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Lauren Ramjee,1 Nesrin Vurgun,1 Christopher Ngai,2 Mit Patel,3 Gabriel Tremblay1 1Health Economics & Outcomes Research (HEOR), Cytel, Inc, Waltham, MA, USA; 2Market Access, Calliditas NA Enterprises, New York, NY, USA; 3Health Economics & Outcomes Research (HEOR), Calliditas NA Enterprises, New York, NY, USACorrespondence: Gabriel Tremblay, Cytel, Inc, 1050 Winter Street #2700, Waltham, MA, 02451, USA, Tel +1 581-980-3151, Email gabriel.tremblay@cytel.comPurpose: To estimate the cost-effectiveness of Nefecon in addition to the best supportive care (BSC) vs BSC in a hypothetical cohort of commercially insured adult patients with primary immunoglobulin A nephropathy (IgAN) from a United States (US) societal perspective.Methods: A lifetime horizon, semi-Markov model was developed that consisted of nine health states: chronic kidney disease (CKD) stage 1, 2, 3a, 3b, 4, end-stage renal disease (ESRD) with dialysis, ESRD without dialysis, post-kidney transplant, and death. Health state occupancy was estimated from individual patient-level data from the Phase 3 randomized controlled trial NefIgArd Part A (NCT03643965). Additional scenarios evaluated the impact of varying the time horizon, discounting, costs included, rounds of treatment, and the method used to calculate transition probabilities.Results: In the deterministic base case analysis over a lifetime horizon, Nefecon plus BSC (hereafter Nefecon) had an incremental cost of $3,810 vs BSC. Nefecon resulted in a mean survival gain of 0.247 quality-adjusted life years (QALYs), 0.195 life years (LYs), and 0.244 equal value life years (evLYs) vs BSC alone – this resulted in incremental cost-effectiveness ratios (ICERs) of $15,428 per QALY, $19,502 per LY, and $15,611 per evLY gained. Probabilistic sensitivity analyses estimated that with willingness to pay thresholds of $100,000, $150,000, and $250,000 per QALY gained, Nefecon would be cost-effective over BSC in 66.70%, 75.02%, and 86.82% of cases, respectively. In the scenario analysis, Nefecon remained cost-effective with 4 rounds of treatment.Conclusion: Nefecon was associated with LY and QALY gains vs BSC, with an incremental cost of $3,810. Based on these values, with a willingness to pay threshold of $100,000 per QALY gained, Nefecon was found to be a cost-effective treatment for US adults with primary IgAN.Keywords: primary glomerulonephritis, glomerular disease, end-stage kidney disease, ESRD, TARPEYO®, targeted-release budesonide, Nefecon

Aim: This research evaluated standard Weibull mixture cure (WMC) network meta-analysis (NMA) with Bayesian hierarchical (BH) WMC NMA to inform long-term survival of therapies. Materials & methods: Four trials in previously treated metastatic non-small-cell lung cancer with PD-L1 >1% were used comparing docetaxel with nivolumab, pembrolizumab and atezolizumab. Cure parameters related to a certain treatment class were assumed to share a common distribution. Results: Standard WMC NMA predicted cure rates were 0.03 (0.01; 0.07), 0.18 (0.12; 0.24), 0.07 (0.02; 0.15) and 0.03 (0.00; 0.09) for docetaxel, nivolumab, pembrolizumab and atezolizumab, respectively, with corresponding incremental life years (LY) of 3.11 (1.65; 4.66), 1.06 (0.41; 2.37) and 0.42 (-0.57; 1.68). The Bayesian hierarchical-WMC-NMA rates were 0.06 (0.03; 0.10), 0.17 (0.11; 0.23), 0.12 (0.05; 0.20) and 0.12 (0.03; 0.23), respectively, with incremental LY of 2.35 (1.04; 3.93), 1.67 (0.68; 2.96) and 1.36 (-0.05; 3.64). Conclusion: BH-WMC-NMA impacts incremental mean LYs and cost–effectiveness ratios, potentially affecting reimbursement decisions.

