Higher Quality-adjusted Life Years Research Articles

Abstract 891: Cost-effectiveness of CDK4/6 inhibitors in the first-line treatment of HR+/HER2- metastatic breast cancer in postmenopausal women in the United States

Abstract BACKGROUND: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are changing the management of the patients with hormone receptor-positive/HER2-negative metastatic breast cancer (HR+/HER2- MBC). The addition of CDK4/6 inhibitors to endocrine therapy is more efficacious than endocrine therapy alone for HR+/HER2- MBC patients, but it is also more expensive. This cost-effectiveness analysis study was designed to evaluate the economic value of adding CDK4/6 inhibitors to letrozole, an aromatase inhibitor. OBJECTIVE: We aimed to evaluate the cost-effectiveness of abemaciclib plus letrozole or ribociclib plus letrozole or palbociclib plus letrozole versus letrozole monotherapy in the first-line treatment of HR+/HER2− MBC in the United States. METHODS: We constructed a Markov-based decision-analytic model using TreeAge Software LLC, Cambridge, MA. Our model simulates lifetime costs and health outcomes over a 40-year lifetime horizon from a third-party payer perspective. The model incorporated the clinical course of a progression-free or stable disease, progressed disease, death, Neutropenia as a major adverse effect, and cancer-specific mortality. All clinical and utilities data were derived from the literature and clinical trials, including PALOMA-2, MONALEESA-2, and MONARCH-3. For consistent comparison, only letrozole specific data was derived from MONARCH-3. Outcomes were measured by costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs). Deterministic and probabilistic sensitivity analyses were performed to evaluate the robustness of the results against uncertainties in the model parameters. RESULTS: In our base case, the total health care costs for Palbociclib, Ribociclib, and Abemaciclib plus letrozole were $680,596, $ 676,292, and $ 635,606, respectively while the cost of letrozole monotherapy was $162,378. Palbociclib plus letrozole and Ribociclib plus letrozole were dominated strategies by Abemaciclib plus letrozole. Higher QALYs was associated with Abemaciclib plus letrozole (6.91 QALYs vs 5.83 QALYs for letrozole). Compared to letrozole monotherapy, Abemaciclib plus letrozole resulted in ICER of $ 436,855 per QALY. At willingness-to-pay thresholds of $100,000 per QALY gained, none of the strategies was found to be cost-effective. Letrozole monotherapy was the optimal choice. The model was sensitive to certain parameters such as cost of Abemaciclib, and transition probability of stable to the progressed state for Abemaciclib and letrozole. Base case results were consistent with the findings from the Monte Carlo simulation. CONCLUSIONS: Our study found that none of the CDK4/6 inhibitors were cost-effective. Because of the current cost of CDK4/6 inhibitors, letrozole monotherapy was found to be an optimal choice for the first-line treatment of HR+/HER2- MBC. Citation Format: Prajakta P. Masurkar, Haluk Damgacioglu, Ashish Deshmukh, Meghana Trivedi. Cost-effectiveness of CDK4/6 inhibitors in the first-line treatment of HR+/HER2- metastatic breast cancer in postmenopausal women in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 891.

Exploring the Appropriate Price of Semaglutide for Type 2 Diabetes Patients Based on Cost-Utility Analysis in China.

Introduction: Semaglutide is the first and only oral version of a glucagon-like peptide-1 analogue approved by the FDA for the treatment of type 2 diabetes (T2D). This research was designed to explore the appropriate price of once-weekly (OW) semaglutide for T2D patients in China based on cost-utility analysis. Methods: The baseline patient cohorts of OW semaglutide and once-daily (OD) empagliflozin were sourced from a patient-level meta-analysis integrating the SUSTAIN 2, SUSTAIN 3, SUSTAIN 8 and PIONEER 2 trials. The long-term health and economic outcomes were simulated using the United Kingdom Prospective Diabetes Study Outcome Model 2 from the Chinese healthcare provider’s perspective. The appropriate price of semaglutide was explored by binary search. One-way sensitivity analysis (one-way SA), probabilistic sensitivity analysis and scenario analysis were applied to solve the uncertainty. Results: Under the assumption that the annual cost of semaglutide is equal to that of OD empagliflozin, OW semaglutide was superior to OD empagliflozin due to its higher quality adjusted life years and lower total costs. After binary search, the incremental cost-utility ratio of OW semaglutide vs. OD empagliflozin was approximately equal to 3λ with an annual cost of semaglutide of $1,007.18 and approximately equal to λ with an annual cost of semaglutide of $708.11. Subsequently, the incremental cost-utility ratio of OW semaglutide vs. OD empagliflozin was approximately 3λ and λ, with annual costs of semaglutide of $877.43 and $667.04, respectively, adjusted by one-way SA. Ultimately, the cost-utility results with annual costs of semaglutide of $877.43 and $667.04 were robust to probabilistic sensitivity analysis and scenario analysis. Conclusion: In conclusion, the annual cost of semaglutide appears to be appropriate between $667.04 and $877.43 for T2D patients in China.

