Hemoglobin and End-Organ Damage in Individuals with Sickle Cell Disease.

Background: Sickle cell disease (SCD) is an inherited, chronic, multifaceted blood disorder. Patients with SCD develop anemia, which has been associated with end-organ damage (EOD). Objectives: This retrospective, observational, repeated-measures study systematically characterizes the relationship between hemoglobin (Hb) level and EOD in adolescent and adult patients with SCD. Methods: The study population comprised patients with SCD aged ≥12 years with available Hb data from a US provider-centric health care database. For each patient, each Hb value over time was included as a separate observation. Study outcomes-the onset of any new EOD, including chronic kidney disease, pulmonary hypertension, stroke, and leg ulcer-were ascertained during the 1-year period after each Hb assessment. The association between Hb levels and risk of new EOD was estimated using multivariable generalized estimating equations. Results: A total of 16,043 unique patients with SCD contributed 44,913 observations. Adjusted odds of any EOD during the 1-year follow-up were significantly lower with higher Hb level. Risk reductions with higher Hb levels for chronic kidney disease, pulmonary hypertension, and leg ulcer were comparable. The risk of new EOD was significantly lower among adolescent and adult patients with higher Hb levels. Conclusions: In patients with SCD, higher Hb levels are associated with a reduced risk of developing EOD. Therapeutic strategies that result in higher Hb levels may offer clinical and economic value for patients with SCD. (Curr Ther Res Clin Exp. 2023; 84:XXX-XXX).

Quality-Adjusted Survival with Ribociclib Plus Fulvestrant Versus Placebo Plus Fulvestrant in Postmenopausal Women with HR±HER2- Advanced Breast Cancer in the MONALEESA-3 Trial.

BACKGROUND: MONALEESA-3 demonstrated an overall survival (OS) benefit for ribociclib plus fulvestrant (R+F) in postmenopausal women with hormone receptor (HR) positive, HER2 negative advanced breast cancer (ABC). This study estimated quality-adjusted (QA) survival outcomes for patients receiving R+F vs. placebo (P)+F in MONALEESA-3. METHODS: Kaplan-Meier OS was partitioned into health states: (1) toxicity (TOX)=time spent with grade 3 -4 adverse events before progression (DP); (2) progression (PROG)=time between DP and death; and (3) time without symptoms or toxicity (TWiST)=time not in TOX or PROG. QA time was calculated by combining estimated mean time in each health state with treatment-group specific health-state utility values estimated using EQ-5D-5L questionnaire. Outcomes included QA progression-free survival (QAPFS), QAOS, and QA TWiST (Q-TWiST). Q-TWiST was calculated with health-state utility values for TOX and PROG defined relative to TWiST. RESULTS: Mean PFS and OS were significantly greater with R+F vs. P+F (difference 0.56 and 0.19 years). Mean time in TOX and TWiST were greater with R+F; mean time in PROG was greater with P+F. QAPFS was 0.45 years (95% CI 0.27 -0.63) greater with R+F than P+F (P <.001). QAOS was numerically greater with R+F vs. P+F (0.16 years, 95% CI 0.07 -0.45, P = .0569). Q-TWiST was 0.23 years greater with R+F (95% CI 0.07 -0.45, P = .0069). In a sensitivity analysis using an estimate of disutility for PROG, the difference in QAOS was 0.23 years (95% CI 0.08 -0.41, P = .0022). CONCLUSION: R+F in postmenopausal women with HR+/HER2- ABC improves QAPFS, resulting in clinically important improvements in Q-TWiST and may improve QAOS.

Matching-Adjusted Indirect Comparison of Ribociclib Plus Fulvestrant versus Palbociclib Plus Letrozole as First-Line Treatment of HR+/HER2- Advanced Breast Cancer.

PURPOSE: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) plus endocrine therapy are recommended for first-line treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). However, not all CDK4/6i trials have reported significant overall survival (OS) benefit, and there have been no head-to-head trials. Two trials have reported OS outcomes in first-line patients: MONALEESA-3 reported significant OS benefit with first- or second-line ribociclib plus fulvestrant (RIB+FUL) versus placebo plus fulvestrant (PBO+FUL), while PALOMA-1 reported no significant OS benefit for palbociclib plus letrozole (PAL+LET) versus LET in first-line postmenopausal patients. Matched-adjusted indirect comparisons (MAICs) are an established method for comparing efficacy of treatments from different trials. We used an MAIC to compare first-line patients from MONALEESA-3 and PALOMA-1. PATIENTS AND METHODS: An unanchored MAIC of progression-free survival (PFS) and OS in first-line patients with HR+/HER2- ABC treated with RIB+FUL versus PAL+LET was conducted using individual patient data from MONALEESA-3 and aggregated data from PALOMA-1. To match patients in PALOMA-1, patients in MONALEESA-3 were limited to those with no prior endocrine therapy for ABC and no (neo) adjuvant LET ≤12 months before enrollment. PFS and OS were compared using Kaplan-Meier estimators and Cox regression. RESULTS: A total of 329 and 178 patients from RIB+FUL and PBO+FUL arms, respectively, of MONALEESA-3 were matched to 84 and 81 patients from PAL+LET and LET arms of PALOMA-1. After weighting, OS was significantly longer for RIB+FUL versus PAL+LET (hazard ratio [HR], 0.50; 95% CI, 0.32-0.77; p = 0.0020). PFS favored RIB+FUL versus PAL+LET, although the difference was not statistically significant (HR, 0.77; 95% CI, 0.54-1.10; p = 0.1553). CONCLUSION: Using MAIC to adjust for trial differences, OS comparisons favored RIB+FUL over PAL+LET as first-line treatment in postmenopausal patients with HR+/HER2- ABC. These exploratory results suggest a significant increase in OS benefit with RIB treatment compared with PAL.