Background and Objective Nearly all patients with multiple myeloma undergo multiple rounds of therapy. The phase III BOSTON trial of once-weekly selinexor and once-weekly bortezomib with dexamethasone (XVd) vs twice-weekly bortezomib and dexamethasone (Vd) is the basis for this cost-effectiveness analysis in previously treated multiple myeloma from a US commercial payer perspective over a lifetime horizon. Methods A partitioned survival model enabled use of direct overall survival and progression-free survival curves from BOSTON to generate four health states for XVd and Vd: progression-free survival on treatment, progression-free survival off treatment, post-progression, and mortality. Using a 1-week cycle length, benefits and costs were discounted at 3.0% annually. Additional comparators were included in an exploratory analysis that compared XVd against seven additional regimens (six triplets, one doublet). Results After considering costs, utility, progression, and survival, the base-case incremental cost-effectiveness ratio of XVd vs Vd was $475,430/quality-adjusted life-year (QALY). The 50% cost-effectiveness probability midpoint was near $470,000/QALY, based on a probabilistic sensitivity analysis. The robustness of the analysis was supported by additional scenario assessment and deterministic and probabilistic sensitivity analyses, which generally demonstrated little variance, with greatest sensitivity to variations in discount rates and utility values. In an exploratory analysis against external comparators, XVd showed a higher QALY gain with a lower cost (i.e., dominance) compared with lenalidomide/dexamethasone (Rd), pomalidomide/bortezomib/dexamethasone (PVd), and carfilzomib/pomalidomide/dexamethasone (KPd). Conclusions Addition of XVd to the previously treated multiple myeloma treatment landscape provides a novel oral treatment option, which, when compared to Vd in the base-case analysis resulted in an incremental cost-effectiveness ratio of $475,430/QALY. Exploratory analyses comparing against external comparators suggest that XVd was dominant vs Rd, PVd, and KPd. Supplementary Information The online version contains supplementary material available at 10.1007/s40273-021-01068-9., Plain Language Summary Patients with multiple myeloma often relapse and require multiple treatments to extend survival while maintaining quality of life. Many of the standard treatment regimens include twice-weekly bortezomib, which is associated with potentially severe peripheral neuropathy. The novel triplet regimen of once-weekly selinexor and once-weekly bortezomib with dexamethasone (XVd) improves cancer response and progression-free survival while decreasing the rate of peripheral neuropathy. This study used economic modeling to calculate the cost of the triplet XVd regimen per life-year gained and per quality-adjusted life-year gained. XVd had a lower cost with a higher quality-adjusted life-year benefit compared with lenalidomide/dexamethasone, pomalidomide/bortezomib/dexamethasone, and carfilzomib/pomalidomide/dexamethasone in previously treated multiple myeloma. Supplementary Information The online version contains supplementary material available at 10.1007/s40273-021-01068-9.

Background: Despite the availability of new treatments, multiple myeloma (MM) is an incurable cancer with nearly all patients relapsing and undergoing multiple lines of treatment. Performing head-to-head comparisons of all treatment options is not feasible. Thus, network meta-analyses play an important role in allowing health-care decision makers to compare the effectiveness of treatment options. Objectives: A Bayesian network meta-analysis (NMA) was developed from studies identified from a systematic literature review (SLR) to evaluate the efficacy of once weekly oral selinexor with once weekly bortezomib and low-dose dexamethasone (XVd) relative to other therapies in previously treated MM. Methods: Ovid was systematically searched for phase 2-3 randomized clinical trials (RCTs) in MM that assessed progression-free survival (PFS), overall survival (OS) and overall response rates (ORR). Two population subsets were assessed: second-line patients (2L) and third-line or greater patients (3L+). Base case results compared all regimens against twice weekly bortezomib and dexamethasone (Vd) as the anchored comparator regimen. Results: Forty-seven RCTs met inclusion. For 2L PFS, OS and ORR, XVd had, on average, out of all iterations, the 6th (out of 21), 4th (out of 15), and 5th (out of 20) best result, respectively, versus Vd. For 3L+ PFS, OS and ORR, XVd had the 12th (out of 24), 11th (out of 22), and 8th (out of 25) best result, respectively, versus Vd. There was no statistically significant difference between XVd and other top-ranking therapies for PFS, OS, and ORR in either 2L and 3L+ except for daratumumab/bortezomib/dexamethasone [DVd], which was favorable versus XVd (2L PFS only). Discussion: Results for XVd were more favorable in 2L, having a higher probability of being a top 5 regimen, compared with 3L+ therapies based on the reported clinical trial results. However, in typical clinical practice, most triplet regimens have been modified using weekly bortezomib dosing, raising questions about the actual efficacy of these regimens versus the reported results using twice weekly bortezomib dosing. Conclusions: The addition of XVd, which was designed with once weekly bortezomib dosing, to the treatment landscape for previously treated MM provides a regimen that may potentially be noninferior to the other top 5 regimens in both 2L and 3L+ settings and is associated with less peripheral neuropathy.

Background Severe aplastic anemia (SAA) is a rare autoimmune condition resulting in low blood cell counts across lineages. Immunosuppressive therapy (IST) has demonstrated low response, toxicity, and risk of transformation. In a Phase I/II trial, the addition of eltrombopag to first-line IST increased response rates relative to an IST-only historical cohort. Methods A model was developed to estimate the budget impact of treating SAA with eltrombopag-based therapy from a US private healthcare system perspective. A simulated cohort of newly diagnosed SAA patients based on the total US population received 6 months of IST ± eltrombopag and were followed for 1 year, with mutually exclusive patient cohorts entering in years 1, 2, and 3. The model assessed the budget impact of first-year treatment for each cohort without considering subsequent years. At 6 months, responders in either arm received maintenance therapy (low-dose cyclosporine), and non-responders received 6 months of second-line eltrombopag monotherapy. Costs considered included first-line, maintenance, and second-line therapy, administration, routine care, mortality, and adverse events (AEs). All cost data were reported in 2018 US dollars. Results The annual incidence of aplastic anemia was 0.000234%, with 83.8% of cases assumed to be SAA. Based on trial data, 94% of patients receiving eltrombopag and IST responded versus 66% of patients receiving IST, with a 0.3% reduction in the annual risk of mortality for the eltrombopag + IST group. Use of first-line eltrombopag in a model SAA population based on the total US population increased overall costs by $50 million over 3 years. First-line drug costs accounted for an increase of $69 million, while improved response produced $19 million in secondary therapy cost savings. Sensitivity analyses confirmed the robustness of the analysis. Conclusion High response rates combined with reduced rescue medication use and mortality in patients treated with eltrombopag and IST mediated higher medication costs.