Cost-effectiveness analysis of nonoperative management versus open and laparoscopic surgery for uncomplicated acute appendicitis in Colombia

BackgroundTraditionally, uncomplicated acute appendicitis (AA) has been treated with appendectomy. However, the surgical alternatives might carry out significant complications, impaired quality of life, and higher costs than nonoperative treatment. Consequently, it is necessary to evaluate the different therapeutic alternatives' cost-effectiveness in patients diagnosed with uncomplicated appendicitis.MethodsWe performed a model-based cost-effectiveness analysis comparing nonoperative management (NOM) with open appendectomy (OA) and laparoscopic appendectomy (LA) in patients otherwise healthy adults aged 18–60 years with a diagnosis of uncomplicated AA from the payer´s perspective at the secondary and tertiary health care level. The time horizon was 5 years. A discount rate of 5% was applied to both costs and outcomes. The health outcomes were quality-adjusted life years (QALYs). Costs were identified, quantified, and valorized from a payer perspective; therefore, only direct health costs were included. An incremental analysis was estimated to determine the incremental cost-effectiveness ratio (ICER). In addition, the net monetary benefit (NMB) was calculated for each alternative using a willingness to pay lower than one gross domestic product. A deterministic and probabilistic sensitivity analysis was performed.MethodsWe performed a model-based cost-effectiveness analysis comparing nonoperative management (NOM) with open appendectomy (OA) and laparoscopic appendectomy (LA) in patients otherwise healthy adults aged 18–60 years with a diagnosis of uncomplicated AA from the payer’s perspective at the secondary and tertiary health care level. The time horizon was five years. A discount rate of 5% was applied to both costs and outcomes. The health outcomes were quality-adjusted life years (QALYs). Costs were identified, quantified, and valorized from a payer perspective; therefore, only direct health costs were included. An incremental analysis was estimated to determine the incremental cost-effectiveness ratio (ICER). In addition, the net monetary benefit (NMB) was calculated for each alternative using a willingness to pay lower than one gross domestic product. A deterministic and probabilistic sensitivity analysis was performed.ResultsLA presents a lower cost ($363 ± 35) than OA ($384 ± 41) and NOM ($392 ± 44). NOM exhibited higher QALYs (3.3332 ± 0.0276) in contrast with LA (3.3310 ± 0.057) and OA (3.3261 ± 0.0707). LA dominated the OA. The ICER between LA and NOM was $24,000/QALY. LA has a 52% probability of generating the highest NMB versus its counterparts, followed by NOM (30%) and OA (18%). There is a probability of 0.69 that laparoscopy generates more significant benefit than medical management. The mean value of that incremental NMB would be $93.7 per patient.ConclusionsLA is a cost-effectiveness alternative in the management of patients with uncomplicated AA. Besides, LA has a high probability of producing more significant monetary benefits than NOM and OA from the payer’s perspective in the Colombian health system.

PNS85 Economic Evaluations of Digital Therapeutics (DTX) from a US Perspective

DTx represent a potentially transformative approach to support self-management of chronic conditions and to complement conventional disease monitoring and treatment. While DTx have not yet notably impacted patient care or service delivery in the US, these technologies have the potential to increase efficiency, improve outcomes, and expand access to care while reducing costs. In the absence of a large body of published research or consensus guidelines on DTx, US payers have posed questions about how to determine whether the effectiveness of a DTx merits the time, effort, and costs of utilizing the technology. We therefore sought to identify economic evaluations of DTx from the US perspective. A strategic literature review was conducted using the pearl growing/snowball method, wherein core publications were identified using an initial PubMed search strategy with the MeSH term “mobile applications/economics*”. Of 46 publications identified, two core publications were used to establish keywords and for bibliographic and prospective citation searches to identify additional relevant publications. ISPOR and AMCP congress abstracts also were searched from 2018 to 2020. Our search identified ten US-focused economic evaluations of DTx. Therapeutic areas included general mental health (1), depression (1), opioid use disorder (2), eating disorders (1), and diabetes (5, including 1 with hypertension). Five studies were claims analyses (one also included a cost-effectiveness (CEA) and budget impact model), and the remaining 5 studies included 3 CEAs and 2 cost-consequence models. Model horizons ranged from 3 months to 10 years, with longer-term models demonstrating higher quality-adjusted life year gains and cost savings. DTx represent an emerging opportunity to reduce healthcare expenditures while empowering patients and improving outcomes, but the existing evidence base is sparse. There are relatively few economic evaluations of DTx from the US perspective, presenting a challenge to payers seeking to develop coverage policies for this novel treatment modality.

PDB15 Cost-Effectiveness of a NOVEL Treatment for Diabetic Foot Ulcer Among Patients with Diabetes: A Modeling Study

