Quality-adjusted Life-year Outcomes Research Articles

Ferric derisomaltose versus usual care in patients with heart failure, reduced ejection fraction, and iron deficiency: a short-term UK cost-utility analysis based on the IRONMAN RCT

Abstract Background In the IRONMAN trial, patients with heart failure (HF), a reduced ejection fraction and iron deficiency who were randomly assigned to ferric derisomaltose (FDI), rather than usual care, had a lower rate of the composite of hospitalization for heart failure (HHF) and cardiovascular (CV) death (rate ratio, RR, 0.82; 95% CI 0.66 to 1.02; p=0.07). A COVID-19 sensitivity analysis, censoring data at 1 year of follow-up showed a greater magnitude of treatment effect (RR 0.66; 95% CI 0.48 to 0.91; p=0.011). Purpose Patient-level data from IRONMAN were used to evaluate the effectiveness and cost-utility of FDI compared to usual care for patients with a current or recent HHF, or raised plasma natriuretic peptide concentrations, from a UK National Health Service (NHS) perspective. Methods A cost-utility analysis (CUA) was conducted covering the first year after randomization. Numbers-needed-to-treat (NNTs) were calculated for the primary endpoint censored at 1 year. In the CUA model, patient survival and rates of (re)hospitalization due to HF, other CV events, infections, respiratory conditions, and other non-CV events were modeled based directly on data from the IRONMAN RCT. UK-specific costs were obtained from the national schedule of NHS costs. Quality of life was estimated based on EQ-5D-5L data collected from patients included in the IRONMAN RCT. Results were undiscounted and reported as absolute and incremental costs in 2023 pounds sterling, and quality-adjusted life expectancy in quality-adjusted life years (QALYs). A willingness-to-pay threshold of £20,000 per QALY was adopted to allow calculation of a net monetary benefit (NMB), a summary measure of the overall value of FDI in monetary terms, capturing changes in both cost and QALY outcomes. Results The NNT analysis showed that 9 patients would need to be treated with FDI to avoid one composite primary endpoint event (CV death and HHF) over 1 year. Relative to usual care, FDI was associated with an improvement of 0.01 QALYs per patient over 1 year (0.58 versus 0.57 QALYs). Total average costs per-patient were £1,672 for FDI, versus £1,975 for usual care, leading to a saving of £302 per patient with FDI. The cost of iron procurement was more than offset by reductions in costs of (re)hospitalizations (Figure). FDI was therefore dominant over usual care, yielding an NMB of £483 over 1 year. Conclusions This short-term, within-trial CUA suggests that FDI both improves QALYs and reduces healthcare expenditure versus usual care when administered to patients with HF and iron deficiency in the UK. Iron repletion with FDI may be a prudent allocation of healthcare resources in this patient population.Breakdown of costs

Economic Assessment in Resource-Constrained Systems: Individual-Level Simulation Model in Wet Age-Related Macular Degeneration and Diabetic Macular Oedema.

Cost-effectiveness analyses typically ignore healthcare system resource constraints. Ophthalmology is affected by resource constraints because of increasing disease prevalence and the use of resource-intensive treatments. This study evaluated the impact of resource constraints on the cost-effectiveness of faricimab 6mg, compared with aflibercept 2mg and ranibizumab biosimilar 0.5mg, for treating wet age-related macular degeneration (wAMD) or diabetic macular oedema (DMO) over a 5-year horizon. A microsimulation model estimated the impact of resource constraints on patients visits, delays, costs and quality-adjusted life-year (QALY) losses due to treatment delays at a typical UK National Health Service eye hospital treating 1500 patients with wAMD and 500 patients with DMO. Patient characteristics, treatment regimens and treatment intervals were informed using published literature and expert opinion. Resource constraint was represented by limiting the number of available intravitreal injection appointments per week, with growing demand caused by rising disease prevalence. The model compared outcomes across three scenarios; each scenario involved treating all patients with one of the three treatments. Over 5years, in a resource-constrained hospital, compared with aflibercept, faricimab use resulted in the avoidance of 12,596 delays, saved GBP/£15,108,609 in cost and avoided the loss of 60.06 QALYs. Compared with ranibizumab biosimilar, faricimab use resulted in the avoidance of 18,910 delays, incurred £2,069,088 extra cost and avoided the loss of 105.70 QALYs, resulting in an incremental cost-effectiveness ratio of £19,574/QALY. Accounting for resource constraints in health economic evaluation is crucial. Emerging therapies that are more durable and require less frequent clinic visits can reduce treatment delays, leading to improved QALY outcomes and reduced burden on healthcare systems. Faricimab reduced the number of delayed injections, leading to improved QALY outcomes for patients in a healthcare system with resource constraints. Faricimab is cost-saving when compared with aflibercept and cost-effective when compared with ranibizumab biosimilar.

