Quality-adjusted Life-year Threshold Research Articles

Cost-utility of nelarabine for the first-line treatment of newly diagnosed pediatric T-cell acute lymphoblastic leukemia in Canada.

The Children's Oncology Group (COG)-AALL0434 trial investigated the addition of nelarabine to the augmented Berlin-Frankfurt-Münster (aBFM) protocol in patients (1.0-30.99years) with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL). Despite demonstrating superior outcomes, nelarabine is not currently funded by many health systems, in part due to a lack of cost-effectiveness data. We estimated the cost-utility of nelarabine for this indication from a Canadian public healthcare payer perspective. We developed a microsimulation model that followed hypothetical patients with newly diagnosed T-ALL from post-induction therapy to death. Three health states were modeled: relapse-free, post-relapse, and death. Efficacy was estimated using AALL0434 and retrospective data from Ontario, Canada. Costs were obtained from Canadian sources. Utility estimates and long-term mortality risks were sourced from literature. Total healthcare costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were reported. Probabilistic and scenario analyses were conducted. Incorporating nelarabine in the aBFM protocol increased costs by $51,670 Canadian dollars per patient, but resulted in 1.97 more QALYs and an ICER of $26,184/QALY. Most of the identified cost and benefit were accrued within the AALL0434 trial period (first 11years post diagnosis) and while patients were in the relapse-free health state. Across multiple scenarios, the ICER was stable under an assumed $50,000/QALY threshold. Incorporating nelarabine into aBFM was cost-effective across different scenarios and assumptions. These results support its funding by public and private payers.

Cost-effectiveness analysis of polymyxin B versus colistin for treating patients with carbapenem-resistant gram-negative bacterial infections

The prevalence of carbapenem-resistant gram-negative bacterial (CRGNB) infection is continuously increasing, and polymyxin B and colistin are considered last-resort drugs. This study compared the cost-effectiveness of polymyxin B with that of colistin for the treatment of intensive care unit patients with CRGNB infection from the Chinese healthcare perspective. A decision-analytic Markov model was constructed to assess the cost-effectiveness of polymyxin B compared with colistin over a period of 5 years using evidence from phase trials and other publicly available studies. The model was developed in Treeage Pro 2022 and comprises a decision tree depicting initial hospitalization and a Markov model with four states projecting long-term health and economic impacts following discharge. Uncertainty was tested with one-way sensitivity analyses and probabilistic sensitivity analyses. The quality-adjusted life years (QALYs), direct medical costs, and incremental cost-effectiveness ratio (ICER) were estimated at willingness-to-pay (WTP) thresholds of $12,674 to $38,024 per QALY. According to the base analyses, the cost incurred by patients receiving colistin treatment was $12,244.77, leading to a gain of 1.35 QALYs. In contrast, patients treated with polymyxin B had a lower cost of $7,306.71 but yielded 1.07 QALYs. The ICRE of colistin was $18032.25/QALY. At a $12,674/QALY threshold, the results were sensitive to several variables, including the probability of cure with polymyxin B, the cost of drugs, the utility of discharge to home, the utility of discharge to long-term care, and the cost of nephrotoxicity with renal replacement therapy. After all model inputs varied across a wide range of reasonable values, only the probability of being cured with polymyxin B resulted in an ICER above the $38,024/QALY threshold. According to the probabilistic sensitivity analyses, colistin was the optimal strategy in 38.2% and 62.8% of the simulations, at $12,674/QALY and $38,024/QALY, respectively. Our study findings suggest that, when considering the Chinese healthcare perspective, colistin is likely to be more cost-effective than polymyxin B for patients with CRGNB infection, especially when the WTP threshold is set at one-time the per capita GDP. However, as the WTP threshold increases from one to three times the per capita GDP, the cost-effectiveness acceptability of colistin improves, increasing from 38.2 to 62.8%.

Cost Analysis of Scleral Buckle and Pars Plana Vitrectomy for Retinal Detachment Surgery.

To compare the cost and utility of scleral buckle (SB) and pars plana vitrectomy (PPV) techniques for repairing moderately complex rhegmatogenous retinal detachment (RRD). A cost-utility analysis was conducted using data from the Primary Retinal Detachment Outcomes Study (PRO) and a study conducted by the author. Total costs, patient utility over a lifetime, and cost per quality-adjusted life year (QALY) were calculated for each surgical procedure. The cost of scleral buckle surgery was €287.93, with an estimated lifetime QALY of 7.49. Costs per QALY were €38.44. According to the PRO study and Belin et al, total costs were $5975, with a lifetime QALY of 5.4 and costs per QALY of $1106. The cost of pars plana vitrectomy (PPV) was €1468.26, with an estimated lifetime QALY of 6.84 and costs per QALY of €214.65. Based on the PRO study and Belin et al, total costs were $8125, with a lifetime QALY of 4.7 and costs per QALY of $2196. Repairing moderately complex RRD presents a highly cost-effective profile for both SB and PPV techniques, well below recommended QALY thresholds. SB demonstrated a slightly more favorable profile compared to PPV.

