Probabilistic Sensitivity Analysis Research Articles

Cost-Effectiveness Analysis of Digital Breast Tomosynthesis and Mammography in Breast Cancer Screening: A Markov Modeling Study.

Mammography (MG) has demonstrated its effectiveness in diminishing mortality and advanced-stage breast cancer incidences in breast screening initiatives. Notably, research has accentuated the superior diagnostic efficacy and cost-effectiveness of digital breast tomosynthesis (DBT). However, the scope of evidence validating the cost-effectiveness of DBT remains limited, prompting a requisite for more comprehensive investigation. The present study aimed to rigorously evaluate the cost-effectiveness of DBT plus MG (DBT-MG) compared to MG alone within the framework of Taiwan's National Health Insurance program. All parameters for the Markov decision tree model, encompassing event probabilities, costs, and utilities (quality-adjusted life years, QALYs), were sourced from reputable literature, expert opinions, and official records. With 10,000 iterations, a 2-year cycle length, a 30-year time horizon, and a 2% annual discount rate, the analysis determined the incremental cost-effectiveness ratio (ICER) to compare the cost-effectiveness of the two screening methods. Probabilistic and one-way sensitivity analyses were also conducted to demonstrate the robustness of findings. The ICER of DBT-MG compared to MG was US$5971.5764/QALYs. At a willingness-to-pay (WTP) threshold of US$33,004 (Gross Domestic Product of Taiwan in 2021) per QALY, more than 98% of the probabilistic simulations favored adopting DBT-MG versus MG. The one-way sensitivity analysis also shows that the ICER depended heavily on recall rates, biopsy rates, and positive predictive value (PPV2). DBT-MG shows enhanced diagnostic efficacy, potentially diminishing recall costs. While exhibiting a higher biopsy rate, DBT-MG aids in the detection of early-stage breast cancers, reduces recall rates, and exhibits notably superior cost-effectiveness.

Cost-effectiveness of a complex continuum of care intervention targeting women and children: protocol for an economic evaluation of the Bukhali trial in South Africa

IntroductionAs nearly two-thirds of women presenting at their first antenatal visit are either overweight or obese in urban South Africa, the preconception period is an opportunity to optimise health and...

Cost-utility analysis and drug pricing for tirzepatide for type 2 diabetes in the Chinese market compared with semaglutide.

To investigate the most matchable price of tirzepatide (TIRZ) compared with semaglutide (SEMA) in the treatment of type 2 diabetes in China. The patient cohort and clinical efficacy data were derived from the SURPASS-2 trial. Cost-utility analysis and a binary search were performed to identify the most matchable price of TIRZ from a Chinese healthcare provider's perspective. After lifetime simulation, the quality-adjusted life years of TIRZ 5, 10, 15 mg and SEMA 1 mg were 11.17, 11.21, 11.27 and 11.12 years, respectively. Despite an initial assumption that the annual cost of TIRZ equals that of SEMA, our analysis revealed that TIRZ is probably more cost-effective than SEMA. A thorough evaluation of pricing showed that the cost ranges for TIRZ at doses of 5, 10 and 15 mg were $1628.61-$1846.23, $1738.40-$2140.95 and $1800.30-$2430.81, respectively. After adjustment in the univariate sensitivity analysis, the cost ranges for TIRZ 5, 10 and 15 mg were $1542.68-$1757.57, $1573.00-$1967.16 and $1576.54-$2133.96, respectively. These cost intervals were validated through robust probabilistic sensitivity analysis and scenario analysis, except for the cost range for TIRZ 5 mg. This study shows that, using SEMA as a reference, the annual costs for TIRZ 10 and 15 mg are $1573.00-$1967.16 and $1576.54-$2133.96, respectively, for patients with type 2 diabetes in China.

Cost-effectiveness of sutimlimab in cold agglutinin disease.

Primary cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia caused by cold-reactive antibodies that bind to red blood cells and lead to complement-mediated hemolysis. Patients with primary CAD experience the burden of increased health resource utilization and reduced quality of life. The standard-of-care (SOC) in patients with primary CAD has included cold avoidance, transfusion support, and chemoimmunotherapy. The use of sutimlimab, a humanized monoclonal antibody that selectively inhibits C1-mediated hemolysis, was shown to reduce transfusion-dependence and improve quality of life across two pivotal phase 3 studies, further supported by 2-year extension data. Using data from the transfusion-dependent patient population that led to sutimlimab's initial FDA approval, we performed the first-ever cost-effectiveness analysis in primary CAD. The projected incremental cost-effectiveness ratio (ICER) in our Markov model was $2 340 000/QALY, significantly above an upper-end conventional US willingness-to-pay threshold of $150 000/QALY. These results are consistent across scenarios of higher body weight and a pan-refractory SOC patient phenotype (i.e., treated sequentially with bendamustine-rituximab, bortezomib, ibrutinib, and eculizumab). No parameter variations in deterministic sensitivity analyses changed our conclusion. In probabilistic sensitivity analysis, SOC was favored over sutimlimab in 100% of 10 000 iterations. Exploratory threshold analyses showed that significant price reduction (>80%) or time-limited treatment (<18 months) followed by lifelong clinical remission off sutimlimab would allow sutimlimab to become cost-effective. The impact of sutimlimab on health system costs with longer term follow-up data merits future study and consideration through a distributional cost-effectiveness framework.

