Cost-effectiveness of emicizumab prophylaxis for haemophilia A with inhibitors: an adaptive health technology assessment for the Indian setting.

OBJECTIVE: To assess the cost-effectiveness of emicizumab prophylaxis for patients having haemophilia A with inhibitors in the Indian context using an adaptive health technology assessment (aHTA) methodology. DESIGN: Economic evaluation using multiple approaches aimed at adjusting previously generated cost-effectiveness results based on (1) price differences only ('simple') and (2) differences in cost and expected treatment duration ('moderate') and differences in cost, inflation and life expectancy ('complex'). SETTING: Typical haemophilia care in India. PARTICIPANTS: Patients with haemophilia A and inhibitors. INTERVENTION: Emicizumab prophylaxis using two vial strengths (30 or 150 mg/mL) in comparison to no prophylaxis. MAIN OUTCOME MEASURES: Adjusted incremental cost-effectiveness ratio (ICERa), incremental costs and incremental quality-adjusted life years associated with emicizumab prophylaxis from both the health system and societal perspectives. RESULTS: Using the simple ICER adjustment method, emicizumab prophylaxis resulted in potential cost savings from the payers' perspective for both vial strengths in patients aged ≥12 and <12 years. However, from a societal perspective, emicizumab prophylaxis was not cost-effective. Using the moderate adjustment method, emicizumab prophylaxis showed potential cost saving from the health system perspective. The complex adjustment method also revealed cost savings for emicizumab prophylaxis from the health system and societal perspectives across different age groups. CONCLUSION: We found that implementing emicizumab prophylaxis for patients with haemophilia A and inhibitors in India has the potential to result in cost savings. This study highlights the feasibility of using the expanded aHTA methodology for rapid evidence generation in the Indian context. However, it is crucial to address certain research gaps, including data limitations, challenges in translating international evidence to Indian context and associated uncertainties. Additionally, conducting a comprehensive budget impact analysis is necessary. These findings hold significant implications for decision-making regarding the potential provision of emicizumab prophylaxis through federal or/and state government-funded programmes and institutions in India.

Economic Evaluations of Chimeric Antigen Receptor T-Cell Therapies for Hematologic and Solid Malignancies: A Systematic Review.

OBJECTIVES: This study aimed to systematically review evidence on the cost-effectiveness of chimeric antigen receptor T-cell (CAR-T) therapies for patients with cancer. METHODS: Electronic databases were searched in October 2022 and updated in September 2023. Systematic reviews, health technology assessments, and economic evaluations that compared costs and effects of CAR-T therapy in patients with cancer were included. Two reviewers independently screened studies, extracted data, synthesized results, and critically appraised studies using the Philips checklist. Cost data were presented in 2022 US dollars. RESULTS: Our search yielded 1809 records, 47 of which were included. Most of included studies were cost-utility analysis, published between 2018 and 2023, and conducted in the United States. Tisagenlecleucel, axicabtagene ciloleucel, idecabtagene vicleucel, ciltacabtagene autoleucel, lisocabtagene maraleucel, brexucabtagene autoleucel, and relmacabtagene autoleucel were compared with various standard of care chemotherapies. The incremental cost-effectiveness ratio (ICER) for CAR-T therapies ranged from $9424 to $4 124 105 per quality-adjusted life-year (QALY) in adults and from $20 784 to $243 177 per QALY in pediatric patients. Incremental cost-effectiveness ratios were found to improve over longer time horizons or when an earlier cure point was assumed. Most studies failed to meet the Philips checklist due to a lack of head-to-head comparisons and uncertainty surrounding CAR-T costs and curative effects. CONCLUSIONS: CAR-T therapies were more expensive and generated more QALYs than comparators, but their cost-effectiveness was uncertain and dependent on patient population, cancer type, and model assumptions. This highlights the need for more nuanced economic evaluations and continued research to better understand the value of CAR-T therapies in diverse patient populations.

The value and impact of health technology assessment: discussions and recommendations from the 2023 Health Technology Assessment International Global Policy Forum.