Background Current strategies for risk stratification of patients with acute myeloid leukemia assign approximately 40% of patients to the intermediate-risk group, where uncertainty about optimal therapy still persists. Objective The objective of this study was to assess the cost effectiveness of a HMGA2 prognostic test based on HMGA2+/HMGA2− expression, which improves genetic risk stratification in acute myeloid leukemia, and compare this test with the current standard of care in Canada. Methods A cost-effectiveness model was developed from the Canadian National Healthcare Service and societal perspective using data from the Quebec Leukemia Cell Bank, published literature, and physician surveys. The model includes a lifetime horizon assessing the HMGA2 test vs. standard of care. Results The HMGA2 test outperformed the standard of care at all time horizons culminating with estimated improvements of 1.92 and 3.12 months in leukemia-free survival and overall survival, respectively. Costs associated with the HMGA2 test were consistently lower, except diagnostic costs, routine medical costs, and costs related to infections and false positives. From a societal perspective, total lifetime costs were $161,358 CAD and $151,908 CAD with the standard of care and the HMGA2 test, respectively. The incremental quality-adjusted life-year gain was 0.138, which led to dominance over the standard of care. Deterministic sensitivity analyses confirmed the results of the base-case scenario. Probabilistic sensitivity analyses revealed that for a willingness-to-pay threshold of $100,000 CAD, the probability of cost effectiveness was 87.19%. Conclusions The HMGA2 test is estimated to improve leukemia-free survival and overall survival outcomes, and yield costs savings from a healthcare system and societal perspective. Electronic supplementary material The online version of this article (10.1007/s40258-019-00503-5) contains supplementary material, which is available to authorized users.

Purpose To estimate the budget impact of selinexor, bortezomib, and dexamethasone (XVd) in patients with previously treated multiple myeloma (MM) from the perspective of a private third-party payer and Medicare in the US. Methods The introduction of XVd as an option for patients with previously treated MM compared to no introduction of XVd was considered from a private third-party US payer (with 1,000,000 members) and a Medicare perspective in one-year increments for 3 years. Total annual treatment costs were calculated as the sum of drug costs, costs of treating serious treatment emergent adverse events (grade ≥3), ongoing best supportive care costs, and mortality costs. Results The absolute budget impact (Millions, USD) of including XVd from a private third-party payer plan perspective was $0.06, $0.07, $0.08 and $0.22 for years 1, 2, 3, and overall, respectively. The relative budget impact of including XVd was 0.33%, 0.40%, 0.43%, and 0.38% for years 1, 2, 3, and overall, respectively. This translated to a per member per month (PMPM) budget impact of $0.005, $0.006, $0.007, and $0.006 (USD), for years 1, 2, 3, and overall, respectively. From a Medicare perspective, the absolute budget impact (Millions, USD) of including XVd was $29.68, $36.62, $39.42 and $105.72 for years 1, 2, 3, and overall, respectively. The relative budget impact of including XVd was 0.33%, 0.40%, 0.43%, and 0.38% percent for years 1, 2, 3, and overall, respectively. This translated to a PMPM budget impact of $0.041, $0.051, $0.054, and $0.049 (USD), for years 1, 2, 3, and overall, respectively. Sensitivity analyses showed general consistency with the base-case findings. Conclusion Understanding the potential budget impact of new therapies in MM is vital for payers to manage spending and assess treatment value. The introduction of XVd presents a manageable budget impact for a third-party US payer and Medicare.

Background: Two combination therapies recently approved and recommended for use in combination with low-dose cytarabine (LDAC) in acute myeloid leukemia patients unfit for intensive chemotherapy are glasdegib+LDAC and venetoclax+LDAC. Materials & methods: An indirect treatment comparison used median overall survival, overall survival hazard ratios, complete remission (CR), CR+CR with incomplete blood count recovery and transfusion independence to assess comparative effectiveness, and a simulated treatment comparison accounted for differences in patient characteristics between trials. Results: Differences in efficacy between glasdegib+LDAC and venetoclax+LDAC were suggestive and not statistically significant. Conclusion: With no significant differences in comparative effectiveness, considerations such as safety profiles, burden of administration and patient preference are likely to guide treatment decisions.