Informing optimal treatment (tx) sequences for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma (la/mUC) in the United States: Results of a clinical simulation modeling exercise.

e13514 Background: Platinum-based chemotherapy (PBT) followed by avelumab (AVE) as first-line (1L) maintenance for patients with nonprogressive disease (PBT ± AVE) is the standard of care in la/mUC. This study compared the overall survival (OS) and cost-effectiveness of the tx sequence of PBT ± AVE followed by enfortumab vedotin (EV) or other therapies, including immuno-oncology (IO), in second line (2L; ie, PBT + 2L EV/IO or PBT + AVE + 2L EV/IO) vs 1L EV + pembrolizumab (PEM) for PBT-eligible patients (PBTp) from a US commercial payer perspective. Methods: A partitioned survival model compared outcomes with PBT ± AVE and EV + PEM among PBTp. Inputs included progression-free survival and OS, time to tx discontinuation, adverse event (AE) incidence, and health utilities and costs. Efficacy inputs were sourced and extrapolated from patient data in JAVELIN Bladder 100 (data cut: Jun 4, 2021), AVENANCE real-world study (1), and published data (EV-302 trial). Safety data were sourced from US prescribing information. Drug, subsequent tx, disease management, and AE management costs (2023 USD) were calculated. The optimal tx sequencing scenario assumed 80% of patients starting PBT were eligible to receive AVE (2023 Flatiron data cut; (2)), 70% of patients progressing on PBT ± AVE would start 2L, and 70% of those would be eligible for EV. Outcomes included life-years (LYs), quality-adjusted LYs (QALYs), costs, and incremental cost-effectiveness ratio (ICER). Scenarios and probabilistic sensitivity analyses (PSAs) were conducted to assess uncertainty. Results: LY, QALY, costs, and ICER modeling outcomes are shown in the Table. Use of EV in 2L after PBT ± AVE is associated with 0.76 lower QALYs, but given the large cost saving, it represents a cost-effective use of resources at the $150,000/QALY willingness to pay (WTP) threshold. PSAs showed that PBT ± AVE is likely to be more cost-effective over a broad and relevant WTP threshold range ($0-500,000/QALY). Results were sensitive to drug acquisition costs and eligibility to receive AVE and 2L EV. Conclusions: Based on this simulation exercise, the use of 2L EV after PBT ± AVE achieves considerable survival benefit at substantially lower costs vs 1L EV + PEM in PBTp with la/mUC. Given the shift toward value-based care in oncology, such analyses are becoming increasingly relevant to guide clinical decision-making. There is a need to assess tx alternatives that balance healthcare costs while optimizing outcomes in patients with la/mUC. 1. Barthélémy et al, J Clin Oncol 2024;42[suppl 4]: Abstract 561. 2. Moon et al, J Clin Oncol 2023;41[suppl 16]: Abstract 4567. [Table: see text]

Short-term cost-utility analysis of biventricular cardiac resynchronization therapy in comparison with left bundle branch area pacing cardiac resynchronization therapy

Abstract Background Cardiac resynchronisation therapy (CRT) is a well-established form of treatment for patients with heart failure and cardiac dyssynchrony. Recently, left bundle branch area pacing (LBBAP) has emerged as a more physiological alternative for biventricular pacing (BiVP) cardiac resynchronization therapy (1,2). Purpose The purpose of this study was to conduct a cost-utility analysis for LBBAP CRT, compared to BiVP CRT in a cohort of patients with heart failure from the Spanish health system perspective. Methods A multicenter prospective quasi-experimental study in which 44 consecutive patients underwent CRT was conducted. According to the study protocol, the four centers would perform their usual clinical practice: two out of them would perform conventional BiVP-CRT while the other half LBBAP-CRT. Intention-to-treat analysis was carried-out. Health outcomes were quality-adjusted life years (QALYs), measured by the EuroQol-5D-5L questionnaire, which the patients were asked to complete at baseline and 12 weeks after the CRT device implantation. The total direct costs include device, leads, guidewires, introducer kits, sheats and operating theater time. The results were expressed as the incremental cost-utility ratio (ICUR). In order to analyze the uncertainty of ICUR results, we performed a non-parametric bootstrapping with 1000 replications. Results The LBBAP procedure was attempted for a total of 26 consecutive patients (1 patient underwent rescue BiVP), while BiVP was attempted for 18 patients (2 patients switched to LBBAP). Mean QALYs over 3 months were 0.1914 ± 0.009 in the LBBAP CRT group and 0.1904 ± 0.0112 in the BiVP CRT. Improvements from baseline were greater in the LBBA CRT group but not statistically significant. The total costs at the end of the intervention were 7546.6 €± 602.15€ in the LBBAP CRT group and 16064.56€ ± 723.7€ in the BiVP CRT group. When excluding from the analysis the cases in which ICD was implanted, the mean difference in QALYs is 0.002; 95% confidence interval [95%CI]: -0.03 to 0.036) and the mean saving is -3.510.38 €. The LBBAP CRT leads to cost savings for the health system and similar QALYs outcomes; 95%CI: -6.660 to -360.71. Based on 1000 bootstrapping replication, the cost savings of using LBBAP vs BiVP occur in 99% of the simulations. Conclusion LBBAP CRT is an efficient alternative to BiVP CRT for cardiac resynchronization in patients with heart failure with similar results in terms of QALYs but with significant average savings per patient.Cost-utility plane for 1000 bootstrappedBaseline characteristics of patients

Cost Effectiveness of Mosunetuzumab and CAR-T Cell Therapy in Relapsed/Refractory Follicular Lymphoma

