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 2.6 vs 4.8 months. 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 3.3 months) and median length of negotiation (3.1 vs 3.6 months) 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.

Economic Evaluation of Neoadjuvant Versus Adjuvant Chemotherapy in Cancer Treatment: A Systematic Review and Meta-Analysis.

OBJECTIVES: In the absence of evidence on whether neoadjuvant (NAC) or adjuvant chemotherapy (AC) is more beneficial for various tumor treatments, economic evaluation (EE) can assist medical decision making. There is limited evidence on their cost-effectiveness and their prospective evaluation is less likely in the future. Therefore, a systematic review and meta-analysis about EE for NAC versus AC in solid tumor help compare these therapies from various perspectives. METHODS: Various databases were searched for studies published from inception to 2021. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines and economic-specific guidelines. The data were pooled using a random effects model when possible. RESULTS: The retrieval identified 15 EE studies of NAC versus AC in 8 types of cancer. NAC is the dominant strategy for pancreatic, head and neck, rectal, prostate cancers and colorectal liver metastases. For ovarian cancer, NAC is cost-effective with a lower cost and higher or similar quality-adjusted life-year. There were no significant differences in cost and outcomes for lung cancer. For stage IV or high-risk patients with ovarian or prostate cancer, NAC was cost-effective but not for patients who were not high risk. CONCLUSIONS: The EEs results for NAC versus AC were inconsistent because of their different model structures, assumptions, cost inclusions, and a shortage of studies. There are multiple sources of heterogeneity across EEs evidence synthesis. More high-quality EE studies on NAC versus AC in initial cancer treatment are necessary.

Methodologic and Reporting Quality of Economic Evaluations in Hand and Wrist Surgery: A Systematic Review.

BACKGROUND: Economic evaluations can inform decision-making; however, previous publications have identified poor quality of economic evaluations in surgical specialties. METHODS: Study periods were from January 1, 2006, to April 20, 2020 (methodologic quality) and January 1, 2014, to April 20, 2020 (reporting quality). Primary outcomes were methodologic quality [Guidelines for Authors and Peer Reviewers of Economic Submissions to The BMJ (Drummond's checklist), 33 points; Quality of Health Economic Studies (QHES), 100 points; Consensus on Health Economic Criteria (CHEC), 19 points] and reporting quality (Consolidated Health Economic Evaluation Standards (CHEERS) statement, 24 points). RESULTS: Forty-seven hand economic evaluations were included. Partial economic analyses (i.e., cost analysis) were the most common (n = 34; 72 percent). Average scores of full economic evaluations (i.e., cost-utility analysis and cost-effectiveness analysis) were: Drummond's checklist, 27.08 of 33 (82.05 percent); QHES, 79.76 of 100 (79.76 percent); CHEC, 15.54 of 19 (81.78 percent); and CHEERS, 20.25 of 24 (84.38 percent). Cost utility analyses had the highest methodologic and reporting quality scores: Drummond's checklist, 28.89 of 35 (82.54 percent); QHES, 86.56 of 100 (86.56 percent); CHEC, 16.78 of 19 (88.30 percent); and CHEERS, 20.8 of 24 (86.67 percent). The association (multiple R) between CHEC and CHEERS was strongest: CHEC, 0.953; Drummond's checklist, 0.907; and QHES, 0.909. CONCLUSIONS: Partial economic evaluations in hand surgery are prevalent but not very useful. The Consensus on Health Economic Criteria and Consolidated Health Economic Evaluation Standards should be used in tandem when undertaking and evaluating economic evaluation in hand surgery.

Comparing Modeling Approaches for Discrete Event Simulations With Competing Risks Based on Censored Individual Patient Data: A Simulation Study and Illustration in Colorectal Cancer.