We evaluated the cost-effectiveness of a novel treatment - ON101 cream, which was recently introduced for treating diabetic foot ulcer (DFU) as add-on to standard care (SC), versus SC among diabetic patients from the healthcare sector perspective. A Markov model with six health states (i.e., uninfected DFU, infected DFU, healed DFU, history of amputation, gangrene, and all-cause death) was adopted to assess the cost-effectiveness of ON101 versus SC for treating DFU, with one-month cycle length for a 5-year simulation in the base-case analysis. Data from the ON101 phase 3 trial involving 236 DFU cases for a 16-week follow-up were used to generate efficacy parameters (transition probabilities between health states) for the model. Costs and health utilities associated with health states were drawn from published literature and estimated using Taiwan’s National Health Insurance Research Database. Costs were expressed in 2020 U.S. dollars. Future costs and effectiveness were discounted at 3% annually. One-way and probabilistic sensitivity analyses were performed to examine the robustness of study results. Attributed by a higher healing rate and shorter healing time of using ON101, the base-case analysis showed that ON101 treatment was associated with lower costs and higher quality-adjusted life years (QALYs) over 5 years. The total healthcare cost per ON101-treated patient was lower than that of a patient with SC (i.e., $14,270 versus $22,135), while QALYs per ON101-treated patient were higher than those of a patient with SC (i.e., 3.565 versus 3.545 QALYs). Results were robust across the sensitivity analyses. The novel treatment, ON101, versus SC would be cost-saving for DFU owing to its better efficacy.

P493 Cost-effectiveness of venous thromboembolism prophylaxis after hospitalization in patients with Inflammatory Bowel Disease

Abstract Background Patients with inflammatory bowel disease (IBD) have a 2- to 3-fold greater risk of venous thromboembolism (VTE) than the general population, with increased risk during hospitalization. However, recent evidence suggests that this increased risk persists post-discharge. As such, we aimed to determine the cost-effectiveness of post-discharge VTE prophylaxis among hospitalized patients with IBD. Methods A decision tree was used to compare inpatient prophylaxis alone versus 4 weeks of post-discharge VTE prophylaxis with rivaroxaban 10 mg/day. Our primary outcome was quality-adjusted life years (QALYs) over one year, and strategies were compared using a willingness to pay of $100,000/QALY from a societal perspective. Costs (in 2020 $US), incremental cost-effectiveness ratios (ICERs), and number needed to treat (NNT) to prevent one VTE and VTE death were calculated. Deterministic 1-way and probabilistic analyses were performed to assess uncertainty within the model. Results Four-week post-discharge prophylaxis with rivaroxaban resulted in 1.68 higher QALYs per 1000 persons and an incremental cost of $185,778 per QALY as compared to no post-discharge prophylaxis. The NNT to prevent a single VTE was 78 individuals, while the NNT to prevent a single VTE-related death was 3190 individuals. One-way sensitivity analyses showed that higher baseline VTE risk >4.5% or decreased cost of rivaroxaban ≤$280 can reduce the ICER to <$100,000/QALY. Probabilistic sensitivity analyses favored post-discharge prophylaxis in 26.5% of iterations. Abbreviations: QALY (Quality-Adjusted Life Years), ICER (Incremental Cost-Effectiveness Ratio), NNT (Number Needed to Treat), VTE (Venous Thromboembolism) Figure. Tornado diagram showing main drivers (variables and sensitivity ranges) of the incremental cost-effectiveness ratio (ICER). *Values represent threshold values that reduce the ICER to <$100,000/QALY. Abbreviations: VTE (Venous Thromboembolism), DVT (Deep Vein Thrombosis), PE (Pulmonary Embolism), PTS (Post-Thrombotic Syndrome), WTP (Willingness To Pay), EV (Expected Value) Conclusion Four weeks of post-discharge VTE prophylaxis results in higher QALYs as compared to inpatient prophylaxis alone, and can prevent one post-discharge VTE among 78 patients with IBD. As such, post-discharge VTE prophylaxis in patients with IBD should be considered in a case-by-case scenario considering VTE risk profile, costs, and patient preference.

Cost-Effectiveness of Serum Galactomannan Surveillance during Mould-Active Antifungal Prophylaxis

Serial galactomannan (GM) monitoring can aid the diagnosis of invasive aspergillosis (IA) and optimise treatment decisions. However, widespread adoption of mould-active prophylaxis has reduced the incidence of IA and challenged its use. We evaluated the cost-effectiveness of prophylaxis-biomarker strategies. A Markov model simulating high-risk patients undergoing routine GM surveillance with mould-active versus non-mould-active prophylaxis was constructed. The incremental cost for each additional quality-adjusted life-year (QALY) gained over a lifetime horizon was calculated. In 40- and 60-year-old patients receiving mould-active prophylaxis coupled with routine GM surveillance, the total cost accrued was the lowest at SGD 11,227 (USD 8255) and SGD 9234 (USD 6790), respectively, along with higher QALYs gained (5.3272 and 1.1693). This strategy, being less costly and more effective, dominated mould-active prophylaxis with no GM monitoring or GM surveillance during non-mould-active prophylaxis. The prescription of empiric antifungal treatment was influential in the cost-effectiveness. When the GM test sensitivity was reduced from 80% to 30%, as might be anticipated with the use of mould-active prophylactic agents, the conclusion remained unchanged. The likelihood of GM surveillance with concurrent mould-active prophylaxis being cost-effective was 77%. Routine GM surveillance remained cost-effective during mould-active prophylaxis despite lower IA breakthroughs. Cost-saving from reduced empirical antifungal treatment was an important contributing factor.

Cost-effectiveness of the Oncotype DX Breast Recurrence Score test in postmenopausal women with node-positive early breast cancer based on the RxPONDER trial.