Background: T cell engaging therapies including mosunetuzumab (mosun), a CD20/CD3 bispecific antibody, and two CAR-T cell products - axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), are FDA approved for the treatment of third line and beyond relapsed/refractory (R/R) follicular lymphoma (FL). There are no randomized comparative effectiveness trials between mosun, axi-cel and tisa-cel to guide sequencing of treatment. These products differ in their administration, hospitalization requirements, and toxicity profiles. Knowledge of relative quality-of-life and cost effectiveness may play a role in patient and clinician therapy selection. Methods: We created a Markov model from one year to ten years from the perspective of a US payer to reflect costs and quality of life utilities associated with various health states in the course of treatment for R/R FL. Rates of complete response, partial response, days of inpatient hospitalization, incidence of toxicities such as cytokine release syndrome, neurotoxicity or neutropenia and their associated supportive care costs were derived from ZUMA-5, ELARA and Phase II mosun published data (Budde et al. Lancet Onc 2022). Additional health states in the model included re treatment with mosun if patients achieved an initial response followed by progression, palliative care or observation, other third line treatments including switch to alternative T-cell engaging therapy and death. Progression-free survival and overall survival were calibrated over a 2-year time horizon. In our base case analysis, we calculated discounted cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). We then incorporated costs and QALY to calculate the net monetary benefit (NMB) for each treatment using a willingness-to-pay threshold of $150,000 per QALY. Results : Based on the 2-year follow up published clinical trial data, we estimated the 5 and 10-year PFS rates to be 14.41% and 2.72% at 5 and 10 years for mosun, 28.39% and 8.13% for axi-cel, and 16.59% and 3.03% for tisa-cel. In our base case analysis, the one-year total cost of mosun is $308,992, compared to $523,468 for axi-cel and $500,305 for tisa-cel (Table 1). When comparing mosun with axi-cel, mosun showed slightly improved QALY over axi-cel at years 1 and 2 (0.67 and 1.24 vs. 0.65 and 1.23, respectively), mosun and axi-cel had equivalent QALYs at 5 years (2.53), and axi-cel showing slightly improved QALY at year 10 (3.68 for mosun vs. 3.70 for axi-cel). NMB favored mosun over axi-cel at all time points with $217,853 at year 1, $170,052 at year 2, $110,606 at year 5 and $88,000 at year 10 (Figure 1). NMB favored mosun even with the slightly improved QALY at year 10 seen with axi-cel. The overall cost and QALY outcomes suggest axi-cel would cost an additional $5.4 million per QALY gained compared to mosun over this ten-year time horizon. When comparing mosun to tisa-cel, mosun showed improved costs and slightly improved QALY. NMB favored mosun over tisa-cel at all time points with $197,137 at year 1, $162,126 at year 2, $128,423 at year 5, and $125,128 at year 10. The overall cost and QALY outcomes suggest tisa-cel would cost an additional $2 million per QALY gained compared to mosun over this ten-year time horizon. Adjusting for varying response rates, toxicities, and utilities in a one-way sensitivity analysis showed that the discounted NMB per patient over time continued to favor mosun compared to both CAR-T cell products. Even assuming axi-cel and tisa-cel could be delivered as fully outpatient therapy, mosun remained cost effective at all time points over axi-cel (10 year NMB $72,004 favoring mosun) and tisa-cel (10 year NMB $119,331 favoring mosun). Conclusions: Our model indicates that mosun is more cost-effective compared to both axi-cel and tisa-cel at 1, 2, 5 and 10 years for treatment of R/R FL. Axi-cel showed improved QALY at 10 years due to improved long term PFS, however mosun remained cost effectiveness even at the 10 year horizon. Longer term follow up of patients treated with mosun as well as real world data of ORR, PFS and OS of patients treated with CAR-T after bispecific antibodies may impact future cost effectiveness and QALY comparisons.

Economic evaluation of a mobile phone text-message intervention for Australian adults with type 2 diabetes.

The rising prevalence of type 2 diabetes in Australia is a public health concern, contributing to significant disease burden and economic costs. Text-message programs have been shown to improve health outcomes for people with type 2 diabetes, however they remain underutilized, and no evidence exists on their cost-effectiveness or costs of scale up to a population level in Australia. This study aimed to determine the cost-effectiveness and cost-utility of a 6-month text-message intervention (DTEXT) to improve glycated hemoglobin (HbA1c) and self-management behaviors for Australian adults with type 2 diabetes. A within-trial economic evaluation was conducted on the DTEXT randomized controlled trial. Incremental cost-effectiveness ratios (ICERs) were determined per 11 mmol/mol (1%) reduced HbA1c and per quality adjusted life year (QALY) gained, compared to usual care. Cost-effectiveness acceptability curves (CEAC) determined the probability of the intervention being cost-effective over a range of willingness to pay thresholds. A scenario analysis was conducted to determine how cost-effectiveness was impacted by using current implementation costs. The DTEXT intervention cost AU$36 (INT$24) per participant, with an ICER of AU$311 (INT$211) per 11 mmol/mol (1%) reduced HbA1c. Based on HbA1c outcomes, DTEXT had a 33% probability of being effective and cost-saving. Based on the QALY outcomes, the intervention had only a 24% probability of being cost-effective. Scenario analysis indicated costs per participant of AU$13 (INT$9) to deliver the intervention, with a reduced incremental cost effectiveness ratio of AU$151 (INT$103) per 11 mmol/mol (1%) reduced HbA1c and a 38% probability of being effective and cost-saving. DTEXT was low cost and potentially scalable, but only had a low to moderate probability of being effective and cost saving. Further research should determine more targeted approaches that may improve cost-effectiveness. ACTRN12617000416392.