Lifetime Costs for Treated Follicular Lymphoma Patients in the US.

BACKGROUND AND OBJECTIVE: The objective of this study was to estimate the lifetime costs of patients receiving treatment for follicular lymphoma (FL) in the United States. METHODS: A Markov model was programmed in heRo3 with a 6-month cycle length, 35-year time horizon (lifetime projection), and health states for line of treatment, response, receipt of maintenance therapy among responders, transformation to diffuse large B-cell lymphoma (DLBCL), development of second primary malignancy (SPM), and death. The model was used to estimate the expected lifetime costs of FL (in 2019 USD), including costs of drug acquisition and administration, transplant procedures, radiotherapy, adverse events, follow-up, DLBCL, SPM, end-of-life care, and indirect costs. Model inputs were based on published sources. RESULTS: In the US, patients with FL receiving treatment have a life expectancy of approximately 14.5 years from initiation of treatment and expected lifetime direct and indirect costs of US$515,884. Costs of drugs for induction therapy represent the largest expenditure (US$233,174), followed by maintenance therapy costs (US$88,971) and terminal care costs (US$57,065). Despite the relatively advanced age of these patients, indirect costs (due to patient morbidity and mortality and caregiver lost work time) represent a substantial share of total costs (US$40,280). Treated FL patients spend approximately 6.9 years in the health states associated with first-line therapy. Approximately 66 and 46% continue to second- and third-line therapies, respectively. The mean (95% credible interval) of expected lifetime costs based on the probabilistic sensitivity analyses was US$559,202 (421,997-762,553). CONCLUSIONS: In the US, the expected lifetime costs of care for FL patients who receive treatment is high. The results highlight the potential economic benefits that might be achieved by treatments for FL that prevent or delay disease progression.

Cost Effectiveness of Ribociclib in Combination with Fulvestrant for the Treatment of Postmenopausal Women with HR+/HER2- Advanced Breast Cancer Who Have Received No or Only One Prior Line of Endocrine Therapy: A Canadian Healthcare Perspective.

BACKGROUND: The MONALEESA-3 trial demonstrated the efficacy and safety of ribociclib plus fulvestrant versus placebo plus fulvestrant for patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). This analysis evaluated the cost effectiveness of ribociclib plus fulvestrant versus fulvestrant in patients with HR+/HER2- ABC from a Canadian healthcare payer perspective. METHODS: The incremental cost-effectiveness ratio (ICER), expressed as incremental costs per quality-adjusted life-year (QALY) gained for ribociclib plus fulvestrant versus fulvestrant, was estimated using a semi-Markov cohort model developed in Microsoft Excel, with states for progression-free, post-progression, and dead. A 15-year time horizon was used. Survival distributions for progression-free survival (PFS), post-progression survival (PPS), and time to discontinuation (TTD) were based on parametric survival distributions fit to data from MONALEESA-3. Health-state utilities were estimated using EQ-5D index values collected in MONALEESA-3. Direct costs of ABC treatment (medication and administration costs, follow-up and monitoring, adverse events, subsequent treatments) were based on Canadian-specific values from published sources. Costs (2019 CAN$) and QALYs were discounted at 1.5% annually. RESULTS: In the base case, ribociclib plus fulvestrant was estimated to result in gains of 1.19 life-years and 0.96 QALYs versus fulvestrant, at an incremental cost of $151,371. The ICER of ribociclib plus fulvestrant versus fulvestrant was $157,343 per QALY gained based on the mean of probabilistic analyses. Results were sensitive to parametric distributions used for projecting long-term TTD, PFS, and PPS. CONCLUSIONS: For patients with HR+/HER2- ABC, ribociclib plus fulvestrant is projected to result in substantial gains in QALYs compared with fulvestrant. At its current list price, ribociclib used in combination with fulvestrant is likely to be cost effective in these patients at a threshold ICER of $157,343. These results may be useful in deliberations regarding reimbursement and access to this treatment.

Cost Effectiveness of Ribociclib Plus a Nonsteroidal Aromatase Inhibitor in Pre-/Perimenopausal, HR+ and HER2- Advanced Breast Cancer: A Canadian Healthcare Perspective.