OBJECTIVES: This study aimed to provide detailed guidance on modeling approaches for implementing competing events in discrete event simulations based on censored individual patient data (IPD). METHODS: The event-specific distributions (ESDs) approach sampled times from event-specific time-to-event distributions and simulated the first event to occur. The unimodal distribution and regression approach sampled a time from a combined unimodal time-to-event distribution, representing all events, and used a (multinomial) logistic regression model to select the event to be simulated. A simulation study assessed performance in terms of relative absolute event incidence difference and relative entropy of time-to-event distributions for different types and levels of right censoring, numbers of events, distribution overlap, and sample sizes. Differences in cost-effectiveness estimates were illustrated in a colorectal cancer case study. RESULTS: Increased levels of censoring negatively affected the modeling approaches' performance. A lower number of competing events and higher overlap of distributions improved performance. When IPD were censored at random times, ESD performed best. When censoring occurred owing to a maximum follow-up time for 2 events, ESD performed better for a low level of censoring (ie, 10%). For 3 or 4 competing events, ESD better represented the probabilities of events, whereas unimodal distribution and regression better represented the time to events. Differences in cost-effectiveness estimates, both compared with no censoring and between approaches, increased with increasing censoring levels. CONCLUSIONS: Modelers should be aware of the different modeling approaches available and that selection between approaches may be informed by data characteristics. Performing and reporting extensive validation efforts remains essential to ensure IPD are appropriately represented.

Ultrasound-Guided Injection Treatments Versus Surgical Neurectomy for Morton Neuroma: A Cost-Effectiveness Analysis.

BACKGROUND. Morton neuroma is a common, painful disorder of the foot with multiple treatment options of varying cost and effectiveness. OBJECTIVE. The aim of this study was to determine the most cost-effective treatment pathway for symptomatic Morton neuromas when conservative management has failed. METHODS. An incremental cost-utility analysis was performed comparing a direct to surgical neurectomy strategy with three selective injection strategies in which one or more ultrasound-guided injection therapies was tried first before surgery for patients who did not respond to treatment. The three selective injection strategies were selective steroid injection, selective alcohol injection, and selective steroid/alcohol injection in which both steroid injections and alcohol sclerosing injections were trialed successively before surgical neurectomy. The direct-to-surgery approach was compared with the three different selective injection strategies and with a no-treatment strategy in a decision-analytic model for a hypothetical group of patients with symptomatic Morton neuroma in whom conservative management had failed. Model parameters, including treatment costs, effectiveness, complication rates, and health utility states, were estimated from the literature, reimbursement databases, and expert opinion. The outcome was cost per quality-adjusted life year (QALY) with a time horizon of 3 years. A societal cost perspective was adopted with a willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses for key model parameters were performed. RESULTS. For the base input values, the steroid/alcohol selective injection strategy was dominant and yielded an incremental cost-effectiveness ratio of $4401.61/QALY compared with no treatment. The probabilistic sensitivity analysis supported this strategy in 74% of 10,000 simulated trials. Results were robust with low sensitivity to most input parameters. However, when the probability of successful alcohol injection treatment dropped below 40%, the steroid selective injection strategy became most cost-effective. CONCLUSION. A trial of ultrasound-guided injection therapies for Morton neuroma is a cost-effective strategy compared with proceeding directly to surgical neurectomy. CLINICAL IMPACT. Ultrasound-guided injection therapies are indicated as first-line treatment of patients with symptomatic Morton neuromas when conservative management fails.

Value in acute care surgery, Part 1: Methods of quantifying cost.

BACKGROUND: With health care expenditures continuing to increase rapidly, the need to understand and provide value has become more important than ever. In order to determine the value of care, the ability to accurately measure cost is essential. The acute care surgeon leader is an integral part of driving improvement by engaging in value increasing discussions. Different approaches to quantifying cost exist depending on the purpose of the analysis and available resources. Cost analysis methods range from detailed microcosting and time-driven activity-based costing to less complex gross and expenditure-based approaches. An overview of these methods and a practical approach to costing based on the needs of the acute care surgeon leader is presented.

COST ANALYSIS OF SCLERAL BUCKLE, PARS PLANA VITRECTOMY, AND PARS PLANA VITRECTOMY WITH SCLERAL BUCKLE FOR RETINAL DETACHMENT REPAIR.