Health technology assessment (HTA) programs inform decision making about the value and reimbursement of new and existing health technologies; however, they are under increasing pressure to demonstrate that they are a cost-effective use of finite healthcare resources themselves. The 2023 HTAi Global Policy Forum (GPF) discussed the value and impact of HTA, including how it is assessed and communicated, and how it could be enhanced in the future. This article summarizes the discussions held at the 2023 HTAi GPF, where the challenges and opportunities related to the value and impact of HTA were debated. Core themes and recommendations identified that defining the purpose of value and impact assessment is an essential first step prior to undertaking it, and that it can be done through the use and expansion of existing tools. Further work around aligning HTA programs with underlying societal values is needed to ensure the long-term value and impact of HTA. HTA could also have a role in assessing the efficiency of the wider health system by applying HTA methods or concepts to broader budgetary allocations and organizational aspects of health care. Stakeholders (particularly patients, industry, and clinicians but also payers, wider society, and the media) should ideally be actively engaged when undertaking the value and impact assessment of HTA. More concerted efforts in communicating the role and remit of HTA bodies would also help stakeholders to better understand the value and impact of HTA, which in turn could improve the implementation of HTA recommendations and application to future actions in the lifecycle of technologies.

Rule of Prevention: a potential framework to evaluate preventive interventions for rare diseases.

Background: The benefits of preventive interventions lack comprehensive evaluation in standard health technology assessments (HTA), particularly for rare and transmissible diseases. Objective: To identify possible considerations for future HTA using analogies between the treatment and prevention of rare diseases. Study design: An Expert panel meeting assessed whether one HTA assessment framework can be applied to assess both rare disease treatments and preventive interventions. Experts also evaluated the range of value elements currently included in HTAs and their applicability to rare, transmissible, and/or preventable diseases. Results: A broad range of value should be considered when assessing rare, transmissible disease prevention. Although standard HTA can be applied to transmissible diseases, the risk of local outbreaks and the need for large-scale prevention programs suggest a modified assessment framework, capable of incorporating prevention-specific value elements in HTAs. A 'Rule of Prevention' framework was proposed to allow broader value considerations anchored to severity, equity, and prevention benefits in decision-making for preventive interventions for rare transmissible diseases. Conclusion: The proposed prevention framework introduces an explicit initial approach to consistently assess rare transmissible diseases, and to incorporate the broader value of preventive interventions compared with treatment.

The impact of external reference pricing on pharmaceutical costs and market dynamics.

Growth in the cost of prescription drugs in the US has generated significant interest in the use of external reference pricing (ERP) to tie prices paid for drugs to those in other countries. We used data from the Pricentric ONE™ database, an international drug pricing database, to examine product launch timing, launch price, and price changes from January 2010 - October 2021 in both ERP and non-ERP settings, with a focus on 100 high-priced drugs of interest to Medicare and Medicaid. We found that ERP policies were associated with a 73% reduction in the likelihood of drug launch within 9 months of regulatory approval relative to non-ERP settings. In addition, while ERP was associated with statistically significant reductions in annual drug price changes, such policies did not impact launch price. In addition, no single ERP feature (e.g., number of countries referenced, ERP calculation) was materially associated with the outcomes of interest. We conclude that ERP policies do not appear to impact drug launch price and may delay access to new therapies, raising questions about the utility of such policies in the US and potential consequences abroad.

Health technology assessment 2025 and beyond: lifecycle approaches to promote engagement and efficiency in health technology assessment.

Lifecycle considerations have always been part of health technology assessment (HTA). However, the concept of taking a fuller, more holistic "lifecycle approach" is gaining interest in the HTA community. The 2022 HTAi Global Policy Forum (GPF) discussed how adopting a lifecycle approach could promote stakeholder engagement and robust evidence generation, and whether it could enhance information sharing and transparency across stakeholder groups. This article summarizes the discussions held at the 2022 HTAi GPF and subsequent HTAi Annual Meeting panel session that debated some of the key challenges and opportunities, with particular focus on the pre- and postmarket and disinvestment phase activities. Core themes and recommendations identified that collaboration and patient involvement are happening but still needs to be strengthened, and moving to disease-based approaches may help, although individual contexts still need to be considered. Appropriately developed and mandated core outcome sets may help with information sharing and efficiency in all lifecycle activities. Further, methods for the appropriate use of big data and digital data collection should be developed and driven by the HTA community. The value of lifecycle activities should be reviewed; in particular, scientific advice appears valuable, but the magnitude of effect is somewhat unknown due to the challenges around the confidential nature of these activities. Not all lifecycle activities can be conducted for every technology, and while there is a move away from disinvestment phase activities, more structured prioritization criteria are required. This article ends with suggested next steps to bring forward some of the priority recommendations.

