Different Models, Same Results: Considerations When Choosing Between Approaches to Model Cost Effectiveness of Chimeric-Antigen Receptor T-Cell Therapy Versus Standard of Care.

OBJECTIVE: Chimeric antigen-receptor T-cell therapy (CAR-T) is characterised by early phase data at the time of registration, high upfront cost and a complex manufacturing and administration process compared with standard therapies. Our objective was to compare the performance of different models to assess the cost effectiveness of CAR-T using a state-transition model (STM), partitioned survival model (PSM) and discrete event simulation (DES). METHODS: Individual data for tisagenlecleucel for the treatment of young patients with acute lymphoblastic leukaemia (ALL) were used to populate the models. Costs and benefits were measured over a lifetime to generate a cost per quality-adjusted life-year (QALY). Model performance was compared quantitatively on the outcomes generated and a checklist developed summarising the components captured by each model type relevant to assessing cost effectiveness of CAR-T. RESULTS: Models generated similar results with base-case analyses ranging from an incremental cost per QALY of $96,074-$99,625. DES was the only model to specifically capture CAR-T wait time, demonstrating a substantial loss of benefit of CAR-T with increased wait time. CONCLUSION: Although model type did not meaningfully impact base-case results, the ability to incorporate an outcome-based payment arrangement (OBA) and wait time are important elements to consider when selecting a model for CAR-T. DES provided greater flexibility compared with STM and PSM approaches to deal with the complex manufacturing and administration process that can lead to extended wait times and substantially reduce the benefit of CAR-T. This is an important consideration when selecting a model type for CAR-T, so major drivers of uncertainty are considered in funding decisions.

Estimating Australian Population Utilities for Inherited Retinal Disease Using Time Trade-Off.

PURPOSE: Inherited retinal disease (IRD) causes progressive loss of visual function, degenerating towards complete blindness. Economic evaluation of gene therapies for rare forms of genetic IRDs have had to rely on health-related quality of life (HR-QoL) estimates from other diseases because there is limited data available for such a rare condition. This study aimed to estimate Australian societal-based utility values for IRD health states that can be used in cost-utility analyses (CUA) using a time trade-off (TTO) protocol adapted from a UK study. METHODS: The EuroQol Valuation Technology (EQVT) protocol composite TTO (cTTO) framework was followed, which includes worse-than-death (WTD) states and quality control (QC) measures. Preferences were collected from a general population sample of 110 Australian adult participants. Five health state vignettes from the UK study which had been validated with patients and clinicians were presented randomly to participants during videoconferencing (VC) interviews with one of four interviewers. Technical and protocol feasibility were assessed in a pilot of 10 interviews. QC measures were used to monitor interviewers' performance during the study. RESULTS: One participant withdrew consent. The final analysis was conducted on 109 respondents (including 4 non-traders). The average time to complete the interview was 44.2 minutes (SD 8.7). Participants reported mean visual analogue scale (VAS) scores between 63.15 for 'moderate impairment' and 17.98 for 'hand motion' to 'no light perception'. Mean health state utilities (HSU) varied between 0.76 (SD 0.26) in 'moderate impairment', and 0.20 (SD 0.58) in 'hand motion' to 'no light perception'. Of all HSU evaluations, 14% were considered WTD which most commonly occurred in the most severe visually impaired health state. CONCLUSION: This study provides valuable information on HSUs across a range of IRD health states from the Australian general population perspective. The utilities obtained in this study can be used as inputs into CUA of IRD therapies.

A systematic review to assess the utility of genomic autopsy using exome or genome sequencing in cases of congenital anomalies and perinatal death.