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be a lifesaving treatment for hematologic malignancies, but acute graft-versus-host-disease (aGVHD) is a potentially deadly adverse effect experienced by up to half of allo-HSCT recipients. Inadequate response to steroid therapy for aGVHD is associated with poor prognosis and high mortality, including among pediatric patients, who are the focus of this study. Ruxolitinib and remestemcel-L-rknd were evaluated for the treatment of steroid-refractory (SR) aGVHD in two separate single-arm trials. To effectively compare the safety and efficacy of these treatments without a head-to-head trial, a simulated treatment comparison (STC) was conducted. Methods: Regression techniques were used to adjust individual patient-level data from the remestemcel-L-rknd trial to mutually reported baseline characteristics from the ruxolitinib trial. Outcomes of interest included a 28-day overall response rate (ORR), a 28-day ORR in the grade III-IV aGVHD population, and adverse events (AEs). Results: In the full populations, the STC of risk ratios (RRs) found treatment with remestemcel-L-rknd to be associated with a numerical but not statistically significant improvement in the 28-day ORR versus ruxolitinib. In the grade III-IV aGVHD sub-group, the STC showed significantly improved 28-day ORR for remestemcel-L-rknd versus ruxolitinib (P=0.04). Remestemcel-L-rknd was also associated with improved safety outcomes (P

Gabriel Tremblay,1 Mike Dolph,1 Menaka Bhor,2 Qayyim Said,2 Brian Elliott,2 Andrew Briggs3 1Department of Health Economics, Purple Squirrel Economics, New York, NY, USA; 2Department of Health Economics and Outcomes Research, Novartis Pharmaceuticals, East Hanover, NJ, USA; 3William R. Lindsay Chair of Health Economics, University of Glasgow, Glasgow, Scotland, UK Background: Thrombopoietin-receptor agonists eltrombopag (EPAG) and romiplostim (ROMI) are treatment options for adults with chronic immune thrombocytopenia (cITP) who have had an insufficient response to corticosteroids or immunoglobulins. Methods: A cost-consequence model was developed to evaluate the costs relative to treatment success of EPAG, ROMI, and watch and rescue (W&R) in previously treated patients. The primary endpoint assessed was severe bleeding, derived from all identified phase III registered clinical trials. Health outcomes were compared via indirect treatment comparison. Costs incorporated in the model included drug and administration, routine care, rescue medications, bleeding-related adverse events, other adverse events, and mortality costs. A trial (26-week) time horizon was used, as certain endpoints used in the model were bound to within-trial results. Results: In the intent-to-treat (ITT) population, the overall estimated cost per patient for EPAG was US$66,560 compared to US$91,039 for ROMI and US$30,099 for W&R. Compared to the ITT population, the difference in cost between EPAG and ROMI was slightly greater in splenectomized patients (US$65,998 for EPAG compared to US$91,485 for ROMI) and slightly less in non-splenectomized patients (US$67,151 for EPAG compared to US$91,455 for ROMI), though the overall trend remained the same. When assessing cost per severe bleeding event avoided in the ITT population, EPAG dominated (less expensive, more effective) ROMI. Sensitivity analyses confirmed these results. Conclusion: EPAG was preferred over ROMI in the treatment of cITP, largely driven by the reduction in severe bleeding events associated with its use. Keywords: chronic immune thrombocytopenia, eltrombopag, romiplostim, cost consequence, cost analysis, USA

Gabriel Tremblay,1 Mike Dolph,1 Menaka Bhor,2 Qayyim Said,2 Anuja Roy,2 Brian Elliott,3 Andrew Briggs4 1Health Economics, Purple Squirrel Economics, NewYork,NY, USA; 2Health Economics and Outcomes Research, Novartis Pharmaceuticals, EastHanover, NJ, USA; 3Hematology, Novartis Pharmaceuticals, East Hanover, NJ, USA; 4Health Economics and Health Technology Assessment, University of Glasgow, Glasgow,Scotland, UK Background: Immune thrombocytopenia (ITP) is an auto-immune disorder characterized by enhanced platelet destruction and, subsequently, the potential for increased bleeding. Thrombopoietin receptor (TPO-R) agonists have recently emerged as promising therapies for ITP patients who are refractory to other treatments. While eltrombopag (EPAG) is the only TPO-R agonist US Food and Drug Administration approved for use in pediatric patients, romiplostin (ROMI) has been used in Phase III clinical studies. Methods: A cost-consequence model (CCM) was developed to evaluate the costs of EPAG, ROMI, and watch-and-rescue (W&R) in relation to their respective treatment outcomes in previously-treated pediatric chronic ITP (cITP) over a 26-week time horizon. The costs of drugs, administration, routine care, rescue medications, adverse events, and mortality were included. Data on platelet count response rate, bleeding events, and adverse events were derived from all relevant identified Phase III-registered clinical trials, health outcomes were compared via indirect treatment comparison. Results: The overall estimated cost of EPAG per patient was US$66,550, compared to US$101,056 for ROMI and US$32,720 for W&R. EPAG’s lower cost compared to ROMI was largely due to lower drug costs (US$62,202 vs US$84,396), administration costs (US$0 vs US$1,955), and significantly lower costs due to severe bleeding (US$354 vs US$10,191). When assessing cost per severe bleeding event avoided, EPAG was dominant over ROMI (less expensive and more effective). EPAG was again dominant over ROMI when assessing the cost per responder and per bleeding event (any grade). Sensitivity analysis was consistent with the base case findings. Conclusion: EPAG was the preferred TPO-R agonist to treat cITP when indirectly compared to ROMI, largely driven by its favorable severe bleeding outcomes and lower drug and administration costs. Keywords: chronic immune thrombocytopenia, eltrombopag, romiplostim, cost-consequence, USA

