Cost-Effectiveness of Once-Weekly Selinexor, Bortezomib, and Dexamethasone (SVd) Versus Twice-Weekly Bortezomib and Dexamethasone (Vd) in Relapsed or Refractory Multiple Myeloma

Introduction: The phase III BOSTON trial reported that once-weekly therapy with selinexor, bortezomib, and dexamethasone (SVd) significantly prolonged progression-free survival for patients with relapsed or refractory (R/R) multiple myeloma compared to twice-weekly treatment with bortezomib and dexamethasone alone (Vd). Although once-weekly SVd reduces the risk of disease progression as well as the cumulative exposure of patients to bortezomib and dexamethasone, selinexor is a costly drug-priced at nearly $22,000 per month-and is associated with significant toxicity. As a result, it is unclear whether SVd provides sufficient value in this clinical setting. In this study, we assess the cost-effectiveness of once-weekly SVd versus twice-weekly Vd in patients with R/R multiple myeloma. Methods: Our cost-effectiveness analysis was based on a Markov model. Simulated patients mirrored the cohort studied in the BOSTON trial; the median age of the population was 66 years, 57% were male and all had received 1-3 prior lines of therapy. Patients entered the model with R/R myeloma and received treatment with SVd or Vd; upon disease progression, all patients subsequently received identical lines of post-progression therapy. Our base-case model (Figure 1) followed SVd/Vd progression sequentially with daratumumab, carfilzomib, and dexamethasone (DKd), pomalidomide and dexamethasone (Pd), and best supportive care. We derived transition probabilities from large randomized trials using parametric survival modeling. The utility of each health state and the costs of treatment, adverse events, and terminal care were derived from literature and Medicare fee schedules. As data evaluating the quality of life with SVd vs Vd is not yet available, we assumed identical utility values for both treatment regimens. We calculated the incremental cost effectiveness ratio (ICER) from a US payer perspective, using a lifetime horizon, an annual discount rate of 3%, and a willingness-to-pay threshold of $150,000/quality-adjusted life year (QALY). One-way and probabilistic sensitivity analyses were conducted to evaluate uncertainty in our model. Results: In our base-case model, SVd was associated with an improvement of 0.37 QALYs compared to Vd alone (3.43 vs 3.06 QALYs, respectively). However, the incremental lifetime cost of SVd was $177,126 ($1,013,851 vs $836,725, respectively), leading to an ICER of $479,572/QALY. The monthly cost of selinexor would need to be decreased by approximately 51%, from $21,424 to $10,415, in order for SVd to be cost-effective compared to Vd alone in R/R patients. Our model was most sensitive to the hazard ratio of SVd relative to Vd; decreasing the HR from 0.70 to 0.53 decreased the ICER to $285,251/QALY, while increasing the HR to 0.93 increased the ICER to $1,738,546/QALY. Of note, all ICERs during one-way sensitivity analysis and >99% of ICERs during probabilistic sensitivity analysis remained above the willingness-to-pay threshold of $150,000 QALY. We also incorporated two scenario analyses; in the first, patients in the Vd arm received therapy with selinexor and dexamethasone (Sd) after progression from Pd, before receiving best supportive care. In this scenario, SVd was associated with an incremental cost of $112,445 ($1,013,851 vs $901,406), an incremental effectiveness of 0.24 QALYs (3.43 vs 3.19 QALYs), and an ICER of $464,557/QALY. In the second scenario analysis, we assumed that patients had received DKd prior to SVd/Vd; as a result, patients that progressed on SVd or Vd subsequently received Pd followed by best supportive care. Here, SVd was associated with an incremental cost of $222,864 ($418,526 vs $195,662), an incremental effectiveness of 0.49 QALYs (1.90 vs 1.41 QALYs), and an ICER of $456,080/QALY. Conclusions: Use of once-weekly SVd for patients with relapsed or refractory multiple myeloma is unlikely to be cost-effective under current pricing, compared to twice-weekly Vd. The price of selinexor would need to be decreased substantially in order to reduce the ICER of SVd to widely acceptable values. Disclosures Huntington: DTRM: Research Funding; Pharmacyclics: Honoraria; TG Therapeutics: Research Funding; Genentech: Consultancy; Celgene: Consultancy, Research Funding; Bayer: Consultancy, Honoraria; Astrazeneca: Honoraria; AbbVie: Consultancy; Novartis: Consultancy. Giri:Carevive Systems: Research Funding; Carevive Systems: Honoraria; Pack Health: Research Funding.

Download Full-text

Cost-effectiveness of dual-mobility components in patients with displaced femoral neck fractures

The Bone & Joint Journal ◽

10.1302/0301-620x.103b12.bjj-2021-0495.r2 ◽

2021 ◽

Vol 103-B (12) ◽

pp. 1783-1790

Author(s):

Spencer Montgomery ◽

Jonathan Bourget-Murray ◽

Daniel Z. You ◽

Leo Nherera ◽

Amir Khoshbin ◽

...

