Institute For Clinical And Economic Review Research Articles

Estimation of the Eligible Population For Resmetirom Among Adults in the United States for Treatment of Non-Cirrhotic NASH with Moderate-to-Advanced Liver Fibrosis.

As of March 2024, resmetirom is the first and only therapy approved in the United States (US) for the treatment of adults with non-cirrhotic nonalcoholic steatohepatitis (NASH) with moderate-to-advanced liver fibrosis (MALF) consistent with stages F2/F3 fibrosis. Estimates of the diagnosed, treatment-eligible NASH population are poorly understood due to diagnostic variability. This study provides a contemporary estimate of the size of the US resmetirom treatment-eligible population. A dynamic population calculator was developed combining literature, screening guidelines, resmetirom study criteria, and analyses of the NHANES 2017-March 2020 cycle. It computes NASH prevalence, proportion non-cirrhotic NASH with MALF, Year 1 diagnosis, and new diagnoses in Years 2 and 3. NASH prevalence was estimated by applying the American Association of Clinical Endocrinology screening algorithm and recommended NIT cut-offs in the NHANES dataset. The proportion of non-cirrhotic NASH with MALF was informed by analyses of the Forian US integrated medical claims database using NASH and cirrhosis-specific ICD-10-CM codes and FIB-4 scores. NASH diagnosis rates were obtained from published estimates and NHANES responses. Treatment-eligible population growth was projected using published incidence data. Estimates were compared to a NASH budget-impact-analysis (BIA) from the Institute for Clinical and Economic Review (ICER). In the base case, a NASH prevalence of 4.6% was modeled (range 1.3-14.2%). This value was multiplied by the proportion estimated to have non-cirrhotic MALF (i.e., 35%). Published analyses suggest a diagnosis rate of~10% (range 3.3-14.3%) and~16% year-over-year growth in the treatment-eligible population. Assuming a 1-million commercial-member population, the resmetirom treatment-eligible population was estimated as 1255-1699 in Years 1-3 following approval. Sensitivity analyses were conducted and comparison to the ICER BIA was influenced by different diagnosis rates. Estimation of the treatment-eligible population for resmetirom depends importantly on NASH diagnosis rates, which are predicted to be<15% in the 3years after drug approval. Nonalcoholic steatohepatitis (NASH) is an advanced form of nonalcoholic fatty liver disease. Previously there were no treatments for NASH in the United States (US), but as of March 2024, the US Food and Drug Administration (FDA) approved resmetirom (REZDIFFRA™), a once-daily, oral therapy, in conjunction with diet and exercise, under accelerated approval for the treatment of adults (aged 18years or older) with non-cirrhotic NASH with moderate-to-advanced liver fibrosis (MALF), consistent with stages F2-F3. It is not well understood how many diagnosed patients with NASH would be eligible for treatment with resmetirom; thus, this study aimed to estimate the size of the US resmetirom treatment-eligible population. To do so, we created a flexible population calculator that considers how many people have NASH, what proportion would be eligible for resmetirom treatment-i.e., have non-cirrhotic NASH with MALF-and of those how many people would be diagnosed. We used published literature, screening guidelines, resmetirom study criteria, and analyses of national surveys to inform our range of estimates. In the main analysis, we modeled a NASH prevalence of 4.6% (range 1.3-14.2%), which was then limited to the proportion estimated to have non-cirrhotic NASH with MALF (i.e., 35%) and diagnosed (i.e., 10%, range 3.3-14.3%). A year-over-year growth of approximately 16% in the treatment-eligible population was modeled in years following approval. Assuming a population of 1million commercial insurance enrollees, the resmetirom treatment-eligible population was estimated to be 1255-1699 in Years 1-3 following approval. We assessed alternative scenarios and have compared our results to existing models.

Evaluating the cost-effectiveness of voclosporin for the treatment of lupus nephritis in the United States.

Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus; up to 30% of patients with LN will develop end-stage kidney disease (ESKD). One of the main treatment goals for LN is preservation of kidney function, with early decreases in proteinuria associated with improved long-term outcomes. Voclosporin, a second-generation calcineurin inhibitor, was approved in the United States in 2021 for the treatment of active LN combined with background immunosuppression. The AURORA 1 study found that the use of voclosporin with low doses of mycophenolate mofetil and glucocorticoids yielded significant reductions in proteinuria. The AURORA 2 study showed long-term efficacy and safety of voclosporin over a 3-year period with kidney function preservation. The Institute for Clinical and Economic Review (ICER) is a nonprofit organization that evaluates medical evidence to help improve patient outcomes and control costs. In 2021, ICER published an economic model to estimate the impact and cost-effectiveness of LN therapies. From a US health care perspective, voclosporin was cost-effective at $149,260 per quality-adjusted life-year (QALY) and $131,528 per equal value of life-years gained (evLYG). At the time of the LN cost-effectiveness model (CEM) development, voclosporin was not yet approved in the United States and the cost of treating patients with LN with ESKD was not captured in the literature. To evaluate the cost-effectiveness of voclosporin given the emergence of new data. The LN CEM uses a short-term trial-based Markov model and long-term extrapolation using partitioned survival modeling data assuming adults with LN start with active disease, transitioning to complete or partial renal response, kidney failure, or death. In the current analysis, clinical data for voclosporin, duration of voclosporin treatment for nonresponders, and drug costs reflecting the 2023 price of voclosporin were updated. Additionally, health care payer costs of disease management were incorporated based on real-world claims data on the costs of treating patients with LN. Using the LN CEM with inputs reflecting the latest and most relevant evidence, the incremental cost of voclosporin per QALY was $88,076 and per evLYG was $77,643. For a subpopulation of Black, Hispanic, and Latino patients, the incremental cost of voclosporin per QALY was $77,435 and per evLYG was $67,828. Following the inclusion of updated data in the cost-effectiveness analysis, voclosporin remains a cost-effective therapy for the treatment of active LN including in a Black, Hispanic, and Latino subpopulation, substantially below the ICER willingness-to-pay threshold of $150,000/QALY.

Access in all areas? A round up of developments in market access and health technology assessment: part 3.

In this latest update, we explore some of the key updates in market access over recent months including the UK's voluntary scheme for branded medicines pricing, access and growth (VPAG), the first drugs funded by the Innovative Medicines Fund in the UK and the Direct Access Scheme in France, and, finally, the new Institute for Clinical and Economic Review (ICER) value assessment framework in the USA.

Proposed changes ICER 2023 value assessment framework

Since 2006, the Institute for Clinical and Economic Review (ICER) in the United States has assessed the clinical and economic value of innovative medical technologies and made pricing recommendations with the goal of achieving “sustainable access to highly effective treatments for all patients”. The methodological framework developed by ICER assesses the longterm economic value of health interventions and their availability in the shortest possible time.

White bagging, brown bagging and site of service policies: best practices in addressing provider markup in the commercial insurance market.

New Institute for Clinical and Economic Review (ICER) analysis evaluates potential risks and advantages of reforms to current policies related to white bagging, brown bagging, and site of service policies that aim to address provider markup in the commercial insurance market.

The evolution of payer management of oncology drugs in the United States between 2017 and 2022.