Economic evaluation of NALIRIFOX vs. nab-paclitaxel and gemcitabine regimens for first-line treatment of metastatic pancreatic ductal adenocarcinoma from U.S. perspective

BackgroundThe cost-effectiveness of NALIRIFOX as a potential new standard of care for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) has yet to be established. Our objective was to evaluate the cost-effectiveness of NALIRIFOX vs. nab-paclitaxel and gemcitabine in this indication from the perspective of U.S. public payers.MethodsA partitioned survival model was constructed from the perspective of U.S. public payers, drawing on baseline patient characteristics and vital clinical data from the NAPOLI-3 trial. Costs and utilities were sourced from publicly accessible databases and literature. A lifetime horizon was applied, with an annual discount rate of 3%. We calculated and compared cumulative costs, life years, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICER). To evaluate the model’s robustness, sensitivity analyses, scenario analyses, and subgroup analyses were carried out. Additionally, a price simulation for the costly liposomal irinotecan was conducted to inform the pricing strategy at the given willingness to pay (WTP) threshold.ResultsIn the base-case analysis, NALIRIFOX provided an additional 0.29 QALYs with an ICER of $206,340.69 /QALY compared to nab-paclitaxel and gemcitabine, indicating it is not cost-effective at a $150,000/QALY threshold. Sensitivity analysis showed the model was most sensitive to the costs of liposomal irinotecan, capecitabine, and post-progression care. Probabilistic sensitivity analysis indicated a 17.66% probability of NALIRIFOX being cost-effective at $150,000/QALY, rising to 47.48% at $200,000/QALY. Pricing simulations suggested NALIRIFOX could become cost-effective at $150,000/QALY if the price of irinotecan liposome drops to $53.24/mg (a 14.8% reduction).ConclusionsNALIRIFOX may not be cost-effective at its current price as a first-line treatment for patients with mPDAC in the long term. The cost of liposomal irinotecan has the greatest impact. It may become cost-effective only if its cost is reduced by 14.8%, with a WTP threshold of $150,000 /QALY.

Cost-Utility Analysis of Adjuvant Olaparib for Germline BRCA1/2-Mutated, High-Risk HER2-Negative Early Breast Cancer in Spain.

Here we estimate the cost-effectiveness of olaparib in the Spanish National Health Service (SNHS) as adjuvant treatment of early germline mutations in the BRCA1/2 genes (gBRCAm) HER2-negative (HER2neg) breast cancer (BC) with high risk of recurrence. A semi-Markov model was adapted to the Spanish healthcare setting, using the perspective of the SNHS, and a lifetime horizon. Two scenarios were compared: receiving olaparib versus standard of care (SoC) treatment. The model comprised five health states and included the clinical results of the OlympiA trial, along with the direct healthcare costs associated with the use of early BC and subsequent treatment resources (€2023). A discount rate of 3% was applied for future cost and quality-of-life outcomes. A probabilistic sensitivity analysis (PSA) was carried out. The introduction of olaparib as adjuvant treatment for patients with early gBRCAm HER2neg BC with high risk of recurrence could involve an incremental cost of €44,273 and €50,164, with an improvement of 1.14 and 1.28 quality-adjusted life years (QALYs) for hormone receptor-positive (HR+) and triple-negative (TN) patients, respectively. Therefore, adjuvant olaparib could be cost-effective for early gBRCAm HER2neg BC, with an incremental cost-effectiveness ratio of €38,839/QALY and €39,084/QALY for HR+ and TN patients, respectively. The results from the PSA showed that 75.7% and 82.2% of the simulations fell below the €60,000/QALY threshold. Olaparib as adjuvant treatment could be cost-effective in gBRCAm patients with early HER2neg BC in Spain.

Long-term outcomes in virtual surgical planning for mandibular reconstruction: A cost-effectiveness analysis.

This study is an economic evaluation comparing virtual surgical planning (VSP) utilization to free hand mandibular reconstruction (FHR) for advanced oral cavity cancer, for which the cost effectiveness remains poorly understood. The proposed clinical benefits of VSP must be weighed against the additional upfront costs. A Markov decision analysis model was created for VSP and FHR based on literature review and institutional data over a 35-year time horizon. Model parameters were derived and averaged from systematic review and institutional experience. VSP cost and surgical time saving was incorporated. We accounted for long-term risks including cancer recurrence and hardware failure/exposure. We calculated cost in US dollars and effectiveness in quality-adjusted-life-years (QALYs). A health care perspective was adopted, discounting costs and effectiveness at 3%/year. Deterministic and probabilistic sensitivity analyses tested model robustness. In the base case scenario, total VSP strategy cost was $49,498 with 8.37 QALYs gained while FHR cost was $42,478 with 8.27 QALY gained. An incremental cost-effectiveness ratio (ICER), or the difference in cost/difference in effectiveness, for VSP was calculated at $68,382/QALY gained. VSP strategy favorability was sensitive to variations of patient age at diagnosis and institutional VSP cost with one-way sensitivity analysis. VSP was less economically favorable for patients >75.5 years of age or for institutional VSP costs >$10,745. In a probabilistic sensitivity analysis, 55% of iterations demonstrated an ICER value below a $100,000/QALY threshold. VSP is economically favorable compared to FHR in patients requiring mandibular reconstruction for advanced oral cancer, but these results are sensitive to the patient's age at diagnosis and the institutional VSP cost. Our results do not suggest if one "should or should not" use VSP, rather, emphasizes the need for patient selection regarding which patients would most benefit from VSP when evaluating quality of life and long-term complications. Further studies are necessary to demonstrate improved long-term risk for hardware failure/exposure in VSP compared to FHR.