534 Background: The Oncotype DX test is a predictive and prognostic multigene assay used to guide adjuvant chemotherapy in HR+/HER2- early breast cancer. The ability of the Oncotype DX test to predict the benefit of chemotherapy in node-positive early breast cancer was demonstrated in SWOG-8814. This evidence, in combination with findings from a bespoke analysis of the TransATAC study, informed an economic evaluation of the Oncotype DX test by the National Institute for Health and Care Excellence in the UK. This study examined the impact of new evidence from the RxPONDER trial on the cost-effectiveness of the Oncotype DX test in postmenopausal women with node-positive early breast cancer. Methods: The cost-effectiveness of the Oncotype DX test compared to clinical risk tools only in postmenopausal HR+/HER2- early breast cancer was estimated using a model in Microsoft Excel. The pre-RxPONDER analysis using the old cut points (RS 0-17, RS 18-30, RS 31-100) was informed by TransATAC and SWOG-8814. The model was updated with 5-year probability of distant recurrence as first site estimates based on new RS cut points (RS 0-25, RS 26-100) from RxPONDER. The impact on incremental lifetime costs and quality-adjusted life-years (QALYs) gained was examined based on the list price for the Oncotype DX test in the UK. Results: The impact of adding data from RxPONDER into the cost-effectiveness analysis is summarized in the table below. Conclusions: The RxPONDER trial demonstrated that the addition of chemotherapy to endocrine therapy had no benefit for distant recurrence in postmenopausal women with RS 0-25, regardless of clinical features, which suggests that most patients with 1-3 positive nodes can be safely spared adjuvant chemotherapy. In the model this was reflected in reduced cost of chemotherapy and higher QALYs from avoiding short and long-term adverse effects of chemotherapy. Targeted chemotherapy of a minority (17%) of patients with RS 26-100 reduced the cost of distant recurrence and improved survival based on the model results. RxPONDER provides direct evidence to inform the probability of distant recurrence with endocrine and chemo-endocrine therapy, whilst previous models have had to synthesize multiple sources of DRFI and chemotherapy treatment effect. Future studies should examine the impact of the RxPONDER findings on chemotherapy treatment decision-making in routine clinical practice.[Table: see text]

Systematic Review: Economic Evaluation of Treatment for Human Epithelial Growth Factor Receptor 2-positive Metastatic Breast Cancer from a National Health Insurance Perspective

Background: Economic evaluation is often held from the societal perspective. Even it is important, as the therapy affects greatly to the patients’ life in society, economic evaluation from the payer perspective, is as important as it may help National Health Insurance (NHI) as the payer avert budget deficit as was observed in Indonesia. Unfortunately economic evaluation from the payer’s perspective is very rare to be done. This article compiles and reviews research articles of economic evaluation of therapy for human epithelial growth factor receptor 2-positive metastatic Breast Cancer (mBC) as an alternative to trastuzumab therapy, which has recently been removed from Indonesia’s National Health Insurance coverage. Methods: The literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and PICO methodology (Population, Intervention, Comparison, and Outcome). Relevant articles were retrieved from online biomedical databases Scopus, PubMed, ScienceDirect, and SAGE Journals. Quality appraisal was performed using a standardized checklist which consisted of items in the CHEC checklist. Results: A total of six articles pertaining to economic evaluation of therapy for HER2-positive mBC from the NHI perspective (period: 2008–2018) were reviewed. Trastuzumab+chemotherapy showed the longest overall survival (OS, 37.8 months) with Progression-free Survival (PFS) of 12.7 months. Trastuzumab+docetaxel as 1st line therapy were associated with the longest PFS (19 months) with a total cost of US$ 12,732. With respect to therapy sequence, 1st line, trastuzumab+pertuzumab+docetaxel; 2nd line, trastuzumab+emtansine ; and 3rd line, lapatinib+capecitabine was associated with the highest quality-adjusted life year (QALY; 1.81) but also the highest total cost and incremental cost (US$360,880 and US$197,250, respectively). The sequence of 1st line, trastuzumab/docetaxel; 2nd line, T-DM1; and 3rd line, trastuzumab/lapatinib was associated the lowest QALY (1.27) but was the most cost-effective (total cost: $158,293). Lapatinib+capecitabine as 2nd line therapy and exemestane monotherapy were associated with the lowest total cost (US$3,190). Conclusion: Lapatinib+capecitabine as 2nd line therapy and exemestane monotherapy show potential as alternatives to trastuzumab therapy for HER-2 positive mBC.

Cost-effectiveness of baloxavir marboxil compared with laninamivir for the treatment of influenza in patients at high risk for complications in Japan