PURPOSE: Exome or genome sequencing (ES or GS) can identify genetic causes of otherwise unexplained congenital anomaly and perinatal death (PND) but is not routine practice. The evidence base for "genomic autopsy" after termination of pregnancy for fetal anomaly (TOPFA) and PND has been synthesized to determine the value of this investigation. METHODS: We conducted a systematic review and meta-analysis of studies meeting prespecified inclusion criteria and containing ≥10 cases of TOPFA or PND (with or without major congenital abnormality), in which ES or GS was conducted. We determined test performance, including diagnostic yield, accuracy, and reliability. We also reported outcomes associated with clinical utility and harms, where described. RESULTS: From 2245 potentially eligible studies, 32 publications were eligible and had data extracted, representing 2120 cases that could be meta-analyzed. No diagnostic accuracy or comparative studies were identified, although some analysis of concordance between different ES/GS methodologies could be performed. Studies reporting parent-related outcomes or long-term follow-up did not do so in a systematic or quantifiable manner. CONCLUSION: Evidence suggests that approximately one-fourth to one-third of fetal losses associated with TOPFA or unexplained PND are associated with a genetic cause identifiable on ES or GS-albeit this estimate varies depending on phenotypic and background risk factors. Despite the large body of evidence on ES and GS, little research has attempted to validate the accuracy of testing, nor measure the clinical or societal outcomes in families that follow the diagnostic investigation in this context.

Economic Evaluations of Obesity-Targeted Sugar-Sweetened Beverage (SSB) Taxes-A Review to Identify Methodological Issues.

INTRODUCTION: Economic evaluations of public health interventions like sugar-sweetened beverage (SSB) taxes face difficulties similar to those previously identified in other public health areas. This stems from challenges in accurately attributing effects, capturing outcomes and costs beyond health, and integrating equity effects. This review examines how these challenges were addressed in economic evaluations of SSB taxes. METHODS: A systematic review was conducted to identify economic evaluations of SSB taxes focused on addressing obesity in adults, published up to February 2021. The methodological challenges examined include measuring effects, valuing outcomes, assessing costs, and incorporating equity. RESULTS: Fourteen economic evaluations of SSB taxes were identified. Across these evaluations, estimating SSB tax effects was uncertain due to a reliance on indirect evidence that was less robust than evidence from randomised controlled trials. Health outcomes, like quality-adjusted life years, along with a healthcare system perspective for costs, dominated the evaluations of SSB taxes, with a limited focus on broader non-health consequences. Equity analyses were common but employed significantly different approaches and exhibited varying degrees of quality. CONCLUSION: Addressing the methodological challenges remains an issue for economic evaluations of public health interventions like SSB taxes, suggesting the need for increased attention on those issues in future studies. Dedicated methodological guidelines, in particular addressing the measurement of effect and incorporation of equity impacts, are warranted.

Discrete Event Simulation to Incorporate Infusion Wait-Time When Assessing Cost-Effectiveness of a Chimeric-Antigen Receptor T Cell Therapy.

OBJECTIVES: The main objective was to use discrete event simulation to model the impact of wait-time, defined as the time between leukapheresis and chimeric antigen receptor (CAR-T) infusion, when assessing the cost-effectiveness of tisagenlecleucel in young patients with relapsed/refractory acute lymphoblastic leukemia. METHODS: The movement of patients through the model was determined by parametric time-to-event distributions, with the competing risk of an event determining the costs and quality-adjusted life-years (QALYs) assigned. Cost-effectiveness was expressed using the incremental cost-effectiveness ratio (ICER) for tisagenlecleucel compared with chemotherapy over the lifetime. RESULTS: The base case generated a total of 5.79 QALYs and $622 872 for tisagenlecleucel and 1.19 QALYs and $181 219 for blinatumomab, resulting in an ICER of $96 074 per QALY. An increase in mean CAR-T wait-time to 6.20 months reduced the benefit and costs of tisagenlecleucel to 2.78 QALYs and $294 478 because of fewer patients proceeding to infusion, reducing the ICER to $71 112 per QALY. Alternatively, when the cost of tisagenlecleucel was assigned pre-infusion in sensitivity analysis, the ICER increased with increasing wait-time. CONCLUSIONS: Under a payment arrangement where CAR-T cost is incurred post-infusion, the loss of benefit to patients is not reflected in the ICER. This may be misguiding to decision makers, where cost-effectiveness ratios are used to guide resource allocation. discrete event simulation is an important tool for economic modeling of CAR-T as it is amenable to capturing the impact of wait-time, facilitating better understanding of factors affecting service delivery and consequently informed decision making to deliver faster access to CAR-T for patients.