Objectives To evaluate the cost effectiveness of dolutegravir + abacavir/lamivudine (DTG + ABC/3TC) compared with raltegravir + abacavir/lamivudine (RAL + ABC/3TC) and ritonavir-boosted darunavir + abacavir/lamivudine (DRV/r + ABC/3TC) in HIV-1–infected treatment-naive patients in Russia. Methods A dynamic Markov model was developed with five response states and six CD4+-based health states. Efficacy estimated as probability of viral suppression (HIV RNA Results The viral suppression rate among patients receiving DTG + ABC/3TC was 71.7% compared with 65.2% for RAL + ABC/3TC and 59.6% for DRV/r + ABC/3TC. The mean duration of response per patient was 116.6 months for DTG + ABC/3TC, 108.6 months for RAL + ABC/3TC, and 98.9 months for DRV/r + ABC/3TC. Total discounted costs for treatment over patient lifetime were RUB 2.89, 5.32, and 4.38million for DTG + ABC/3TC, RAL + ABC/3TC, and DRV/r + ABC/3TC, respectively. Lifetime discounted QALYs were 12.73 for patients on DTG + ABC/3TC and 12.72 each for patients on RAL + ABC/3TC and DRV/r + ABC/3TC. DTG + ABC/3TC thus dominated the other two alternatives. Conclusions With lower costs, higher response rates, and comparable QALYs, DTG + ABC/3TC can be considered as a cost-effective alternative.

BackgroundThe World Health Organisation recommended dolutegravir (DTG)-based antiretroviral therapy (ART) regimens are available but not reimbursed through the public reimbursement system in China. The objective of this analysis was to evaluate the cost-effectiveness of DTG (DTG + TDF/3TC) compared to efavirenz (EFV + TDF/3TC) in treatment-naive and ritonavir-boosted lopinavir (LPV/r + TDF/3TC) in first-line ART failure HIV-1-infected patients in China.MethodsA dynamic Markov model comprising of 5 response states and 6 CD4+ count-based health states was used. Efficacy, estimated as probability of virologic suppression (HIV RNA ResultsThe viral suppression rates for DTG + TDF/3TC were higher than EFV + TDF/3TC (75.3% vs 64.0%) in treatment-naive and LPV/r + TDF/3TC (74.8% vs 58.4%) in first-line ART failure patients. This resulted in higher QALYs for DTG + TDF/3TC in treatment-naive (4.232 vs 4.227) and first-line failure settings (4.224 vs 4.221). Total discounted cost for DTG + TDF/3TC patients (RMB 219.259 in treatment-naive and RMB 238,746 in first-line failures) were lower than comparators (EFV + TDF/3TC:RMB 221,605; LPV/r + TDF/3TC:RMB 244,364), thereby DTG dominated in both settings. Probabilistic sensitivity analyses indicated the probability of DTG + TDF/3TC being cost effective was 98.2% in treatment-naive setting and 100% in first-line failure setting at a willingness to pay threshold of RMB 100,000/QALY.ConclusionsWith lower costs, higher response rates and higher QALYs, DTG + TDF/3TC can be considered as a cost-effective alternative for treatment naive and first-line failure patients in China.

Aim: Eltrombopag and romiplostim are comparable second-line therapies in chronic immune thrombocytopenia. Treatment decisions are made in different contexts. A framework was created to outline decision pathways for physicians and payers. Materials & methods: The costs of drugs, administration, routine care, bleeding, other adverse events and mortality were included in the year-long calculation of total costs from a US private payer perspective. Treatment parameters and outcome data were obtained from relevant clinical trials. Results: The total cost per year, per patient of eltrombopag was US$51,000 versus US$76,000 for romiplostim. Drug costs and costs associated with bleeding-related events were the main drivers of cost difference. Conclusion: This framework facilitates decision-making in the management of chronic immune thrombocytopenia with eltrombopag and romiplostim.