Examining US commercial health plans' use of The Institute for Clinical and Economic Review's reports in specialty drug coverage decisions.

BACKGROUND: The Institute for Clinical and Economic Review (ICER) has emerged in a visible role in US health care. However, it is unclear to what extent US commercial health plans use ICER value assessments in their specialty drug coverage decisions. OBJECTIVE: To evaluate the relationship between ICER's reported cost-effectiveness ratios (CERs) and coverage restrictiveness. Also, to examine the frequency with which plans have cited ICER in their coverage policies and to investigate how frequently health plans adjusted their drug coverage criteria in the 12 months after ICER's assessments. METHODS: We analyzed the Tufts Medical Center Specialty Drug Evidence and Coverage Database, which includes specialty drug coverage decisions issued by 17 large US commercial health plans. For ICER-assessed drugs, we recorded ICER's estimated CERs in the form of cost per quality-adjusted life-year (QALY) gained. First, we used multivariate logistic regression to examine the association between ICER's reported CERs and plan coverage restrictiveness, when controlling for other factors that were likely to affect decision-making. Next, we examined how often plans cited ICER's assessments in coverage decisions issued in years 2017-2020. Lastly, we examined whether plans added or removed coverage restrictions (eg, patient subgroup restrictions or step therapy protocols) in the 12 months following ICER's assessment. RESULTS: Plans tended to cover drugs with higher (less favorable) CERs more restrictively than drugs with CERs less than $100,000 per QALY: odds ratio (OR) = 4.48 if $100,000-$175,000 per QALY; OR = 2.00 if $175,000-$500,000 per QALY; and OR = 2.10 if $500,000 or more per QALY (all P < 0.01). Plans cited ICER in 0.8% (5/622) of coverage policies in 2017, 0.6% (5/833) in 2018, 1.7% (19/1,139) in 2019, and 2.4% (33/1,406) in 2020. For drugs with CERs less than $175,000 per QALY, plans adjusted coverage in 37% of cases: added restrictions in 20%, removed restrictions in 15%, and added one restriction but removed another in 2%. For drugs with CERs of $175,000 or more, plans changed coverage criteria in 29% of cases: added restrictions in 21%, removed restrictions in 5%, and added one restriction but removed another in 4%. CONCLUSIONS: We found that when controlling for other factors, health plans' specialty drug coverage decisions were associated with ICER's estimated CERs. Plans infrequently cited ICER value assessments. We did not observe a trend for plans more often narrowing coverage criteria for drugs with CERs $175,000 or more compared with drugs with CERs less than $175,000. DISCLOSURES: This research study was supported by a consortium of funders: Amgen, Genen-tech, Janssen Pharmaceuticals, Otsuka, and GSK.

The Value of New: Consideration of Product Novelty in Health Technology Assessments of Pharmaceuticals.

BACKGROUND: Efforts to understand how treatments affect patients and society have broadened the criteria that health technology assessment (HTA) organizations apply to value assessments. We examined whether HTA agencies in eight countries consider treatment novelty in methods and deliberations. METHODS: We defined a novel pharmaceutical product to be one that offers a new approach to treatment (e.g., new mechanism of action), addresses an unmet need (e.g., targets a rare condition without effective treatments), or has a broader impact beyond what is typically measured in an HTA. We reviewed peer-reviewed publications and technical guidance materials from HTA organizations in Australia, Canada, England, France, The Netherlands, Norway, Sweden, and the United States (US). In addition, we explored how HTA organizations integrated novelty considerations into deliberations and recommendations related to two newer therapies-voretigene neparvovec for an inherited retinal disorder and ocrelizumab for multiple sclerosis. RESULTS: None of the HTA organizations acknowledge treatment novelty as an explicit value criterion in their assessments of pharmaceutical products. However, drugs that have novel characteristics are given special consideration, particularly when they address an unmet need. Several organizations document a willingness to expend more resources and accept greater evidence uncertainty for such treatments. Qualitative deliberations about the additional unquantified potential benefits of treatment may also influence HTA recommendations. CONCLUSION: Major HTA organizations do not recognize novelty as an explicit value criterion, although drugs with novel characteristics may receive special consideration. There is an opportunity for organizations to codify their approach to evaluating novelty in value assessment.