Use of Health Technology Assessment for the Continued Funding of Health Technologies: The Case of Immunoglobulins for the Management of Multifocal Motor Neuropathy.

INTRODUCTION: Funding decisions for many health technologies occur without undergoing health technology assessment (HTA), in particular, without assessment of cost effectiveness (CE). Immunoglobulins in Australia are an interesting case study because they have been used for a long time for various rare disorders and their price is publicly available. Undertaking an HTA enables us to assess CE for an intervention for which there is limited clinical and economic evidence. This study presents a post-market review to assess the CE of immunoglobulins for the treatment of multifocal motor neuropathy (MMN) compared with best supportive care. METHODS: A Markov model was used to estimate costs and quality-adjusted life-years (QALYs). Input sources included randomised controlled trials, single-arm studies, the Australian clinical criteria for MMN, clinical guidelines, previous Medical Services Advisory Committee (MSAC) reports and inputs from clinical experts. Sensitivity analyses were conducted to assess the uncertainty and robustness of the CE results. RESULTS: The cost per patient of treating MMN with immunoglobulin was AU$275,853 versus AU$26,191when no treatment was provided, with accrued QALYs of 6.83 versus 6.04, respectively. The latter translated into a high incremental cost-effectiveness ratio (ICER) of AU$317,552/QALY. The ICER was most sensitive to the utility weights and the price of immunoglobulins. MSAC advised to continue funding of immunoglobulins on the grounds of efficacy, despite the high and uncertain ICER. CONCLUSIONS: Beyond the ICER framework, other factors were acknowledged, including the high clinical need in a patient population for which there are no other active treatments available. This case study highlights the challenges of conducting HTA for already funded interventions, and the efficiency trade-offs required to fund effective high-cost therapies in rare conditions.

A systematic review of economic evaluations for RPE65-mediated inherited retinal disease including HTA assessment of broader value.

OBJECTIVE: To summarize the key methodological challenges identified by health technology assessment (HTA) agencies assessing gene therapy (GT) and consideration of broad elements of value. METHOD: Economic evaluations (EEs) of voretigene neparvovec (VN) in RPE65-mediated inherited retinal disease (IRD) published in English were selected. HTA evaluations from Australia, Canada, Ireland, Scotland, England, and the United States were reviewed. An existing methodological framework was used to identify the challenges and considerations. RESULTS: Eight unique EEs were identified of which six were evaluated by HTA agencies. Incremental cost-effectiveness ratios ranged from $68,951 to $643,813 per quality-adjusted life-years (QALY) gained (healthcare perspective) and dominant to $480,130 per QALY gained (societal perspective). The key challenges were the lack of validated surrogate outcome, utility values and indirect costs from IRD patients, and limited evidence of the long-term treatment effect. Two HTA agencies reviewed a range of novel broader elements of value and whether they were associated with VN while other agencies discussed some elements of broader value. Caregiver disutility was included in some, but not all, evaluations. CONCLUSION: The methodological challenges were consistent with innovative interventions for rare diseases and managed using standard methods. Broader value was important to decision-makers but inconsistently applied across agencies. Possible reasons are limitations in the evidence available of the broader benefits that VN offers and how to incorporate these within an EE. A need exists for greater guidance and consistency across jurisdictions regarding the consideration of broader value that considers latest best practice.

The Cost of Raising Individuals with Fragile X or Chromosome 15 Imprinting Disorders in Australia.

The study characterised differences in costs associated with raising a child between four rare disorders and examined the associations between these costs with clinical severity. Caregivers of 108 individuals with Prader-Willi, Angelman (AS), Chromosome 15q Duplication and fragile X (FXS) syndromes completed a modified Client Services Receipt Inventory and participants completed intellectual/developmental functioning and autism assessments. AS incurred the highest yearly costs per individual ($AUD96,994), while FXS had the lowest costs ($AUD33,221). Intellectual functioning negatively predicted total costs, after controlling for diagnosis. The effect of intellectual functioning on total costs for those with AS was significantly different to the other syndromes. The study highlights the significant costs associated with these syndromes, particularly AS, linked with severity of intellectual functioning.