Anna Forsythe,1 Patricia S Brandt,2 Mike Dolph,1 Sachin Patel,3 Adrian Paul J Rabe,1 Gabriel Tremblay1 1Purple Squirrel Economics, New York, NY, 2Novartis Pharmaceuticals, East Hanover, NJ, USA; 3Novartis Pharmaceuticals UK Limited, Frimley, Camberley, Surrey, UK Background: Cost-utility analyses for acute myeloid leukemia (AML) require health state utility values (HSUVs) in order to calculate quality-adjusted life-years (QALYs) for each health state. Aim: This study reviewed AML-related HSUVs that could be used in economic evaluation studies. Materials and methods: EMBASE, MEDLINE, and Cochrane databases were searched from January 2000 to November 2016 for relevant studies that reported quality of life (QoL) and HSUVs in AML. Identified relevant European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 values were mapped to HSUVs. HSUVs for each health state in the AML treatment pathway were then collated. Results: Ten relevant studies were identified. Six were cost-effectiveness analyses utilizing HSUVs for calculation of QALYs, one was an effectiveness analysis (incremental QALY), and two were QoL studies reporting AML-specific utilities. An additional study reported QoL for patients undergoing stem cell transplantation (SCT). Since no study reported HSUVs for relapse, values from a study of secondary AML patients who failed prior treatment for myelodysplastic syndrome were used. Where multiple HSUVs were available, collected values were given priority over assumed values. AML treatment (induction, consolidation, or SCT) was associated with decreased HSUV, while post-treatment complete remission led to increased HSUV. Conclusion: There are some methodologically robust HSUVs that can be directly used in economic evaluations for AML. Careful interpretation is advised considering significant differences in methodologies and patient population (inclusion, size). We need to develop HSUVs with larger-sized studies, making greater use of condition-specific data. Keywords: acute myeloid leukemia, EQ-5D, health-related quality of life, utility, systematic review, economic analysis, QALY

Gabriel Tremblay1, Tracy Westley1, Joseph C Cappelleri2, Bhakti Arondekar2, Geoffrey Chan2, Timothy J Bell2, Andrew Briggs3 1Purple Squirrel Economics, New York, NY, USA; 2Pfizer Inc, New York, NY, USA; 3William R Lindsay Chair of Health Economics, Health Economics and Technology Assessment, Institute of Health & Wellbeing, University of Glasgow, Glasgow, UKCorrespondence: Gabriel TremblayPurple Squirrel Economics, 4 Lexington Avenue, Suite 15K, New York, NY 10010, USATel +1 646 478 8213Email gabrieltremblay@pshta.comBackground: Until recently, treatments for older patients with AML ineligible to receive intensive chemotherapies were limited to hypomethylating agents, low-dose cytarabine (LDAC), or clinical trials. In 2018, the FDA approved combination glasdegib (GLAS) plus LDAC based on Phase II results demonstrating improved overall survival (OS) versus LDAC alone in previously untreated AML. However, no randomized clinical trials have directly compared GLAS+LDAC with other AML treatments.Objective: Using both indirect treatment comparison (ITC) and simulated treatment comparison (STC), which adjusts for baseline differences between trials, the comparative effectiveness of GLAS+LDAC was compared with hypomethylating agent azacitidine (AZA) or decitabine (DEC).Methods: A systematic literature review identified published trials of AZA or DEC versus LDAC among older AML patients ineligible for high-intensity chemotherapy. In addition to standard and covariate-adjusted ITC, STC was performed following guidance from the NICE Decision Support Unit (DSU). Using individual patient data from the Phase II GLAS+LDAC study, population-specific OS hazard ratios (HR) for GLAS+LDAC versus AZA or DEC were compared. Furthermore, covariate-adjusted ITC (Cox multivariate models) and STC were repeated using GLAS+LDAC versus LDAC data propensity-weighted for within-trial mean cytogenetic risk. As this initial step was not specified in the DSU, results from this second method were compared to the first STC following DSU guidance only.Results: Standard ITC and STC both demonstrated significantly improved OS for GLAS+LDAC versus either AZA or DEC. Adjusting for key covariates, STC stepwise exponential models demonstrated GLAS+LDAC superiority to both AZA (HR=0.424; 95% CI: 0.228, 0.789) and DEC (HR=0.505; 95% CI: 0.269, 0.949). These significant results held using full or step-wise approaches, following DSU guidance only or the weighted STC approach.Conclusion: Using ITC and STC, GLAS+LDAC demonstrated superior OS to AZA or DEC in an adult population with previously untreated AML for whom intensive chemotherapy is not an option.Keywords: acute myeloid leukemia, simulated treatment comparison, indirect treatment comparison, glasdegib, comparative effectiveness &nbsp