PURPOSE: To compare the cost and utility of scleral buckle (SB), pars plana vitrectomy (PPV), and PPV with SB (PPV/SB) for moderately complex rhegmatogenous retinal detachment repair. METHODS: Cost-utility analysis using data from the Primary Retinal Detachment Outcomes Study. The model estimated costs, lifetime utility, and lifetime cost per quality-adjusted life year for treatment of moderately complex rhegmatogenous retinal detachment with SB, PPV, or PPV/SB. Data from the Centers for Medicare and Medicaid Services were used to calculate costs in hospital and ambulatory surgery center settings. RESULTS: Total costs (2020 US dollars) for repair of a moderately complex rhegmatogenous retinal detachment in hospital (ambulatory surgery center) settings were $5,975 ($3,774) for the SB group, $8,125 ($5,082) for the PPV group, and $7,551 ($4,713) for the PPV/SB group. The estimated lifetime quality-adjusted life years gained were 5.4, 4.7, and 4.7 in the SB, PPV, and PPV/SB groups, respectively. The cost per quality-adjusted life year for hospital and ambulatory surgery center settings was $1,106 a ($699) for the SB group, $1729 ($1,081) for the PPV group, and $1,607 ($1,003) for the PPV/SB group. CONCLUSION: Scleral buckle, PPV, and PPV/SB yielded very favorable cost-utility results for the repair of moderately complex rhegmatogenous retinal detachment, with slightly better results for SB, compared with current willingness to pay standards.

A comparison of six approaches for measuring utility values among patients with locally advanced cervical cancer.

BACKGROUND: Several instruments are available to measure health utility values. However, limited studies have not yet comprehensively assessed the agreement among these instruments. This study therefore aimed to investigate the performance and agreement of six instruments for utility measures: EQ-5D-3L, EQ-5D-5L (cTTO model), EQ-5D-5L (DCE model), EQ-5D-5L (Hybrid model), TTO, and VAS, among locally advanced cervical cancer (LACC) patients in Thailand. METHODS: We compared utility scores derived from six approaches using Friedman's test. We also assessed the agreement of utility scores between each pairwise comparison by intraclass correlation coefficient (ICC) and Bland-Altman plot. RESULTS: The mean (SD) utility values derived from six approaches were as follows: 0.755 ± 0.248 (EQ-5D-3L), 0.801 ± 280 (TTO), 0.806 ± 0.156 (VAS), 0.871 ± 0.184 (cTTO model), 0.875 ± 0.168 (Hybrid model), and 0.900 ± 0.142 (DCE model). Significant differences across six approaches were found in Friedman's test. The ICC showed high agreement between EQ-5D-5L and EQ-5D-3L, and very high agreement between all three models of EQ-5D-5L. The Bland-Altman plots showed wide limit of agreement, except the pairwise comparison, between each model of the EQ-5D-5L. CONCLUSION: TTO, VAS, EQ-5D-3L and EQ-5D-5L could not be used interchangeably in LACC patients. The impact of using different instruments on economic evaluation findings warrants further investigation.

A sexual rehabilitation intervention for women with gynaecological cancer receiving radiotherapy (SPARC study): design of a multicentre randomized controlled trial.

BACKGROUND: Sexual problems are frequently reported after treatment with radiotherapy (RT) for gynaecological cancer (GC), in particular after combined external beam radiotherapy and brachytherapy (EBRT+BT). Studies demonstrate that psychosexual support should include cognitive behavioural interventions and involvement of the patient's partner, if available. Therefore, we developed a nurse-led sexual rehabilitation intervention, including these key components. The intervention was previously pilot-tested and results demonstrated that this intervention improves women's sexual functioning and increases dilator compliance. The objective of the current study is to investigate the (cost-)effectiveness of the intervention compared to optimal care as usual (CAU). We expect that women who receive the intervention will report a statistically significant greater improvement in sexual functioning and - for women who receive EBRT+BT - higher compliance with dilator use, from baseline to 12 months post-RT than women who receive optimal care as usual (CAU). METHODS/DESIGN: The intervention is evaluated in the SPARC (Sexual rehabilitation Programme After Radiotherapy for gynaecological Cancer) study, a multicentre, randomized controlled trial (RCT). The primary endpoint is sexual functioning. Secondary outcomes include body image, fear of sexual activity, sexual-, treatment-related- and psychological distress, health-related quality of life and relationship satisfaction. A cost-effectiveness analysis (CEA) will be conducted in which the costs of the intervention will be related to shifts in other health care costs and the impact on patient outcome. The study sample will consist of 220 women with GC treated with RT in specialized GC treatment centres (N = 10). Participants are randomized to either the intervention- or CAU control group (1:1), and within each centre stratified by type of radiotherapy (EBRT+BT vs. EBRT only) and having a partner (yes/no). All women complete questionnaires at baseline (T1) and at 1, 3, 6, and 12 months post-RT (T2, T3, T4 and T5, respectively). DISCUSSION: There is a need to improve sexual functioning after RT for GC. This RCT will provide evidence about the (cost-)effectiveness of a nurse-led sexual rehabilitation intervention. If proven effective, the intervention will be a much needed addition to care offered to GC survivors and will result in improved quality of life. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03611517 . Registered 2 August 2018.