Estimating the willingness-to-pay to avoid the consequences of foodborne illnesses: a discrete choice experiment.

Lost productivity is one of the largest costs associated with foodborne illness (FBI); however, the methods used to estimate lost productivity are often criticised for overestimating the actual burden of illness. A discrete choice experiment (DCE) was undertaken to elicit preferences to avoid six possible FBIs and estimate whether ability to work, availability of paid sick leave and health-related quality of life affect willingness-to-pay (WTP) to avoid FBI. Respondents (N = 1918) each completed 20 DCE tasks covering two different FBIs [gastrointestinal illness, flu-like illness, irritable bowel syndrome (IBS), Guillain-Barre syndrome (GBS), reactive arthritis (ReA), or haemolytic uraemic syndrome (HUS)]. Attributes included: ability to work, availability of sick leave, treatment costs and illness duration. Choices were modelled using mixed logit regression and WTP was estimated. The WTP to avoid a severe illness was higher than a mild illness. For chronic conditions, the marginal WTP to avoid a chronic illness for one year, ranged from $531 for mild ReA ($1412 for severe ReA) to $1025 for mild HUS ($2195 for severe HUS). There was a substantial increase in the marginal WTP to avoid all the chronic conditions when the ability to work was reduced and paid sick leave was not available, ranging from $6289 for mild IBS to $11,352 for severe ReA. Including factors that reflect productivity and compensation to workers influenced the WTP to avoid a range of FBIs for both acute and chronic conditions. These results have implications for estimating the burden and cost of FBI.

Cost-effectiveness Analysis of Tisagenlecleucel Versus Blinatumomab in Children and Young Adults with Acute Lymphoblastic Leukemia: Partitioned Survival Model to Assess the Impact of an Outcome-Based Payment Arrangement.

OBJECTIVE: This research assesses the impact of an outcome-based payment arrangement (OBA) linking complete remission (CR) to survival as a means of maintaining cost-effectiveness for a chimeric antigen receptor T cell (CAR-T) therapy in young patients with acute lymphoblastic leukemia (ALL). METHODS: A partitioned survival model (PSM) was used to model the cost-effectiveness of tisagenlecleucel versus blinatumomab in ALL from the Australian healthcare system perspective. A decision tree modeled different OBAs by funneling patients into a series of PSMs based on response. Outcomes were informed by individual patient data, while costs followed Australian treatment practices. Costs and quality-adjusted life years (QALYs) were combined to calculate a single incremental cost-effectiveness ratio (ICER), reported in US dollars (2022) at a discount rate of 5% on costs and outcomes. RESULTS: For the base case, incremental costs and benefit were $379,595 and 4.27 QALYs, giving an ICER of $88,979. The ICER was most sensitive to discount rate ($57,660-$75,081), "cure point" ($62,718-$116,206) and extrapolation method ($76,018-$94,049). OBAs had a modest effect on the ICER when response rates varied. A responder-only payment was the most effective arrangement for maintaining the ICER ($88,249-$89,434), although this option was associated with the greatest financial uncertainty. A split payment arrangement (payment on infusion followed by payment on response) reduced variability in the ICER ($82,650-$99,154) compared with a single, upfront payment ($77,599-$107,273). CONCLUSION: OBAs had a modest impact on reducing cost-effectiveness uncertainty. The value of OBAs should be weighed against the additional resources needed to administer such arrangements, and importantly overall cost to government.

Responses to direct-to-consumer advertising in Australia: Comparing experience.

AbsractThis paper examines the potential effect of Direct-to-Consumer (DTC) advertising on consumers' behavioral intentions in relation to a medical issue. Using an online experiment, 1295 people were randomized to two information conditions. One group watched an advertisement for a hypothetical cold sore medicine, while a second (control) group did not view the advertisement, before both groups answered questions on symptoms. The responses were analyzed based on group allocation and the respondents' experience with cold sores. Results indicate that those who viewed the advertisement were more likely to choose the product, and the advertisement had larger effects based on consumer experience.