Patient and Caregiver Views on Measures of the Value of Health Interventions.

Purpose: We aimed to investigate patient and caregiver views on the relative importance of traditional and nontraditional domains of value, and to determine if these views differed according to key demographic characteristics. Patients and Methods: We conducted a modified Delphi approach using a web-based survey of adult patients managing a chronic condition or caregivers of a patient with chronic illness who were recruited using purposive sampling focused on demographic and clinical characteristics. The first survey round asked participants to rate the 13 domains of value on a 5-point Likert scale and rank each domain that they rated as important or very important. In the second survey round, participants reconsidered their own and aggregated round 1 results. New questions were added, including "rescuing" domains, challenges faced in taking medication, and a free-text option to add domains not already captured. Results: Initial recruitment resulted in 79 participants. Sixty-three (79.7%) completed the first round, and 58 participants completed both rounds. Overall ratings and rankings were consistent between survey rounds, and respondents ranked most highly domains considered traditional domains of value (for example, survival, costs). Patient activists were about six times more likely to rate each domain as important or very important compared to general disease advocates. Significant factors associated with a higher odds of rating a domain as important or very important were age 35-54 and 55-64 compared to 18-34, while factors associated with a decreased odds were males and patients compared to caregivers. Conclusion: Patients and caregivers place significant emphasis on traditional measures of value compared to nontraditional measures, and participants' prior beliefs impact what aspects of value they deem important.

Low-Value Prostate-Specific Antigen Test for Prostate Cancer Screening and Subsequent Health Care Utilization and Spending.

Importance: Delivering low-value care can lead to unnecessary follow-up services and associated costs, and such care cascades have not been well examined in common clinical scenarios. Objective: To evaluate the utilization and costs of care cascades of prostate-specific antigen (PSA) tests for prostate cancer screening, as the routine use of which among asymptomatic men aged 70 years and older is discouraged by multiple guidelines. Design, Setting, and Participants: This cross-sectional study included men aged 70 years and older without preexisting prostate conditions enrolled in a Medicare Advantage plan during January 2016 to December 2018 with at least 1 outpatient visit. Medical billing claims data from the deidentified OptumLabs Data Warehouse were used. Data analysis was conducted from September 2020 to August 2021. Exposures: At least 1 claim for low-value PSA tests for prostate cancer screening during the observation period. Main Outcomes and Measures: Utilization of and spending on low-value PSA cancer screening and associated care cascades and the difference in overall health care utilization and spending among individuals receiving low-value PSA cancer screening vs those who did not, adjusting for observed characteristics using inverse probability of treatment weighting. Results: Of 995 442 men (mean [SD] age, 78.0 [5.6] years) aged 70 years or older in a Medicare Advantage plan included in this study, 384 058 (38.6%) received a low-value PSA cancer screening. Utilization increased for each subsequent cohort from 2016 to 2018 (49 802 of 168 951 [29.4%] to 134 404 of 349 228 [38.5%] to 199 852 of 477 203 [41.9%]). Among those receiving initial low-value PSA cancer screening, 241 188 of 384 058 (62.8%) received at least 1 follow-up service. Repeated PSA testing was the most common, and 27 268 (7.1%) incurred high-cost follow-up services, such as imaging, radiation therapy, and prostatectomy. Utilization and spending associated with care cascades also increased from 2016 to 2018. For every $1 spent on a low-value PSA cancer screening, an additional $6 was spent on care cascades. Despite avoidable care cascades, individuals who received low-value PSA cancer screening were not associated with increased overall health care utilization and spending during the 1-year follow-up period compared with an unscreened population. Conclusions and Relevance: In this cross-sectional study, low-value PSA tests for prostate cancer screening remained prevalent among Medicare Advantage plan enrollees and were associated with unnecessary expenditures due to avoidable care cascades. Innovative efforts from clinicians and policy makers, such as payment reforms, to reduce initial low-value care and avoidable care cascades are warranted to decrease harm, enhance equity, and improve health care efficiency.