Intraoperative neuromonitoring in spine surgery: large database analysis of cost-effectiveness

BackgroundGiven the increased attention to functional improvement in spine surgery as it relates to activities of daily living and cost, it is critical to fully understand the health care economic impact of enabling technologies. The use of intraoperative neuromonitoring (IOM) during spine surgery has long been controversial. Questions pertaining to utility, medico-legal considerations, and cost-effectiveness continue to be unresolved. The purpose of this study is to determine the cost-effectiveness by assessing quality-of-life due to adverse events averted, decreased postoperative pain, decreased revision rates, and improved patient reported outcomes (PROs). MethodsThe study patient population was extracted from a large multicenter database collected by a single, national IOM provider. Over 50,000 patient charts were abstracted and included in this analysis. The analysis was conducted in accordance with the second panel on cost-effectiveness health and medicine. Health-related utility was derived from questionnaire answers and expressed in quality-adjusted life years (QALYs). Both cost and QALY outcomes were discounted at a yearly rate of 3% to reflect their present value. Cost-effectiveness was calculated as the incremental cost-effectiveness ratio (ICER) for IOM. A value under the commonly accepted United States-based willingness-to-pay (WTP) threshold of $100,000 per QALY was considered cost-effective. Scenario (including litigation), probabilistic (PSA), and threshold sensitivity analyses were conducted to determine model discrimination and calibration. ResultsThe primary time horizon used to estimate cost and health utility was 2-years following index surgery. On average, index surgery for patients with IOM costs are approximately $1,547 greater than non-IOM cases. The base case assumed an inpatient Medicare population however multiple outpatient and payer scenarios were assessed in the sensitivity analysis. From a health system perspective IOM is cost-effective, yielding better utilities but at a higher cost than the non-IOM strategy (ICER $60,734 per QALY). From a societal perspective the IOM strategy was dominant, suggesting that better outcomes were achieved at less cost. Except for an entirely privately insured population, alternative scenarios such as, outpatient and a 50:50 Medicare/privately insured population sample also demonstrated cost-effectiveness. Notably, IOM benefits were unable to overcome the sheer costs associated many litigation scenarios, but the data was severely limited. In the 5,000 iteration PSA, at a WTP of $100,000, 74% of simulations using IOM were cost-effective. ConclusionsThe use of IOM in spine surgery is cost-effective in most scenarios examined. In the emerging and rapidly expanding field of value-based medicine, there will be an increased demand for these analyses, ensuring surgeons are empowered to make the best, most sustainable solutions for their patients and the health care system.

Health-related quality-of-life and health-utility reporting in critical care.

Mortality is a well-established patient-important outcome in critical care studies. In contrast, morbidity is less uniformly reported (given the myriad of critical care illnesses and complications of each) but may have a common end-impact on a patient’s functional capacity and health-related quality-of-life (HRQoL). Survival with a poor quality-of-life may not be acceptable depending on individual patient values and preferences. Hence, as mortality decreases within critical care, it becomes increasingly important to measure intensive care unit (ICU) survivor HRQoL. HRQoL measurements with a preference-based scoring algorithm can be converted into health utilities on a scale anchored at 0 (representing death) and 1 (representing full health). They can be combined with survival to calculate quality-adjusted life-years (QALY), which are one of the most widely used methods of combining morbidity and mortality into a composite outcome. Although QALYs have been use for health-technology assessment decision-making, an emerging and novel role would be to inform clinical decision-making for patients, families and healthcare providers about what expected HRQoL may be during and after ICU care. Critical care randomized control trials (RCTs) have not routinely measured or reported HRQoL (until more recently), likely due to incapacity of some patients to participate in patient-reported outcome measures. Further differences in HRQoL measurement tools can lead to non-comparable values. To this end, we propose the validation of a gold-standard HRQoL tool in critical care, specifically the EQ-5D-5L. Both combined health-utility and mortality (disaggregated) and QALYs (aggregated) can be reported, with disaggregation allowing for determination of which components are the main drivers of the QALY outcome. Increased use of HRQoL, health-utility, and QALYs in critical care RCTs has the potential to: (1) Increase the likelihood of finding important effects if they exist; (2) improve research efficiency; and (3) help inform optimal management of critically ill patients allowing for decision-making about their HRQoL, in additional to traditional health-technology assessments.

Cost-Effectiveness of iGlarLixi Versus Premix BIAsp 30 in Patients with Type 2 Diabetes Suboptimally Controlled by Basal Insulin in the UK.

IntroductioniGlarLixi is indicated as an adjunct to diet and exercise in addition to metformin (with or without sodium-glucose cotransporter-2 inhibitors) to improve glycemic control in adults with insufficiently controlled type 2 diabetes (T2D). A cost-effectiveness analysis was conducted to compare iGlarLixi with premix biphasic insulin aspart 30 (BIAsp 30) in people with T2D suboptimally controlled with basal insulin (BI).MethodsThe IQVIA CORE Diabetes Model was used to estimate lifetime costs and outcomes for people with T2D from a UK health care perspective at a willingness-to-pay threshold of £20,000. Initial clinical data were based on the phase 3 randomized, open-label, active-controlled SoliMix clinical trial which compared the efficacy and safety of once-daily iGlarLixi with that of twice-daily BIAsp 30. Costs associated with management and complications and utilities values were derived from published sources. Lifetime costs (in £GBP) and quality-adjusted life-years (QALYs) were predicted; extensive scenario and sensitivity analyses were conducted.ResultsEstimated QALYs gained were slightly higher with iGlarLixi (8.9 vs. 8.8) compared with premix BIAsp 30, at a higher cost (£23,204 vs. £21,961). The base case incremental cost-effectiveness ratio (ICER) per QALY was £13,598. Treatment acquisition was the main driver of cost differences (iGlarLixi, £11,750; premix BIAsp 30, £10,395). Costs associated with management and complications were generally similar between comparators.ConclusioniGlarLixi provides improved QALY outcomes at an acceptable cost compared with premix BIAsp 30, with an ICER below the threshold generally considered acceptable by UK authorities. In people with T2D, iGlarLixi is a simple, cost-effective option for advancing therapy of BI, with fewer daily injections than premix BIAsp 30.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01267-3.