Health system costs and days in hospital for colorectal cancer patients in New South Wales, Australia.

INTRODUCTION: Colorectal cancer (CRC) care costs the Australian healthcare system more than any other cancer. We estimated costs and days in hospital for CRC cases, stratified by site (colon/rectal cancer) and disease stage, to inform detailed analyses of CRC-related healthcare. METHODS: Incident CRC patients were identified using the Australian 45 and Up Study cohort linked with cancer registry records. We analysed linked hospital admission records, emergency department records, and reimbursement records for government-subsidised medical services and prescription medicines. Cases' health system costs (2020 Australian dollars) and hospital days were compared with those for cancer-free controls (matched by age, sex, geography, smoking) to estimate excess resources by phase of care, analysed by sociodemographic, health, and disease characteristics. RESULTS: 1200 colon and 546 rectal cancer cases were diagnosed 2006-2013, and followed up to June 2016. Eighty-nine percent of cases had surgery, chemotherapy or radiotherapy, and excess costs were predominantly for hospitalisations. Initial phase (12 months post-diagnosis) mean excess health system costs were $50,434 for colon and $60,877 for rectal cancer cases, with means of 16 and 18.5 excess hospital days, respectively. The annual continuing mean excess costs were $6,779 (colon) and $8,336 (rectal), with a mean of 2 excess hospital days each. Resources utilised (costs and days) in these phases increased with more advanced disease, comorbidities, and younger age. Mean excess costs in the year before death were $74,952 (colon) and $67,733 (rectal), with means of 34 and 30 excess hospital days, respectively-resources utilised were similar across all characteristics, apart from lower costs for cases aged ≥75 at diagnosis. CONCLUSIONS: Health system costs and hospital utilisation for CRC care are greater for people with more advanced disease. These findings provide a benchmark, and will help inform future cost-effectiveness analyses of potential approaches to CRC screening and treatment.

Mapping the EORTC QLQ-C30 to EQ-5D-3L in patients with breast cancer.

BACKGROUND: The types of outcomes measured collected in clinical studies and those required for cost-effectiveness analysis often differ. Decision makers routinely use quality adjusted life years (QALYs) to compare the benefits and costs of treatments across different diseases and treatments using a common metric. QALYs can be calculated using preference-based measures (PBMs) such as EQ-5D-3L, but clinical studies often focus on objective clinician or laboratory measured outcomes and non-preference-based patient outcomes, such as QLQ-C30. We model the relationship between the generic, preference-based EQ-5D-3L and the cancer specific quality of life questionnaire, QLQ-C30 in patients with breast cancer. This will result in a mapping that allows users to convert QLQ-C30 scores into EQ-5D-3L scores for the purposes of cost-effectiveness analysis or economic evaluation. METHODS: We use data from a randomized trial of 602 patients with HER2-positive advanced breast cancer provided 3766 EQ-5D-3L observations. Direct mapping using adjusted, limited dependent variable mixture models (ALDVMM) is compared to a random effects linear regression and indirect mapping using seemingly unrelated ordered probit models. EQ-5D-3L was estimated as a function of the summary scales of the QLQ-C30 and other patient characteristics. RESULTS: A four component mixture model outperformed other models in terms of summary fit statistics. A close fit to the observed data was observed across the range of disease severity. Simulated data from the model closely aligned to the original data and showed that mapping did not significantly underestimate uncertainty. In the simulated data, 22.15% were equal to 1 compared to 21.93% in the original data. Variance was 0.0628 in the simulated data versus 0.0693 in the original data. The preferred mapping is provided in Excel and Stata files for the ease of users. CONCLUSION: A four component adjusted mixture model provides reliable, non-biased estimates of EQ-5D-3L from the QLQ-C30, to link clinical studies to economic evaluation of health technologies for breast cancer. This work adds to a growing body of literature demonstrating the appropriateness of mixture model based approaches in mapping.