Effect of Graded Sensorimotor Retraining on Pain Intensity in Patients With Chronic Low Back Pain: A Randomized Clinical Trial.

Importance: The effects of altered neural processing, defined as altering neural networks responsible for perceptions of pain and function, on chronic pain remains unclear. Objective: To estimate the effect of a graded sensorimotor retraining intervention (RESOLVE) on pain intensity in people with chronic low back pain. Design, Setting, and Participants: This parallel, 2-group, randomized clinical trial recruited participants with chronic (>3 months) nonspecific low back pain from primary care and community settings. A total of 276 adults were randomized (in a 1:1 ratio) to the intervention or sham procedure and attention control groups delivered by clinicians at a medical research institute in Sydney, Australia. The first participant was randomized on December 10, 2015, and the last was randomized on July 25, 2019. Follow-up was completed on February 3, 2020. Interventions: Participants randomized to the intervention group (n = 138) were asked to participate in 12 weekly clinical sessions and home training designed to educate them about and assist them with movement and physical activity while experiencing lower back pain. Participants randomized to the control group (n = 138) were asked to participate in 12 weekly clinical sessions and home training that required similar time as the intervention but did not focus on education, movement, and physical activity. The control group included sham laser and shortwave diathermy applied to the back and sham noninvasive brain stimulation. Main Outcomes and Measures: The primary outcome was pain intensity at 18 weeks, measured on an 11-point numerical rating scale (range, 0 [no pain] to 10 [worst pain imaginable]) for which the between-group minimum clinically important difference is 1.0 point. Results: Among 276 randomized patients (mean [SD] age, 46 [14.3] years; 138 [50%] women), 261 (95%) completed follow-up at 18 weeks. The mean pain intensity was 5.6 at baseline and 3.1 at 18 weeks in the intervention group and 5.8 at baseline and 4.0 at 18 weeks in the control group, with an estimated between-group mean difference at 18 weeks of -1.0 point ([95% CI, -1.5 to -0.4]; P = .001), favoring the intervention group. Conclusions and Relevance: In this randomized clinical trial conducted at a single center among patients with chronic low back pain, graded sensorimotor retraining, compared with a sham procedure and attention control, significantly improved pain intensity at 18 weeks. The improvements in pain intensity were small, and further research is needed to understand the generalizability of the findings. Trial Registration: ANZCTR Identifier: ACTRN12615000610538.

Current Issues in Health Technology Assessment of Cancer Therapies: A Survey of Stakeholders and Opinion Leaders in Australia.

OBJECTIVE: The aim of this study was to find ways of bridging the gap in opinions concerning health technology assessment (HTA) in reimbursement submission between manufacturers and payers to avoid access delays for patients of vital medicines such as oncology drugs. This was done by investigating differences and similarities of opinion among key stakeholders in Australia. METHODS: The survey comprised of nine sections: background demographics, general statements on HTA, clinical claim, extrapolations, quality of life, costs and health resource utilization, agreements, decision making, and capability/capacity. Responses to each question were summarized using descriptive statistics and comparisons were made using chi-square statistics. RESULTS: There were ninety-seven respondents in total, thirty-seven from the public sector (academia/government) and sixty from the private sector (industry/consultancies). Private and public sector respondents had similar views on clinical claims. They were divided when it came to extrapolation of survival data and costs and health resource utilization. However, they generally agreed that rebates are useful, outcomes-based agreements are difficult to implement, managed entry schemes are required when data are limited, and willingness to pay is higher in cancer compared to other therapeutic areas. They also agreed that training mostly takes place through on the job training and that guideline updates were a least favored opportunity for continued training. CONCLUSIONS: Private sector respondents favor methods that reduce the incremental cost-effectiveness ratio when compared to the public sector respondents. There still exist a number of challenges for HTA in oncology and many research opportunities as a result of this study.

Evaluation of the Victorian Healthy Homes Program: protocol for a randomised controlled trial.

