013 dollars) over 2 and 10 years, respectively, in comparison with no screening and resulted in losses of 0.001 and 0.040 life-years, respectively, over 2 and 10 years. Screening was decrementally cost effective, with savings of US$5,248,404 and US$513,036 per quality-adjusted life-year lost over 2 and 10 years, respectively. In subgroup analyses, cost savings were greater for patients with an ejection fraction (EF) of 25-35 % than for those with an EF <25 %. CONCLUSIONS: According to the model, screening of guideline-eligible patients selected for ICDs with I-mIBG imaging may be cost effective and may help reduce costs associated with implantation of ICDs, with a minimal impact on survival.

Costs and clinical outcomes for non-invasive versus invasive diagnostic approaches to patients with suspected in-stent restenosis.

This study compared costs and clinical outcomes of invasive versus non-invasive diagnostic evaluations for patients with suspected in-stent restenosis (ISR) after percutaneous coronary intervention. We developed a decision model to compare 2 year diagnosis-related costs for patients who presented with suspected ISR and were evaluated by: (1) invasive coronary angiography (ICA); (2) non-invasive stress testing strategy of myocardial perfusion imaging (MPI) with referral to ICA based on MPI; (3) coronary CT angiography-based testing strategy with referral to ICA based on CCTA. Costs were modeled from the payer's perspective using 2014 Medicare rates. 56 % of patients underwent follow-up diagnostic testing over 2 years. Compared to ICA, MPI (98.6 %) and CCTA (98.1 %) exhibited lower rates of correct diagnoses. Non-invasive strategies were associated with reduced referrals to ICA and costs compared to an ICA-based strategy, with diagnostic costs lower for CCTA than MPI. Overall 2-year costs were highest for ICA for both metallic as well as BVS stents ($1656 and $1656, respectively) when compared to MPI ($1444 and $1411) and CCTA. CCTA costs differed based upon stent size and type, and were highest for metallic stents >3.0 mm followed by metallic stents <3.0 mm, BVS < 3.0 mm and BVS > 3.0 mm ($1466 vs. $1242 vs. $855 vs. $490, respectively). MPI for suspected ISR results in lower costs and rates of complications than invasive strategies using ICA while maintaining high diagnostic performance. Depending upon stent size and type, CCTA results in lower costs than MPI.

Budget Impact of Enzalutamide for Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: Prostate cancer is expected to account for approximately one quarter of all new diagnoses of cancer in American men in 2015. The cost of prostate cancer care is expected to reach $15.1 billion by the year 2020, up from $11.9 billion in 2010. Given the high burden of prostate cancer, health care payers are interested in quantifying the potential budget impact of new therapies. OBJECTIVE: To estimate the budget impact of enzalutamide for the treatment of chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) from a U.S. payer perspective. METHODS: A model was developed to assess the budget impact of enzalutamide for treatment of chemotherapy-naïve mCRPC patients in a hypothetical 1-million-member U.S. health plan over a 1-year time horizon. Comparators included abiraterone acetate, sipuleucel-T, radium Ra 223 dichloride, and docetaxel. Epidemiologic data, including National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) incidence rates, were used to estimate the number of chemotherapy-naïve mCRPC patients. Dosing, administration, duration of therapy, and adverse event rates were based on package inserts and pivotal studies. Drug costs were obtained from RED BOOK and Centers for Medicare & Medicaid Services (CMS) average sales price pricing files, costs of administration and monitoring from the CMS physician fee schedule, and adverse events from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project and published literature. Market shares were estimated for each comparator before and after adoption of enzalutamide. The incremental aggregate budget impact, per patient per year (PPPY), per patient per month (PPPM), and per member per month (PMPM), was calculated. One-way sensitivity analyses were performed. RESULTS: In a population of 115 chemotherapy-naïve mCRPC patients, adopting enzalutamide had an annual incremental budget impact of $510,641 ($4,426 PPPY, $369 PPPM, and $0.04 PMPM). Results were most sensitive to enzalutamide drug cost, size of the chemotherapy-naïve mCRPC patient population, and enzalutamide adoption rate. CONCLUSIONS: Results indicate a modest 1-year budget impact of adopting enzalutamide for chemotherapy-naïve mCRPC patients, partly because of the cost offset of a moderate incidence of adverse events and lack of additional required monitoring.

Cost-effectiveness of natalizumab vs fingolimod for the treatment of relapsing-remitting multiple sclerosis: analyses in Sweden.