Keyword(s):

Sensitivity Analysis ◽

Cost Effectiveness ◽

Femoral Neck ◽

Incremental Cost ◽

Probabilistic Sensitivity Analysis ◽

Cost Effective ◽

Physiological Age ◽

Base Case ◽

Dual Mobility ◽

Displaced Femoral Neck Fractures

Aims Total hip arthroplasty (THA) with dual-mobility components (DM-THA) has been shown to decrease the risk of dislocation in the setting of a displaced neck of femur fracture compared to conventional single-bearing THA (SB-THA). This study assesses if the clinical benefit of a reduced dislocation rate can justify the incremental cost increase of DM-THA compared to SB-THA. Methods Costs and benefits were established for patients aged 75 to 79 years over a five-year time period in the base case from the Canadian Health Payer’s perspective. One-way and probabilistic sensitivity analysis assessed the robustness of the base case model conclusions. Results DM-THA was found to be cost-effective, with an estimated incremental cost-effectiveness ratio (ICER) of CAD $46,556 (£27,074) per quality-adjusted life year (QALY). Sensitivity analysis revealed DM-THA was not cost-effective across all age groups in the first two years. DM-THA becomes cost-effective for those aged under 80 years at time periods from five to 15 years, but was not cost-effective for those aged 80 years and over at any timepoint. To be cost-effective at ten years in the base case, DM-THA must reduce the risk of dislocation compared to SB-THA by at least 62%. Probabilistic sensitivity analysis showed DM-THA was 58% likely to be cost-effective in the base case. Conclusion Treating patients with a displaced femoral neck fracture using DM-THA components may be cost-effective compared to SB-THA in patients aged under 80 years. However, future research will help determine if the modelled rates of adverse events hold true. Surgeons should continue to use clinical judgement and consider individual patients’ physiological age and risk factors for dislocation. Cite this article: Bone Joint J 2021;103-B(12):1783–1790.

Download Full-text

What Is the Most Cost-Effective Strategy for Treating Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia (CML) after Imatinib Loses Patent Exclusivity?

Blood ◽

10.1182/blood.v124.21.738.738 ◽

2014 ◽

Vol 124 (21) ◽

pp. 738-738 ◽

Cited By ~ 6

Author(s):

Richard A. Larson ◽

Rena Conti ◽

William V. Padula ◽

Jane F. Apperley ◽

Michele Baccarani ◽

...

Keyword(s):