Engaging Patients and Caregivers in an Early Health Economic Evaluation: Discerning Treatment Value Based on Lived Experience.

BACKGROUND: Traditionally, economic evaluations have engaged clinicians and policymakers; however, patients and their caregivers have insight that can ensure that the economic evaluation process appropriately reflects disease consequences and adequately addresses their priorities related to treatment. OBJECTIVE: We aimed to identify patient priorities to inform an early economic evaluation of chimeric antigen receptor T-cell therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukemia. METHODS: We conducted two online group discussions of four participants each, involving patients with experience of hematological cancer and a caregiver. We used an adapted version of the nominal group technique, a consensus-building discussion approach, to generate focused qualitative data. RESULTS: Patients and a caregiver acknowledged both the costs directly related to clinical care, such as the out-of-pocket cost of drugs, and the indirect treatment costs, such as the cost of transport, accommodation, and food. The emotional and physical toll of treatment and the influence of treatment on employment and education were additional costs emphasized by participants. Treatment benefits prioritized by participants included the efficacy of treatment, manageable side effects, improved quality of life, accessibility of treatment, and short treatment duration. CONCLUSIONS: Engaging patients and caregivers in an early economic evaluation could help identify additional costs and benefits of therapies that are not typically recognized in economic evaluations but have the potential to increase the commercial viability of novel therapies. This research also demonstrates how patients and caregivers can be engaged at different levels in the development of early economic evaluation models.

State-Level Variation In Low-Value Care For Commercially Insured And Medicare Advantage Populations.

Low-value care is a major source of health care inefficiency in the US. Our analysis of 2009-19 administrative claims data from OptumLabs Data Warehouse found that low-value care and associated spending remain prevalent among commercially insured and Medicare Advantage enrollees. The aggregated prevalence of twenty-three low-value services was 1,920 per 100,000 eligible enrollees, which amounted to $3.7 billion in wasteful expenditures during the study period. State-level variation in spending was greater than variation in utilization, and much of the variation in spending was driven by differences in average procedure prices. If the average price for twenty-three low-value services among the top ten states in spending were set to the national average, their spending would decrease by 19.8 percent (from $735,000 to $590,000 per 100,000 eligible enrollees). State-level actions to improve the routine measurement and reporting of low-value care could identify sources of variation and help design state-specific policies that lead to better patient-centered outcomes, enhanced equity, and more efficient spending.

Challenges of Health Technology Assessment in Pluralistic Healthcare Systems: An ISPOR Council Report.

Health technology assessment (HTA) has been growing in use over the past 40 years, especially in its impact on decisions regarding the reimbursement, adoption, and use of new drugs, devices, and procedures. In countries or jurisdictions with "pluralistic" healthcare systems, there are multiple payers or sectors, each of which could potentially benefit from HTA. Nevertheless, a single HTA, conducted centrally, may not meet the needs of these different actors, who may have different budgets, current standards of care, populations to serve, or decision-making processes. This article reports on the research conducted by an ISPOR Health Technology Assessment Council Working Group established to examine the specific challenges of conducting and using HTA in countries with pluralistic healthcare systems. The Group used its own knowledge and expertise, supplemented by a narrative literature review and survey of US payers, to identify existing challenges and any initiatives taken to address them. We recommend that countries with pluralistic healthcare systems establish a national focus for HTA, develop a uniform set of HTA methods guidelines, ensure that HTAs are produced in a timely fashion, facilitate the use of HTA in the local setting, and develop a framework to encourage transparency in HTA. These efforts can be enhanced by the development of good practice guidance from ISPOR or similar groups and increased training to facilitate local use of HTA.

Effect of the 2012 US Preventive Services Task Force Recommendations on Prostate-Specific Antigen Screening in a Medicare Advantage Population.