Cost-effectiveness of PCV20 to Prevent Pneumococcal Disease in the Pediatric Population: A German Societal Perspective Analysis.

Since 2009, a pneumococcal conjugate vaccine (PCV) covering 13 serotypes (PCV13) has been included by Germany's Standing Committee on Vaccinations for infants, resulting in major reductions in pneumococcal disease (PD). Higher-valent vaccines may further reduce PD burden. This cost-effectiveness analysis compared 20-valent PCV (PCV20) under a 3+1 schedule with 15-valent PCV (PCV15) and PCV13, both under 2+1 schedule, in Germany's pediatric population. A Markov model with annual cycles over a 10-year time horizon was adapted to simulate the clinical and economic impact of pediatric vaccination with PCV20 versus lower-valent PCVs in Germany. The model used PCV13 clinical effectiveness and impact studies as well as PCV7 efficacy studies for vaccine direct and indirect effect estimates. Epidemiologic, utility, and medical cost inputs were obtained from published sources. Benefits and costs were discounted at 3% from a German societal perspective. Outcomes included PD cases, deaths, costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). In the base case, PCV20 provided greater health benefits than PCV13, averting more cases of invasive pneumococcal disease (IPD; 15,301), hospitalized and non-hospitalized pneumonia (460,197 and 472,365, respectively), otitis media (531,634), and 59,265 deaths over 10 years. This resulted in 904,854 additional QALYs and a total cost saving of €2,393,263,611, making PCV20 a dominant strategy compared with PCV13. Compared to PCV15, PCV20 was estimated to avert an additional 11,334 IPD, 704,948 pneumonia, and 441,643 otitis media cases, as well as 41,596 deaths. PCV20 was associated with a higher QALY gain and lower cost (i.e., dominance) compared with PCV15. The robustness of the results was confirmed through scenario analyses as well as deterministic and probabilistic sensitivity analyses. PCV20 3+1 dominated both PCV13 2+1 and PCV15 2+1 over 10 years. Replacing lower-valent PCVs with PCV20 would result in greater clinical and economic benefits, given PCV20's broader serotype coverage.

Cost-effectiveness Analysis of Maternal Immunization with RSVpreF Vaccine for the Prevention of Respiratory Syncytial Virus Among Infants in Spain.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections (ALRI) in children under one year of age. In high-income countries, RSV infections cause a significant overload of care every winter, imposing a significant burden to the healthcare system, which has made the development of prevention strategies a major global health priority. In this context, a new bivalent RSV prefusion F protein-based vaccine (RSVpreF) has recently been approved. The objective of this study was to evaluate the cost-effectiveness of vaccinating pregnant women with the RSVpreF vaccine to prevent RSV in infants from the Spanish National Healthcare System (NHS) perspective. A hypothetical cohort framework and a Markov-type process were used to estimate clinical outcomes, costs, quality-adjusted life years (QALY) and cost-per-QALY gained (willingness-to-pay threshold: €25,000/QALY) for newborn infants born to RSV-vaccinated versus unvaccinated mothers over an RSV season. The base case analysis was performed from the NHS perspective including direct costs (€2023) and applying a discount of 3% to future costs and outcomes. To evaluate the robustness of the model, several scenarios, and deterministic and probabilistic analyses were carried out. All the parameters and assumptions were validated by a panel of experts. The results of the study showed that year-round maternal vaccination program with 70% coverage is a dominant option compared to no intervention, resulting in direct cost savings of €1.8 million each year, with an increase of 551 QALYs. Maternal vaccination could prevent 38% of hospital admissions, 23% of emergency room visits, 19% of primary care visits, and 34% of deaths due to RSV. All scenario analyses showed consistent results, and according to the probabilistic sensitivity analysis (PSA), the probability of maternal vaccination being cost-effective versus no intervention was 99%. From the Spanish NHS perspective, maternal vaccination with bivalent RSVpreF is a dominant alternative compared with a non-prevention strategy.