Sensitivity Analysis ◽

Monte Carlo ◽

Cost Effectiveness ◽

Incremental Cost ◽

Probabilistic Sensitivity Analysis ◽

Research Funding ◽

Chronic Phase ◽

Cost Effective ◽

Generic Competition ◽

The Us

Abstract We analyzed and compared the cost-effectiveness of 2 strategies for treating CML patients -- using imatinib first in all (altering therapy as needed in a stepwise approach) or by physician’s choice, starting either imatinib or one of the approved second-generation tyrosine kinase inhibitors (TKIs) dasatinib or nilotinib. Currently, each TKI is patent-protected and commands about one-third of front-line CML treatment. Life-long treatment is recommended. Imatinib is losing patent exclusivity and facing generic competition presently in the US (in early 2016) and in EU member countries; its price is expected to drop 70-90% within two years following generic entry. We constructed a Markov model simulating outcomes over 5 years when imatinib 400 mg is used first for all incident chronic phase CML patients, or alternatively by physician choice using any of the 3 TKIs first. The model assumes the commercial payer or health system perspective. In the stepwise approach, if imatinib fails, patients are switched to dasatinib or nilotinib in equal proportions. Patients are assumed to switch drugs if they were intolerant or failed standard efficacy endpoints: complete cytogenetic response (CCyR) or major molecular response (MMR) as defined in the ELN recommendations (Baccarani et al. Blood 2013). The model adjusts the price of imatinib over time as generic competition begins within each market: 100% of the branded price for first 6-months; 60-80% for the second 6-months; 10-30% thereafter. For each drug, tolerance, efficacy and probabilities of treatment choice, failure, and switching were drawn from published clinical trials (principally IRIS, ENESTnd, DASISON, and second-line phase II and transplant studies) and used Sokal or Euro risk group data where available. Quality-adjusted life years (QALYs) were based on CML-specific health utilities (Szabo et al, 2010). For the US model, direct medical costs per patient were drawn from Marketscan (2001-2007) and included US annual drug prices: imatinib ($76,800), dasatinib and nilotinib ($102,000). Additional costs included patient monitoring, hospitalization, and allogeneic transplantation, if required. Costs and QALYs were discounted at 3% ($US; 2013 values). Univariate and multivariate sensitivity analyses tested parameters with the greatest impact on results. We also considered cost savings in years 4 and 5 from TKI discontinuation in a fraction of patients achieving MR4.5 in years 2 and 3. Results were interpreted from a willingness-to-pay (WTP) of $100,000/QALY. Compared to physician choice starting any TKI regimen ($172,076; 3.36 QALYs) over the first 5 years, stepwise therapy costs less and offers clinically-equivalent utility ($147,091; 3.25 QALYs) when generic imatinib is available. Thus, stepwise therapy is estimated to have an incremental cost-effectiveness ratio (ICER) of $227,136/QALY. The ICER was favorable for stepwise therapy for each Sokal risk group. The results are robust to changes based on univariate analyses of the most sensitive parameters (imatinib-associated probability of CCyR/MMR, price drops, and the health utility of suboptimal response or treatment failure). A Bayesian multivariate probabilistic sensitivity analysis using 10,000 Monte Carlo simulations suggested that stepwise therapy is cost-effective in 73.3% of simulations (point estimates above the diagonal WTP line in Figure 1). Limitations include efficacy data drawn from prospective trials; thus, results may not apply to patients with co-morbidities, older age, or lack of access to appropriate specialty care. We conclude that when imatinib loses patent protection in 2016 in the US and its price declines, it will be the cost-effective initial treatment strategy for chronic phase CML compared to dasatinib and nilotinib. Our model and results demonstrate that system-level cost-effectiveness can be estimated based on country-specific (1) CML incidence and prevalence, (2) CML treatment patterns and associated costs across all medical inputs, including drugs, (3) expected date for loss of patent exclusivity, and (4) pricing policies for generic drugs and formulary placement decisions. Comparative cost-effectiveness data for the US, UK, and other selected EU countries will be presented. Figure 1 Scatterplot of incremental cost-effectiveness ratios for physician’s choice vs stepwise therapy in Monte Carlo probabilistic sensitivity analysis Figure 1. Scatterplot of incremental cost-effectiveness ratios for physician’s choice vs stepwise therapy in Monte Carlo probabilistic sensitivity analysis Disclosures Larson: Ariad: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy. Apperley:Ariad: Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Research Funding; Pfizer: Research Funding. Baccarani:Ariad: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Eigendorff:Bristol Myers Squibb: Research Funding; Novartis: Research Funding. Martinelli:Ariad: Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Research Funding; Pfizer: Research Funding. Mueller:Ariad: Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Research Funding; Pfizer: Research Funding. Niederwieser:Novartis: Research Funding. Saussele:Bristol Myers Squibb: Research Funding; Novartis: Research Funding; Pfizer: Research Funding. Silver:Novartis: Research Funding. Hehlmann:Novartis: Research Funding; Bristol Myers Squibb: Research Funding.

Download Full-text

Cost-Effectiveness of Remdesivir Plus Supportive Care for Patients with COVID-19 in Iran

10.21203/rs.3.rs-757595/v1 ◽

2021 ◽

Author(s):

Mohammad Tasavon Gholamhoseini ◽

Reza Goudarzi ◽

Vahid Yazdi-Feyzabadi ◽

Mohammad Hossein Mehrolhassani ◽

Meysam Yousefi

Keyword(s):

Sensitivity Analysis ◽

Cost Effectiveness ◽

Supportive Care ◽

Purchasing Power Parity ◽

Transition Probabilities ◽

Cost Effective ◽

Sensitivity Analyses ◽

Base Case ◽

Power Parity ◽

System Perspective

Abstract Background: Remdesivir is a medication used for moderate to severe Coronavirus disease 2019 (COVID-19) patients with favorable effects. However, it is an expensive medication. Therefore, the present study aimed to assess the cost-effectiveness of remdesivir plus supportive care (SC) for COVID-19 patients in Iran.Methods: Markov model was used to compare costs and quality-adjusted life-days (QALDs) of remdesivir+SC and SC for patients with COVID-19. The model simulated a cycle length of one day and a 30-day time horizonin TreeAge 2020 software. The costs from the healthcare system perspective were obtained from Afzalipour hospital as a referral hospital for the hospitalization of COVID-19 patients in Kerman, Iran. All the costs were converted to 2018 purchasing power parity (PPP) US dollars. Utility values were derived from published sources. The results were presented as an incremental cost-effectiveness ratio (ICER) at a willingness-to-pay (WTP) threshold of three times the Gross Domestic Product per capita of Iran. Both deterministic and probabilistic sensitivity analyses were performed.Results: The base-case results showed that the treatment of COVID-19 patients with remdesivir+SC had a cost of 8795 PPP US dollars for 21.13 QALD gained. The SC alone cost 8637 PPP US dollars with a gain of 20.20 QALD. Our findings demonstrated that at a WTP threshold of 159 PPP US dollars per QALD, remdesivir+SC was not cost-effective with an ICER of 168 PPP US dollars per QALD. Deterministic sensitivity analysis indicated ICER to be sensitive to the transition probabilities and costs. Probabilistic sensitivity analysis revealed that remdesivir+SC was cost-effective at a WTP of 159 PPP US dollars per QALD in 47% of iterations.Conclusions: Our findings demonstrated thatremdesivir+SC is not cost-effective, compared to SC alone. Considering the lack of studies on the effectiveness of remdesivir, the findings should be interpreted with caution. Further evaluations are recommended to determine the efficacy and effectiveness of remdesivir in COVID-19 patients.