INTRODUCTION: The evaluation of the Victorian Healthy Homes Program (VHHP) will generate evidence about the efficacy and cost-effectiveness of home upgrades to improve thermal comfort, reduce energy use and produce health and economic benefits to vulnerable households in Victoria, Australia. METHODS AND ANALYSIS: The VHHP evaluation will use a staggered, parallel group clustered randomised controlled trial to test the home energy intervention in 1000 households. All households will receive the intervention either before (intervention group) or after (control group) winter (defined as 22 June to 21 September). The trial spans three winters with differing numbers of households in each cohort. The primary outcome is the mean difference in indoor average daily temperature between intervention and control households during the winter period. Secondary outcomes include household energy consumption and residential energy efficiency, self-reported respiratory symptoms, health-related quality of life, healthcare utilisation, absences from school/work and self-reported conditions within the home. Linear and logistic regression will be used to analyse the primary and secondary outcomes, controlling for clustering of households by area and the possible confounders of year and timing of intervention, to compare the treatment and control groups over the winter period. Economic evaluation will include a cost-effectiveness and cost-benefit analysis. ETHICS AND DISSEMINATION: Ethical approval was received from Victorian Department of Human Services Human Research Ethics Committee (reference number: 04/17), University of Technology Sydney Human Research Ethics Committee (reference number: ETH18-2273) and Australian Government Department of Veterans Affairs. Study results will be disseminated in a final report and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12618000160235.

Sunbeam Program Reduces Rate of Falls in Long-Term Care Residents With Mild to Moderate Cognitive Impairment or Dementia: Subgroup Analysis of a Cluster Randomized Controlled Trial.

OBJECTIVES: The Sunbeam trial significantly reduced falls in long-term aged care (LTC) residents. The current study's primary objective was to undertake subgroup analysis of the Sunbeam trial, to determine whether the intervention was effective for reducing falls in LTC residents with mild-moderate cognitive impairment/dementia. Secondary objectives were to determine intervention effects on cognitive and physical function. DESIGN: Subgroup analysis of a cluster randomized controlled trial (RCT). SETTING AND PARTICIPANTS: Permanent residents of LTC in Australia who participated in the Sunbeam trial with Addenbrooke's Cognitive Examination-Revised (ACE-R) scores <83 (Mini-Mental State Examination >14 = main trial inclusion criteria). METHODS: Of 221 participants, 148 had an ACE-R <83 and were included in this study. Sixteen LTC residences (clusters) were randomized to receive either the Sunbeam program or usual care. The Sunbeam program involved two 1-hour sessions/week of tailored and progressive resistance and balance training for 25 weeks followed by a maintenance program (two 30-min sessions/week of nonprogressive exercise for 6 months). Assessments were conducted at baseline, 6 months, and 12 months. Falls were recorded using routinely collected data from the LTC incident management systems. RESULTS: Rate of falls (50%) and risk of falls (31%), multiple falls (40%), and injurious falls (44%) were reduced in the intervention group. The intervention group had significantly better balance (static and dynamic) and sit-to-stand ability when compared with the control group at 6 months and significantly better dynamic balance at 12 months. There were no serious adverse events. CONCLUSIONS AND IMPLICATIONS: The Sunbeam Program significantly reduced falls and improved physical performance in cognitively impaired LTC residents. This is a novel and important finding, as many previous studies have excluded people with cognitive impairment/dementia and inconsistent findings have been reported when this population has been studied. Our findings suggest that progressive resistance and balance exercise is a safe and effective fall prevention intervention in LTC residents with mild-moderate cognitive impairment/dementia.

Facilitated case conferences on end-of-life care for persons with advanced dementia-a qualitative study of interactions between long-term care clinicians and family members.