The potential long-term comparative effectiveness of larotrectinib vs standard of care for treatment of metastatic TRK fusion thyroid cancer, colorectal cancer, and soft tissue sarcoma

BACKGROUND: Larotrectinib is approved for patients with metastatic TRK fusion cancers, including differentiated thyroid (DTC), colorectal cancer (CRC), and soft tissue sarcoma (STS). Given the basket clinical trial design of larotrectinib, direct comparisons against standard of care in each of the mentioned cancers have not been assessed. Also, owing to the limited duration of follow-up in clinical trials, long-term outcomes for treatments are generally not known or estimated. OBJECTIVE: To compare expected life-years (LYs) and quality-adjusted life-years (QALYs) for patients with metastatic DTC, CRC, and STS who are eligible to receive larotrectinib against patients with unknown NTRK gene fusion status receiving standard-of-care therapy. METHODS: We developed a partitioned survival model to estimate the long-term comparative effectiveness of larotrectinib and standard of care for 3 tumor types. Larotrectinib survival data, assessed by independent review committee, were derived from an updated July 2020 analysis of 19, 8, and 23 adult patients (aged ≥ 18 years) with metastatic TRK fusion DTC, CRC, and STS, respectively. The DTC survival data also included 2 patients aged less than 18 years for a total of 21 patients. Survival estimates for standard of care were derived from published clinical trials. Progressionfree and overall survival for all treatments were estimated using survival distributions (Exponential, Weibull, Log-logistic, and Lognormal) fit to the available data. The final exponential form was selected based on goodness-of-fit and clinical plausibility. QALYs were estimated by adjusting the time spent in the preprogression and postprogression health states by utility weights derived from publicly available literature. RESULTS: Patients receiving larotrectinib experienced more LYs and QALYs compared with those receiving standard-of-care treatments across all 3 assessed cancer types. In DTC, patients receiving larotrectinib had 7.15-8.26 additional LYs (5.87-6.12 QALYs); in CRC, patients receiving larotrectinib had 1.26-1.27 additional LYs (1.00 QALYs); and in STS, patients receiving larotrectinib had 5.56 additional LYs (1.99 QALYs). CONCLUSIONS: Compared with standard of care in metastatic TRK wild-type cancers, larotrectinib is estimated to result in improved LY and QALY outcomes based on parametric extrapolations of intrial survival data. Because patient-level data were unavailable for adjusted analyses, a cross-trial comparison was performed. Given the limitations of this analytic approach and the small sample size for larotrectinib in trials, future studies should reassess the comparative effectiveness of larotrectinib vs standard of care as treated patients accrue and long-term survival data mature. DISCLOSURES: K. Suh, J. Carlson, and S. Sullivan report consulting fees from Bayer US LLC. F. Xia and T. Williamson are employees of Bayer US LLC. This study was funded by Bayer US LLC. The sponsor had no role in the design of the study and did not have any role in the execution, analyses, interpretation of the data, or decision to submit results.

A Cost-Utility Analysis of the Syncope: Pacing or Recording in The Later Years (SPRITELY) Trial

BackgroundThe Syncope: Pacing or Recording in the Later Years (SPRITELY) trial reported that a strategy of empiric permanent pacing in patients with syncope and bifascicular block reduces major adverse events more effectively than acting on the results of an implantable cardiac monitor (ICM). Our objective was to determine the cost-effectiveness of using the ICM, compared with a pacemaker (PM), in the management of older adults (age > 50 years) with bifascicular block and syncope enrolled in the SPRITELY trial. MethodsSPRITELY was a pragmatic, open-label randomized controlled trial with a median follow-up of 33 months. The primary outcome of this analysis is the cost per additional quality-adjusted life-year (QALY). Resource utilization and utility data were collected prospectively, and outcomes at 2 years were compared between the 2 arms. A decision analytic model simulated a 3-year time horizon. ResultsThe mean cost incurred by participants randomized to the PM arm was $9918, compared to $15,416 (both in Canadian dollars) for participants randomized to the ICM arm. The ICM strategy resulted in 0.167 QALYs fewer than the PM strategy. Cost and QALY outcomes are sensitive to the proportion of participants randomized to the ICM arm who subsequently required PM insertion. In 40,000 iterations of probabilistic sensitivity analysis, the PM strategy resulted in cost-savings in 99.7% of iterations, compared with the ICM strategy. ConclusionsThe PM strategy was dominant—that is, less costly and estimated to result in a greater number of QALYs. For patients with unexplained syncope, bifascicular block, and age > 50 years, a PM is more likely to be cost-effective than an ICM.

A Prospective Study of Lumbar Facet Arthroplasty in the Treatment of Degenerative Spondylolisthesis and Stenosis: Early Cost-effective Assessment from the Total Posterior Spine System (TOPS™) IDE Study.

Background: Given the increased attention to functional improvement in spine surgery as it relates to motion preservation, activities of daily living, and cost, it is critical to fully understand the healthcare economic impact of new devices being tested in large FDA randomized controlled trials (RCT). The purpose of this analysis was to comprehensively evaluate the cost-effectiveness of the novel Total Posterior Spine (TOPS™) System investigational device compared with the trial control group, standard transforaminal lumbar interbody fusion (TLIF).Objective: To evaluate the cost-effectiveness of TOPS™ compared with TLIF.Methods: The study patient population was extracted from a multicenter RCT with current enrollment at n=121 with complete 1-year follow-up. The primary outcome was cost-effectiveness, expressed as the incremental cost-effectiveness ratio. Secondary outcomes were health-related utility, presented as quality-adjusted life-years (QALYs), and cost, calculated in US dollars. Analysis was conducted following Second Panel on Cost-Effectiveness Health and Medicine recommendations. The base case analysis utilized SF-36 survey data from the RCT. Both cost and QALY outcomes were discounted at a yearly rate of 3% to reflect their present value. A cohort Markov model was constructed to analyze perioperative and postoperative costs and QALYs for both TOPS™ and control groups. Scenario, probabilistic, and threshold sensitivity analyses were conducted to determine model discrimination and calibration.Results: The primary time horizon used to estimate cost and health utility was 2 years after index surgery. From a health system perspective, assuming a 50/50 split between Medicare and private payers, the TOPS™ cohort is cost-effective 2 years postoperatively ($6158/QALY) compared with control. At 6 years and beyond, TOPS™ becomes dominant, irrespective of payer mix and surgical setting. At willingness-to-pay thresholds of $100 000/QALY, 63% of all 5000 input parameter simulations favor TOPS, even with a $4000 upcharge vs TLIF.Discussion: The novel TOPS™ device is cost-effective compared with TLIF and becomes the dominant economic strategy over time.Conclusions: In the emerging, rapidly expanding field of value-based medicine, there will be an increased demand for these analyses, ensuring surgeons are empowered to make the best, most sustainable solutions for their patients and society.