Download Full-text

Cost-effectiveness of atezolizumab monotherapy versus pembrolizumab monotherapy for first-line (1L) treatment of metastatic non-small cell lung cancer (mNSCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18847 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18847-e18847

Author(s):

Chia-Wei Lin ◽

Katherine Rosettie ◽

Pinar Bilir ◽

Hazal Celik ◽

Seye Abogunrin ◽

...

Keyword(s):

Sensitivity Analysis ◽

Cost Effectiveness ◽

Incremental Cost ◽

Cost Effective ◽

Sensitivity Analyses ◽

Base Case ◽

First Line ◽

Deterministic Sensitivity Analysis ◽

Anaplastic Lymphoma ◽

Life Years

e18847 Background: Atezolizumab monotherapy is indicated as 1L treatment for mNSCLC patients with high programmed death ligand-1 (PD-L1) expression (≥ 50%) and without epidermal growth factor receptor or anaplastic lymphoma kinase mutations. This analysis assessed the cost-effectiveness of 1L atezolizumab monotherapy vs. pembrolizumab monotherapy for mNSCLC patients with high PD-L1 expression from a US third-party payer perspective. Methods: A Markov model with progression-free, progressive disease (PD), and death states was developed in Microsoft Excel to compare clinical and cost outcomes of atezolizumab monotherapy vs. pembrolizumab monotherapy. Efficacy, safety, and utility data were derived from systematic reviews and indirect comparisons of the IMpower110, Keynote-024, and Keynote-042 trials. Product prescribing information and clinical trials informed dosing and administration. Wholesale acquisition cost (WAC, accessed in January 2021) for drugs were used while other cost inputs were derived from publicly available fee schedules and peer-reviewed literature. The key outcome of interest was the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained. Deterministic sensitivity analysis with 20% variation and probabilistic sensitivity analyses (PSA) were performed to address uncertainties around input parameters. Results: In the base case, 1L atezolizumab monotherapy was projected to increase life expectancy for patients by 0.60 life-years (4.35 vs. 3.75) and 0.47 QALYs (3.46 vs. 2.98) over pembrolizumab monotherapy at an incremental cost of $27,947 (mean total cost: $396,811 vs. $368,864), resulting in an ICER of $58,841/QALY gained. Results of the deterministic sensitivity analysis were most sensitive to changes in discount rates for costs and care costs in the PD state. The PSA showed that the probability of atezolizumab being cost-effective at willingness-to-pay thresholds of $100,000 and $150,000 was 41% and 49%, respectively. Conclusions: First-line atezolizumab monotherapy had 0.6 life-years and 0.47 QALYs gained compared with pembrolizumab monotherapy and was estimated to be cost-effective (ICER $58,841/QALY). As the ICER falls below the US cost-effectiveness thresholds ( < $100,000-$150,000/QALY), clinicians and payers should consider atezolizumab monotherapy as a cost-effective 1L option for mNSCLC patients with high PD-L1 expression.

Download Full-text

Cost-effectiveness of mobile health-based integrated care for atrial fibrillation: Model development and data analysis (Preprint)

10.2196/preprints.29408 ◽

2021 ◽

Author(s):

Xueyan Luo ◽

Wei Xu ◽

Quan Yuan ◽

Han Lai ◽

Chunji Huang

Keyword(s):