BACKGROUND AND OBJECTIVES: The MONALEESA-7 trial demonstrated the efficacy and safety of ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) [with goserelin] for pre-/perimenopausal women with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer. This analysis evaluated the cost effectiveness of ribociclib plus NSAI vs NSAI monotherapy and tamoxifen monotherapy from the perspective of the Canadian healthcare system. METHODS: The incremental cost-effectiveness ratio expressed as incremental costs per quality-adjusted life-year (QALY) gained for ribociclib plus an NSAI vs an NSAI and vs tamoxifen was estimated using a semi-Markov cohort model developed in Microsoft Excel with a 15-year time horizon and states for progression-free survival, post-progression survival, and dead. Survival distributions for progression-free survival, post-progression survival, and time to discontinuation as well as health-state utilities were estimated using data from MONALEESA-7. Direct costs of advanced breast cancer treatment were based on Canadian-specific values from published sources. Costs ($CAN 2019) and QALYs were discounted at 1.5% annually. RESULTS: Ribociclib plus an NSAI was estimated to yield gains of 1.42 life-years and 1.17 QALYs vs an NSAI, and 2.61 life-years and 2.12 QALYs vs tamoxifen, at incremental costs of $209,701 and $220,836, respectively. In probabilistic analyses, the incremental cost-effectiveness ratio for ribociclib plus an NSAI was estimated to be $178,872 per QALY gained vs an NSAI and $104,400 per QALY gained vs tamoxifen. Results of deterministic analyses were similar (incremental cost-effectiveness ratios of $177,245 and $103,316 vs NSAI and tamoxifen, respectively). Results were sensitive to parametric distributions used for projecting progression-free survival and the time horizon. CONCLUSIONS: At its current list price, ribociclib used in combination with NSAI is likely to be co-effective relative to an NSAI alone or tamoxifen alone if the willingness-to-pay threshold is less than approximately $178,000 per QALY. These results have informed deliberations regarding reimbursement and access to this treatment in Canada and may be useful for decision makers in other settings.

Real-world treatment patterns, healthcare use and costs in triple-class exposed relapsed and refractory multiple myeloma patients in the USA.

Aim: To estimate treatment patterns and healthcare costs among triple-class exposed relapsed and refractory multiple myeloma (RRMM) patients. Materials & methods: Eligible patients had ≥1 line of therapy (LOT) each of proteasome inhibitors, immunomodulatory drugs and daratumumab in December 2015-September 2018 and received a new LOT. Results: A total of 154 patients were included with a median follow-up of 6.2 months. Median time from diagnosis to new LOT was 41.0 months. Kaplan-Meier estimate of median time to therapy discontinuation was 4.2 months. Mean per-patient, per-month MM-related costs were USD 35,657. Most frequently observed regimens were lenalidomide or pomalidomide + daratumumab (18.2%), lenalidomide or pomalidomide + proteasome inhibitors (15.6%) and lenalidomide or pomalidomide monotherapy (11.0%). Conclusion: Triple-class exposed RRMM patients receive heterogeneous treatments for a short duration with high healthcare resource utilization and costs.

Preferences of Canadian Patients and Physicians for Treatment of HR+/HER2- Advanced Breast Cancer.

(1) Background: Past research suggests that patients with advanced breast cancer prefer treatments with improved clinical outcomes and lower risk of side effects. Evidence on preferences of Canadian patients and physicians for treatments for advanced breast cancer is limited. (2) Methods: Patients' and physicians' preferences for treatments for HR+/HER2-, pre-/peri-menopausal advanced breast cancer were assessed by an online discrete choice experiment (DCE). Treatment alternatives were characterized by seven attributes regarding dosing, efficacy, and toxicities, with levels corresponding to those for ribociclib plus a non-steroidal aromatase inhibitor (NSAI), NSAI, and tamoxifen. For patients, impacts of advanced breast cancer on quality of life (QOL) and ability to work/perform activities of daily living also were assessed. Patients were recruited by a Canadian breast cancer patient advocacy group through email and social media. Physicians were recruited by email. (3) Results: Among 118 patients starting the survey, 23 completed ≥ 1 DCE question (19%). Among 271 physicians who were sent the e-mail invitation, 21 completed ≥ 1 DCE question (8%). For both patients and physicians, the increased probability of remaining alive and without cancer progression over 2 years was the most important attribute. A treatment with attributes consistent with ribociclib plus NSAI was chosen by patients and physicians in 70% and 88% of the time, respectively. A substantial proportion of patients reported worrying about future diagnostic tests and their cancer getting worse; (4) Conclusions: Canadian patients and physicians are generally concordant in preference for advanced breast cancer treatments, preferring ribociclib plus NSAI to other options.

Budget Impact of Dabrafenib and Trametinib in Combination as Adjuvant Treatment of BRAF V600E/K Mutation-Positive Melanoma from a U.S. Commercial Payer Perspective.