A Prospective Study of Lumbar Facet Arthroplasty in the Treatment of Degenerative Spondylolisthesis and Stenosis: Early Cost-effective Assessment from the Total Posterior Spine System (TOPS™) IDE Study

Background: Given the increased attention to functional improvement in spine surgery as it relates to motion preservation, activities of daily living, and cost, it is critical to fully understand the healthcare economic impact of new devices being tested in large FDA randomized controlled trials (RCT). The purpose of this analysis was to comprehensively evaluate the cost-effectiveness of the novel Total Posterior Spine (TOPS™) System investigational device compared with the trial control group, standard transforaminal lumbar interbody fusion (TLIF). Objective: To evaluate the cost-effectiveness of TOPS™ compared with TLIF. Methods: The study patient population was extracted from a multicenter RCT with current enrollment at n=121 with complete 1-year follow-up. The primary outcome was cost-effectiveness, expressed as the incremental cost-effectiveness ratio. Secondary outcomes were health-related utility, presented as quality-adjusted life-years (QALYs), and cost, calculated in US dollars. Analysis was conducted following Second Panel on Cost-Effectiveness Health and Medicine recommendations. The base case analysis utilized SF-36 survey data from the RCT. Both cost and QALY outcomes were discounted at a yearly rate of 3% to reflect their present value. A cohort Markov model was constructed to analyze perioperative and postoperative costs and QALYs for both TOPS™ and control groups. Scenario, probabilistic, and threshold sensitivity analyses were conducted to determine model discrimination and calibration. Results: The primary time horizon used to estimate cost and health utility was 2 years after index surgery. From a health system perspective, assuming a 50/50 split between Medicare and private payers, the TOPS™ cohort is cost-effective 2 years postoperatively ($6158/QALY) compared with control. At 6 years and beyond, TOPS™ becomes dominant, irrespective of payer mix and surgical setting. At willingness-to-pay thresholds of $100 000/QALY, 63% of all 5000 input parameter simulations favor TOPS, even with a $4000 upcharge vs TLIF. Discussion: The novel TOPS™ device is cost-effective compared with TLIF and becomes the dominant economic strategy over time. Conclusions: In the emerging, rapidly expanding field of value-based medicine, there will be an increased demand for these analyses, ensuring surgeons are empowered to make the best, most sustainable solutions for their patients and society.

Cost-effectiveness of Artificial Intelligence as a Decision-Support System Applied to the Detection and Grading of Melanoma, Dental Caries, and Diabetic Retinopathy

To assess the cost-effectiveness of artificial intelligence (AI) for supporting clinicians in detecting and grading diseases in dermatology, dentistry, and ophthalmology. AI has been referred to as a facilitator for more precise, personalized, and safer health care, and AI algorithms have been reported to have diagnostic accuracies at or above the average physician in dermatology, dentistry, and ophthalmology. This economic evaluation analyzed data from 3 Markov models used in previous cost-effectiveness studies that were adapted to compare AI vs standard of care to detect melanoma on skin photographs, dental caries on radiographs, and diabetic retinopathy on retina fundus imaging. The general US and German population aged 50 and 12 years, respectively, as well as individuals with diabetes in Brazil aged 40 years were modeled over their lifetime. Monte Carlo microsimulations and sensitivity analyses were used to capture lifetime efficacy and costs. An annual cycle length was chosen. Data were analyzed between February 2021 and August 2021. AI vs standard of care. Association of AI with tooth retention-years for dentistry and quality-adjusted life-years (QALYs) for individuals in dermatology and ophthalmology; diagnostic costs. In 1000 microsimulations with 1000 random samples, AI as a diagnostic-support system showed limited cost-savings and gains in tooth retention-years and QALYs. In dermatology, AI showed mean costs of $750 (95% CI, $608-$970) and was associated with 86.5 QALYs (95% CI, 84.9-87.9 QALYs), while the control showed higher costs $759 (95% CI, $618-$970) with similar QALY outcome. In dentistry, AI accumulated costs of €320 (95% CI, €299-€341) (purchasing power parity [PPP] conversion, $429 [95% CI, $400-$458]) with 62.4 years per tooth retention (95% CI, 60.7-65.1 years). The control was associated with higher cost, €342 (95% CI, €318-€368) (PPP, $458; 95% CI, $426-$493) and fewer tooth retention-years (60.9 years; 95% CI, 60.5-63.1 years). In ophthalmology, AI accrued costs of R $1321 (95% CI, R $1283-R $1364) (PPP, $559; 95% CI, $543-$577) at 8.4 QALYs (95% CI, 8.0-8.7 QALYs), while the control was less expensive (R $1260; 95% CI, R $1222-R $1303) (PPP, $533; 95% CI, $517-$551) and associated with similar QALYs. Dominance in favor of AI was dependent on small differences in the fee paid for the service and the treatment assumed after diagnosis. The fee paid for AI was a factor in patient preferences in cost-effectiveness between strategies. The findings of this study suggest that marginal improvements in diagnostic accuracy when using AI may translate into a marginal improvement in outcomes. The current evidence supporting AI as decision support from a cost-effectiveness perspective is limited; AI should be evaluated on a case-specific basis to capture not only differences in costs and payment mechanisms but also treatment after diagnosis.