BACKGROUND: Prognostic uncertainty and the need for proxy decision-making owing to cognitive impairment in advanced dementia, adds complexity to end-of-life care planning within the long-term care setting. Case conferences provide a structure to facilitate difficult conversations and an opportunity for family and clinicians to engage in prospective planning, and reach agreement on goals of end-of-life care. OBJECTIVE: To explore interactions between multidisciplinary healthcare clinicians and families during facilitated case conferences on end-of-life care for residents with advanced dementia. METHODS: A qualitative approach was used. Transcripts of audio-recorded case conferences facilitated by a trained registered nurse were coded by two independent researchers and analysed inductively. Transcripts were selected from an available pool until thematic saturation was reached. Emerging themes were confirmed with the wider research group. RESULTS: Thematic saturation was reached after 25 transcripts. An overarching theme concerned the ways in which clinicians and families bridged medical and person-centred perspectives. Subthemes included: details of day-to-day care versus establishing overall goals of care; expression of emotion versus retreat from emotion; and missed opportunities versus expressed cues. Successful facilitation served to 'bridge the gap' between family and clinicians. CONCLUSION: Facilitation of case conferences for residents with advanced dementia should focus on ensuring that: clinicians do not miss opportunities to discuss end-of-life care; discussions on the minutiae of care regularly return to the resident's broader goals of care; and information on dementia and treatments provided by clinicians is integrated with advice by family members regarding the resident's premorbid values and likely preferences.

A Systematic Review of Health Technology Assessments of Chimeric Antigen Receptor T-Cell Therapies in Young Compared With Older Patients.

OBJECTIVES: The objective of this review was to identify sources of variability in cost-effectiveness analyses of chimeric antigen receptor T-cell (CAR-T) therapies, tisagenlecleucel and axicabtagene ciloleucel, evaluated by health technology assessment (HTA) agencies, focusing on young compared with older patients. METHODS: HTA evaluations in pediatric acute lymphoblastic leukemia (ALL) and adult diffuse large B-cell lymphoma (DLBCL) were included from Australia, Canada, England, Norway, and the United States. Key clinical evidence, economic approach, and outcomes (costs, quality-adjusted life-years [QALYs] and incremental cost-effectiveness ratios) were summarized. RESULTS: Fourteen HTA evaluations were identified (5 ALL, 9 DLBCL [4 tisagenlecleucel, 5 axicabtagene]). Analyses were naive comparisons of prospective single-arm studies for the CAR-Ts with retrospective cohort studies for the comparators. Key clinical evidence and economic model approaches were generally consistent by CAR-T and indication, although outcomes varied. Notably, incremental QALYs varied substantially in ALL (3.67-10.6 QALYs gained), whereas variation in DLBCL was less (1.21-1.97 [tisagenlecleucel], 1.97-3.40 [axicabtagene]). Discounting of costs and outcomes varied, with the highest QALYs generated for tisagenlecleucel in ALL (10.95) associated with the lowest discount rate (1.5%) and vice versa (4.97 QALYs; 5% discount rate). The approach to extrapolation of overall survival data varied, even where the same empirical data were used. CONCLUSION: Modeled, long-term treatment benefit in young patients may be associated with greater uncertainty compared with adults because of potential life-long benefits with cell and gene therapies. This reflects the methodological challenges identified by HTA agencies associated with single-arm, short-term studies.

The Cost-Effectiveness of Adjuvant Tamoxifen Treatment of Hormone Receptor-Positive Early Breast Cancer Among Premenopausal and Perimenopausal Ghanaian Women.

OBJECTIVES: Most breast cancer cases in Ghana occur in premenopausal and perimenopausal (PPM) women. This study evaluated the cost-effectiveness of tamoxifen compared with no tamoxifen for the adjuvant treatment of hormone receptor-positive (HR+) early breast cancer (EBC) among PPM Ghanaian women. METHODS: A Markov model was constructed to synthesize data on the effectiveness, costs, and health benefits of tamoxifen. Effectiveness and utility data were sourced from a literature review. Resource use and healthcare costs were estimated from Ghanaian sources. The evaluation was conducted in 2017 from the perspective of the health system over a 15-year time horizon. The financial impact of funding tamoxifen on Ghana's National Health Insurance Scheme (NHIS) was also estimated. RESULTS: Adjuvant tamoxifen treatment for women with HR+ EBC was more effective and more costly than no-tamoxifen therapy. The incremental benefit and costs were estimated to be 1.38 quality-adjusted life-years gained and Ghana cedis (GHC) 2338 ($520), respectively. The incremental cost-effectiveness ratio was estimated to be GHC 1694 ($376). The model was sensitive to the cost of tamoxifen and utility values. The cost of tamoxifen for the treatment of HR+ EBC represents less than 0.01% GHC 96 960 ($21 547) of the current NHIS total claims expenditure. CONCLUSIONS: Tamoxifen provides additional benefits to PPM Ghanaian women with HR+ EBC and is cost-effective compared with no tamoxifen. These results support the public funding of tamoxifen under the NHIS and provide Ghanaian policy makers with vital information for future budgetary planning.