Cost-utility analysis of add-on vericiguat for the treatment of chronic heart failure with reduced ejection fraction in China

ObjectiveThis study aimed to evaluate the cost-utility of the addition of vericiguat for treating chronic heart failure (CHF) in China from the healthcare payer’s perspective.MethodsA Markov model was built to estimate the cost and utility of treating CHF using vericiguat plus standard treatment (vericiguat group) vs. standard treatment alone (standard treatment group). The clinical parameters (mortality of cardiovascular and hospitalization rate of HF) were calculated according to the VICTORIA clinical trial. The HF cost and utility data were obtained from the literature published in China. One-way sensitivity analysis and probability sensitivity analysis were performed.ResultsAccording to the 13-year model, vericiguat was more expensive (155599.07 CNY vs. 259396.83 CNY) and more effective (4.41 QALYs vs. 4.54 QALYs). The incremental cost‐utility ratio (ICUR) was 802389.27 CNY per QALY. One-way sensitivity analysis revealed that cardiovascular mortality in the two groups was the parameter that had the greatest impact on the results. The GDP per capita in 2022 in China was 85,700 CNY. The probability sensitivity analysis (PSA) showed that the probability of vericiguat being cost-effective was only 41.7% at the willingness-to-pay (WTP) threshold of 3 times GDP per capita (257,100 CNY).ConclusionsIn China, the treatment of CHF with vericiguat is not cost-effective. The drug price could decrease to 145.8 CNY, which could be considered cost-effective.

Fetoscopic laser versus amnioreduction, septostomy, and expected management for the treatment of twin-twin transfusion syndrome (TTTS): an economic evaluation analysis in Iran

BackgroundTwin-twin transfusion syndrome (TTTS) affects 10–15% of monochorionic twin pregnancies. Without treatment, their mortality rates would be considerable. There are differences in survival rate between different therapeutic modalities. This study aims to compare the cost-effectiveness of Fetoscopic laser versus amnioreduction, septostomy, and expected management in the treatment of twin-to-twin transfusion syndrome (TTTS).MethodsThis is a cost-effectiveness analysis of the treatment strategies in patients with TTTS. A decision tree model was used to estimate the clinical and economic outcomes with a pregnancy period time horizon. Medical direct costs were extracted in a quantitative study, and survival rates were determined as effectiveness measures based on a review. A probabilistic sensitivity analysis was used to measure the effects of uncertainty in the model parameters. The TreeAge, Excel and R software were used for analyzing data.ResultsIn the first phase, 75 studies were included in the review. Based on the meta-analysis, a total of 7183 women treated with Fetoscopic laser, the perinatal survival of at least one twin-based pregnancy was 69%. In the second phase, the results showed that expected management and amnioreduction have the lowest (791.6$) and highest cost (2020.8$), respectively. Based on the decision model analysis, expected management had the lowest cost ($791.67) and the highest rate in at least one survival (89%), it was used only in early stages of TTTS. Fetoscopic laser surgery, with the mean cost 871.46$ and an overall survival rate of 0.69 considered the most cost-effectiveness strategy in other stages of TTTS.ConclusionOur model found Fetoscopic laser surgery in all stages of TTTS to be the most cost-effective therapy for patients with TTTS. Fetoscopic laser surgery thus should be considered a reasonable treatment option for TTTS.

Cost-effectiveness and cost–benefit analyses of fluoride varnish for caries prevention in Guangxi, China

ObjectivesThe objectives of this study were to evaluate the cost-effectiveness and cost-benefit of fluoride varnish (FV) interventions for preventing caries in the first permanent molars (FPMs) among children in rural areas in Guangxi, China.MethodsThis study constituted a secondary analysis of data from a randomised controlled trial, analysed from a social perspective. A total of 1,335 children aged 6–8 years in remote rural areas of Guangxi were enrolled in this three-year follow-up controlled study. Children in the experimental group (EG) and the control group (CG) received oral health education and were provided with a toothbrush and toothpaste once every six months. Additionally, FV was applied in the EG. A decision tree model was developed, and single-factor and probabilistic sensitivity analyses were conducted.ResultsAfter three years of intervention, the prevalence of caries in the EG was 50.85%, with an average decayed, missing, and filled teeth (DMFT) index score of 1.12, and that in the CG was 59.04%, with a DMFT index score of 1.36. The total cost of caries intervention and postcaries treatment was 42,719.55 USD for the EG and 46,622.13 USD for the CG. The incremental cost-effectiveness ratio (ICER) of the EG was 25.36 USD per caries prevented, and the cost–benefit ratio (CBR) was 1.74 USD benefits per 1 USD cost. The results of the sensitivity analyses showed that the increase in the average DMFT index score was the largest variable affecting the ICER and CBR.ConclusionsCompared to oral health education alone, a comprehensive intervention combining FV application with oral health education is more cost-effective and beneficial for preventing caries in the FPMs of children living in economically disadvantaged rural areas. These findings could provide a basis for policy-making and clinical choices to improve children’s oral health.