Impact of Fall Risk and Direct Oral Anticoagulant Treatment on Quality-Adjusted Life-Years in Older Adults with Atrial Fibrillation: A Markov Decision Analysis.

The decision to initiate anticoagulation in older adults with atrial fibrillation is complicated by the benefit of ischemic stroke prevention vs the risk of falls resulting in major bleeds. The objective of this study was to assess the impact of different treatments including direct oral anticoagulants on quality-adjusted life-years (QALYs) in patients aged 75 years and older with atrial fibrillation in the context of falls. A Markov decision process was constructed for older patients with atrial fibrillation taking no anti-thrombotic, aspirin, warfarin, rivaroxaban, and apixaban. Input probabilities for clinical events were estimated from the available literature. One-way and two-way sensitivity analyses were performed by measuring the impact of varying input probabilities of clinical events on QALY outcomes. The base-case scenario estimated that older adults treated with no anti-thrombotic, aspirin, warfarin, rivaroxaban, and apixaban had QALYs of 8.03, 8.69, 10.38, 11.02, and 11.56, respectively. The sensitivity analysis estimated that an older adult would need to fall over 45 (rivaroxaban) and 458 (apixaban) times per year for the QALY of a direct oral anticoagulant to be lower than that of aspirin. Older adults with atrial fibrillation benefit from stroke protection of anticoagulants, especially direct oral anticoagulants, even if they are at high risk of falls. Clinicians should not consider fall risk as a deciding factor for withholding anticoagulation in this population of patients.

Modifying the quality-adjusted life year calculation to account for meaningful change in health-related quality of life: insights from a pragmatic clinical trial.

We propose a modified quality-adjusted life year (QALY) calculation that aims to be consistent with guidance for interpreting change in patient-reported outcomes. This calculation incorporates the minimally important difference (MID) in generic preference-based health-related quality of life (HRQL) change scores to reflect what might be considered meaningful HRQL improvement/deterioration. In doing so, we review common issues in QALY calculations such as adjustment for baseline scores and standardizing for between-group differences. Using EQ-5D-5L outcome data from the Alberta TEAMCare-Primary Care Network trial in the management of depression for patients with type 2 diabetes (n = 98), this study compared results from different QALY calculation methods to investigate the impact of (i) adjusting for baseline HRQL score, (ii) standardizing between-group differences at baseline, and (iii) adjusting for 'meaningful' HRQL changes. The following QALY calculation methods are examined: area under curve (QALY-AUC), change from baseline (QALY-CFB), regression modelling (QALY-R), and incorporating an MID for HRQL changes from baseline (QALY-MID). The incremental QALY-AUC estimate favoured the Collaborative Care group (0.031) while the incremental QALY-CFB (-0.028) estimate favoured Enhanced Care. Adjusting for meaningful HRQL changes resulted in a crude incremental QALY-MID of -0.023; however, after adjusting for between-group differences at baseline, QALY-R and adjusted incremental QALY-MID estimates were -0.007 and -0.001, respectively. In addition, recursive regression analyses showed that very low baseline HRQL scores impact incremental QALY estimates. Uncertainty in incremental QALY estimates reflects uncertainty in the value of small within-individual change as well as the impact of small differences between groups at baseline. Applying a responder-definition approach yielded crude and adjusted QALY-MID estimates that were more in favour of Collaborative Care than QALY-CFB and QALY-R estimates, respectively, suggesting that ambiguous small changes in HRQL scores have the potential to influence QALY outcomes used in economic or non-economic applications.

Cost evaluation of adjunctive osimertinib use in resected epidermal growth factor receptor-positive non-small cell lung cancer.

8525 Background: About 30% of patients with epidermal growth factor receptor positive (EGFR+) non small cell lung cancer (NSCLC) are eligible for surgical resection. Osimertinib, a first line therapy for advanced EGFR+ NSCLC (stages 1B, 2, 3A), has shown clinical efficacy compared to placebo as an adjunctive therapy post resection. We evaluated the cost effectiveness/utility of this regimen. Methods: A two health state Markov model was built (disease free vs. disease recurrence or death). Disease free survival (DFS) curves were digitized and fitted to exponential function. 3 year timeline as patients received osimertinib for 3 years in published data. US payer perspective and 3% discount rate were applied. Drug costs were per Redbook whole acquisition cost and monitoring costs were from published data (US$ 2020). No adverse events > 5% were reported hence none were included. Life years (LY) and quality adjusted life years (QALY) were estimated for each stage. Incremental cost-effectiveness and utility ratios (ICER/ICUR) for LY and QALY gained were estimated in base case (BCA) and probabilistic sensitivity analyses (PSA). Results: Shown in the table are BCA and (PSA) results. Using LY as outcome, for stage 1B, incremental DFSLY of 0.40 (0.39) and incremental cost of $500,782 ($501,034) yielded an ICER/DFSLYG of ̃$1.3 million (M) (̃$1.2 M). For stage 2, incremental DFSLY of 0.79 (0.79) and incremental cost of $503,144 ($503,092) resulted in an ICER/DFSLYG of $636,913 ($638,278). For stage 3A, incremental of DFSLY of 0.18 (0.07) and incremental cost of $322,356 ($293,377) yielded an ICER/DFSLYG of ̃$1.2 M (̃1.2 M). The incremental costs are the same for QALY outcomes. Using QALY as outcome, for stage 1B, incremental of DFSQALY of 0.26 (0.27) yielded an ICUR/DFSQALY of ̃$1.9 M. In stage 2, incremental DFSQALY of 0.53 (0.53) resulted in an ICUR/DFSQALY of $950,616 ($952,654). For stage 1C, incremental DFSQALY of 0.18 (0.07) yielded an ICUR/DFSQALY of ̃$1.8 M (̃$3.7 M). Conclusions: The ICERs and ICURs indicate that cost effectiveness varies markedly across stages of disease. Stage 2 showed the lowest cost to outcome association. In general, the cost burden of adjunctive maintenance therapy with osimertinib in resected EGFR+ NSCLC is substantial relative to the observed clinical benefit. The incremental benefit of osimertinib in stage 2b is more evident than the ones in 1B and 3A.[Table: see text]