BACKGROUND: Before the approval of dabrafenib and trametinib in combination, there were no approved therapies in the adjuvant setting that target the RAS/RAF/MEK/ERK pathway. OBJECTIVE: To evaluate the budget impact of dabrafenib and trametinib in combination for adjuvant treatment of patients with BRAF V600 mutation-positive resected Stage IIIA, IIIB, or IIIC melanoma from a U.S. commercial payer perspective using data from the COMBI-AD trial, as well as other sources. METHODS: The budget impact of dabrafenib and trametinib in combination for patients with BRAF V600E/K mutation-positive, resected Stage IIIA, IIIB, or IIIC melanoma was evaluated from the perspective of a hypothetical population of 1 million members with demographic characteristics consistent with those of a commercially insured U.S. insurance plan (i.e., adults aged less than 65 years) using an economic model developed in Microsoft Excel. The model compared melanoma-related health care costs over a 3-year projection period under 2 scenarios: (1) a reference scenario in which dabrafenib and trametinib are assumed to be unavailable for adjuvant therapy and (2) a new scenario in which the combination is assumed to be available. Treatments potentially displaced by dabrafenib and trametinib were assumed to include observation, high-dose interferon alpha-2b, ipilimumab, and nivolumab. Costs considered in the model include those of adjuvant therapies and treatment of locoregional and distant recurrences. The numbers of patients eligible for treatment with dabrafenib and trametinib were based on data from cancer registries, published sources, and assumptions. Treatment mixes under the reference and new scenarios were based on market research data, clinical expert opinion, and assumptions. Probabilities of recurrence and death were based on data from the COMBI-AD trial and an indirect treatment comparison. Medication costs were based on wholesale acquisition cost prices. Costs of distant recurrence were from a health insurance claims study. RESULTS: In a hypothetical population of 1 million commercially insured members, 48 patients were estimated to become eligible for treatment with dabrafenib and trametinib in combination over the 3-year projection period; in the new scenario, 10 patients were projected to receive such treatment. Cumulative costs of melanoma-related care were estimated to be $6.3 million in the reference scenario and $6.9 million in the new scenario. The budget impact of dabrafenib and trametinib in combination was an increase of $549 thousand overall and 1.5 cents per member per month. CONCLUSIONS: For a hypothetical U.S. commercial health plan of 1 million members, the budget impact of dabrafenib and trametinib in combination as adjuvant treatment for melanoma is likely to be relatively modest and within the range of published estimates for oncology therapies. These results may assist payers in making coverage decisions regarding the use of adjuvant dabrafenib and trametinib in melanoma. DISCLOSURES: Funding for this research was provided to Policy Analysis Inc. (PAI) by Novartis Pharmaceuticals. Stellato, Moynahan, and Delea are employed by PAI. Ndife, Koruth, Mishra, and Gunda are employed by Novartis. Ghate was employed by Novartis at the time of this study and is shareholder in Novartis, Provectus Biopharmaceuticals, and Mannkind Corporation. Gerbasi was employed by PAI at the time of this study and is currently an employee, and stockholder, of Sage Therapeutics. Delea reports grant funding from Merck and research funding from Amgen, Novartis, Sanofi, Seattle Genetics, Takeda, Jazz, EMD Serono, and 21st Century Oncology, unrelated to this work.

Cost-effectiveness of dabrafenib and trametinib in combination as adjuvant treatment of BRAF V600E/K mutation-positive melanoma from a US healthcare payer perspective.

Objective: The COMBI-AD trial demonstrated the efficacy and safety of dabrafenib and trametinib in combination vs placebo as adjuvant treatment of patients with BRAF V600E/K mutation-positive resected Stage IIIA (lymph node metastasis >1 mm), IIIB, or IIIC melanoma. This analysis evaluated the cost-effectiveness of dabrafenib and trametinib vs observation from a US healthcare payer perspective.Methods: This evaluation employed a non-homogeneous, semi-Markov, cohort model with health states for relapse-free survival (RFS), post-locoregional recurrence (LR), post-distant recurrence (DR) receiving first-line treatment, and post-DR receiving second-line treatment. A 50-year modeling time horizon was used. Transition probabilities were estimated based on individual patient data (IPD) from the COMBI-AD trial. Health-state utilities were estimated using EuroQol (EQ-5D) index values from COMBI-AD and published sources. Direct medical costs associated with treatment of melanoma were considered, including costs of BRAF mutation testing, medication and administration costs for adjuvant and metastatic treatments, costs of treating recurrence, and costs of adverse events. Costs and quality-adjusted life-years (QALYs) were discounted at 3.0% annually.Results: Compared with observation, adjuvant dabrafenib and trametinib was estimated to result in a gain of 2.15 QALYs at an incremental cost of $74,518. The incremental cost-effectiveness ratio (ICER) was estimated to be $34,689 per QALY. In deterministic sensitivity analyses, the ICER was sensitive to the cost of dabrafenib and trametinib and the distribution used for projecting RFS beyond the end of follow-up in the COMBI-AD trial. At a cost-effectiveness threshold of $100,000 per QALY, the probability that dabrafenib and trametinib is cost-effective was estimated to be 92%.Conclusions: Given generally-accepted cost-effectiveness threshold values in the US, dabrafenib plus trametinib is likely to be a cost-effective adjuvant therapy for patients with BRAF mutation positive melanoma. These results may be useful for policy-makers in their deliberations regarding reimbursement and access to this treatment.