Cost-Effectiveness of Unselected Multigene Germline and Somatic Genetic Testing for Epithelial Ovarian Cancer.

Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)-based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone. Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated. Compared with clinical criteria/FH-based BRCA testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline testing and BRCA1/BRCA2 somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of $175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of £11,291/QALY or $68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year's testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths. Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone.

Cost-utility of geriatric assessment (GA) in older adults with cancer: A model-based economic evaluation of four randomized controlled trials (RCTs).

1509 Background: Geriatric assessment (GA) is a guideline-recommended approach to optimize cancer management in older adults undergoing chemotherapy. Our recent cost-utility analysis of the published 5C (Clinical and Cost-effectiveness of a Comprehensive geriatric assessment and management for Canadian elders with Cancer) RCT comparing GA and management (GAM) with usual care in older adults with cancer did not demonstrate cost-effectiveness overall. However, the trial was limited by <5% of study participants receiving GA prior to starting treatment. Three other GAM RCTs (GAIN, GAP-70, and INTEGERATE) have recently been published with evidence of efficacy on clinically relevant endpoints. Whether these are more cost effective than 5C is unclear. We evaluated the cost-effectiveness of GAM versus usual care in older adults with cancer using a decision model under a range of plausible scenarios representing the 4 trials. Methods: We performed cost-effectiveness analyses using the healthcare payer perspective and a 12-month time horizon. We incorporated Canadian costs and utility data from 5C, and used intervention details and effectiveness data from the three RCTs. We reported healthcare costs per quality-adjusted life year (QALY) and the incremental net monetary benefit (INMB) using a $50,000 per QALY threshold. In scenario analyses we examined the main cost drivers. Results: Across trials, the average QALY per patient ranged 0.577–0.662 for GA and 0.606–0.665 for UC, and the average total costs $31,234–$39,432 for GA and $29,261–$41,756 for UC. Chemotherapy expenses accounted for 46%-66% of total costs across trials. The INTEGERATE trial had a positive INMB of $6,074. The GAIN and GAP-70 trials had negative INMB value of -$2,123 and -$1,172, respectively. In comparison, in 5C, the total costs were $39,812 and $37,450 for GAM and UC, respectively, and QALYs were 0.728 and 0.751, respectively; the INMB was $-2,713. Conclusions: Trial results and the associated model of care from INTEGERATE suggested a positive net monetary benefit, primarily driven by reduced hospitalization. Evaluation of cost-effectiveness under a range of plausible scenarios from RCTs can provide important insights about GAM. Our results add to the growing data supporting the need to implement GAM in older adults with cancer starting chemotherapy and argue for its cost effectiveness under specific scenarios. Future trials should include hospitalization outcomes. Future economic analyses need to accurately capture chemotherapy costs.

Comparison of surgical or non-surgical management for non-acute anterior cruciate ligament injury: the ACL SNNAP RCT.