Reassessing the cost-effectiveness of nivolumab for the treatment of renal cell carcinoma based on mature survival data, updated safety and lower comparator price.

Aims: The aim of this study was to estimate the cost-effectiveness of nivolumab versus everolimus for second-line treatment of renal cell carcinoma (RCC) based on mature data, updated safety and decreased everolimus price.Materials and methods: A 3-state (pre-progression/progression-free disease, progressive disease and death) Markov model was developed from the perspective of the Australian health care system. Two scenarios were tested. Scenario 1 used 30-months clinical data and scenario 2 used updated 80-months clinical data with updated everolimus price. Inputs for quality-of-life and costs were informed by the literature and government sources. Incremental cost-effectiveness ratio (ICER) per quality adjusted life years (QALY) gained was reported and an ICER threshold of AU$75,000 was assumed. Threshold analysis was performed, and uncertainty was explored using one-way and probabilistic sensitivity analyses.Results: In scenario 1, the model estimated 1.73 QALYs at a cost of AU$105,000 for nivolumab and 1.48 QALYs at AU$38,000 for everolimus with an ICER = AU$266,871/QALY gained. A rebate of 54.4% was needed for nivolumab to reach the ICER threshold. For scenario 2, 1.93 QALYs at AU$111,418 was estimated for nivolumab and 1.60 QALYs at AU$31,942 for everolimus with an ICER of AU$213,320/QALY gained. The rebate needed to reach the ICER threshold was 54.9%. One-way sensitivity analyses for both scenarios showed that the cost of nivolumab, time horizon and utilities were main drivers. The cost-effectiveness acceptability curves highlighted the differences in cost-effectiveness of the two scenarios, as well as significant uncertainty in the results.Conclusions: A 54% rebate of the published price is needed for nivolumab to be cost-effective in Australia for the treatment of RCC. At that rebate, nivolumab remains cost-effective despite severe price erosion of everolimus because of improved longer term follow-up data. We recommend that generic price erosion should be accounted for when performing cost-effectiveness analysis.

Clinical assessment of chemotherapy-induced peripheral neuropathy: a discrete choice experiment of patient preferences.

PURPOSE: Up to 40% of cancer patients treated with neurotoxic chemotherapies experience chemotherapy-induced peripheral neuropathy (CIPN). Currently, there is no gold standard assessment tool for CIPN and there is little information in the literature on patient preferences for such assessments. This study aims to address this gap by identifying the features of a CIPN assessment tool that cancer patients value. METHODS: An online discrete choice experiment (DCE) survey of neurotoxic chemotherapy-treated patients was implemented. Respondents completed 8 choice questions each. In each choice question, they chose between two hypothetical CIPN assessment tools, each described by six attributes: impact on quality of life; level of nerve damage detected; questionnaire length; physical tests involved; impact on clinic time; impact on care. RESULTS: The survey was completed by 117 respondents who had a range of cancers of which breast cancer was the most common. Respondents favoured an assessment tool that includes a physical test and that asks about impact on quality of life. Respondents were strongly opposed to clinicians, alone, deciding how the results of a CIPN assessment might influence their care especially their chemotherapy treatment. They were concerned about small changes in their CIPN, independent of clinical relevance. Respondents were willing to add half an hour to the usual clinic time to accommodate the CIPN assessment. CONCLUSION: The findings of this DCE will assist clinicians in choosing an assessment tool for CIPN that is satisfactory to both clinician and patient.