Cost Effectiveness of Blinatumomab Versus Inotuzumab Ozogamicin in Adult Patients with Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia in the United States.

BACKGROUND AND OBJECTIVE: The TOWER and INO-VATE-ALL trials demonstrated the efficacy and safety of blinatumomab and inotuzumab ozogamicin (inotuzumab), respectively, versus standard-of-care (SOC) chemotherapy in adults with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL). The cost effectiveness of blinatumomab versus inotuzumab has not previously been examined. METHODS: Cost effectiveness of blinatumomab versus inotuzumab in R/R B-cell precursor ALL patients with one or no prior salvage therapy from a United States (US) payer perspective was estimated using a partitioned survival model. Health outcomes were estimated based on published aggregate data from INO-VATE-ALL and individual patient data from TOWER weighted to match patients in INO-VATE-ALL using matching adjusted indirect comparison (MAIC). Analyses were conducted using five approaches relating to use of anchored versus unanchored comparisons of health outcomes and, for the anchored comparisons, the reference treatment to which treatment effects on health outcomes were applied. Estimates from TOWER including the probabilities of complete remission and allogeneic stem-cell transplant (allo-SCT), overall and event-free survival, utilities, duration of therapy, and use of subsequent therapies were MAIC adjusted to match INO-VATE-ALL. Costs of treatment, adverse events, allo-SCT, subsequent therapies, and terminal care were from published sources. A 50-year time horizon and 3% annual discount rate were used. RESULTS: Incremental costs for blinatumomab versus inotuzumab ranged from US$7023 to US$36,244, depending on the approach used for estimating relative effectiveness. Incremental quality-adjusted life-years (QALYs) ranged from 0.54 to 1.78. Cost effectiveness for blinatumomab versus inotuzumab ranged from US$4006 to US$20,737 per QALY gained. CONCLUSIONS: Blinatumomab is estimated to be cost effective versus inotuzumab in R/R B-cell precursor ALL adults who have received one or no prior salvage therapy from a US payer perspective.

Healthcare utilization and costs among relapsed or refractory multiple myeloma patients on carfilzomib or pomalidomide as monotherapy or in combination with dexamethasone.

Aim: To compare monthly healthcare resource utilization (HRU) and costs among adult patients with multiple myeloma (MM) receiving second or subsequent line of treatment (LOT) with carfilzomib or pomalidomide as monotherapy or in combination with dexamethasone. Methods and materials: Adult MM patients who received carfilzomib or pomalidomide as second/subsequent LOT between 2006 and 2014 were selected from the MarketScan databases. LOT was determined using Medical/pharmacy claims using a published algorithm. For each patient, first LOT with carfilzomib or pomalidomide was defined as index LOT. Patients with first LOT as index LOT, who received other chemotherapy in combination with carfilzomib or pomalidomide, or who underwent stem cell transplant (STC) during index LOT were excluded. Monthly HRU and costs during index LOT were compared using inverse probability of treatment weights (IPTW) based on propensity scores for receipt of carfilzomib estimated by logistic regression with LOT, patient demographics, Charlson index, comorbidities, pre-index healthcare cost, and receipt of prior SCT as covariates. Results: After weighting, baseline characteristics were well balanced among 114 carfilzomib and 144 pomalidomide patients. Mean (95% CI) numbers of outpatient visits per month were 7.1 (5.2-8.0) with carfilzomib and 4.7 (3.9-6.1) with pomalidomide (p = 0.006). Otherwise, there were no statistically significant differences between the groups in mean monthly HRU and costs or median time to therapy discontinuation. Mean (95% CI) monthly total healthcare costs were $19,776 (15,322-27,748) with pomalidomide and $17,321 (12,412-21,874) with carfilzomib (p = 0.522). Limitations: Comparison of carfilzomib vs pomalidomide may be biased if there are unobserved factors not balanced by IPTW. The relatively small sample size limits the power of analyses to detect potential differences between treatment groups. Conclusions: Monthly HRU and costs are similar among patients with relapse or refractory MM patients receiving carfilzomib or pomalidomide as monotherapy or in combination with dexamethasone.

Cost-effectiveness of brentuximab vedotin plus chemotherapy as frontline treatment of stage III or IV classical Hodgkin lymphoma.