Anterior cruciate ligament injury of the knee is common and leads to decreased activity and risk of secondary osteoarthritis of the knee. Management of patients with a non-acute anterior cruciate ligament injury can be non-surgical (rehabilitation) or surgical (reconstruction). However, insufficient evidence exists to guide treatment. To determine in patients with non-acute anterior cruciate ligament injury and symptoms of instability whether a strategy of surgical management (reconstruction) without prior rehabilitation was more clinically and cost-effective than non-surgical management (rehabilitation). A pragmatic, multicentre, superiority, randomised controlled trial with two-arm parallel groups and 1:1 allocation. Due to the nature of the interventions, no blinding could be carried out. Twenty-nine NHS orthopaedic units in the United Kingdom. Participants with a symptomatic (instability) non-acute anterior cruciate ligament-injured knee. Patients in the surgical management arm underwent surgical anterior cruciate ligament reconstruction as soon as possible and without any further rehabilitation. Patients in the rehabilitation arm attended physiotherapy sessions and only were listed for reconstructive surgery on continued instability following rehabilitation. Surgery following initial rehabilitation was an expected outcome for many patients and within protocol. The primary outcome was the Knee Injury and Osteoarthritis Outcome Score 4 at 18 months post randomisation. Secondary outcomes included return to sport/activity, intervention-related complications, patient satisfaction, expectations of activity, generic health quality of life, knee-specific quality of life and resource usage. Three hundred and sixteen participants were recruited between February 2017 and April 2020 with 156 randomised to surgical management and 160 to rehabilitation. Forty-one per cent (n = 65) of those allocated to rehabilitation underwent subsequent reconstruction within 18 months with 38% (n = 61) completing rehabilitation and not undergoing surgery. Seventy-two per cent (n = 113) of those allocated to surgery underwent reconstruction within 18 months. Follow-up at the primary outcome time point was 78% (n = 248; surgical, n = 128; rehabilitation, n = 120). Both groups improved over time. Adjusted mean Knee Injury and Osteoarthritis Outcome Score 4 scores at 18 months had increased to 73.0 in the surgical arm and to 64.6 in the rehabilitation arm. The adjusted mean difference was 7.9 (95% confidence interval 2.5 to 13.2; p = 0.005) in favour of surgical management. The per-protocol analyses supported the intention-to-treat results, with all treatment effects favouring surgical management at a level reaching statistical significance. There was a significant difference in Tegner Activity Score at 18 months. Sixty-eight per cent (n = 65) of surgery patients did not reach their expected activity level compared to 73% (n = 63) in the rehabilitation arm. There were no differences between groups in surgical complications (n = 1 surgery, n = 2 rehab) or clinical events (n = 11 surgery, n = 12 rehab). Of surgery patients, 82.9% were satisfied compared to 68.1% of rehabilitation patients. Health economic analysis found that surgical management led to improved health-related quality of life compared to non-surgical management (0.052 quality-adjusted life-years, p = 0.177), but with higher NHS healthcare costs (£1107, p < 0.001). The incremental cost-effectiveness ratio for the surgical management programme versus rehabilitation was £19,346 per quality-adjusted life-year gained. Using £20,000-30,000 per quality-adjusted life-year thresholds, surgical management is cost-effective in the UK setting with a probability of being the most cost-effective option at 51% and 72%, respectively. Not all surgical patients underwent reconstruction, but this did not affect trial interpretation. The adherence to physiotherapy was patchy, but the trial was designed as pragmatic. Surgical management (reconstruction) for non-acute anterior cruciate ligament-injured patients was superior to non-surgical management (rehabilitation). Although physiotherapy can still provide benefit, later-presenting non-acute anterior cruciate ligament-injured patients benefit more from surgical reconstruction without delaying for a prior period of rehabilitation. Confirmatory studies and those to explore the influence of fidelity and compliance will be useful. This trial is registered as Current Controlled Trials ISRCTN10110685; ClinicalTrials.gov Identifier: NCT02980367. This award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/140/63) and is published in full in Health Technology Assessment; Vol. 28, No. 27. See the NIHR Funding and Awards website for further award information.

Long-term cost-utility analysis of family therapy vs. treatment as usual for young people seen after self-harm

BackgroundThe joint evidence of the cost and the effectiveness of family-based therapies is modest.ObjectiveTo study the cost-effectiveness of family therapy (FT) versus treatment-as-usual (TAU) for young people seen after self-harm combining data from an 18-month trial and hospital records up to 60-month from randomisation.MethodsWe estimate the cost-effectiveness of FT compared to TAU over 5 years using a quasi-Markov state model based on self-harm hospitalisations where probabilities of belonging in a state are directly estimated from hospital data. The primary outcome is quality-adjusted life years (QALY). Cost perspective is NHS and PSS and includes treatment costs, health care use, and hospital attendances whether it is for self-harm or not. Incremental cost-effectiveness ratios are calculated and deterministic and probabilistic sensitivity analyses are conducted.ResultsBoth trial arms show a significant decrease in hospitalisations over the 60-month follow-up. In the base case scenario, FT participants incur higher costs (mean +£1,693) and negative incremental QALYs (-0.01) than TAU patients. The associated ICER at 5 years is dominated and the incremental health benefit at the £30,000 per QALY threshold is -0.067. Probabilistic Sensitivity Analysis finds the probability that FT is cost-effective is around 3 − 2% up to a maximum willingness to pay of £50,000 per QALY. This suggest that the extension of the data to 60 months show no difference in effectiveness between treatments.ConclusionWhilst extended trial follow-up from routinely collected statistics is useful to improve the modelling of longer-term cost-effectiveness, FT is not cost-effective relative to TAU and dominated in a cost-utility analysis.

Clinical effectiveness and cost-effectiveness of a brief accessible cognitive behavioural therapy programme for stress in school-aged adolescents (BESST): a cluster randomised controlled trial in the UK