The Lifetime Health and Economic Burden of Smokeless Tobacco use in Bangladesh, India, and Pakistan: Results From ASTRAMOD.

Under the current policy landscapes, the lifetime health and economic burden of smokeless tobacco (ST) products, consumed by over 297 million ST users in South Asia, is unknown. The aim of this study was to estimate the lifetime health effects and costs attributable to current and future ST use in Bangladesh, India, and Pakistan where the majority of ST users live. We developed a Markov-based state-transition model (ASTRAMOD) to predict the lifetime costs of treatment of four diseases (oral, pharyngeal, esophageal cancers, and stroke) and disability-adjusted life years (DALYs), attributable to the current and future use of ST under existing ST policy scenario. Country-specific Global Adult Tobacco Surveys, life tables, and meta-analyses of South Asian and South East Asian studies were used to populate the model. A probabilistic sensitivity analysis evaluated the uncertainty in model predictions. If there were no change in the current ST policies, the lifetime ST-attributable treatment costs would be over US$19 billion in India, over US$1.5 billion in Bangladesh, and over US$3 billion in Pakistan. For all countries, the attributable costs are higher for younger cohorts with costs declining with increasing age for those over 50. The model predicted that a typical 15-year-old male adoloscent would gain 0.07-0.18 life years, avert 0.07-0.19 DALYs, and generate a cost-savings of US$7-21 on healthcare spending if ST policies were changed to eliminate ST use. Policy interventions aimed at decreasing the uptake of ST and increasing quitting success have the potential to substantially decrease the economic and health burden of ST. This study provides the most comprehensive estimates of the lifetime health and economic burden of ST by 5-year age and sex cohorts. This is also the first study that highlights the scale of health and economic burden of ST in Bangladesh, India, and Pakistan if there were no changes in the current ST policies. Policymakers and practitioners can use the reported data to justify their decisions to improve current ST policies and practices in their country. Researchers can use the ASTRAMOD methodology to estimate the impact of future ST policy changes.

Cost-effectiveness of the adjuvanted quadrivalent influenza vaccine for older adults in South Korea

ABSTRACT South Korea’s National Immunization Program administers the quadrivalent influenza vaccine (QIV) to manage seasonal influenza, with a particular focus on the elderly. After reviewing the safety and immune response triggered by the adjuvanted QIV (aQIV) in individuals aged 65 and older, the Ministry of Food and Drug Safety in Korea approved its use. However, the extensive impact of aQIV on public health is yet to be fully understood. This study assessed the cost-effectiveness of replacing QIV with aQIV in South Korean adults aged 65 years and older. A dynamic transmission model, calibrated with national influenza data, was applied to compare the influence of aQIV and QIV on older adults and the broader population throughout a single influenza season. This study considered both the direct and indirect effects of vaccination on the elderly. We derived the incremental cost-effectiveness ratios (ICERs) from quality-adjusted life-years (QALYs) and costs incurred, validated through a probabilistic sensitivity analysis with 5,000 simulations. Findings suggest that transitioning to aQIV from QIV in the elderly would be cost-effective, particularly if aQIV’s efficacy reaches or exceeds 56.1%. With an ICER of $29,267/QALY, considerably lower than the $34,998/QALY willingness-to-pay threshold, aQIV presents as a cost-effective option. Thus, implementing aQIV with at least 56.1% efficacy is beneficial from both financial and public health perspectives in mitigating seasonal influenza in South Korea.

A cost analysis of a simplified model for HCV screening and treatment at a tertiary hospital in Zimbabwe

ABSTRACT Background The treatment of chronic hepatitis C virus (HCV) infection using directly acting antivirals was recently adopted in the treatment guidelines of Zimbabwe. The objectives of this study were to design a simplified model of HCV care and estimate the cost of screening and treatment of hepatitis C infection at a tertiary hospital in Zimbabwe. Methods We developed a model of care for HCV using WHO 2018 guidelines for the treatment of HCV infection and expert opinion. We then performed a micro-costing to estimate the costs of implementing the model of care from the healthcare sector perspective. Deterministic and probabilistic sensitivity analyses were performed to explore the impact of uncertainty in input parameters on the estimated total cost of care. Results The total cost of screening and treatment was estimated to be US$2448 (SD=$290) per patient over a 12-week treatment duration using sofosbuvir/velpatasvir. The cost of directly acting antivirals contributed 57.5% to the total cost of care. The second largest cost driver was the cost of diagnosis, US$819, contributing 34.6% to the total cost of care. Conclusion Screening and treatment of HCV-infected individuals using directly acting antivirals at a tertiary hospital in Zimbabwe may require substantial financial resources.