Atrial Fibrillation ◽

Sensitivity Analysis ◽

Cost Effectiveness ◽

Integrated Care ◽

Mobile Health ◽

Cost Effective ◽

Sensitivity Analyses ◽

Base Case ◽

Life Years ◽

Mhealth Technology

BACKGROUND Mobile health (mhealth) technology is increasingly used in disease management. Using mhealth tools to integrate and streamline care was found to improve atrial fibrillation (AF) patients’ clinical outcomes. OBJECTIVE This study aimed to investigate the potential clinical and health economic outcomes of mhealth-based integrated care for AF from the perspective of a public healthcare provider in China. METHODS A Markov model was designed to compare outcomes of mhealth-based care and usual care in a hypothetical cohort of AF patients in China. The time horizon was 30 years with monthly cycles. Model outcomes measured were direct medical cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were conducted to examine the robustness of base-case results. RESULTS In the base-case analysis, mhealth-based care gained higher QALYs of 0.0818 with an incurred cost of USD1,778. Using USD33,438 per QALY (three times gross domestic product) as the willingness-to-pay threshold, mhealth-based care was cost-effective, with an ICER of USD21,739 per QALY. The one-way sensitivity analysis found compliance to mhealth-based care had the greatest impact on the ICER. In probabilistic sensitivity analysis, mhealth-based care was accepted as cost-effective in 80.91% of 10,000 iterations. CONCLUSIONS This study suggested that the use of mhealth technology in streamlining and integrating care for AF patients was cost-effective in China.

Download Full-text

Sustained acoustic medicine as a non-surgical and non-opioid knee osteoarthritis treatment option: a health economic cost-effectiveness analysis for symptom management

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-020-01987-x ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Thomas M. Best ◽

Stephanie Petterson ◽

Kevin Plancher

Keyword(s):

Sensitivity Analysis ◽

Cost Effectiveness ◽

Incremental Cost ◽

Symptom Management ◽

Treatment Options ◽

Base Case ◽

Treatment Pathways ◽

Knee Oa ◽

Cost Effective Treatment ◽

The Cost

Abstract Background Patients diagnosed with osteoarthritis (OA) and presenting with symptoms are seeking conservative treatment options to reduce pain, improve function, and avoid surgery. Sustained acoustic medicine (SAM), a multi-hour treatment has demonstrated improved clinical outcomes for patients with knee OA. The purpose of this analysis was to compare the costs and effectiveness of multi-hour SAM treatment versus the standard of care (SOC) over a 6-month timeframe for OA symptom management. Methods A decision tree analysis was used to compare the costs and effectiveness of SAM treatment versus SOC in patients with OA. Probabilities of success for OA treatment and effectiveness were derived from the literature using systematic reviews and meta-analyses. Costs were derived from Medicare payment rates and manufacturer prices. Functional effectiveness was measured as the effect size of a therapy and treatment pathways compared to a SOC treatment pathway. A sensitivity analysis was performed to determine which cost variables had the greatest effect on deciding which option was the least costly. An incremental cost-effectiveness plot comparing SAM treatment vs. SOC was also generated using 1000 iterations of the model. Lastly, the incremental cost-effectiveness ratio (ICER) was calculated as the (cost of SAM minus cost of SOC) divided by (functional effectiveness of SAM minus functional effectiveness of SOC). Results Base case demonstrated that over 6 months, the cost and functional effectiveness of SAM was $8641 and 0.52 versus SOC at: $6281 and 0.39, respectively. Sensitivity analysis demonstrated that in order for SAM to be the less expensive option, the cost per 15-min session of PT would need to be greater than $88, or SAM would need to be priced at less than or equal to $2276. Incremental cost-effectiveness demonstrated that most of the time (84%) SAM treatment resulted in improved functional effectiveness but at a higher cost than SOC. Conclusion In patients with osteoarthritis, SAM treatment demonstrated improved pain and functional gains compared to SOC but at an increased cost. Based on the SAM treatment ICER score being ≤ $50,000, it appears that SAM is a cost-effective treatment for knee OA.

Download Full-text

Evaluating the cost-effectiveness of hydrogel spacer in radiotherapy (RT) of prostate cancer (PC).

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.43 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 43-43

Author(s):

Rahul Ramesh Khairnar ◽

Joseph Levy ◽

Mark Mishra

Keyword(s):