Depression and anxiety are increasingly prevalent in adolescents. The Brief Educational Workshops in Secondary Schools Trial investigated the effectiveness of a brief accessible stress workshop programme for 16-18-year-olds. We aimed to investigate the clinical effectiveness and cost-effectiveness of the DISCOVER cognitive behavioural therapy (CBT) workshop on symptoms of depression in 16-18-year-olds at 6 months compared with treatment-as-usual. We conducted a multicentre, cluster randomised controlled trial in UK schools or colleges with sixth forms to evaluate clinical effectiveness and cost-effectiveness of a brief CBT workshop (DISCOVER) compared with treatment-as-usual. We planned to enrol 60 schools and 900 adolescents, using a self-referral system to recruit participants. Schools were randomised in a 1:1 ratio for participants to receive either the DISCOVER workshop or treatment-as-usual, stratified by site and balanced on school size and index of multiple deprivation. Participants were included if they were 16-18 years old, attending for the full school year, seeking help for stress, and fluent in English and able to provide written informed consent. The outcome assessors, senior health economist, senior statistician, and chief investigator were masked. People with lived experience were involved in the study. The primary outcome was depression symptoms measured with the Mood and Feelings Questionnaire (MFQ) at 6-month follow-up, in the intention-to-treat population of all participants with full covariate data. The trial was registered with the ISRCTN registry (ISRCTN90912799). 111 schools were invited to participate in the study, seven were deemed ineligible, and 47 did not provide consent. Between Oct 4, 2021, and Nov 10, 2022, 933 students at 57 schools were screened for eligibility, seven were not eligible for inclusion, and 26 did not attend the baseline meeting and assessment, resulting in 900 adolescents participating in the study. The DISCOVER group included 443 participants (295 [67%] female and 136 [31%] male) and the treatment-as-usual group included 457 participants (346 [76%] female and 92 [20%] male). 468 (52%) of the 900 participants were White, and the overall age of the participants was 17·2 years (SD 0·6). 873 (97%) adolescents were followed up in the intention-to-treat population. The primary intention-to-treat analysis (n=854) found an adjusted mean difference in MFQ of -2·06 (95% CI -3·35 to -0·76; Cohen's d=-0·17; p=0·0019) at the 6-month follow-up, indicating a clinical improvement in the DISCOVER group. The probability that DISCOVER is cost- effective compared with treatment-as-usual ranged from 61% to 78% at a £20 000 to £30 000 per quality-adjusted life-year threshold. Nine adverse events (two of which were classified as serious) were reported in the DISCOVER group and 14 (two of which were classified as serious) were reported in the treatment-as-usual group. Our findings indicate that the DISCOVER intervention is modestly clinically effective and economically viable and could be a promising early intervention in schools. Given the importance of addressing mental health needs early in this adolescent population, additional research is warranted to explore this intervention. National Institute for Health and Care Research Health Technology Assessment Programme.

Toripalimab plus chemotherapy in American patients with recurrent or metastatic nasopharyngeal carcinoma: A cost-effectiveness analysis.

Toripalimab, combined with gemcitabine and cisplatin, has been approved as the first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), representing a significant milestone as the first FDA-approved innovative therapy for this condition. Despite this achievement, there's a lack of data on the cost-effectiveness of toripalimab for RM-NPC patients in the American context. To assess the cost-effectiveness of toripalimab plus chemotherapy versus chemotherapy alone, a 3-state partitioned survival model was constructed. The study involved participants with characteristics matching those in the JUPITER-02 trial. Cost and utility inputs were collected from literature. Main outcomes measured were quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER). Univariate and probabilistic sensitivity analyses, subgroup analyses, and scenario analyses were conducted to verify the robustness of results. The study found that the toripalimab regimen resulted in 4.390 QALYs at a cost of $361,813, while the chemotherapy-only regimen yielded 1.685 QALYs at a cost of $161,632. This translates to an ICER of $74,004/QALY, below the willingness-to-pay threshold of $150,000/QALY. Sensitivity analyses indicated that utility values, discount rate, and the price of toripalimab significantly impact INMB. With an 87.10% probability of being cost-effective at a $150,000/QALY threshold, the probabilistic sensitivity analysis supports toripalimab plus chemotherapy as a viable option. Scenario analysis showed that toripalimab remains cost-effective unless its price increases by 125%. Additionally, a simulated 15-year study period increases the ICER to $88,026/QALY. Subgroup analysis revealed ICERs of $76,538/QALY for PD-L1 positive and $70,158/QALY for PD-L1 negative groups. Toripalimab in combination with chemotherapy is likely to be a cost-effective alternative to standard chemotherapy for American patients with RM-NPC. This evidence can guide clinical and reimbursement decision-making in treating RM-NPC patients.

Cost-Effectiveness of Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review of Cost-Effectiveness Studies for the American College of Physicians.

In the United States, costs of antidiabetes medications exceed $327 billion. To systematically review cost-effectiveness analyses (CEAs) of newer antidiabetes medications for type 2 diabetes. Bibliographic databases from 1 January 2010 through 13 July 2023, limited to English. Nonindustry-funded CEAs, done from a U.S. perspective that estimated cost per quality-adjusted life-year (QALY) gained for newer antidiabetic medications. Two reviewers screened the literature; disagreements were resolved with a third reviewer. Cost-effectiveness analyses were reviewed for treatment comparisons, model inputs, and outcomes. Risk of bias (RoB) of the CEAs was assessed using Drummond criteria and certainty of evidence (CoE) was assessed using GRADE (Grading of Recommendations Assessment, Development, and Evaluations). Certainty of evidence was determined using cost per QALY thresholds predetermined by the American College of Physicians Clinical Guidelines Committee; low (>$150 000), intermediate ($50 to $150 000), or high (<$50 000) value per QALY compared with the alternative. Nine CEAs were eligible (2 low, 1 high, and 6 some concerns RoB), evaluating glucagon-like peptide-1 agonists (GLP1a), dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucose-dependent insulinotropic peptide agonist (GIP/GLP1a), and insulin. Comparators were metformin, sulfonylureas, neutral protamine Hagedorn (NPH) insulin, and others. Compared with metformin, GLP1a and SGLT2i are low value as first-line therapy (high CoE) but may be of intermediate value when added to metformin or background therapy compared with adding nothing (low CoE). Insulin analogues may be similarly effective but more expensive than NPH insulin (low CoE). The GIP/GLP1a value is uncertain (insufficient CoE). Cost-effectiveness analyses varied in methodological approach, assumptions, and drug comparisons. Risk of bias and GRADE method for CEAs are not well established. Glucagon-like peptide-1 agonists and SGLT2i are of low value as first-line therapy but may be of intermediate value when added to metformin or other background therapy compared with adding nothing. Other drugs and comparisons are of low or uncertain value. Results are sensitive to drug effectiveness and cost assumptions. American College of Physicians. (PROSPERO: CRD42022382315).