OBJECTIVE: The ECHELON-1 trial demonstrated efficacy and safety of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline therapy for stage III/IV classical Hodgkin lymphoma. This analysis evaluated the cost-effectiveness of A + AVD from a US healthcare payer perspective. METHODS: The incremental cost-effectiveness ratio (ICER), defined as the incremental costs per quality-adjusted life year (QALY) gained, was estimated using a non-homogenous semi-Markov cohort model with health states defined on progression following frontline treatment, and for those with progression, receipt of autologous stem-cell transplant (ASCT), and progression after ASCT. Patients undergoing ASCT were classified as refractory or relapsed based on timing of progression. Probabilities of progression/death with frontline therapy were based on parametric survival distributions fit to data on modified progression-free survival (mPFS) from ECHELON-1. Duration of frontline treatment and incidence of adverse events were from ECHELON-1. Utility values for patients in the frontline mPFS state were based on EQ-5D data from ECHELON-1. Other inputs were from published sources. A lifetime time horizon was used. Costs and QALYs were discounted at 3%. Analyses were conducted alternately using data on mPFS for the overall and North American populations of ECHELON-1. RESULTS: The ICER for A + AVD vs ABVD was $172,074/QALY gained in the analysis using data on mPFS for the overall population and $69,442/QALY gained in the analysis using data on mPFS for the North American population of ECHELON-1. The ICER is sensitive to estimated costs of ASCT and frontline failure. CONCLUSION: The ICER for A + AVD vs ABVD based on ECHELON-1 is within the range of threshold values for cost-effectiveness in the US. A + AVD is, therefore, likely to be a cost-effective frontline therapy for patients with stage III/IV classical Hodgkin lymphoma from a US healthcare payer perspective.

Healthcare resource utilization and costs in patients with newly diagnosed acute myeloid leukemia.

AIM: Acute myeloid leukemia (AML) is associated with high disease burden. This analysis estimated HRU and costs among newly diagnosed AML patients in a US commercially insured population. MATERIALS AND METHODS: This was a retrospective observational study using the IMS Health PharMetrics Plus and Hospital Charge Detail Master databases. Patients included adults who were newly diagnosed with AML between January 2007 and June 2016 ("study period"). Patients with <12 months of continuous enrollment prior to the index date were excluded, as were those whose first diagnosis was AML in remission/relapse, those diagnosed with acute promyelocytic leukemia, those on Medicare supplemental insurance, or those with a diagnosis of AML in remission/relapse without evidence of treatment during the study period. Patients were stratified by receipt of AML treatment (chemotherapy/hematopoietic cell transplantation [HCT]), and their follow-up was partitioned into initial, remission, and relapsed health states. Mean HRU and costs were tallied by treatment and, for treated patients, by health state and time since entry into health state (≤6 vs >6 months). RESULTS: A total of 9,455 patients met study criteria, including 6,415 (68%) treated and 3,040 (32%) untreated patients, with mean follow-up of 18.3 and 16.4 months, respectively. Mean age was 55 years in treated patients and 60 years in untreated patients. Mean total costs per patient were $386,077 in treated patients and $79,382 in untreated patients. For treated patients, 60% of total costs ($231,867 per patient) were incurred during the initial health state, representing time without remission/relapse. Mean monthly total healthcare costs were $21,055 and $4,854 among treated and untreated patients, respectively. LIMITATIONS AND CONCLUSIONS: HRU and costs of managing AML patients are substantial. In treated patients, the majority of costs were incurred during the initial treatment period, without claims indicating remission/relapse.

Budget Impact Analysis of PCSK9 Inhibitors for the Management of Adult Patients with Heterozygous Familial Hypercholesterolemia or Clinical Atherosclerotic Cardiovascular Disease.

OBJECTIVE: The aim of this study was to assess the budget impact of introducing the proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) alirocumab and evolocumab to market for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular (CV) disease requiring additional lowering of low-density lipoprotein cholesterol (LDL-C). METHODS: A 3-year model estimated the costs of lipid-modifying therapy (LMT) and CV events to a hypothetical US health plan of 1 million members, comparing two scenarios-with and without the availability of PCSK9i as add-on therapy to statins. Proportions of patients with uncontrolled LDL-C despite receiving statins, and at risk of CV events, were estimated from real-world data. Total undiscounted annual LMT costs (2017 prices, including PCSK9i costs of $14,563.50), dispensing and healthcare costs, including the costs of CV events, were estimated for all prevalent patients in the target population, based on baseline risk factors. Maximum PCSK9i utilization of 1-5% over 3 years according to risk group (following the same pattern as current ezetimibe use), and 5-10% as a secondary scenario, were assumed. RESULTS: Total healthcare budget impacts per target patient (and per member) per month for years 1, 2 and 3 were $3.62($0.10), $7.22($0.20) and $10.79($0.30), respectively, assuming 1-5% maximum PCSK9i utilization, and $15.81($0.44), $31.52($0.88) and $47.12($1.31), respectively, assuming 5-10% utilization. Results were sensitive to changes in model timeframe, years to maximum PCSK9i utilization and PCSK9i costs. CONCLUSIONS: The budget impact of PCSK9i as add-on therapy to statins for patients with hypercholesterolemia is relatively low compared with published estimates for other specialty biologics. Drug cost rebates and discounts are likely to further reduce budget impact.