Cost-effectiveness analysis of pembrolizumab plus chemotherapy as first-line therapy for extensive-stage small-cell lung cancer.

BACKGROUND: The phase III KEYNOTE-604 study confirmed the benefit of pembrolizumab combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (ES-SCLC). Taken into account the clinical benefits of pembrolizumab and its high cost, this study aimed to assess the cost-effectiveness of adding pembrolizumab to standard first-line etoposide-platinum (EP) for patients with ES-SCLC from the US payer perspective. METHODS: A Markov model was developed to compare the cost and quality-adjusted life-year (QALY) of pembrolizumab plus EP and placebo plus EP over a 10-year time horizon. Clinical efficacy and safety data were pooled from the KEYNOTE-604 trial. Utilities were obtained from published resources. Costs were mainly collected from Medicare in 2020. Sensitivity analyses were performed to examine the robustness of our model. RESULTS: Adding pembrolizumab to standard first-line EP resulted in the better effectiveness than EP chemotherapy alone for ES-SCLC by 0.22 QALYs. Pembrolizumab plus EP was dominated economically by placebo plus EP, leading to an incremental cost-effectiveness ratio (ICER) of $334,373/ QALY. Deterministic sensitivity analyses indicated that the uncertainty in model parameters exerted no substantial effect on our results. Probability sensitivity analysis indicated that probabilities for pembrolizumab plus EP being cost-effective within a wide range of willingness to pay were modest. CONCLUSION: From the US payer perspective, the first-line treatment for ES-SCLC with pembrolizumab plus EP was not cost-effective compared with placebo plus EP. Although pembrolizumab combination chemotherapy was beneficial to the survival of ES-SCLC, price reduction may be the necessary to improve its cost-effectiveness.

Cost-effectiveness analysis of FOLFIRINOX vs gemcitabine with nab-paclitaxel as adjuvant treatment for resected pancreatic cancer in the United States based on PRODIGE-24 and APACT trials.

BACKGROUND: Pancreatic cancer is associated with low median overall survival. Combination chemotherapy regimens FOLFIRINOX and gemcitabine with nab-paclitaxel (GemNab) are the new adjuvant treatment standards for resectable pancreatic cancer. PRODIGE-24 and APACT trials demonstrated superior clinical outcomes with FOLFIRINOX and GemNab, each vs gemcitabine monotherapy. OBJECTIVE: To evaluate the cost-effectiveness of FOLFIRINOX vs GemNab for resectable pancreatic cancer in adults from the U.S. payer perspective, in order to inform decision makers about which of these treatments is optimal. METHODS: A Markov model with 3 disease states (relapse free, progressive disease, and death) was developed. Cycle length was 1 month, and time horizon was 10 years. Transition probabilities were derived from PRODIGE-24 and APACT survival data. All cost and utility input parameters were obtained from published literature. Cost-effectiveness analysis was performed to obtain total costs, quality-adjusted life-years (QALYs), life-years (LYs), and incremental cost-effectiveness ratio (ICER). A 3% annual discount rate was applied to costs and outcomes. The effect of uncertainty on model parameters was assessed with 1-way and probabilistic sensitivity analysis (PSA). RESULTS: Our analysis estimated that the cost for FOLFIRINOX was $40,831 higher than GemNab ($99,669 vs. $58,837). Despite increased toxicity, FOLFIRINOX was associated with additional 0.18 QALYs and 0.25 LYs compared with GemNab (QALY: 1.65 vs. 1.47; LY: 2.09 vs. 1.84). The ICER for FOLFIRINOX vs GemNab was $226,841 per QALY and $163,325 per LY. FOLFIRINOX was not cost-effective at a willingness-to-pay (WTP) threshold of $200,000 per QALY, and this was confirmed by the PSA. CONCLUSIONS: Total monthly cost for FOLFIRINOX was approximately 1.7 times higher than GemNab. If the WTP threshold increases to or above $250,000 per QALY, FOLFIRINOX then becomes a cost-effective treatment option. DISCLOSURES: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to declare.