The impact of willingness-to-pay threshold on price reduction recommendations for oncology drugs: a review of assessments conducted by the Canadian Agency for Drugs and Technologies in Health.

Since late 2020, the Canadian Agency of Drugs and Technologies in Health (CADTH) has been using a threshold of $50,000(CAD)per quality-adjusted life-year (QALY) for both oncology and non-oncology drugs. When used for oncology products, this threshold is hypothesized to have a higher impact on the time to access these drugs in Canada. We studied the impact of price reductions on time to engagement and negotiation with the pan-Canadian Pharmaceutical Alliance for oncology drugs reviewed by CADTH between January 2020 and December 2022. Overall, 103 assessments reported data on price reductions recommended by CADTH to meet the cost-effectiveness threshold for reimbursement. Of these assessments, 57% (59/103) recommendations included a price reduction of greater than 70% off the list price. Eight percent (8/103) were not cost-effective even at a 100% price reduction. Of the 47 assessments that had a clear benefit, in 21 (45%) CADTH recommended a price reduction of at least 70%. The median time to price negotiation (not including time to engagement) for assessments that received at least 70% vs >70% price reduction was 2.6vs 4.8months. This study showed that there is a divergence between drug sponsor's incremental cost-effectiveness ratio (ICER) and CADTH revised ICER leading to a price reduction to meet the $50,000/QALY threshold. For the submissions with clear clinical benefit the median length of engagement (2.5 vs 3.3months) and median length of negotiation (3.1 vs 3.6months) were slightly shorter compared with the submissions where uncertainties were noted in the clinical benefit according to CADTH. This study shows that using a $50,000 per QALY threshold for oncology products potentially impacts timely access to life saving medications.

Cost-effectiveness of therapist-assisted internet-delivered psychological therapies for PTSD differing in trauma focus in England: an economic evaluation based on the STOP-PTSD trial

Although there are effective psychological treatments for post-traumatic stress disorder (PTSD), they remain inaccessible for many people. Digitally enabled therapy is a way to overcome this problem; however, there is little evidence on which forms of these therapies are most cost effective in PTSD. We aimed to assess the cost-effectiveness of the STOP-PTSD trial, which evaluated two therapist-assisted, internet-delivered cognitive behavioural therapies: cognitive therapy for PTSD (iCT-PTSD) and a programme focusing on stress management (iStress-PTSD). In this health economic evaluation, we used data from the STOP-PTSD trial (n=217), a single-blind, randomised controlled trial, to compare iCT-PTSD and iStress-PTSD in terms of resource use and health outcomes. In the trial, participants (aged ≥18 years) who met DSM-5 criteria for PTSD were recruited from primary care therapy services in South East England. The interventions were delivered online with therapist support for the first 12 weeks, and three telephone calls over the next 3 months. Participants completed questionnaires on symptoms, wellbeing, quality of life, and resource use at baseline, 13 weeks, 26 weeks, and 39 weeks after randomisation. We used a cost-effectiveness analysis to assess cost per quality-adjusted life year (QALY) at 39 weeks post-randomisation, from the perspective of the English National Health Service (NHS) and personal social services and on the basis of intention-to-treat for complete cases. Treatment modules and the platform design were developed with extensive input from service users: service users also advised on the trial protocol and methods, including the health economic measures. This is a pre-planned analysis of the STOP-PTSD trial; the trial was registered prospectively on the ISRCTN Registry (ISRCTN16806208). NHS costs were similar across treatment groups, but clinical outcomes were superior for iCT-PTSD compared with iStress-PTSD. The incremental cost-effectiveness ratio for NHS costs and personal social services was estimated as £1921 per QALY. iCT-PTSD had an estimated 91·6% chance of being cost effective at the £20 000 per QALY threshold. From the societal perspective, iCT-PTSD was cost saving compared with iStress-PTSD. iCT-PTSD is a cost-effective form of therapist-assisted, internet-delivered psychological therapy relative to iStress-PTSD, and it could be considered for clinical implementation. Wellcome Trust and National Institute of Health Research Oxford Health Biomedical Research Centre.