Midostaurin (MIDO) combined with standard chemotherapy was approved by the European Medicines Agency in 2017 for the treatment of adults with newly diagnosed FLT3-mutated acute myeloid leukemia (AML) based on results from the RATIFY trial. A cost-effectiveness model was developed to compare MIDO and standard-of-care (SOC) to SOC alone in France. Per Haute Autorite de Sante (HAS) guidelines, a partitioned survival model with eight health states was used: diagnosis/induction, complete remission, relapse, hematopoietic stem cell transplantation (HSCT), HSCT recovery, post-HSCT recovery (stabilized after HSCT recovery), post-HSCT relapse, and mortality. A lifetime horizon was used beginning at diagnosis with a “cure model,”, which assumed natural mortality after trial cut-off. Utility values were obtained from a systematic literature review and included disutilities. Resource utilization was based on HAS clinical guidelines and a survey of French physicians and included drugs and administration, adverse events, routine medical care, HSCT, and end-of-life care costs. In RATIFY and after extrapolation, MIDO improved survival compared to SOC, translating into MIDO-treated patients gaining 1.12 life years (LYs) and 1.23 quality-adjusted life years (QALYs) versus SOC. The incremental cost-effectiveness ratio (ICER) for MIDO versus SOC was €68,781 per LY and €62,305 per QALY. Sensitivity analyses showed consistency with base case findings. MIDO represents a clinically significant advancement in the management of newly diagnosed FLT3-mutated AML. In this analysis, MIDO add-on therapy showed gains in LYs and QALYs versus SOC alone and was found to be a cost-effective option at a €100,000 per QALY threshold for end-of-life treatment.

Gabriel Tremblay,1 Unnati Majethia,2 Janis L Breeze,3 Ilias Kontoudis,4 Jeongae Park5 1Geneconomics Inc., Lévis, Quebec, Canada; 2Global Value and Access, Eisai Inc., Woodcliff Lake, NJ, 3Tufts Clinical and Translational Science Institute, Tufts University, and Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA; 4Global Value and Access, Eisai Limited, Hatfield, Hertfordshire, UK; 5Eisai Korea Inc., Gangnam-gu, Seoul, South Korea Background: Metastatic breast cancer (MBC) is associated with poor prognosis, particularly for those patients with human epidermal growth factor receptor (HER2)-negative tumor. Similar to the rest of the world, treatment options are limited in South Korea following first-line chemotherapy with anthracyclines and/or taxanes. This study examined the cost-effectiveness and cost-utility of eribulin in South Korean patients with HER2-negative MBC who have progressed after usage of at least one chemotherapeutic regimen for advanced disease (second-line therapy).Methods: A partition survival model was developed from the perspective of the South Korean health care system. The economic impact of introducing eribulin as second-line therapy for HER2-negative MBC was compared to that of capecitabine and vinorelbine. The analysis estimated incremental cost per life-year (LY), that is, cost-effectiveness, and cost per quality-adjusted life-year (QALY), that is, cost-utility, of eribulin for management of HER2-negative MBC in South Korea. The model accounted for overall survival, progression-free survival, drug costs, grade 3/4 adverse events, and health care utilization. Deterministic and probabilistic sensitivity analyses were performed to identify uncertainty in the results of the economic evaluation.Results: Second-line eribulin was associated with greater benefits in terms of LY and QALY, compared to capecitabine and vinorelbine. The incremental cost-effectiveness ratio was ₩10.5M (approximately USD 9,200) per LY, and the incremental cost-utility ratio was ₩17M (approximately USD 14,800) per QALY in the basecase analysis. The incremental cost-utility ratio ranged from ₩12M (USD 10,461) to ₩27M (USD 23,538) per QALY in the deterministic sensitivity analysis. In the probabilistic sensitivity analysis, >99% of the simulations were below ₩50M (USD 42,300), and the lower and upper 95% confidence intervals were ₩3M (USD 2,600) and ₩24M (USD 20,900) per QALY, respectively.Conclusion: There currently exist a limited number of treatment choices for women with HER2-negative MBC. Eribulin is a cost-effective option for second-line therapy in South Korea and should be added to the current indications for reimbursement. Keywords: eribulin, metastatic breast cancer, cost-utility, economic analysis

Gabriel Tremblay,1 Christopher Livings,2 Lydia Crowe,2 Venediktos Kapetanakis,2 Andrew Briggs3 1Global Health Economics and Health Technology Assessment, Eisai Inc., Woodcliff Lake, NJ, USA; 2Health Economics, Decision Resources Group, Bicester, Oxfordshire, 3Health Economics and Health Technology Assessment, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK Background: Cost-effectiveness models for the treatment of long-term conditions often require information on survival beyond the period of available data. Objectives: This paper aims to identify a robust and reliable method for the extrapolation of overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer receiving lenvatinib or placebo. Methods: Data from 392 patients (lenvatinib: 261, placebo: 131) from the SELECT trial are used over a 34-month period of follow-up. A previously published criterion-based approach is employed to ascertain credible estimates of OS beyond the trial data. Parametric models with and without a treatment covariate and piecewise models are used to extrapolate OS, and a holistic approach, where a series of statistical and visual tests are considered collectively, is taken in determining the most appropriate extrapolation model. Results: A piecewise model, in which the Kaplan–Meier survivor function is used over the trial period and an extrapolated tail is based on the Exponential distribution, is identified as the optimal model. Conclusion: In the absence of long-term survival estimates from clinical trials, survival estimates often need to be extrapolated from the available data. The use of a systematic method based on a priori determined selection criteria provides a transparent approach and reduces the risk of bias. The extrapolated OS estimates will be used to investigate the potential long-term benefits of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer patients and populate future cost-effectiveness analyses. Keywords: survival analysis, parametric extrapolation, piecewise models, decision criteria, radioiodine-refractory differentiated thyroid cancer