Objective Baloxavir marboxil (baloxavir) is a single-dose antiviral which was previously found to be a cost-effective alternative to laninamivir in otherwise healthy adults in Japan. This study aimed at investigating the cost-effectiveness of baloxavir versus laninamivir in patients with influenza at high risk for complications. Methods A decision tree was utilized to estimate costs and health gains associated with the use of antivirals. A lifetime horizon was applied to capture the long-term impact of influenza complications, and other events with associated costs and health outcomes were accounted for one influenza season. The study population was stratified into three categories: adolescents and non-elderly adults with high-risk conditions (HRC), elderly without other HRC, and elderly with other HRC. The cost-effectiveness was assessed from a public healthcare payer’s perspective. The duration of influenza symptoms, probabilities of complications and probabilities of adverse events were obtained from a clinical trial and network meta-analysis. The costs of influenza and adverse events management were derived from the JammNet claims database. Utility values were informed by the clinical trial data and literature. Sensitivity analyses were also performed. Results The baloxavir strategy was associated with higher costs (+¥144) and higher quality-adjusted life-years (QALYs) in adults with HRC, elderly without HRC and elderly with HRC (+0.00078, +0.00183 and +0.00350 respectively). The overall incremental cost/QALY for baloxavir versus laninamivir was ¥68,855, which was below the willingness-to-pay threshold of ¥5 million/QALY gained. Key drivers of the model results were the probability of pneumonia and bronchitis. The probability of baloxavir being cost-effective was 72%. Conclusions This study suggests that influenza treatment with baloxavir is cost-effective compared with laninamivir in the adult high-risk population in Japan.

Gene-Specific Variation in Colorectal Cancer Surveillance Strategies for Lynch Syndrome

Lynch syndrome is associated with pathogenic variants in 4 mismatch repair (MMR) genes that increase lifetime risk of colorectal cancer. Guidelines recommend intensive colorectal cancer surveillance with colonoscopy every 1-2 years starting at age 25 years for all carriers of Lynch syndrome-associated variants, regardless of gene product. We constructed a simulation model to analyze the effects of different ages of colonoscopy initiation and surveillance intervals for each MMR gene (MLH1, MSH2, MSH6, and PMS2) on colorectal cancer incidence and mortality, quality-adjusted life-years, and cost. Using published literature, we developed a Markov simulation model of Lynch syndrome progression for patients with each MMR variant. The model simulated clinical trials of Lynch syndrome carriers, varying age of colonoscopy initiation (5-year increments from 25-40 years), and surveillance intervals (1-5 years). We assessed the optimal strategy for each gene, defined as the strategy with the highest quality-adjusted life-years and incremental cost-effectiveness ratio below a $100,000 willingness-to-pay threshold. Optimal surveillance for patients with pathogenic variants in the MLH1 and MSH2 genes was colonoscopy starting at age 25 years, with 1- to 2-year surveillance intervals. Initiating colonoscopy at age 35 and 40 years, with 3-year intervals, was cost-effective for patients with pathogenic variants in MSH6 or PMS2, respectively. We developed a simulation model to select optimal surveillance starting ages and intervals for patients with Lynch syndrome based on MMR variant. The model supports recommendations for intensive surveillance of patients with Lynch syndrome-associated variants in MLH1 or MSH2. However, for patients with Lynch syndrome-associated variants of MSH6 or PMS2, later initiation of surveillance at 35 and 40 years, respectively, and at 3-year intervals, can be considered.

Comprehensive Comparison Between Adjuvant Targeted Therapy and Chemotherapy for EGFR-Mutant NSCLC Patients: A Cost-Effectiveness Analysis.

BackgroundChemotherapy has been the current standard adjuvant treatment for early-stage non-small-cell lung cancer (NSCLC) patients, while recent studies showed benefits of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). We conducted a cost-effectiveness analysis to comprehensively evaluate the benefit of EGFR-TKI compared with chemotherapy for early-stage EGFR-mutant NSCLC patients after resection from the perspective of the Chinese health care system.MethodA Markov model was established. Clinical data were based on the phase 3, ADJUVANT trial, where stage II-IIIA, EGFR-mutant NSCLC patients were randomized into gefitinib group or chemotherapy group after resection. Cost parameters mainly included costs of drugs, examinations, and adverse events (AEs). Effect parameters were evaluated by quality-adjusted life year (QALY). Outcomes contained incremental cost-effective ratio (ICER), average cost-effective ratio (ACER), and net benefit. The willingness-to-pay threshold was set as 3 times per capita gross domestic product ($30,828/QALY). Sensitivity analyses were also conducted to verify the stability of the model.ResultsPatients who received gefitinib had both a higher cost ($12,057.98 vs. $11,883.73) and a higher QALY (1.55 vs. 1.42) than patients who received chemotherapy. With an ICER of $1,345.62/QALY, adjuvant gefitinib was of economic benefit compared with chemotherapy. The ACER and net benefit were also consistent (gefitinib vs. chemotherapy, ACER: $7,802.30/QALY vs. $8,392.77/QALY; net benefit: $35,584.85 vs. $31,767.17). Sensitivity analyses indicated the stability of the model and the impact of utility.ConclusionAdjuvant EGFR-TKI application for early-stage EGFR-mutant NSCLC patients was cost-effective compared with chemotherapy, which might provide a reference for clinical decision-making and medical insurance policy formulation in China.