Cost-Effectiveness of 20-Valent Pneumococcal Conjugate Vaccine in Argentinean Adults.

In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23; PCV13 → PPSV23) has been recommended for all adults aged ≥ 65 years and younger adults with chronic medical ("moderate-risk") or immunocompromising ("high-risk") conditions since 2017. With the approval of a 20-valent PCV (PCV20), we evaluated the cost-effectiveness of PCV20 versus current recommendations for moderate-/high-risk adults aged 18-64 years and all adults 65-99 years. A probabilistic cohort model was used to project lifetime outcomes and costs associated with invasive pneumococcal disease (IPD) and all-cause non-bacteremic pneumonia (NBP), and the expected impact of vaccination. Clinical outcomes were projected annually based on Argentinean data. Economic costs were estimated based on cases and corresponding medical costs (adjusted to 2023 USD) and costs of vaccine and administration. Cost-effectiveness of PCV20 was evaluated versus the current strategy, PCV13 → PPSV23, and alternatively, versus sequentially administered 15-valent PCV and PPSV23 (PCV15 → PPSV23), and presented as cost per quality-adjusted life year gained; a healthcare system perspective was used. Costs and benefits were discounted at 3%/year. PCV20 in lieu of PCV13 → PPSV23 among moderate-/high-risk adults aged 18-64 years and all adults 65-99 years (N = 13.4M) prevented 3838 IPD, 4377 inpatient NBP, and 6003 outpatient NBP cases, and 1865 disease-related deaths; relative to PCV15 → PPSV23 the corresponding reductions were 2775, 3285, 4518, and 1348. PCV20 was projected to be the dominant strategy versus PCV13 → PPSV23 and PCV15 → PPSV23 as overall costs were lower by $87.6M and $80.8M, respectively. In probabilistic sensitivity analyses, PCV20 was dominant (i.e., more effective, less costly) in 100% of 1000 simulations. Analyses suggest implementing a PCV20 vaccination program in moderate-/high-risk adults aged 18-64 years and all adults ≥ 65 years-in lieu of PCV13 → PPSV23-would yield substantial reductions in pneumococcal disease and would be cost saving to the Argentinean healthcare system.

The impact of different perspectives on the cost-effectiveness of remote patient monitoring for patients with heart failure in different European countries.

Heart failure (HF) is a complex clinical syndrome with high mortality and hospitalization rates. Non-invasive remote patient monitoring (RPM) interventions have the potential to prevent disease worsening. However, the long-term cost-effectiveness of RPM remains unclear. This study aimed to assess the cost-effectiveness of RPM in the Netherlands (NL), the United Kingdom (UK), and Germany (DE) highlighting the differences between cost-effectiveness from a societal and healthcare perspective. We developed a Markov model with a lifetime horizon to assess the cost-effectiveness of RPM compared with usual care. We included HF-related hospitalization and non-hospitalization costs, intervention costs, other medical costs, informal care costs, and costs of non-medical consumption. A probabilistic sensitivity analysis and scenario analyses were performed. RPM led to reductions in HF-related hospitalization costs, but total lifetime costs were higher in all three countries compared to usual care. The estimated incremental cost-effectiveness ratios (ICERs), from a societal perspective, were €27,921, €32,263, and €35,258 in NL, UK, and DE respectively. The lower ICER in the Netherlands was mainly explained by lower costs of non-medical consumption and HF-related costs outside of the hospital. ICERs, from a healthcare perspective, were €12,977, €11,432, and €11,546 in NL, the UK, and DE, respectively. The ICER was most sensitive to the effectiveness of RPM and utility values. This study demonstrates that RPM for HF can be cost-effective from both healthcare and societal perspective. Including costs of living longer, such as informal care and non-medical consumption during life years gained, increased the ICER.