OBJECTIVE: To assess the cost-effectiveness of natalizumab vs fingolimod over 2 years in relapsing-remitting multiple sclerosis (RRMS) patients and patients with rapidly evolving severe disease in Sweden. METHODS: A decision analytic model was developed to estimate the incremental cost per relapse avoided of natalizumab and fingolimod from the perspective of the Swedish healthcare system. Modeled 2-year costs in Swedish kronor of treating RRMS patients included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided using data from the AFFIRM and FREEDOMS trials for all patients with RRMS and from post-hoc sub-group analyses for patients with rapidly evolving severe disease. Probabilistic sensitivity analyses were conducted to assess uncertainty. RESULTS: The analysis showed that, in all patients with MS, treatment with fingolimod costs less (440,463 Kr vs 444,324 Kr), but treatment with natalizumab results in more relapses avoided (0.74 vs 0.59), resulting in an incremental cost-effectiveness ratio (ICER) of 25,448 Kr per relapse avoided. In patients with rapidly evolving severe disease, natalizumab dominated fingolimod. Results of the sensitivity analysis demonstrate the robustness of the model results. At a willingness-to-pay (WTP) threshold of 500,000 Kr per relapse avoided, natalizumab is cost-effective in >80% of simulations in both patient populations. LIMITATIONS: Limitations include absence of data from direct head-to-head studies comparing natalizumab and fingolimod, use of relapse rate reduction rather than sustained disability progression as the primary model outcome, assumption of 100% adherence to MS treatment, and exclusion of adverse event costs in the model. CONCLUSIONS: Natalizumab remains a cost-effective treatment option for patients with MS in Sweden. In the RRMS patient population, the incremental cost per relapse avoided is well below a 500,000 Kr WTP threshold per relapse avoided. In the rapidly evolving severe disease patient population, natalizumab dominates fingolimod.

Cost-effectiveness of lurasidone vs quetiapine extended-release (XR) in patients with bipolar depression.

OBJECTIVE: Bipolar disorder imposes a high economic burden on patients and society. Lurasidone and quetiapine extended-release (XR) are atypical antipsychotic agents indicated for monotherapy treatment of bipolar depression. Lurasidone is also indicated as adjunctive therapy with lithium or valproate for depressive episodes associated with bipolar disorder. The objective of this analysis was to estimate the cost-effectiveness of lurasidone and quetiapine XR in patients with bipolar depression. METHODS: A cost-effectiveness model was developed to compare lurasidone to quetiapine XR. The model was based on a US third-party payer perspective over a 3-month time horizon. The effectiveness measure in the model was the percentage of patients achieving remission (Montgomery-Åsberg Depression Rating Scale [MADRS] total score ≤12 by weeks 6-8). The comparison of remission rates was made through an adjusted indirect treatment comparison of lurasidone and quetiapine XR pivotal trials using placebo as the common comparator. Resource utilization for remission vs no remission was estimated from published expert panel data, and resource costs were obtained from a retrospective database study of bipolar I depression patients. Drug costs were estimated using the mean dose from clinical trials and wholesale acquisition costs. RESULTS: Over the 3-month model time period, lurasidone and quetiapine XR patients, respectively, had similar mean numbers of emergency department visits (0.48 vs 0.50), inpatient days (2.1 vs 2.2), and office visits (9.3 vs 9.6). More lurasidone than quetiapine XR patients achieved remission (52.0% vs 43.2%) with slightly higher total costs ($4982 vs $4676), resulting in an incremental cost-effectiveness ratio of $3474 per remission. The probabilistic sensitivity analysis showed lurasidone had an 86% probability of being cost-effective compared to quetiapine XR at a willingness-to-pay threshold of $10,000 per remission. CONCLUSIONS: Lurasidone may be a cost-effective option when compared to quetiapine XR for the treatment of adults with bipolar depression.

Long-term cost-effectiveness of atypical antipsychotics in the treatment of adults with schizophrenia in the US.

BACKGROUND: The purpose of this study was to evaluate the long-term cost-effectiveness (including hospitalizations and cardiometabolic consequences) of atypical antipsychotics among adults with schizophrenia. METHODS: A 5-year Markov cohort cost-effectiveness model, from a US payer perspective, was developed to compare lurasidone, generic risperidone, generic olanzapine, generic ziprasidone, aripiprazole, and quetiapine extended-release. Health states included in the model were patients: on an initial atypical antipsychotic; switched to a second atypical antipsychotic; and on clozapine after failing a second atypical antipsychotic. Incremental cost-effectiveness ratios (ICERs) assessed incremental cost/hospitalization avoided. Effectiveness inputs included discontinuations, hospitalizations, weight change, and cholesterol change from comparative clinical trials for lurasidone and for aripiprazole, and the Clinical Antipsychotic Trials of Intervention Effectiveness for other comparators. Atypical antipsychotic-specific relative risk of diabetes obtained from a retrospective analysis was used to predict cardiometabolic events per Framingham body mass index risk equation. Mental health costs (relapsing versus nonrelapsing patients) and medical costs associated with cardiometabolic consequences (cardiovascular events and diabetes management) were obtained from published sources. Atypical antipsychotic costs were estimated from Red Book® prices at dose(s) reported in clinical data sources used in the model (weighted average dose of lurasidone and average dose for all other comparators). Costs and outcomes were discounted at 3%, and model robustness was tested using one-way and probabilistic sensitivity analyses. RESULTS: Ziprasidone, olanzapine, quetiapine extended-release, and aripiprazole were dominated by other comparators and removed from the comparative analysis. ICER for lurasidone versus risperidone was $25,884/relapse-related hospitalization avoided. At a $50,000 willingness-to-pay threshold, lurasidone has an 86.5% probability of being cost-effective, followed by a 7.2% probability for olanzapine, and 6.3% for risperidone. One-way sensitivity analysis showed the model is sensitive to lurasidone and generic risperidone hospitalization rates. CONCLUSION: Generic risperidone is the least costly atypical antipsychotic. Lurasidone is more costly and more effective than risperidone and is cost-effective at willingness-to-pay thresholds of greater than $25,844 per hospitalization avoided. The favorable cost-effectiveness of lurasidone is driven by its clinical benefits (eg, efficacy in preventing hospitalizations in patients with schizophrenia) and its minimal cardiometabolic adverse effect profile.