Cost-Effectiveness of Thoracic Radiation Therapy for Extensive-Stage Small Cell Lung Cancer Using Evidence From the Chest Radiotherapy Extensive-Stage Small Cell Lung Cancer Trial (CREST).

PURPOSE: The Chest Radiotherapy Extensive-Stage Small Cell Lung Cancer Trial (CREST) showed that adding thoracic radiation therapy (TRT) to the standard treatment (ST) paradigm of chemotherapy and prophylactic cranial irradiation improves overall survival and progression-free survival (PFS) in patients with extensive-stage small cell lung cancer (ES-SCLC). We evaluated the cost-effectiveness of adding TRT to ST in ES-SCLC patients. METHODS AND MATERIALS: A cost-utility analysis was performed comparing TRT plus ST versus ST alone. The base-case time horizon was 24 months, consistent with the maximum PFS reported in the CREST. Overall survival was partitioned into 2 health states: PFS and postprogression survival. The proportion of patients in each health state over time was estimated by fitting parametric probability distributions to the CREST survival data. Costs were from a US health care payer perspective, and utilities were derived from the literature. Incremental cost-effectiveness ratios (ICERs) were calculated per quality-adjusted life-year (QALY) using a 3% discount rate. Sensitivity analyses addressed uncertainty in key variables. RESULTS: In the base-case analysis, adding TRT to ST was both cost saving and more effective, thereby strongly dominating ST alone. At willingness-to-pay thresholds of $50,000/QALY, $100,000/QALY, and $200,000/QALY, TRT was preferred 68%, 81%, and 96% of the time, respectively. In the lifetime scenario analysis, the TRT ICER increased to $194,726/QALY. CONCLUSIONS: By use of the actual follow-up interval reported in the CREST, adding TRT to ST strongly dominates a strategy of ST alone in ES-SCLC patients. Since the long-term survival benefit of TRT is small relative to ongoing costs of progressive metastatic disease, we estimate less favorable ICERs for TRT over a lifetime horizon.

Cost-effectiveness of pazopanib versus sunitinib for metastatic renal cell carcinoma in the United Kingdom.

BACKGROUND: Sunitinib and pazopanib are the only two targeted therapies for the first-line treatment of locally advanced or metastatic renal cell carcinoma (mRCC) recommended by the United Kingdom's National Institute for Health and Care Excellence. Pazopanib demonstrated non-inferior efficacy and a differentiated safety profile versus sunitinib in the phase III COMPARZ trial. The current analysis provides a direct comparison of the cost-effectiveness of pazopanib versus sunitinib from the perspective of the United Kingdom's National Health Service based on data from COMPARZ and other sources. METHODS: A partitioned-survival analysis model with three health states (alive with no progression, alive with progression, or dead) was used to estimate the incremental cost per quality-adjusted life-year (QALY) gained for pazopanib versus sunitinib over five years (duration of follow-up for final survival analysis in COMPARZ). The proportion of patients in each health state over time was based on Kaplan-Meier distributions for progression-free and overall survival from COMPARZ. Utility values were based on EQ-5D data from the pivotal study of pazopanib versus placebo. Costs were based on medical resource utilisation data from COMPARZ and unit costs from secondary sources. Probabilistic and deterministic sensitivity analyses were conducted to assess uncertainty of model results. RESULTS: In the base case, pazopanib was estimated to provide more QALYs (0.0565, 95% credible interval [CrI]: -0.0920 to 0.2126) at a lower cost (-£1,061, 95% CrI: -£4,328 to £2,067) versus sunitinib. The probability that pazopanib yields more QALYs than sunitinib was estimated to be 76%. For a threshold value of £30,000 per QALY gained, the probability that pazopanib is cost-effective versus sunitinib was estimated to be 95%. Pazopanib was dominant in most scenarios examined in deterministic sensitivity analyses. CONCLUSIONS: Pazopanib is likely to be a cost-effective treatment option compared with sunitinib as first-line treatment of mRCC in the United Kingdom.

Estimating outcomes and cost effectiveness using a single-arm clinical trial: ofatumumab for double-refractory chronic lymphocytic leukemia.

BACKGROUND: Ofatumumab (Arzerra®, Novartis) is a treatment for chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab [double refractory (DR-CLL)]. Ofatumumab was licensed on the basis of an uncontrolled Phase II study, Hx-CD20-406, in which patients receiving ofatumumab survived for a median of 13.9 months. However, the lack of an internal control arm presents an obstacle for the estimation of comparative effectiveness. METHODS: The objective of the study was to present a method to estimate the cost effectiveness of ofatumumab in the treatment of DR-CLL. As no suitable historical control was available for modelling, the outcomes from non-responders to ofatumumab were used to model the effect of best supportive care (BSC). This was done via a Cox regression to control for differences in baseline characteristics between groups. This analysis was included in a partitioned survival model built in Microsoft® Excel with utilities and costs taken from published sources, with costs and quality-adjusted life years (QALYs) were discounted at a rate of 3.5% per annum. RESULTS: Using the outcomes seen in non-responders, ofatumumab is expected to add approximately 0.62 life years (1.50 vs. 0.88). Using published utility values this translates to an additional 0.30 QALYs (0.77 vs. 0.47). At the list price, ofatumumab had a cost per QALY of £130,563, and a cost per life year of £63,542. The model was sensitive to changes in assumptions regarding overall survival estimates and utility values. CONCLUSIONS: This study demonstrates the potential of using data for non-responders to model outcomes for BSC in cost-effectiveness evaluations based on single-arm trials. Further research is needed on the estimation of comparative effectiveness using uncontrolled clinical studies.