Cost‐effectiveness analysis of sequential fecal microbiota transplantation for fulminant Clostridioides difficile infection

Fulminant Clostridioides difficile infections (FCDI) account for 8% of cases and substantial healthcare burden. Fecal microbiota transplantation is recommended for recurrent CDI, but emerging data support use for FCDI. We aimed to assess the cost-effectiveness of a sequential fecal microbiota transplantation (sFMT) protocol for FCDI compared with current standard therapy. A Markov model simulated patients with FCDI in a 1-year time horizon. The treatment algorithm for up to three sFMTs, clinical probabilities, and direct costs were used from published sources. Outcomes were quality-adjusted life years (QALYs) and costs. The healthcare sector perspective was used with a willingness-to-pay threshold of $100000 per QALY. Sequential fecal microbiota transplantation (FMT) for FCDI was associated with lower overall cost ($28309 vs $33980) and higher QALY (0.765 vs 0.686) compared with standard therapy. sFMT is cost-effective in 100% of iterations. sFMT remained cost-effective at cure rates>44.8% for the first FMT and at stool preparation cost<$6944 per instillation. We find a wide range of efficacies for the first versus second FMT at which sFMT is still preferred. Value of information analysis estimates the expected value of perfect information to be low at $1.89 per person, quantified with net monetary benefit. An sFMT strategy strongly dominates standard therapy, with lower cost and higher QALY. Sensitivity analysis demonstrates benefit even if FMT cure rates are lower than expected and when multiple FMTs are required. FMT material in 2020 was priced at $1695 per treatment but remains cost-effective at a much higher cost.

Cost-Utility Analysis of Anterior Vertebral Body Tethering versus Spinal Fusion in Idiopathic Scoliosis from a US Integrated Healthcare Delivery System Perspective

PurposeAnterior vertebral body tethering (VBT) is a non-fusion, minimally invasive, growth-modulating procedure with some early positive clinical outcomes reported in pediatric patients with idiopathic scoliosis (IS). VBT offers potential health-related quality of life (HRQoL) benefits over spinal fusion in allowing patients to retain a greater range of motion after surgery. We conducted an early cost-utility analysis (CUA) to compare VBT with fusion as a first-choice surgical treatment for skeletally immature patients (age >10 years) with moderate to severe IS, who have failed nonoperative management, from a US integrated healthcare delivery system perspective.Patients and MethodsThe CUA uses a Markov state transition model, capturing a 15-year period following index surgery. Transition probabilities, including revision risk and subsequent fusion, were based on published surgical outcomes and an ongoing VBT observational study (NCT02897453). Patients were assigned utilities derived from published patient-reported outcomes (PROs; SRS-22r mapped to EQ-5D) following fusion and the above VBT study. Index and revision procedure costs were included. Probabilistic (PSA) and deterministic sensitivity analyses (DSA) were performed.ResultsVBT was associated with higher costs but also higher quality-adjusted life years (QALYs) than fusion (incremental costs: $45,546; QALYs gained: 0.54). The subsequent incremental cost-effectiveness ratio for VBT vs fusion was $84,391/QALY gained. Mean PSA results were similar to the base case, indicating that results were generally robust to uncertainty. The DSA indicated that results were most sensitive to variations in utility values.ConclusionThis is the first CUA comparing VBT with fusion in pediatric patients with IS and suggests that VBT may be a cost-effective alternative to fusion in the US, given recommended willingness-to-pay thresholds ($100,000–$150,000). The results rely on HRQoL benefits for VBT compared with fusion. For improved model accuracy, further analyses with longer-term PROs for VBT, and comparative effectiveness studies, would be needed.

P0611 / #1112: ANTIMICROBIAL STEWARDSHIP AND PROCALCITONIN TESTING TO OPTIMIZE SEPSIS CARE IN CRITICALLY ILL PEDIATRIC PATIENTS

Aims & Objectives: We aim to prospectively evaluate an antimicrobial stewardship program (ASP) and Procalcitonin (PCT) testing on septic pediatric intensive care (PICU) patients. Methods: We performed a 30-week baseline collection (Phase 1), and a 30-week evaluation (Phase 2) of ASP and PCT in PICU patients with suspected or confirmed sepsis (inclusion criteria: temperature >38.0 or <36.0 and requiring IV antibiotic). The primary endpoint was in-hospital mortality; secondary endpoints included antimicrobial adequacy, ASP interventions and acceptance, LOS, re-admissions and economic indices, etc. Segmented logistic and linear regression analyses were performed for associations. Results: Each phase had 40 children, mean age of 3.9 (1.8) years; 56.3% male; PRISM III mean was 3.3 and 7.0 (CI:±2.66,p=0.0068) in each phase, respectively. From 104 antibiotic prescriptions, 91 (88%) were guideline-concordant; 103 ASP recommendations were made in 60 assessments, with 83% full acceptance rate; in 12% of patients antimicrobials were not indicated, in 6% narrower spectrum was suggested. PCT was measured at least once in 95% of patients: in 24% initial PCT values were <0.25 ng/mL (stopping rule) while in 71% were >1 ng/mL (continuation rule). Only 1 patient died (phase 1), mortality 1.2%. In phase 2 the mean ICU LOS was shorter (-6.58 days; 95% CI, -14.51, 1.36, p=0.10) and PICU readmissions decreased (12 vs. 4; p=0.048); costs were lower (-$5,830) and QALYs were higher (0.192 vs 0.188). Conclusions: ASP and PCT testing were effectively implemented, well accepted and helpful, albeit mortality did not differ. Implementation was cost effective with fewer re-admissions and resulted in higher quality-adjusted life years.

Cost-Effectiveness Analysis of Ginkgolide Injection in the Treatment of Ischemic Stroke Based on a Randomized Clinical Trial.