“The Back-up Vasectomy Reversal.” Simultaneous Sperm Retrieval and Vasectomy Reversal in the Couple With Advanced Maternal Age: A Cost-Effectiveness Analysis

ObjectiveTo determine the cost-effectiveness of different fertility options in men who have undergone vasectomy in couples with a female of advanced maternal age (AMA). The options include vasectomy reversal (VR), sperm retrieval (SR) with in vitro fertilization (IVF), and the combination of VR and SR with IVF, which is a treatment pathway that has been understudied. Materials and MethodsUsing TreeAge software, a model-based cost-utility analysis was performed estimating the cost per quality-adjusted life years (QALY) in couples with infertility due to vasectomy and advanced female age over a period of one year. The model stratified for female age (35-37, 38-40, >40) and evaluated four strategies: VR followed by natural conception (NC), SR with IVF, VR and SR followed by failed NC and then IVF, and VR and SR followed by failed IVF and then NC. QALY estimates and outcome probabilities were obtained from the literature and average patient charges were calculated from high-volume centers. ResultsThe most cost-effective fertility strategy was to undergo VR and try for NC (cost-per-QALY: $7,150 (35-37 y), $7,203 (38-40 y), and $7,367 (>40 y)). The second most cost-effective strategy was the “back-up vasectomy reversal”: undergo VR and SR, attempt IVF and switch to NC if IVF fails. ConclusionIn couples with a history of vasectomy and female of AMA, it is most cost-effective to undergo a VR. If the couple opts for SR for IVF, it is more cost-effective to undergo a concomitant VR than SR alone.

Alternative Approaches to Quality-Adjusted Life-Year Estimation Within Standard Cost-Effectiveness Models: Literature Review, Feasibility Assessment, and Impact Evaluation.

The quality-adjusted life-year (QALY) has been long debated, but alternative estimation approaches have not been comprehensively evaluated. Our objective was to identify alternatives, characterize them by implementation feasibility, and evaluate the impact of implementing feasible options in cost-effectiveness models developed for the Institute for Clinical and Economic Review reports. We conducted a literature review combining keywords relating to QALYs, methodology alternatives, and cost-effectiveness in PubMed, EconLit, Web of Science, and MEDLINE. Articles that discussed alternatives to the conventional QALY were included. Alternatives were characterized by type, data availability, calculation burden, and overall implementation feasibility. The subset of feasible alternatives, that is, sufficient data and methodology compatible with incorporation into common modeling approaches, were evaluated according to impact on incremental QALYs, incremental net monetary benefit (iNMB), intervention rankings, and proportion of interventions with a positive iNMB. We identified 28 articles discussing 9 alternatives. Feasible alternatives were using patient preference (PP) data; equity weighting according to baseline utility, fair innings, or proportional QALY shortfall; and the equal value of life-years-gained approach. All alternatives affected the incremental QALY and iNMB outcomes, rankings, and proportion of interventions with a positive iNMB. The PP alternative had the largest and most consistent impact. The PP impact on the proportion of interventions with a positive iNMB, was in the negative direction. Our work is the first comprehensive evaluation of proposed alternatives to the conventional QALY. We found robust literature but few options that were feasible to be implemented in current healthcare decision-making processes.

Life-course impact of child maltreatment on midlife health-related quality of life in women: longitudinal mediation analysis for potential pathways

PurposeWe examined (1) if child maltreatment (CM) is associated with lower health-related quality of life (HRQoL) and fewer quality-adjusted life years (QALY) over a 9-year follow-up of midlife women and (2) if adulthood psychosocial mediators could explain these associations. MethodsWomen (n = 342) completed the Childhood Trauma Questionnaire. Longitudinal HRQoL and QALY outcomes measured at five study visits include 36-item Short-Form Health Survey mental component score and physical component score and the Short Form-6 Dimension health index. Aims 1 and 2 were investigated by generalized estimating equations and sequential structural nested mean models, respectively. ResultsTwenty percent reported 2+ CM types. Compared with women without CM, women who experienced 2+ CM types reported 5- and 4-points lower scores in mental component score and physical component score, respectively, and 28 fewer healthy days per year in QALY. Low optimism, sleep problems, and low social support each explained greater than 10% of the relationship between 2+ CM and HRQoL and QALY over time. ConclusionsCM is a life-course social determinant of HRQoL and QALY throughout midlife, particularly in women who experienced 2+ CM types. Several mediators are modifiable and could be targets of interventions to mitigate the negative impact of CM on midlife HRQoL and QALY in women.