Dehydrated human amnion/chorion membrane to treat venous leg ulcers: a cost-effectiveness analysis.

To evaluate the cost-effectiveness of dehydrated human amnion/chorion membrane (DHACM) in Medicare enrolees who developed a venous leg ulcer (VLU). This economic evaluation used a four-state Markov model to simulate the disease progression of VLUs for patients receiving advanced treatment (AT) with DHACM or no advanced treatment (NAT) over a three-year time horizon from a US Medicare perspective. DHACM treatments were assessed when following parameters for use (FPFU), whereby applications were initiated 30-45 days after the initial VLU diagnosis claim, and reapplications occurred on a weekly to biweekly basis until completion of the treatment episode. The cohort was modelled on the claims of 530,220 Medicare enrolees who developed a VLU between 2015-2019. Direct medical costs, quality-adjusted life years (QALYs), and the net monetary benefit (NMB) at a willingness-to-pay threshold of $100,000/QALY were applied. Univariate and probabilistic sensitivity analyses (PSA) were performed to test the uncertainty of model results. DHACM applied FPFU dominated NAT, yielding a lower per-patient cost of $170 and an increase of 0.010 QALYs over three years. The resulting NMB was $1178 per patient in favour of DHACM FPFU over the same time horizon. The rate of VLU recurrence had a notable impact on model uncertainty. In the PSA, DHACM FPFU was cost-effective in 63.01% of simulations at the $100,000/QALY threshold. In this analysis, DHACM FPFU was the dominant strategy compared to NAT, as it was cost-saving and generated a greater number of QALYs over three years from the US Medicare perspective. A companion VLU Medicare outcomes analysis revealed that patients who received AT with a cellular, acellular and matrix-like product (CAMP) compared to patients who received NAT had the best outcomes. Given the added clinical benefits to patients at lower cost, providers should recommend DHACM FPFU to patients with VLU who qualify. Decision-makers for public insurers (e.g., Medicare and Medicaid) and commercial payers should establish preferential formulary placement for reimbursement of DHACM to reduce budget impact and improve the long-term health of their patient populations dealing with these chronic wounds. Support for this analysis was provided by MiMedx Group, Inc., US. JLD, and RAF are employees of MiMedx Group, Inc. WHT, BH, PS, BGC and WVP were consultants to MiMedx Group, Inc. VD, AO, MRK, JAN, NW and GAM served on the MiMedx Group, Inc. Advisory Board. MRK and JAN served on a speaker's bureau. WVP declares personal fees and equity holdings from Stage Analytics, US.

Understanding the National Institute for Health and Care Excellence Severity Premium: Exploring Its Implementation and the Implications for Decision Making and Patient Access

ObjectivesThis study aimed to evaluate the impact of the National Institute for Health and Care Excellence’s (NICE) new severity modifier, which has replaced the end-of-life (EoL) premium, on future NICE recommendations, considering past decision-making patterns. MethodsNICE technology appraisals (TAs) published between January 2020 and December 2022 were reviewed. Summary statistics were generated to assess how the new severity modifier might affect hypothetical decision making in historical TAs. ResultsA total of 138 data points were identified from 132 TAs. Although the EoL premium was applied in 46 appraisals (33%), 57 (39%) qualify for a severity-based quality-adjusted life-year (QALY) multiplier. Only 19 appraisals (14.6%) not receiving an EoL premium met the severity criteria, the majority (17) qualifying for a 1.2× multiplier. In appraisals predicted to meet the severity criteria, 45 (79%) were in oncology, making them 4.04 times (95% CI 1.91-9.02) more likely to qualify for a severity modifier than nononcology indications. Among historically EoL indications, 42 (91%) were predicted to meet the severity criteria, making them 14.8 times (95% CI 6.37-37.6) more likely to qualify for a severity modifier. ConclusionsThe new severity modifier will predominantly benefit oncology indications, continuing their previous explicit prioritization under the EoL decision modifier. However, the new severity modifier is harder to achieve and less generous; only a fraction of appraisals qualify for the highest effective £51 000 per QALY threshold. The vast majority of indications previously approved at £50 000 per QALY would now need to meet a cost-effectiveness threshold of <£36 000. This may necessitate greater pricing flexibility from manufacturers and increase the likelihood of negative recommendations.

Cost-effectiveness of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) testing and isolation strategies in nursing homes.