Objective: To evaluate the long-term cost-effectiveness of ginkgolide plus aspirin compared with placebo plus aspirin treatment of ischemic stroke.Background: Stroke is the leading cause of death and long-term disability in China, with high incidence, high mortality, and heavy disease burden. In addition to Western medicines, Chinese clinical guidelines for diagnosis and treatment of acute ischemic stroke recommend application of Chinese patent medicines. Ginkgolide injection is commonly used in the clinical treatment of stroke in China to promote blood circulation and remove blood stasis. The economy of ginkgolide injection needs to be evaluated.Methods: A Markov model was constructed consisting of four disease states: no significant disability, disability, stroke recurrence, and death. Therapeutic data were taken from the Ginkgolide in Ischemic Stroke Patients with Large Artery Atherosclerosis (GISAA) study. Utilities and transition probabilities were extracted from the literature. Cost data were obtained from the China Health Statistics Yearbook and hospital record survey. Expected costs and quality-adjusted life-years (QALYs) of 13 years of cycles (calculated by average age of subjects and Chinese life expectancy) were calculated through TreeAge Pro11 software. The willingness-to-pay (WTP) threshold was set as the Chinese per capita Gross Domestic Product (GDP) in 2019, CN¥70,892/QALY. The results were analyzed by single factor and probability sensitivity analyses.Results: Ginkgolide plus aspirin had a higher expected per-patient cost than placebo plus aspirin but a higher QALYs. Compared with placebo plus aspirin, ginkgolide plus aspirin produced an incremental cost-effectiveness ratio of CN¥14,866.06/QALY, which is below the WTP threshold. Probabilistic sensitivity analysis suggested the acceptability of ginkgolide plus aspirin was higher than that of placebo plus aspirin.Conclusions: The present cost-effectiveness analysis showed that addition of ginkgolides to conventional treatment is cost-effective at a threshold the Chinese per capita GDP.

Cost-effectiveness of Prostate Radiation Therapy for Men With Newly Diagnosed Low-Burden Metastatic Prostate Cancer

Prostate radiation therapy (PRT) is a treatment option in men with low-volume metastatic prostate cancer based on the results of the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy Arm H (STAMPEDE-H) trial. However, the cost-effectiveness of this treatment remains unaddressed. To assess the cost-effectiveness of PRT when added to androgen deprivation therapy (ADT) for men with low-volume metastatic hormone-sensitive prostate cancer (mHSPC). This economic evaluation used microsimulation modeling to evaluate the cost-effectiveness of adding PRT to ADT. A simulated cohort of 10 000 individuals with low-volume mHSPC was created. Data from men with low-volume mHSPC were extracted and analyzed from January 18, 2019, through July 4, 2020. Transition probabilities were extracted from the STAMPEDE-H study. Health states included stable disease, progression, second progression, and death. Individual grade 2 or higher genitourinary and gastrointestinal toxic events associated with PRT were tracked. Univariable deterministic and probabilistic sensitivity analyses explored uncertainty with regard to the model assumptions. Health state utility estimates were based on the published literature. The combination of PRT and ADT using regimens of 20 fractions and 6 weekly fractions. Outcomes included net quality-adjusted life-years (QALYs), costs in US dollars, and incremental cost-effectiveness ratios. A strategy was classified as dominant if it was associated with higher QALYs at lower costs than the alternative and dominated if it was associated with fewer QALYs at higher costs than the alternative. For the base case scenario of men 68 years of age with low-volume mHSPC, the modeled outcomes were similar to the target clinical data for overall survival, failure-free survival, and rates of PRT-related toxic effects. The addition of PRT was a dominant strategy compared with ADT alone, with a gain of 0.16 QALYs (95% CI, 0.15-0.17 QALYs) and a reduction in net costs by $19 472 (95% CI, $23 096-$37 362) at 37 months of follow-up and a gain of 0.81 QALYs (95% CI, 0.73-0.89 QALYs) and savings of $30 229 (95% CI, $23 096-$37 362) with lifetime follow-up. In the economic evaluation, PRT was a dominant treatment strategy compared with ADT alone. These findings suggest that addition of PRT to ADT is a cost-effective treatment for men with low-volume mHSPC.

The Clinical Impact and Cost Effectiveness of Intervention Policies Against the SARS-CoV-2 Pandemic: A Mathematical Modelling Analysis

Background: To investigate the clinical and economic outcomes, of intervention policies combining nonpharmaceutical interventions and vaccination programs for dealing with the SARS-CoV-2 pandemic. Methods: An agent-based model transmission model was adopted which describes how a SARS-CoV-2 virus will spread in the populations of China. The model inputs were derived from literature and expert opinion. The following intervention policies were simulated: no intervention, strict nonpharmaceutical interventions, nonpharmaceutical intervention for workplace, community, school and home gradually dismissed by combining vaccination programs in pre-specified age groups. The cumulative infection and death in one calendar year, costs and quality adjusted life years (QALYs) were measured. Findings: When the vaccination program had been at least taken up in ≥20 years and all populations, nonpharmaceutical intervention for workplace and community settings could be gradually dismissed because the cumulative number of infections was < 100 per 100,000 persons. Further dismissing nonpharmaceutical intervention for school and home settings could not meet the target even when the vaccination program had been taken up in all populations. When cumulative death was used as the endpoint, nonpharmaceutical intervention in workplace, community and school settings could be gradually dismissed. Vaccine efficacy and coverage have substantial impacts. Dismissing nonpharmaceutical interventions in workplace settings could produce the lowest cost when vaccination programs are at least taken up at age ≥10 years, which also dominates most intervention strategies due to its lower costs and higher QALYs. Interpretation: Continued nonpharmaceutical interventions might be gradually dismissed until herd immunity is achieved. Funding: None to declare. Declaration of Interest: None to declare.