Cost Effectiveness ◽

Incremental Cost ◽

Intensity Modulated Radiation Therapy ◽

Cost Effective ◽

Credible Interval ◽

Phase Iii ◽

Incremental Effectiveness ◽

Life Years ◽

The Cost ◽

Fee Schedule

43 Background: A hydrogel rectal spacer (HRS) is an FDA-approved medical device used to increase the separation between the rectum and the prostate. A recent phase III trial demonstrated a small reduction in the incidence of RT toxicities associated with use of HRS. We conducted a cost-effectiveness analysis of HRS use in PC patients undergoing intensity modulated radiation therapy (IMRT). Methods: A multi-state Markov model was constructed to examine the cost-effectiveness of HRS in men with localized PC receiving IMRT in the US (arms: IMRT alone vs. IMRT + HRS). Subgroups included delivery site of IMRT (hospital vs. ambulatory) and baseline sexual function (SF) (general population vs. those with good SF). Based on previous studies, recurrence and survival were assumed equal for both arms. Data on SF, gastrointestinal and genitourinary toxicities incidence, as well as potential risks associated with HRS implantation were obtained from a recently published clinical trial. Health utilities and costs were derived from the literature and 2018 Physician Fee Schedule. Quality-adjusted life years (QALYs) and costs were modeled for a 5-year period from receipt of RT. Probabilistic sensitivity analysis (PSA) and value-based threshold analysis were conducted. Costs and utilities were discounted at 3% annually. Results: The per-person 5-year incremental cost for HRS administered in a hospital was $4,008 and the incremental effectiveness was 0.0273 QALYs. The incremental cost-effectiveness ratio (ICER) was $146,746 (95% credible interval from PSA $125,638 – $178,049) for PC patients undergoing HRS insertion in a hospital vs. $73,359 ($66,732 – $86,767) for patients undergoing HRS insertion in an ambulatory facility. For men with good SF, the ICER was $55,153 ($46,002 – $76,090) and $26,542 ($17,399 – $46,044) in hospital vs. ambulatory facility. Conclusions: This study is the first to evaluate the cost-effectiveness of HRS based on long-term toxicity data. Based on the current Medicare Physician Fee Schedule, HRS is cost-effective in men with good SF at a willingness to pay threshold of $100,000 and it is marginally cost-effective for the entire population depending on the facility where the HRS is inserted.

Download Full-text

Cost-Effectiveness of Second-Line Therapies in Adult Patients with Chronic Immune Thrombocytopenia

Blood ◽

10.1182/blood-2021-144819 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 751-751

Author(s):

George Goshua ◽

Pranay Sinha ◽

Lauren Pischel ◽

Alfred Ian Lee ◽

Adam Cuker

Keyword(s):

Sensitivity Analysis ◽

Cost Effectiveness ◽

Research Funding ◽

Cost Effective ◽

Response Rates ◽

Second Line ◽

Treatment Pathways ◽

Treatment Pathway ◽

Overall Response ◽

The Cost

Abstract Introduction: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by accelerated platelet clearance and impaired platelet production. Up to 75% of cases in adults assume a chronic course. Standard second-line treatment options include rituximab, thrombopoietin receptor agonists (TPO-RAs), and splenectomy. The 2019 American Society of Hematology (ASH) guidelines provide three dichomotous evaluations of these treatments with conditional recommendations for 1) splenectomy or TPO-RA, 2) rituximab over splenectomy, and 3) TPO-RA over rituximab. The guideline panel noted that there were no studies available to evaluate the cost-effectiveness of these therapies. We sought to address this knowledge gap by conducting the first cost-effectiveness analysis of second-line therapies for chronic ITP. Methods: We built a Markov model comparing the cost-effectiveness of all six treatment pathways utilizing rituximab, TPO-RA (romiplostim or eltrombopag), and splenectomy. We assumed a median age of 50 at diagnosis and a 20-year time-horizon. Costs were assessed from the health system perspective. Effectiveness was calculated in quality-adjusted life-years (QALYs). The costs of splenectomy treatment included the cost of surgery, postoperative care, accessory spleen imaging and repeat splenectomy, treatment for post-splenectomy sepsis and thromboembolism. The annual risks of post-splenectomy sepsis and thromboembolism were assumed to be the highest reported, every post-splenectomy infectious complication was assumed to be severe septic shock, and patients with thromboembolism accrued the costs of indefinite anticoagulation. To minimize bias against TPO-RAs, TPO-RA therapy was assumed to have no adverse events, a constant high overall response without any loss of effectiveness, and the highest reported rate of successful TPO-RA therapy discontinuation after two years, which we assumed to be permanent. Rituximab treatment was assumed to have no adverse events and overall response rates as previously reported. Cost-effectiveness of each treatment pathway was calculated as the incremental cost-effectiveness ratio (ICER), calculated as ratio of costs to QALYs. The ICER was compared against a 2019 US willingness-to-pay (WTP) threshold of $195,300. We then performed one-way deterministic sensitivity analyses varying all parameters including the costs of splenectomy, TPO-RA, rituximab, splenectomy complications, splenectomy complete response rates, TPO-RA and rituximab overall response rates, utilities of the well and diseases states, annual post-splenectomy septic shock mortality and perioperative splenectomy mortality. We concluded with a probabilistic sensitivity analysis running 10,000 Monte Carlo simulations. Results: The most cost-effective treatment pathway was #5 (splenectomy->rituximab->TPO-RA; Figure). The next most cost-effective pathway was #4 (rituximab followed by splenectomy and then TPO-RA therapy), with an ICER of $369,289. All four remaining treatment pathways (#1-3, 6) utilizing TPO-RA therapy early (first or second) had an ICER above $1 million, far above the US WTP of $195,300, and/or were dominated. Of these, pathways #1 and #3 were externally dominated and #2 was absolutely dominated. No parameter change in one-way deterministic sensitivity analysis in any of the 4 pathways featuring TPO-RA early brought down the ICER to under $1 million. In the probabilistic sensitivity analysis, pathway #5 was favored in 100% of 10,000 Monte Carlo simulations. The cost of TPO-RA would have to be decreased to under $20,000 annually (e.g., >80% reduction in the cost of eltrombopag or romiplostim) before it could become cost-effective in any TPO-early treatment pathway. Conclusion: Four treatment pathways (#1-#4) are consistent and two pathways (#5-#6) are at variance with the ASH guidelines. Although it does not align with the ASH guidelines, pathway #5 (splenectomy->rituximab->TPO-RA) was most cost-effective. Over a 20-year time-horizon, all pathways featuring early use of a TPO-RA exceeded an ICER >$1 million or were dominated. Because our model was designed to maximize the cost-effectiveness of TPO-RA, it is likely that the actual ICER of pathways featuring early use of TPO-RA are higher than what we report here. Preferred second-line treatment strategies in adults with chronic ITP may be worth considering in light of our findings. Figure 1 Figure 1. Disclosures Cuker: Synergy: Consultancy; Novo Nordisk: Research Funding; Alexion: Research Funding; UpToDate: Patents & Royalties; Novartis: Research Funding; Bayer: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Sanofi: Research Funding; Spark Therapeutics: Research Funding.