Aim: For dichotomous outcomes, odds ratio (OR) is one of the usual summary measures of indirect treatment comparison. A corresponding number needed to treat (NNT) estimate may facilitate understanding of the treatment effect. Methods: We show how to estimate NNT based on OR results of a matching adjusted indirect comparison. We also have derived the explicit formula of its 95% CIs by applying the delta method, and as an alternative, a simulation-based method. Results: The method was applied in a case study example in radioiodine-refractory differentiated thyroid cancer (RR-DTC) patients, comparing lenvatinib to sorafenib. For every two RR-DTC patients treated with lenvatinib instead of sorafenib, one fewer would have progressed and for every eight RR-DTC patients treated with lenvatinib instead of sorafenib, one fewer would have died. Conclusion: Using NNT to summarize the results of a matching adjusted indirect comparison can help the clinicians to better understand the results in addition to OR.

Aims Midostaurin (MIDO) has been proposed for the treatment of newly-diagnosed adult patients with FMS-like tyrosine kinase 3 mutation-positive (FLT3+) acute myeloid leukemia (AML) in combination with standard chemotherapy. The cost-effectiveness of MIDO and standard of care (SOC) followed by MIDO monotherapy was compared to SOC alone for newly-diagnosed FLT3+ AML in the UK. Methods A partitioned survival model was developed from a UK public healthcare system perspective to compare the cost-effectiveness of MIDO plus SOC and SOC over a lifetime horizon. The model included the following health states/partitions: induction, consolidation, monotherapy, complete remission (CR), relapse, stem cell transplantation (SCT), SCT recovery, and post-SCT recovery. Data on CR, overall survival, and adverse events were obtained from a Phase III clinical trial. Overall survival was extrapolated beyond the trial horizon using a ‘cure model’ approach and data from the Office for National Statistics. Utilities were identified via a systematic review. Routine care utilization was obtained from the National Institute for Health and Care Excellence single technology appraisal for azacitidine in AML (TA399). The costs of drugs and administration, adverse events, hospitalizations, physician visits, and end-of-life care were incorporated. Results Incremental life years (LYs) and quality-adjusted life years (QALYs) gained by patients on MIDO and SOC versus SOC were 1.67 and 1.47, respectively. At an incremental cost of £54,072 over a lifetime horizon, the ICER was £32,465 per LY and £36,826 per QALY. Sensitivity analyses were generally consistent with the base case findings. Conclusions With limited treatments in FLT3+ AML, MIDO represents a clinically significant advance in the management of newly-diagnosed AML. Using a threshold of £50,000 per QALY for end-of-life treatment, MIDO was shown to be a cost-effective option for newly-diagnosed FLT3+ AML. Electronic supplementary material The online version of this article (10.1186/s12962-018-0153-4) contains supplementary material, which is available to authorized users.

Beth A Fordham,1 Cicely Kerr,1 Hayley M de Freitas,1 Andrew J Lloyd,1 Karissa Johnston,2 Corey L Pelletier,3 Gabriel Tremblay,3 Anna Forsythe,3 Bryan McIver,4 Ezra EW Cohen5 1ICON Patient Reported Outcomes, Oxford, UK; 2ICON Epidemiology, Toronto, ON, Canada; 3Eisai Inc., NJ, 4Moffitt Cancer Center, FL, 5University of California San Diego Moores Cancer Center, La Jolla, CA, USA Purpose: The aim of this study was to elicit utilities for radioactive iodine-refractory differentiated thyroid cancer (RR-DTC) and evaluate the impact of treatment response and toxicities on quality of life.Patients and methods: RR-DTC health states were developed based on data from a previous qualitative study and iterative review by clinical experts. Following piloting, health states underwent valuation by 100 members of the UK public during time trade-off interviews. Mean utilities and descriptive distribution statistics were calculated, and a logistic regression analysis was conducted.Results: The demographic characteristics of the study sample were generally reflective of the UK population. Clear differentiation in valuation between health states was observed. No response/stable disease had an adjusted utility value of 0.87, with a corresponding gain of +0.04 following a treatment response and a decline of –0.35 for disease progression. Adverse events were associated with utility decrements between –0.47 (grade III diarrhea) and –0.05 (grade I/II alopecia).Conclusion: The trade-off interviews derived utility weights show clear differentiation between RR-DTC health states in response to treatment. The values reported in this study are suitable for cost-effectiveness evaluations for new treatments in RR-DTC. Keywords: differentiated thyroid cancer, radioactive iodine-refractory, health-related quality of life, health utility, vignette