Nursing home residents may be particularly vulnerable to coronavirus disease 2019 (COVID-19). Therefore, a question is when and how often nursing homes should test staff for COVID-19 and how this may change as severe acute respiratory coronavirus virus 2 (SARS-CoV-2) evolves. We developed an agent-based model representing a typical nursing home, COVID-19 spread, and its health and economic outcomes to determine the clinical and economic value of various screening and isolation strategies and how it may change under various circumstances. Under winter 2023-2024 SARS-CoV-2 omicron variant conditions, symptom-based antigen testing averted 4.5 COVID-19 cases compared to no testing, saving $191 in direct medical costs. Testing implementation costs far outweighed these savings, resulting in net costs of $990 from the Centers for Medicare & Medicaid Services perspective, $1,545 from the third-party payer perspective, and $57,155 from the societal perspective. Testing did not return sufficient positive health effects to make it cost-effective [$50,000 per quality-adjusted life-year (QALY) threshold], but it exceeded this threshold in ≥59% of simulation trials. Testing remained cost-ineffective when routinely testing staff and varying facemask compliance, vaccine efficacy, and booster coverage. However, all antigen testing strategies became cost-effective (≤$31,906 per QALY) or cost saving (saving ≤$18,372) when the severe outcome risk was ≥3 times higher than that of current omicron variants. SARS-CoV-2 testing costs outweighed benefits under winter 2023-2024 conditions; however, testing became cost-effective with increasingly severe clinical outcomes. Cost-effectiveness can change as the epidemic evolves because it depends on clinical severity and other intervention use. Thus, nursing home administrators and policy makers should monitor and evaluate viral virulence and other interventions over time.

Cost-effectiveness analysis of olaparib maintenance therapy for BRCA mutation ovarian cancer in the public sector in Malaysia.

Ovarian cancer is one of the most common cancer among women in Malaysia. Patients with ovarian cancer are often diagnosed at an advanced stage. Despite initial response to surgery and chemotherapy, most patients will experience a relapse. Olaparib has been reported have promising effects among BRCA mutated ovarian cancer patients. This study aimed to evaluate the cost-effectiveness of olaparib as a maintenance therapy for BRCA ovarian cancer in Malaysia. We developed a four-state partitioned survival model which compared treatment with olaparib versus routine surveillance (RS) from a Malaysian healthcare perspective. Mature overall survival (OS) data from the SOLO-1 study were used and extrapolated using parametric models. Medication costs and healthcare resource usage costs were derived from local inputs and publications. Deterministic and probabilistic sensitivity analyses (PSA) were performed to explore uncertainties. In Malaysia, treating patients with olaparib was found to be more costly compared to RS, with an incremental cost of RM149,858 (USD 33,213). Patients treated with olaparib increased life years by 3.05 years and increased quality adjusted life years (QALY) by 2.76 (9.45 years vs 6.40 years; 7.62 vs 4.86 QALY). This translated to an incremental cost-effectiveness ratio (ICER) of RM 49,159 (USD10,895) per life year gained and RM54,357 (USD 12,047) per QALY gained, respectively. ICERs were most sensitive to time horizon of treatment, discount rate for outcomes, cost of treatment and health state costs, but was above the RM53,770/QALY threshold. The use of olaparib is currently not a cost-effective strategy compared to routine surveillance based upon the current price in Malaysia for people with ovarian cancer with BRCA mutation, despite the improvement in overall survival.

Abstract 138: Cost-Effectiveness of Insertable Cardiac Monitors to Identify Atrial Fibrillation After Stroke Attributed to Large-Artery or Small-Vessel Disease

Introduction: Identification of atrial fibrillation (AF) in patients with stroke is critical for secondary stroke prevention with guideline-recommended oral anticoagulation (OAC). The randomized STROKE AF trial evaluating patients with ischemic stroke attributed to large-artery or small-vessel disease (LAD/SVD) found that insertable cardiac monitors (ICMs) were more likely to detect AF than standard of care (SoC) using intermittent external ECG monitors. However, the cost-effectiveness of ICMs in this population is not known. This study aimed to evaluate the cost-effectiveness of ICMs to detect new AF in patients with LAD/SVD stroke in the U.S. Methods: Using patient data from STROKE AF (N=492, median CHA 2 DS 2 -VASc=5.0), a lifetime Markov model was developed to assess the cost-effectiveness of ICM vs. SoC from a payer perspective. SoC was based on the frequency of ECG/Holter monitoring observed in the trial. AF detection was assumed to result in a switch from aspirin to OAC, unless precluded by prior bleeds. Lifetime risks of stroke and bleeding events were based on underlying presence of AF and the safety and efficacy of the treatment received. Future costs/effects were discounted at 3% annually to adjust to present values. Sensitivity analyses were conducted to assess uncertainty. Results: ICM was associated with a gain of 0.17 quality-adjusted life years (QALYs) versus SoC (6.63 vs. 6.46), driven by higher incidence of OAC and consequent reduction in lifetime ischemic strokes, with 53 fewer strokes projected per 1,000 patients. Total lifetime per-patient costs were $65,989 and $59,703 in the ICM and SoC arms, respectively. The incremental cost-effectiveness ratio was $37,760 per QALY gained compared to SoC (under the $50,000/QALY threshold considered highly cost-effective in the U.S.). Cost-effectiveness improved further in the subset with CHA 2 DS 2 -VASc≥6. In the patients at highest risk of AF detection (left atrial enlargement, heart failure, obesity, or prolonged QRS), the cost/QALY was $22,016. Conclusions: ICMs are likely to be cost-effective in the U.S. for the diagnosis of AF in the population with stroke attributed to LVD or SVD. This strategy was most cost-effective in patients with high CHA 2 DS 2 -VASc scores and those at greatest risk of AF.