BACKGROUND: Research conducted in 2017 by Runyan et al concerning the current and future management of oncology drugs in the United States formed the basis for this research. The authors concluded that despite the high cost of oncology drugs, US payers relied on traditional management tools to manage the category, although these tools were ineffective at controlling costs. Innovative tools were not common in 2017. OBJECTIVE: To compare findings from the 2017 research with findings from a 2022 payer survey to understand how payer management of oncology drugs changed over 5 years. The study evaluates changing trends in oncology drug management. METHODS: The survey that informed the publication by Runyan et al in 2017 was reviewed, updated, and completed by 21 pharmacy and medical directors across 18 organizations representing 121.9 million covered lives. Both surveys included questions about management tools being employed in oncology and challenges to managing oncology. They used case studies in non-small cell lung cancer and chronic lymphocytic leukemia. These disease areas were chosen again in 2022 because they were included in the 2017 survey and because of the increase in competition in both categories from 2017 to 2022. The payer sample was designed to match the 2017 sample. The research was fielded from March to May 2022. The results were analyzed in Microsoft Excel; basic statistical analysis was conducted. Payers' responses for each question were weighted by the number of reported covered lives at their organization so that the organization's site was represented. RESULTS: On average, payers rated the management priority of oncology as a 5.3 and the budget impact as a 6.3 on a scale of 1 to 7, where 1 was low and 7 was high. Traditional tools remain dominant in this therapeutic area. However, there has been an increase in use of innovative tools. Pathways of care are trending upward since the initial survey in 2017. The Institute for Clinical and Economic Review (ICER) also influences payers' decision-making in oncology more than it did 5 years ago. Despite these shifts, most payers allow for unrestricted access of targeted therapies in non-small cell lung cancer and chronic lymphocytic leukemia, in line with each drug's US Food and Drug Administration-approved label. CONCLUSIONS: The increased use of pathways of care, shifting financial risk to providers, and the influence of ICER should continue to be monitored. Future research should focus on the role of pathways of care, comprehensive, evidence-based treatment protocols, in influencing prescribing decisions of hematologists and oncologists. DISCLOSURES: The authors work for Envision Pharma Group (formerly Two Labs), a company that provides consulting services to the pharmaceutical and biotech industries. As such, clients in these industries pay Envision Pharma Group for their services. This study was funded independently by Envision Pharma Group.

Exploring the feasibility of using the ICER Evidence Rating Matrix for Comparative Clinical Effectiveness in assessing treatment benefit and certainty in the clinical evidence on orphan therapies for paediatric indications

BackgroundThe evaluation of clinical evidence takes account of health benefit (efficacy and safety) and the degree of certainty in the estimate of benefit. In orphan indications practical and ethical challenges in conducting clinical trials, particularly in paediatric patients, often limit the available evidence, rendering structured evaluation challenging. While acknowledging the paucity of evidence, regulators and reimbursement authorities compare the efficacy and safety of alternative treatments for a given indication, often in the context of the benefits of other treatments for similar or different conditions. This study explores the feasibility of using the Institute for Clinical and Economic Review (ICER) Evidence Rating Matrix for Comparative Clinical Effectiveness in structured assessment of both the magnitude of clinical benefit (net health benefit, NHB) and the certainty of the effect estimate in a sample of orphan therapies for paediatric indications.ResultsEleven systemic therapies with European Medicines Agency (EMA) orphan medicinal product designation, licensed for 16 paediatric indications between January 2017 and March 2020 were identified using OrphaNet and EMA databases and were selected for evaluation with the ICER Evidence Rating Matrix: burosumab; cannabidiol; cerliponase alfa; chenodeoxycholic acid (CDCA); dinutuximab beta; glibenclamide; metreleptin; nusinersen; tisagenlecleucel; velmanase alfa; and vestronidase alfa. EMA European Public Assessment Reports, PubMed, EMBASE, the Cochrane Library, Clinical Key, and conference presentations from January 2016 to April 2021 were searched for evidence on efficacy and safety. Two of the identified therapies were graded as “substantial” NHB: dinutuximab beta (neuroblastoma maintenance) and nusinersen (Type I SMA), and one as “comparable” NHB (CDCA). The NHB grade of the remaining therapies fell between “comparable” and “substantial”. No therapies were graded as having negative NHB. The certainty of the estimate ranged from “high” (dinutuximab beta in neuroblastoma maintenance) to “low” (CDCA, metreleptin and vestronidase alfa). The certainty of the other therapies was graded between “low” and “high”. The ICER Evidence Rating Matrix overall rating “A” (the highest) was given to two therapies, “B+” to 6 therapies, “C+” to five therapies, and “I” (the lowest) to three therapies. The scores varied between rating authors with mean agreement over all indications of 71.9% for NHB, 56.3% for certainty and 68.8% for the overall rating.ConclusionsUsing the ICER Matrix to grade orphan therapies according to their treatment benefit and certainty is feasible. However, the assessment involves subjective judgements based on heterogenous evidence. Tools such as the ICER Matrix might aid decision makers to evaluate treatment benefit and its certainty when comparing therapies across indications.

HTA68 How Do ICER’s Assessments of Comparative Effectiveness Compare to the German Federal Joint Committee’s Assessments of Added Benefit?