Cost-effectiveness of blinatumomab versus salvage chemotherapy in relapsed or refractory Philadelphia-chromosome-negative B-precursor acute lymphoblastic leukemia from a US payer perspective.

OBJECTIVE: To evaluate the cost-effectiveness of blinatumomab (Blincyto) vs standard of care (SOC) chemotherapy in adults with relapsed or refractory (R/R) Philadelphia-chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL) based on the results of the phase 3 TOWER study from a US healthcare payer perspective. METHODS: The Blincyto Global Economic Model (B-GEM), a partitioned survival model, was used to estimate the incremental cost-effectiveness ratio (ICER) of blinatumomab vs SOC. Response rates, event-free survival (EFS), overall survival (OS), numbers of cycles of blinatumomab and SOC, and transplant rates were estimated from TOWER. EFS and OS were estimated by fitting parametric survival distributions to failure-time data from TOWER. Utility values were based on EORTC-8D derived from EORTC QLQ-C30 assessments in TOWER. A 50-year lifetime horizon and US payer perspective were employed. Costs and outcomes were discounted at 3% per year. RESULTS: The B-GEM projected blinatumomab to yield 1.92 additional life years and 1.64 additional quality-adjusted life years (QALYs) compared with SOC at an incremental cost of $180,642. The ICER for blinatumomab vs SOC was estimated to be $110,108/QALY gained in the base case. Cost-effectiveness was sensitive to the number and cost of inpatient days for administration of blinatumomab and SOC, and was more favorable in the sub-group of patients who had received no prior salvage therapy. At an ICER threshold of $150,000/QALY gained, the probability that blinatumomab is cost-effective was estimated to be 74%. LIMITATIONS: The study does not explicitly consider the impact of adverse events of the treatment; no adjustments for long-term transplant rates were made. CONCLUSIONS: Compared with SOC, blinatumomab is a cost-effective treatment option for adults with R/R Ph - B-precursor ALL from the US healthcare perspective at an ICER threshold of $150,000 per QALY gained. The value of blinatumomab is derived from its incremental survival and health-related quality-of-life (HRQoL) benefit over SOC.

Cost-effectiveness of alternate strategies for childhood immunization against meningococcal disease with monovalent and quadrivalent conjugate vaccines in Canada.

BACKGROUND: Public health programs to prevent invasive meningococcal disease (IMD) with monovalent serogroup C meningococcal conjugate vaccine (MCV-C) and quadrivalent meningococcal conjugate vaccines (MCV-4) in infancy and adolescence vary across Canadian provinces. This study evaluated the cost-effectiveness of various vaccination strategies against IMD using current and anticipated future pricing and recent epidemiology. METHODS: A cohort model was developed to estimate the clinical burden and costs (CAN$2014) of IMD in the Canadian population over a 100-year time horizon for three strategies: (1) MCV-C in infants and adolescents (MCV-C/C); (2) MCV-C in infants and MCV-4 in adolescents (MCV-C/4); and (3) MCV-4 in infants (2 doses) and adolescents (MCV-4/4). The source for IMD incidence was Canadian surveillance data. The effectiveness of MCV-C was based on published literature. The effectiveness of MCV-4 against all vaccination regimens was assumed to be the same as for MCV-C regimens against serogroup C. Herd effects were estimated by calibration to estimates reported in prior analyses. Costs were from published sources. Vaccines prices were projected to decline over time reflecting historical procurement trends. RESULTS: Over the modeling horizon there are a projected 11,438 IMD cases and 1,195 IMD deaths with MCV-C/C; expected total costs are $597.5 million. MCV-C/4 is projected to reduce cases of IMD by 1,826 (16%) and IMD deaths by 161 (13%). Vaccination costs are increased by $32 million but direct and indirect IMD costs are projected to be reduced by $46 million. MCV-C/4 is therefore dominant vs. MCV-C/C in the base case. Cost-effectiveness of MCV-4/4 was $111,286 per QALY gained versus MCV-C/4 (2575/206 IMD cases/deaths prevented; incremental costs $68 million). CONCLUSIONS: If historical trends in Canadian vaccines prices continue, use of MCV-4 instead of MCV-C in adolescents may be cost-effective. From an economic perspective, switching to MCV-4 as the adolescent booster should be considered.