Abstract PO2-03-09: Cost-effectiveness analysis of RAD51 functional biomarker for platinum sensitivity in the GeparSixto trial

Abstract Background: Homologous recombination repair deficiency (HRD) has long been recognized as a predictive biomarker for platinum sensitivity and is present in up to 60% of early triple negative breast cancers (TNBC). Different commercial and lab-developed assays to measure HRD are available, but they do not necessarily reflect homologous recombination functionality. Functional HRD, defined by a low score in RAD51 foci, is emerging as an accurate and dynamic biomarker to predict DNA damaging agents’ response. We performed a cost-effectiveness evaluation of the RAD51 test compared to tumor BRCA1/2 mutation (tBRCA1/2) or genomic HRD by Myriad Mychoice® to identify patients sensitive to platinum-based chemotherapy within the GeparSixto trial. Methods: The effectiveness measure was the primary outcome of the GeparSixto study: rate of pathological complete response (pCR), defined as ypT0 ypN0. The pharmacological costs were calculated following treatment protocol of GeparSixto where TNBC patients received neoadjuvant paclitaxel plus Myocet®-nonpegylated liposomal doxorubicin (PM) or PM plus carboplatin (PMCb), both arms including bevacizumab. Bevacizumab was excluded from the cost analysis as it is not administered by standard practice. The cost of a session/stay at the day hospital was added, as well as the cost of the test used, comparing 4 scenarios: All comers (assuming all patients receiving PMCb); RAD51 test (assuming RAD51 ≤10% received PMCb and RAD51 &amp;gt;10% received PM); tBRCA1/2 test (assuming tBRCA1/2 mutated received PMCb and tBRCA1/2 non-mutated received PM) and genomic HRD by Myriad Mychoice® (HRD score ≥42 received PMCb, and HRD score &amp;lt;42 received PM). The available commercial costs were considered for tBRCA1/2 and Myriad Mychoice®, and the VHIO performance cost was considered for the RAD51 test. Parameter uncertainties were assessed by means of one-way and probabilistic sensitivity analyses. Results: All comers total cost was 20,530€ per patient, with associated pCR rate of 54.5%. Functional RAD51 test was associated with a pCR probability of 55.1% with a Δ cost of 198€, as opposed to tBRCA1/2 which presented a pCR rate of 40.1% with a Δ cost of 814€, and genomic HRD with 47% pCR rate and the higher Δ cost of 1,023€ per patient, when compared to all comers. The incremental cost-effectiveness ratio (Δ cost/Δ pCR) was 33,000 for RAD51 test and dominated in both tBRCA1/2 and genomic HRD tests. These results were robust on one way and probabilistic sensitivity analyses. Conclusion: The most efficient scenarios are the functional RAD51 test and all comers. Both tBRCA1/2 and genomic HRD by Myriad Mychoice® scenarios provide worse health outcomes at a higher cost, based on the data of the GeparSixto trial. This study highlights the potential overall benefit of functional HRD biomarkers to predict PARPi sensitivity. Citation Format: Isabel Pimentel, Carles Forné, Alba Llop-Guevara, Misericòrdia Carles-Lavila, Violeta Serra, Montserrat Rué, Judith Balmaña. Cost-effectiveness analysis of RAD51 functional biomarker for platinum sensitivity in the GeparSixto trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-03-09.

Stratification of Barrett's esophagus surveillance based on p53 immunohistochemistry: a cost effectiveness analysis by an international collaborative group.

Background and Aim Surveillance of non-dysplastic Barrett's esophagus (BE) is recommended to identify progression to dysplasia; however, the most cost-effective strategy remains unclear. Mutation or aberrant expression of p53 has been associated with the development of dysplasia in BE. We sought to determine if surveillance intervals for BE could be stratified based on p53 expression. Methods A Markov model was developed for non-dysplastic BE. Patients with non-dysplastic BE (NDBE) underwent p53 immunohistochemistry (IHC) and those with abnormal p53 expression underwent surveillance endoscopy at 1 year, whilst patients with normal p53 expression underwent surveillance in 3 years. Patients with dysplasia underwent endoscopic therapy and surveillance. Results On base-case analysis, the strategy of stratifying surveillance based on abnormal p53 IHC was cost-effective relative to conventional surveillance and a natural history model, with an ICER of $8,258 for p53 IHC based surveillance. Both conventional and p53 stratified surveillance strategies dominated the natural history model. On probabilistic sensitivity analysis (PSA), the p53 IHC strategy ($28,652, 16.78 QALYs) was more cost-effective than conventional surveillance ($25,679, 16.17 QALYs) with a net monetary benefit (NMB) of $306,873 compared to conventional surveillance ($297,642) with ICER < $50000 in 96% of the iterations. The p53 stratification strategy was associated with a 14.5% reduction in the overall endoscopy burden and a 59% increase in dysplasia. Conclusion: A surveillance strategy for BE based on abnormal p53 IHC is cost-effective relative to a conventional surveillance strategy and is likely to be associated with higher diagnostic rates of dysplasia.