How to Prevent Vaccines Falling Victim to Their Own Success: Intertemporal Dependency of Incidence Levels on Indirect Effects in Economic Reevaluations.

OBJECTIVES: Incremental cost-effectiveness analyses may inform the optimal choice of healthcare interventions. Nevertheless, for many vaccines, benefits fluctuate with incidence levels over time. Reevaluating a vaccine after it has successfully decreased incidences may eventually cause a disease resurgence if switching to a vaccine with lower indirect benefits. Decisions may successively alternate between vaccines alongside repeated rises and falls in incidence and when indirect effects from historic use are ignored. Our suggested proposal aims to prevent suboptimal decision making. METHODS: We used a conceptual model of demand to illustrate alternating decisions between vaccines because of time-varying levels of indirect effects. Similar to the concept of subsidies, we propose internalizing the indirect effects achievable with vaccines. In a case study over 60 years, we simulated a hypothetical 10-year reevaluation of 2 oncogenic human papillomavirus vaccines, of which only 1 protects additionally against anogenital warts. RESULTS: Our case study showed that the vaccine with additional warts protection is initially valued higher than the vaccine without additional warts protection. After 10 years, this differential decreases because of declines in warts incidence, which supports switching to the nonwarts vaccine that causes a warts resurgence eventually. Instead, pricing the indirect effects separately supports continuing with the warts vaccine. CONCLUSIONS: Ignoring how the observed incidences depend on the indirect effects achieved with a particular vaccine may lead to repeated changes in vaccines at successive reevaluations, with unintended resurgences, economic inefficiencies, and eroding vaccine confidence. We propose internalizing indirect effects to prevent vaccines falling victim to their own success.

Estimating the Theoretical Cost Implications of Funding New Drugs Considered Not to Be Cost-Effective.

This study aims to estimate the theoretical excess expenditure that would be incurred by the Irish state-payer, should drugs be reimbursed at their original asking ("list") price rather than at a price at which the drug is considered cost-effective. In Ireland, all new drugs are evaluated by the National Centre for Pharmacoeconomics. For this study, drugs that were submitted by pharmaceutical companies from 2012 to 2017 and considered not cost-effective at list price were reviewed. A total of 43 such drugs met our inclusion criteria, and their pharmacoeconomic evaluations were further assessed. The price at which the drug could be considered cost-effective (cost-effective price) at the upper cost-effectiveness threshold used in Ireland (€ 45 000/quality adjusted life-year) was estimated for 18 drugs with an available cost-effectiveness model. Then, for each drug, the list price and cost-effective price (both per unit) were both individually applied to 1 year of national real-world drug utilization data. This allowed the estimation of the expected expenditures under the assumptions of list price paid and cost-effective price paid. The resulting theoretical excess expenditure, the expenditure at list price minus the expenditure at the cost-effective price, was estimated to be €108.2 million. This estimate is theoretical because of the confidentiality of actual drug prices. The estimation is calculated using the list price and likely overestimates the actual excess expenditure, which would reduce to zero if cost-effective prices are agreed. Nevertheless, this estimate illustrates the importance of a process to assess the value of new drugs so that potential excess drug expenditure is identified.

Cost-Effectiveness of a Serum Biomarker Test for Risk-Stratified Liver Ultrasound Screening for Hepatocellular Carcinoma.