The Institute for Clinical and Economic Review (ICER) previously proposed translating its ratings of comparative clinical effectiveness into the system of added benefit ratings used by Germany. This study compared ICER and German evidence ratings and explored which factors may explain any disagreement.

HPR59 Influence of Institute for Clinical and Economic Review (ICER) Reports in Formulary Decision Making

The Institute for Clinical and Economic Review (ICER) is a non-profit organization which conducts evidence-based reviews of health care interventions. The ICER Integrated Evidence Rating™ assesses the comparative clinical effectiveness and comparative value based on price expectation to arrive at an overall rating. This method for rating the clinical effectiveness is modeled on the “Evidence-Based Medicine (EBM) matrix.”

EE183 Cost-Effectiveness Model for PTAH Oral Immunotherapy in Peanut Allergy Using Two-Year Extension Trial Data

The Institute for Clinical and Economic Review (ICER) published a report of the cost-effectiveness of peanut allergy immunotherapy treatment AR-101 (Peanut (Arachis hypogaea) Allergen Powder-dnfp, “PTAH”) compared to avoidance alone in 2019. PTAH was approved by the FDA in 2020 and two-year extension trial data is now available. Our objective was to replicate and update the previously developed ICER model for PTAH to include extension trial data and updates to drug costs.

HTA51 Impact of ICER Assessments on Payer Decision Making in the United States

To evaluate how payers utilize Institute for Clinical and Economic Review (ICER) assessments to inform coverage or formulary decisions.

P37 Review of Institute for Clinical and Economic Review (ICER) Reports: Use and Accessibility of Surveys to Incorporate the Patient Perspective

P37 Review of Institute for Clinical and Economic Review (ICER) Reports: Use and Accessibility of Surveys to Incorporate the Patient Perspective

HPR50 Exploring the Contribution of Health Gains and Cost-Offsets to Value-Based Drug Prices in Prior ICER Reviews

Rarely do discussions on value-based drug prices (VBPs) highlight the relative contribution of health gains and cost-offsets. Our objective was to explore the extent to which VBPs are driven by health gains and cost-offsets using interventions evaluated by the Institute for Clinical and Economic Review (ICER).

HTA15 Beyond Value Assessment: Payer Perceptions of ICER’s Policy Initiatives

To assess how the Institute for Clinical and Economic Review (ICER) has evolved its policy scope beyond value assessments in the last 7 years and explore payer perceptions of ICER’s new policy initiatives.

HPR57 Evidence Demonstration Framework for Medicare Part B and D Products Subject to Inflation Reduction Act (IRA) Price Regulations

The Inflation Reduction Act (IRA) of 2022 enacts a drug price reform allowing the government to negotiate prices of drugs covered under Medicare Parts B and D. Combined with cost-effectiveness reviews by the Institute for Clinical and Economic Review (ICER), the IRA may have a long-term impact on U.S. drug pricing. The objective of this study was to leverage the value framework employed by ICER to determine the best approach for manufacturers subjected to the IRA law during price negotiations.

HPR131 Examination of CMS National Coverage Analyses and Concordance with Other Decision-Making Bodies

The US Centers for Medicare & Medicaid Services (CMS) are authorized to evaluate technologies in order to make reimbursement decisions for millions of Americans through national coverage decisions (NCDs). This research aimed to examine trends in NCDs and identify any correlation between NCDs and coverage recommendations from the Institute for Clinical and Economic Review (ICER) in the US and the National Institute for Health and Care Excellence (NICE) in the UK.

Payer perceptions and use of value assessment tools in the United States.