Cost-effectiveness of lurasidone vs aripiprazole among patients with schizophrenia who have previously failed on an atypical antipsychotic: an indirect comparison of outcomes from clinical trial data.

OBJECTIVE: Compare long-term costs and outcomes of lurasidone to aripiprazole among adults with schizophrenia in the US who previously failed ≥1 atypical antipsychotic (olanzapine, risperidone, quetiapine, or ziprasidone) based on an indirect comparison of outcomes data from clinical trials. METHODS: A 5-year Markov cohort model was developed to compare long-term effectiveness of lurasidone to aripiprazole, including total discontinuations, relapse rates, and hospitalization rates. Cost inputs included pharmacy, mental health, and medical costs associated with cardiometabolic risks (diabetes and cardiovascular [CV] events). Effectiveness inputs were derived from an indirect comparison of aripiprazole and lurasidone using common comparators from CATIE. Cardiometabolic risks were derived from claims data analysis for diabetes, weight change and CV events, and Framingham body mass index (BMI) risk equation. Cost inputs were derived from published sources and Red Book. Costs and outcomes were discounted at 3% and tested with sensitivity analyses. RESULTS: Over 5 years, total discounted costs for lurasidone and aripiprazole patients were $86,480 and $90,500, respectively. During this period, the number of relapses per patient, hospitalizations per patient, diabetes rates, and CV events per 1000 patients, respectively, were estimated to be lower for lurasidone (0.442, 0.245, 7.29%, and 37.3) than aripiprazole (0.478, 0.369, 7.36%, and 37.8). Results were sensitive to lurasidone and aripiprazole hospitalization rates. At a willingness-to-pay threshold of $50,000 per hospitalization avoided, lurasidone had a 100% probability of being more cost-effective than aripiprazole. LIMITATIONS: The model was based on results from various comparative clinical trials. Differences in patient population and study methods may change estimates from the model. The model does not account for patient heterogeneity. CONCLUSIONS: Based on this model, when switching from another atypical antipsychotic, lurasidone had fewer relapses and hospitalizations with a lower incidence of diabetes and CV events than aripiprazole. Additionally, lurasidone may be less costly than aripiprazole among adults with schizophrenia.

Annual cost of relapses and relapse-related hospitalizations in adults with schizophrenia: results from a 12-month, double-blind, comparative study of lurasidone vs quetiapine extended-release.

PURPOSE: To model the economic impact of annual relapses/relapse-related hospitalizations among adults with schizophrenia treated with lurasidone or quetiapine extended-release (XR). METHODS: A probabilistic model estimating per-patient-per-year (PPPY) direct mental healthcare (MH) cost differences due to relapses/relapse-related hospitalizations was developed using relapse and relapse-related hospitalization rates from a 12-month, double-blind, parallel-group, global comparison study of lurasidone vs quetiapine XR (all patients previously treated with lurasidone or quetiapine XR for 6 weeks). Analyses were conducted for both all subjects and clinical responders. Direct costs associated with inpatient and outpatient mental healthcare-related services were obtained from a large, prospective, observational study of schizophrenia treatment in usual-care settings for relapsing and non-relapsing patients, including psychiatric hospitalizations, emergency services, medication management, and outpatient individual therapy. Model robustness was tested using univariate and probabilistic sensitivity analyses. RESULTS: Model-estimated PPPY MH cost savings associated with relapse-related hospitalization rates in all subjects were $3276 for lurasidone vs quetiapine XR. Lurasidone resulted in PPPY MH cost savings of $2702 vs quetiapine XR in all subjects, using relapse rates. Sensitivity analyses indicated lurasidone had lower 1-year MH costs than quetiapine XR in 100% and 99.7% of simulations, using relapse-related hospitalization rates and relapse rates, respectively, in all subjects. Similar results were seen in clinical responders. LIMITATIONS: The model represents a simplification of treatment patterns and response to treatment. Cost of treatment with lurasidone and quetiapine XR was not included in the model. Estimates of cost savings are likely conservative, as the model did not assess the impact of long-term cardiometabolic consequences. Indirect costs associated with relapses and non-mental health-related costs were also excluded from the model. CONCLUSION: Adults treated for schizophrenia with lurasidone are predicted to have lower 12-month MH costs compared to those treated with quetiapine XR due to fewer relapses and relapse-related hospitalizations.