Download Full-text

Cost Effectiveness Analysis of Venetoclax Plus Azacitidine Versus Azacitidine in Newly Diagnosed Adult Patients with Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy from a United States Payer Perspective

Blood ◽

10.1182/blood-2021-148338 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 112-112

Author(s):

Keith W. Pratz ◽

Xinglei Chai ◽

Jipan Xie ◽

Lei Yin ◽

Xiaoyu Nie ◽

...

Keyword(s):

Cost Effectiveness ◽

Research Funding ◽

Time Horizon ◽

Cost Effective ◽

Sensitivity Analyses ◽

Base Case ◽

Intensive Chemotherapy ◽

Publicly Traded ◽

Analysis Group ◽

Payer Perspective

Abstract Background: The phase 3 VIALE-A trial (NCT02993523) demonstrated that venetoclax plus azacitidine (VEN+AZA) improved overall survival (OS) and led to higher remission rates compared with AZA monotherapy, in patients with newly diagnosed (ND) acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. Based on the results from VIALE-A, VEN+AZA received full United States (US) Food and Drug Administration approval in October 2020 for patients with ND AML aged ≥75 years, or who were ineligible for intensive induction chemotherapy due to comorbidities. This study aims to assess the long-term cost-effectiveness value of the VEN+AZA regimen from the VIALE-A trial from a US third-party payer perspective. Methods: A partitioned survival model with a 28-day cycle was developed to estimate costs and outcomes of treatment with VEN+AZA vs. AZA among patients with ND AML, who are ineligible for intensive chemotherapy, over a lifetime time horizon. The model included three health states: event-free survival (EFS), progressive/relapsed disease, and death. Within the EFS state, patients were further partitioned into time spent in complete remission (CR) or CR with incomplete marrow recovery (CRi), and time spent in non-CR/CRi. Efficacy inputs (OS, EFS, and CR/CRi rate) for both treatment arms were estimated using VIALE-A data. Best-fit parametric models per Akaike information criterion (AIC) were used to extrapolate OS until it reached EFS, and extrapolate EFS for each treatment until Year 5. Patients who remained in EFS after Year 5 were considered cured, and were assumed to have the same mortality as the US general population. Mean time on treatment (ToT) for both regimens was based on the time observed in VIALE-A. The costs for drug acquisition, drug administration for initial and subsequent treatments, subsequent stem cell transplant procedures, adverse events (AEs), and healthcare resource utilization (HRU) associated with each health state were obtained from the literature or publicly available data. All costs were inflated to 2021 US dollars. Utilities for each health state were estimated using EuroQol-5 dimension-5 level (EQ-5D-5L) data from VIALE-A, based on the US crosswalk value set. Information on disutilities due to Grade 3/4 AEs were obtained from the literature. Incremental cost-effectiveness ratios (ICERs) per life year (LY) and quality-adjusted life year (QALY) gained were estimated. Deterministic sensitivity analyses (DSA), scenario analyses and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of the results. Results: Over a lifetime time horizon, compared with AZA, VEN+AZA was associated with an increase of 1.89 LYs (1.10 vs. 2.99, respectively) and 1.45 QALYs (0.84 vs. 2.30, respectively). Patients in the VEN+AZA arm incurred higher total costs ($250,486 vs. $110,034 for patients in the AZA arm). The ICER for VEN+AZA vs. AZA was estimated to be $74,141 per LY gained, and $96,579 per QALY gained. Results from the DSA and scenario analyses supported the base-case findings, with ICERs ranging from $60,922 to $138,554 per QALY gained. The results were most sensitive to alternative approaches for ToT estimation, subsequent treatment HRU costs, cure time point, and the extrapolation approach for EFS. Results from PSA showed that compared with AZA, VEN+AZA was cost-effective in 99.9% of cases at a willingness-to-pay (WTP) threshold of $150,000. Conclusions: Compared with AZA monotherapy, VEN+AZA results in a favorable ICER of $96,579 per QALY gained over a lifetime time horizon. The base-case results suggest that, compared with AZA, VEN+AZA is a cost-effective strategy based on a WTP threshold of $150,000 per QALY gained. Sensitivity analyses support the base-case results. Thus, VEN+AZA offers a cost-effective strategy in the treatment of patients with ND AML who are ineligible for intensive chemotherapy from a US third-party payer perspective. Disclosures Pratz: Agios: Consultancy; Abbvie: Consultancy, Honoraria, Research Funding; University of Pennsylvania: Current Employment; BMS: Consultancy, Honoraria; Novartis: Consultancy; Astellas: Consultancy, Honoraria, Research Funding; Cellgene: Consultancy, Honoraria; Millenium: Research Funding. Chai: Analysis Group, Inc.: Consultancy, Current Employment; Genentech, Inc.: Consultancy. Yin: Analysis Group, Inc.: Consultancy, Current Employment; Genentech, Inc.: Consultancy. Nie: Analysis Group, Inc.: Consultancy, Current Employment; Genentech, Inc.: Consultancy. Montez: Genentech, Inc: Current Employment, Other: May hold equity. Iantuono: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Downs: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Ma: Genentech, Inc.: Current Employment, Other: May hold equity.