BACKGROUND: In 2012, the US Preventive Service Task Force revised its recommendations for prostate-specific antigen (PSA) screening from "insufficient evidence" to "do not recommend" for men aged 70-74 while maintaining "do not recommend" for men aged 75+. METHODS: Using the difference-in-difference approach, we evaluated whether the rate of change in the use of low-value PSA screening differed between the control group (men aged 75+, N=7,856,204 person-years) and the intervention group (men aged 70-74, N=5,329,192 person-years) enrolling in the Medicare Advantage plan without a history of prostate cancer within the OptumLabs Data Warehouse claims data (2009-2019). A generalized estimating equation logistic model was specified with independent variables: an intervention group indicator, a pre- and post-period (after 2012 Q2) indicator, index time, and interaction terms. We assumed a 12-month dissemination period. RESULTS: Before the revised recommendation in 2012, the trends did not significantly differ between the 2 age groups with the odds of receiving PSA screening decreasing by 1.2% (95% confidence interval [1.0, 1.4%]) per quarter. However, the odds of receiving PSA screening increased by 3.0% [2.8, 3.2%] per quarter across both groups since the revision. There was no significant additional change in the trend for those aged 70-74 (0.1% [-0.2, 0.5%]). CONCLUSIONS: Although the 2012 US Preventive Service Task Force's recommendations were expected to only change behaviors among men aged 70-74, our analysis found that men aged 70-74 and aged 75+ exhibited similar trends from 2009 to 2019, including the increased use of low-value PSA screening since 2016. Multifaceted efforts to discourage low-value PSA screening would be important for a sustained impact.

Designing and Implementing Deliberative Processes for Health Technology Assessment: A Good Practices Report of a Joint HTAi/ISPOR Task Force.

OBJECTIVES: Deliberative processes for health technology assessment (HTA) are intended to facilitate participatory decision making, using discussion and open dialogue between stakeholders. Increasing attention is being given to deliberative processes, but guidance is lacking for those who wish to design or use them. Health Technology Assessment International (HTAi) and ISPOR-The Professional Society for Health Economics and Outcomes Research initiated a joint Task Force to address this gap. METHODS: The joint Task Force consisted of fifteen members with different backgrounds, perspectives, and expertise relevant to the field. It developed guidance and a checklist for deliberative processes for HTA. The guidance builds upon the few, existing initiatives in the field, as well as input from the HTA community following an established consultation plan. In addition, the guidance was subject to two rounds of peer review. RESULTS: A deliberative process for HTA consists of procedures, activities, and events that support the informed and critical examination of an issue and the weighing of arguments and evidence to guide a subsequent decision. Guidance and an accompanying checklist are provided for (i) developing the governance and structure of an HTA program and (ii) informing how the various stages of an HTA process might be managed using deliberation. CONCLUSIONS: The guidance and the checklist contain a series of questions, grouped by six phases of a model deliberative process. They are offered as practical tools for those wishing to establish or improve deliberative processes for HTA that are fit for local contexts. The tools can also be used for independent scrutiny of deliberative processes.

Designing and Implementing Deliberative Processes for Health Technology Assessment: A Good Practices Report of a Joint HTAi/ISPOR Task Force.

OBJECTIVES: Deliberative processes for health technology assessment (HTA) are intended to facilitate participatory decision making, using discussion and open dialogue between stakeholders. Increasing attention is being given to deliberative processes, but guidance is lacking for those who wish to design or use them. Health Technology Assessment International (HTAi) and ISPOR-The Professional Society for Health Economics and Outcomes Research initiated a joint Task Force to address this gap. METHODS: The joint Task Force consisted of 15 members with different backgrounds, perspectives, and expertise relevant to the field. It developed guidance and a checklist for deliberative processes for HTA. The guidance builds upon the few, existing initiatives in the field, as well as input from the HTA community following an established consultation plan. In addition, the guidance was subject to 2 rounds of peer review. RESULTS: A deliberative process for HTA consists of procedures, activities, and events that support the informed and critical examination of an issue and the weighing of arguments and evidence to guide a subsequent decision. Guidance and an accompanying checklist are provided for (i) developing the governance and structure of an HTA program and (ii) informing how the various stages of an HTA process might be managed using deliberation. CONCLUSIONS: The guidance and the checklist contain a series of questions, grouped by 6 phases of a model deliberative process. They are offered as practical tools for those wishing to establish or improve deliberative processes for HTA that are fit for local contexts. The tools can also be used for independent scrutiny of deliberative processes.