Abstract PO4-10-06: Cost-effectiveness analysis of ribociclib in the treatment for premenopausal or perimenopausal women with HR+/HER2− advanced breast cancer: a public health care system perspective in Mexico

Abstract BACKGROUND: Ribociclib (RIB) an inhibitor of cyclin-dependent kinase 4 and 6 for the treatment of advanced breast cancer (ABC), has demonstrated significant efficacy in prolonging progression-free survival and overall survival when added to endocrine therapy (ET). Because of the high-cost perception of this therapeutic class, it is crucial to assess their relative value compared to existing standards of care in the local setting. Chemotherapy is used as the first line of treatment in a conservative case in almost three-quarters of ABC patients with positive hormone receptors in the Public Health System in Mexico. Additionally, the high use of chemotherapy presents additional clinical and economic challenges for the Institute. Among the clinical challenges, the toxicity associated with chemotherapy regimens stands out. We evaluated the cost-effectiveness of the inclusion of RIB+ ET to usual care in the treatment of premenopausal or perimenopausal ABC from the perspective of the Public Health System in Mexico. Direct medical costs were considered. METHODS: We developed a partitioned survival model to simulate time to cancer progression and to compare lifetime clinical benefit and cost of standard alternative treatment strategies for patients with metastatic disease. Per approved indication, endocrine treatment-naive patients were assigned to RI plus ET or usual care (different chemotherapy schemes). Costs in Mexican Pesos (MXN) were estimated from the perspective of the Public Health System in Mexico. Costs and clinical benefits were discounted at 5% annually. The model assumptions were informed based on published clinical trial data from the randomized Phase III MONALEESA-7 trial and other peer-reviewed studies and indirect treatment comparisons. We carried out one-way and probabilistic sensitivity analyses to assess the robustness of our results to the changes in model assumptions. RESULTS: Ribociclib reduced monthly direct medical costs associated with the administration of breast cancer treatment and the management of adverse events. Direct drug acquisition costs per month of ribociclib were in the range of the cost of current available and used therapies. Indirect treatment comparisons did not show statistical significance of the benefit of ribociclib vs. standard of care, primarily due to heterogeneity leading to a mixed evaluation vs. two comparator groups according to the statistical significance of the survival improvement. Ribociclib is a 100% oral therapy with a manageable safety profile with dosage adjustments, so it does not require institutional resources for its administration or for managing adverse events. Its consolidated cost at 28 days of treatment is up to 40% less than combined chemotherapy regimens and up to 30% less than monotherapy schemes. Average cost-effectiveness for progression-free survival for ribociclib is among the lowest considering chemotherapy options even though generic versions are available for many of them. For the comparators with comparable efficacy, ribociclib was cost-saving at current public market prices. For the comparators where ribociclib showed a significant benefit, the incremental cost-effectiveness ratio of ribociclib vs. standard of care is also below the threshold of 3 GDPs per capita vs. most options, leading to cost-effectiveness. A longer treatment duration due to progression delay was a main driver of incremental cost. CONCLUSIONS: Ribociclib is cost-saving or cost-effective vs. standard of care in the Public Health System in Mexico. Other variables must be considered to inform clinical and funding decisions, such as disease burden and humanistic impact on this young, economically active population. Citation Format: Saúl Campos-Gomez, Christian Pichardo Piña. Cost-effectiveness analysis of ribociclib in the treatment for premenopausal or perimenopausal women with HR+/HER2− advanced breast cancer: a public health care system perspective in Mexico [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-10-06.

Cost-effectiveness of temperature monitoring to help prevent foot ulcer recurrence in people with diabetes: A multicenter randomized controlled trial.

Diabetes-related foot ulcers are common, costly, and frequently recur. Multiple interventions help prevent these ulcers. However, none of these have been prospectively investigated for cost-effectiveness. Our aim was to evaluate the cost-effectiveness of at-home skin temperature monitoring to help prevent diabetes-related foot ulcer recurrence. Multicenter randomized controlled trial. We randomized 304 persons at high diabetes-related foot ulcer risk to either usual foot care plus daily at-home foot skin temperature monitoring (intervention) or usual care alone (control). Primary outcome was cost-effectiveness based on foot care costs and quality-adjusted life years (QALY) during 18 months follow-up. Foot care costs included costs for ulcer prevention (e.g., footwear, podiatry) and for ulcer treatment when required (e.g., consultation, hospitalisation, amputation). Incremental cost-effectiveness ratios were calculated for intervention versus usual care using probabilistic sensitivity analysis for willingness-to-pay/accept levels up to €100,000. The intervention had a 45% probability of being cost-effective at a willingness-to-accept of €50,000 per QALY lost. This resulted from (non-significantly) lower foot care costs in the intervention group (€6067 vs. €7376; p=0.45) because of (significantly) fewer participants with ulcer recurrence(s) in 18months (36% vs. 47%; p=0.045); however, QALYs were (non-significantly) lower in the intervention group (1.09 vs. 1.12; p=0.35), especially in those without foot ulcer recurrence (1.09 vs. 1.17; p=0.10). At-home skin temperature monitoring for diabetes-related foot ulcer prevention compared with usual care is at best equally cost-effective. The intervention resulted in cost-savings due to preventing foot ulcer recurrence and related costs, but this came at the expense of QALY loss, potentially from self-monitoring burdens.