Systematic Review: Economic Evaluation of Treatment for Human Epithelial Growth Factor Receptor 2-positive Metastatic Breast Cancer from a National Health Insurance Perspective

Background: Economic evaluation is often held from the societal perspective. Even it is important, as the therapy affects greatly to the patients’ life in society, economic evaluation from the payer perspective, is as important as it may help National Health Insurance (NHI) as the payer avert budget deficit as was observed in Indonesia. Unfortunately economic evaluation from the payer’s perspective is very rare to be done. This article compiles and reviews research articles of economic evaluation of therapy for human epithelial growth factor receptor 2-positive metastatic Breast Cancer (mBC) as an alternative to trastuzumab therapy, which has recently been removed from Indonesia’s National Health Insurance coverage. Methods: The literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and PICO methodology (Population, Intervention, Comparison, and Outcome). Relevant articles were retrieved from online biomedical databases Scopus, PubMed, ScienceDirect, and SAGE Journals. Quality appraisal was performed using a standardized checklist which consisted of items in the CHEC checklist. Results: A total of six articles pertaining to economic evaluation of therapy for HER2-positive mBC from the NHI perspective (period: 2008–2018) were reviewed. Trastuzumab+chemotherapy showed the longest overall survival (OS, 37.8 months) with Progression-free Survival (PFS) of 12.7 months. Trastuzumab+docetaxel as 1st line therapy were associated with the longest PFS (19 months) with a total cost of US$ 12,732. With respect to therapy sequence, 1st line, trastuzumab+pertuzumab+docetaxel; 2nd line, trastuzumab+emtansine ; and 3rd line, lapatinib+capecitabine was associated with the highest quality-adjusted life year (QALY; 1.81) but also the highest total cost and incremental cost (US$360,880 and US$197,250, respectively). The sequence of 1st line, trastuzumab/docetaxel; 2nd line, T-DM1; and 3rd line, trastuzumab/lapatinib was associated the lowest QALY (1.27) but was the most cost-effective (total cost: $158,293). Lapatinib+capecitabine as 2nd line therapy and exemestane monotherapy were associated with the lowest total cost (US$3,190). Conclusion: Lapatinib+capecitabine as 2nd line therapy and exemestane monotherapy show potential as alternatives to trastuzumab therapy for HER-2 positive mBC.

Primary Bankart Repair Versus Arthroscopic Anatomic Glenoid Reconstruction in Patients with Subcritical Bone Loss: A Cost-Utility Analysis.

Background:Anterior shoulder instability and its treatment is a quickly evolving field of interest in orthopaedics, both for patients and for health-care systems. In this study, we aimed to evaluate the cost-effectiveness of arthroscopic anatomic glenoid reconstruction (AAGR) compared with Bankart repair in the treatment of anterior shoulder instability in patients with subcritical glenoid bone loss.Methods:A cost-utility analysis was performed from the perspective of Canada’s publicly funded health-care system. A decision-tree model was created to simulate the progression of patients undergoing either a primary Bankart repair or AAGR. Recently published data were used to determine the recurrence rate and level of glenoid bone loss for the AAGR procedure; the recurrence rate was 1.4% in a cohort with a mean glenoid bone loss of 25.3%. A literature review on the primary Bankart procedure in patients with at least subcritical levels of glenoid bone loss yielded a recurrence rate of 22.9% in patients with a mean glenoid bone loss of 17.5%. AAGR served as the revision surgery for both primary procedures. Health utility scores for anterior shoulder instability were obtained from published literature. Total procedure costs, including costs of operating-room consumables, anesthesia, diagnostic imaging, and rehabilitation, were sourced from a hospital database. A probabilistic sensitivity analysis using 5,000 Monte Carlo simulations was performed, and results were used to create a cost-effectiveness acceptability curve.Results:The AAGR procedure was less costly and led to an improvement in quality-adjusted life years (QALYs) when compared with the arthroscopic Bankart repair in the treatment of patients with anterior shoulder instability with subcritical glenoid bone loss (AAGR, cost = $16,682.77 [Canadian dollars] and QALYs = 5.76; Bankart, cost = $16,720.29 and QALYs = 5.46), suggesting that the AAGR is dominant, i.e., lower costs with higher QALYs. Applying a commonly used willingness-to-pay threshold of $50,000 per QALY gained, the probability that the primary AAGR was more cost-effective was 85.8%.Conclusions:This study showed that, from the perspective of a publicly funded health-care system, AAGR was the economical treatment option when compared with Bankart repair in anterior shoulder instability with subcritical glenoid bone loss.Level of Evidence:Economic and Decision Analysis Level III. See Instructions for Authors for a complete description of levels of evidence.