OBJECTIVES: Risk-stratified ultrasound screening for hepatocellular carcinoma (HCC), informed by a serum biomarker test, enables resources to be targeted to patients at the highest risk of developing cancer. We aimed to investigate the cost-effectiveness of risk-stratified screening for HCC in the Australian healthcare system. METHODS: A Markov cohort model was constructed to test 3 scenarios for patients with compensated cirrhosis: (1) risk-stratified screening for high-risk patients, (2) all-inclusive screening, and (3) no formal screening. Probabilistic sensitivity analyses were undertaken to determine the impact of uncertainty. Scenario analyses were used to assess cost-effectiveness in Australia's Aboriginal and Torres Strait Islander peoples and to determine the impact of including productivity-related costs of mortality. RESULTS: Both risk-stratified screening and all-inclusive screening programs were cost-effective compared with no formal screening, with incremental cost-effectiveness ratios of A$39 045 and A$23 090 per quality-adjusted life-year (QALY), respectively. All-inclusive screening had an incremental cost-effectiveness ratio of A$4453 compared with risk-stratified screening and had the highest probability of being cost-effective at a willingness-to-pay (WTP) threshold of A$50 000 per QALY. Risk-stratified screening had the highest likelihood of cost-effectiveness when the WTP was between A$25 000 and A$35 000 per QALY. Cost-effectiveness results were further strengthened when applied to an Aboriginal and Torres Strait Islander cohort and when productivity costs were included. CONCLUSIONS: Cirrhosis population-wide screening for HCC is likely to be cost-effective in Australia. Risk-stratified screening using a serum biomarker test may be cost-effective at lower WTP thresholds.

Challenges raised by the economic evaluation of CAR-T-cell therapies. The review by the French National Authority for Health.

Since 2013, the process of pricing of innovative drugs by the French National Health Insurance has considered both cost-effectiveness and budget impact. CAR-T cell therapies were first subject to economic evaluation from 2019 in France. We aim to describe the process and results of the economic evaluation of tisagenlecleucel and axicabtagene ciloleucel as well as the challenges these evaluations raised. Evaluations submitted by the firms were reviewed by HAS and submitted to the Committee of Economic Evaluation and Public Health (CEESP). The CEESP issued opinions related to: (1) the methodological quality of economic evidence and, (2) the cost-effectiveness and budget impact of the drugs. The CEESP invalidated the estimated incremental cost-utility ratios (ICUR) of tisagenlecleucel due to the insufficient clinical evidence and methodological quality to extrapolate the long-term progression of the disease after treatment and compare tisagenlecleucel with alternatives. The CEESP concluded that tisagenlecleucel was not proven cost-effective. The estimated ICUR of axicabtagene ciloleucel at €114,509/QALY vs. chemotherapies was associated with an acceptable level of methodological quality despite being based on a weak indirect comparison and limited data on quality of life. The CEESP considered axicabtagene ciloleucel ICUR to be "very high" and questioned the societal/community willingness-to-pay of the claimed price. The primary source of uncertainty surrounding the ICUR estimates of both drugs was the lack of hindsight on effectiveness. The economic evaluation of CAR-T cell therapies highlights the risk of inefficient resource allocation driven by limited clinical data. It calls for payment schemes accounting for this risk and effective collection of post-marketing data.

Cost-Effectiveness of Magnetic Resonance Imaging-Guided Thrombolysis for Patients With Stroke With Unknown Time of Onset.

OBJECTIVES: Patients waking up with stroke symptoms are often excluded from intravenous thrombolysis with alteplase (IV-tpa). The WAKE-UP trial, a European multicenter randomized controlled trial, proved the clinical effectiveness of magnetic resonance imaging-guided IV-tpa for these patients. This analysis aimed to assess the cost-effectiveness of the intervention compared to placebo. METHODS: A Markov model was designed to analyze the cost-effectiveness over a 25-year time horizon. The model consisted of an inpatient acute care phase and a rest-of-life phase. Health states were defined by the modified Rankin Scale (mRS). Initial transition probabilities to mRS scores were based on WAKE-UP data and health state utilities on literature search. Costs were based on data from the University Medical Center Hamburg-Eppendorf, literature, and expert opinion. Incremental costs and effects over the patients' lifetime were estimated. The analysis was conducted from a formal German healthcare perspective. Univariate and probabilistic sensitivity analyses were performed. RESULTS: Treatment with IV-tpa resulted in cost savings of €51 009 and 1.30 incremental gains in quality-adjusted life-years at a 5% discount rate. Univariate sensitivity analysis revealed incremental cost-effectiveness ratio being sensitive to the relative risk of favorable outcome on mRS for placebo patients after stroke, the costs of long-term care for patients with mRS 4, and patient age at initial stroke event. In all cases, IV-tpa remained cost-effective. Probabilistic sensitivity analysis proved IV-tpa cost-effective in >95% of the simulations results. CONCLUSIONS: Magnetic resonance imaging-guided IV-tpa compared to placebo is cost-effective in patients with ischemic stroke with unknown time of onset.