Cost-Effectiveness of Lovotibeglogene Autotemcel (Lovo-Cel) Gene Therapy for Patients with Sickle Cell Disease and Recurrent Vaso-Occlusive Events in the United States.

Gene therapies for sickle cell disease (SCD) may offer meaningful benefits for patients and society. This study evaluated the cost-effectiveness of lovotibeglogene autotemcel (lovo-cel), a one-time gene therapy administered via autologous hematopoietic stem cell transplantation, compared with common care for patients in the United States (US) with SCD aged ≥12years with ≥4 vaso-occlusive events (VOEs) in the past 24months. We developed a patient-level simulation model accounting for lovo-cel and SCD-related events, complications, and mortality over a lifetime time horizon. The pivotal phase1/2 HGB-206 clinical trial (NCT02140554) served as the basis for lovo-cel efficacy and safety. Cost, quality-of-life, and other clinical data were sourced from HGB-206 data and the literature. Analyses were conducted from US societal and third-party payer perspectives. Uncertainty was assessed through probabilistic sensitivity analysis and extensive scenario analyses. Patients treated with lovo-cel were predicted to survive 23.84years longer on average (standard deviation [SD], 12.80) versus common care (life expectancy, 62.24 versus 38.40years), with associated discounted patient quality-adjusted life-year (QALY) gains of 10.20 (SD, 4.10) and direct costs avoided of $1,329,201 (SD, $1,346,446) per patient. Predicted societal benefits included discounted caregiver QALY losses avoided of 1.19 (SD, 1.38) and indirect costs avoided of $540,416 (SD, $262,353) per patient. Including lovo-cel costs ($3,282,009 [SD, $29,690] per patient) resulted in incremental cost-effectiveness ratios of $191,519 and $124,051 per QALY gained from third-party payer and societal perspectives, respectively. In scenario analyses, the predicted cost-effectiveness of lovo-cel also was sensitive to baseline age and VOE frequency and to the proportion of patients achieving and maintaining complete resolution of VOEs. Our analysis of lovo-cel gene therapy compared with common care for patients in the US with SCD with recurrent VOEs estimated meaningful improvements in survival, quality of life, and other clinical outcomes accompanied by increased overall costs for the health care system and for broader society. The predicted economic value of lovo-cel gene therapy was influenced by uncertainty in long-term clinical effects and by positive spillover effects on patient productivity and caregiver burden.

Cost-Effectiveness of Diffusion Weighted MRI Versus Planned Second-Look Surgery for Cholesteatoma.

To compare the cost-effectiveness of serial non-echo planar diffusion weighted MRI (non-EP DW MRI) versus planned second look surgery following initial canal wall up tympanomastoidectomy for the treatment of cholesteatoma. A decision-analytic model was developed. Model inputs including residual cholesteatoma rates, rates of non-EP DW MRI positivity after surgery, and health utility scores were abstracted from published literature. Cost data were derived from the 2022 Centers for Medicare and Medicaid Services fee rates. Efficacy was defined as increase in quality-adjusted life year (QALY). One- and 2-way sensitivity analyses were performed on variables of interest to probe the model. Total time horizon was 50 years with a willingness to pay (WTP) threshold set at $50 000/QALY. Base case analysis revealed that planned second-look surgery ($11 537, 17.30 QALY) and imaging surveillance with non-EP DWMRI ($10 439, 17.26 QALY) were both cost effective options. Incremental cost effectiveness ratio was $27 298/QALY, which is below the WTP threhshold. One-way sensitivity analyses showed that non-EP DW MRI was more cost effective than planned second-look surgery if the rate of residual disease after surgery increased to 48.3% or if the rate of positive MRI was below 45.9%. A probabilistic sensitivity analysis at WTP of $50 000/QALY found that second-look surgery was more cost-effective in 56.7% of iterations. Non-EP DW MRI surveillance is a cost-effect alternative to planned second-look surgery following primary canal wall up tympanomastoidectomy for cholesteatoma. Cholesteatoma surveillance decisions after initial canal wall up tympanomastoidectomy should be individualized. V.