Download Full-text

Cost-Effectiveness Analysis of Direct Oral Anticoagulants Versus Vitamin K Antagonists for Venous Thromboembolism in China

Frontiers in Pharmacology ◽

10.3389/fphar.2021.716224 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ke-Xin Sun ◽

Bin Cui ◽

Shan-Shan Cao ◽

Qi-Xiang Huang ◽

Ru-Yi Xia ◽

...

Keyword(s):

Decision Making ◽

Sensitivity Analysis ◽

Cost Effectiveness ◽

Markov Model ◽

Clinical Decision Making ◽

Cost Effective ◽

Clinical Decision ◽

Base Case ◽

Effectiveness Analysis ◽

The Cost

Background: The drug therapy of venous thromboembolism (VTE) presents a significant economic burden to the health-care system in low- and middle-income countries. To understand which anticoagulation therapy is most cost-effective for clinical decision-making , the cost-effectiveness of apixaban (API) versus rivaroxaban (RIV), dabigatran (DAB), and low molecular weight heparin (LMWH), followed by vitamin K antagonist (VKA), in the treatment of VTE in China was assessed.Methods: To access the quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs), a long-term cost-effectiveness analysis was constructed using a Markov model with 5 health states. The Markov model was developed using patient data collected from the Xijing Hospital from January 1, 2016 to January 1, 2021. The time horizon was set at 30 years, and a 6-month cycle length was used in the model. Costs and ICERs were reported in 2020 U.S. dollars. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were used to test the uncertainties. A Chinese health-care system perspective was used.Results: In the base case, the data of 231 VTE patients were calculated in the base case analysis retrospectively. The RIV group resulted in a mean VTE attributable to 95% effective treatment. API, DAB, and VKA have a negative ICER (−187017.543, −284,674.922, and −9,283.339, respectively) and were absolutely dominated. The Markov model results confirmed this observation. The ICER of the API and RIV was negative (−216176.977), which belongs to the absolute inferiority scheme, and the ICER value of the DAB and VKA versus RIV was positive (110,577.872 and 836,846.343). Since the ICER of DAB and VKA exceeds the threshold, RIV therapy was likely to be the best choice for the treatment of VTE within the acceptable threshold range. The results of the sensitivity analysis revealed that the model output varied mostly with the cost in the DAB on-treatment therapy. In a probabilistic sensitivity analysis of 1,000 patients for 30 years, RIV has 100% probability of being cost-effective compared with other regimens when the WTP is $10973 per QALY. When WTP exceeded $148,000, DAB was more cost-effective than RIV.Conclusions: Compared with LMWH + VKA and API, the results proved that RIV may be the most cost-effective treatment for VTE patients in China. Our findings could be helpful for physicians in clinical decision-making to select the appropriate treatment option for VTE.

Download Full-text