Comparison of Levonorgestrel-releasing Intrauterine System (LNG-IUS) against Laparoscopic Assisted Supracervical Hysterectomy (LASH) for menorrhagia treatment: An economic evaluation.

BACKGROUND: This economic evaluation and literature review was conducted with the primary aim to compare the cost-effectiveness of laparoscopic assisted supracervical hysterectomy (LASH) with NICE's gold-standard treatment of Levonorgestrel-releasing intrauterine system (LNG-IUS) for menorrhagia. MATERIALS AND METHODS: A cost-utility analysis was conducted from an NHS perspective, using data from two European studies to compare the treatments. Individual costs and benefits were assessed within one year of having the intervention. An Incremental Cost-Effectiveness Ratio (ICER) was calculated, followed by sensitivity analysis. Expected Quality Adjusted Life Years (QALYS) and costs to the NHS were calculated alongside health net benefits (HNB) and monetary net benefits (MNB). RESULTS: A QALY gain of 0.069 was seen in use of LNG-IUS compared to LASH. This yielded a MNB between -£44.99 and -£734.99, alongside a HNB between -0.0705 QALYs and -0.106 QALYS. Using a £20,000-£30,000/QALY limit outlined by NICE,this showed the LNG-IUS to be more cost-effective than LASH, with LASH exceeding the upper bound of the £30,000/QALY limit. Sensitivity analysis lowered the ICER below the given threshold. CONCLUSIONS: The ICER demonstrates it would not be cost-effective to replace the current gold-standard LNG-IUS with LASH, when treating menorrhagia in the UK. The ICER's proximity to the threshold and its high sensitivity alludes to the necessity for further research to generate a more reliable cost-effectiveness estimate. However, LASH could be considered as a first line treatment option in women with no desire to have children.

Cost-effectiveness of prophylactic hysterectomy in first-degree female relatives with Lynch syndrome of patients diagnosed with colorectal cancer in the United States: a microsimulation study.

BACKGROUND: To evaluate the cost-effectiveness of prophylactic hysterectomy (PH) in women with Lynch syndrome (LS). METHODS: We developed a microsimulation model incorporating the natural history for the development of hyperplasia with and without atypia into endometrial cancer (EC) based on the MISCAN-framework. We simulated women identified as first-degree relatives (FDR) with LS of colorectal cancer patients after universal testing for LS. We estimated costs and benefits of offering this cohort PH, accounting for reduced quality of life after PH and for having EC. Three minimum ages (30/35/40) and three maximum ages (70/75/80) were compared to no PH. RESULTS: In the absence of PH, the estimated number of EC cases was 300 per 1,000 women with LS. Total associated costs for treatment of EC were $5.9 million. Offering PH to FDRs aged 40-80 years was considered optimal. This strategy reduced the number of endometrial cancer cases to 5.4 (-98%), resulting in 516 quality-adjusted life years (QALY) gained and increasing the costs (treatment of endometrial cancer and PH) to $15.0 million (+154%) per 1,000 women. PH from earlier ages was more costly and resulted in fewer QALYs, although this finding was sensitive to disutility for PH. CONCLUSIONS: Offering PH to 40- to 80-year-old women with LS is expected to add 0.5 QALY per person at acceptable costs. Women may decide to have PH at a younger age, depending on their individual disutility for PH and premature menopause.