BACKGROUND: As the United States transitions toward value-based payment, value assessment tools to measure the value of health care interventions are emerging. As the field evolves, it is important to evaluate how these tools are influencing treatment and coverage decisions. OBJECTIVE: To examine payer perceptions and use of US value assessment tools and identify how these tools inform payer decision-making. METHODS: A double-blind, web-based survey was conducted from June to July 2022 to assess health care payers' perceptions and use of value assessment tools developed by the American Society of Clinical Oncology, Drug Pricing Lab, Institute for Clinical and Economic Review (ICER), Innovation and Value Initiative, and National Comprehensive Cancer Network. RESULTS: 51 respondents completed the survey. 86% of payers were familiar with at least 4 of 5 value assessment tools. Both ICER and National Comprehensive Cancer Network tools are perceived as very useful for informing formulary decisions (57% and 49%, respectively). When selecting a value assessment tool, payers identified the inclusion of appropriate metrics and outcomes (92%), comparative clinical effectiveness information (88%), and reliance on rigorous, unbiased methods (86%) to be very/extremely important. Payers reported the inclusion of the patient, provider, and societal perspectives as lower importance (32%, 31%, and 20% identify these elements as very/extremely important, respectively). Payers reported using ICER evidence reports to both expand and restrict coverage decisions. To advance more useful and relevant value assessment tools, payers identified the need for greater stakeholder awareness of existing tools, and some recommended that value assessors increase the volume of assessments conducted. CONCLUSIONS: US health care payers perceive select value assessment tools to be useful for informing health care decisions. As policy momentum behind value assessment builds, additional examination of value assessment tools is needed to inform appropriate application of value assessment in US health care decision-making. DISCLOSURES: This study was funded by Xcenda/AmerisourceBergen. Ms Buelt, Ms Loo, Ms Westrich, and Drs Hydery and Zheng report employment with Xcenda/AmerisourceBergen. Drs Dharbhamalla and Graff report employment with AMCP.

Post-Menopausal Quality of Life Claims: Overlooking the Requirements of Normal Science and Fundamental Measurement in ICER'S Cost-Effectiveness Assessment of Fezolinetant for Moderate to Severe Vasomotor Symptoms.

One of the signal failures in health technology assessment is the absence of consideration given, not only to the standards of normal science, but to those of fundamental measurement. A recent evidence report by the Institute for Clinical and Economic Review (ICER) is emblematic of this failure. Based on a simple linear regression model that translates aggregate scores from the ordinal Menopause-specific Quality of Life Questionnaire (MENQOL) to the ordinal EuroQol EQ-5D-5L, ICER has applied these scores to an assumption driven model simulation to produce preferences, QALYs and incremental cost-per-QALY claims for fezolinetant for moderate to severe symptoms associated with menopause. Unfortunately, the attempt to crosswalk multidimensional or multiattribute ordinal scores is mathematically impossible. The 'created' EQ-5D-5L preferences are, as a result, of no interest. The overall result is that the ICER modelled claims for cost-effectiveness fail the required standards for normal science and fundamental measurement. fundamental are impossible. This is unfortunate, although it might be possible to assess certain domains of the MENQOL for their approximation to an interval score with the application of the Rasch Rating Scale Model, this will not support quality of life claims. A preferred approach would be to consider an alternative latent trait for quality of life in menopause, applying Rasch Measurement Theory (RMT), to develop a polytomous instrument that has the required measurement properties. The purpose of this commentary is to point out, as a number of previous commentaries have done, that this framework for creating assumption driven simulated modelled claims has no role in decisions for product assessment, access to formulary and pricing. This commentary expands upon these previous commentaries in placing RMT is the context of a needed paradigm shift to support the evolution of objective knowledge. This is critical if we are to understand, from the individual's perspective, not only an accurate assessment of the burden of menopause but to see this as part of an on-going research program that has to rely on fundamental measurement.

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.

Drug Cost-Effectiveness Assessments Require Standards for Rigor and Inclusion.

The Institute for Clinical and Economic Review (ICER), a nonprofit, nongovernmental organization, is the predominant independent price assessor in the United States. ICER's cost effectiveness assessments are increasingly being used to support health insurance coverage and healthcare policy decisions. ICER often does not apply rigorous data quality and inclusion criteria to either the assumptions embedded within their cost-effectiveness models or the data inputted into the models. Poor quality assumptions and data can lead to poor quality assessments. ICER should re-evaluate their reliance on quality adjusted life-years and equal value of life years gained as measures of drug effectiveness, establish data quality and inclusiveness minimum standards, produce cost-effectiveness assessments only when the minimum data is available, and prominently report data quality and inclusion limitations. These changes will increase the rigor and inclusiveness of drug price assessments and support sustainable access to high-value care for all Americans.