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Nadofaragene firadenovec is a gene therapy for BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) undergoing FDA review. Pembrolizumab is approved for treating BCG-unresponsive NMIBC patients with carcinoma in-situ (CIS). We evaluated the cost-effectiveness of these treatments compared with a hypothetical therapeutic alternative, at a willingness-to-pay (WTP) threshold of $150,000 per quality-adjusted life year (QALY) gained, in CIS and non-CIS BCG-unresponsive NMIBC populations.We developed a Markov cohort simulation model with a three-month cycle length and lifetime horizon to estimate total costs, QALYs and cost per additional QALY from the health sector perspective. Clinical inputs were informed by results of single-arm clinical trials evaluating the treatments and systematic literature reviews were conducted to obtain other model inputs. Sensitivity analyses were conducted to assess uncertainty in model results.Nadofaragene firadenovec, at a placeholder price 10% higher than the price of pembrolizumab, had an incremental cost-effectiveness ratio (ICER) of $263,000 and $145,000 per QALY gained in CIS and non-CIS populations, respectively. Pembrolizumab had an ICER of $168,000 per QALY gained for CIS. A 5.4% reduction in pembrolizumab's price would make it cost-effective. The model was sensitive to many inputs, especially probabilities of disease progression, initial treatment response and durability, and drug price.The cost-effectiveness of nadofaragene firadenovec will depend upon its price. Pembrolizumab, though not cost-effective in our base-case analysis, is an important alternative in this population with an unmet medical need. Comparative trials of these treatments are warranted to better estimate cost-effectiveness.

To evaluate the influence of drug price dynamics in cost-effectiveness analyses (CEAs).We evaluated scenarios involving typical US drug price increases during the exclusivity period and price decreases after the loss of exclusivity (LOE). Worked examples are presented using the Institute for Clinical and Economic Review's assessments of tezepelumab for the treatment of severe asthma and targeted immune modulators for rheumatoid arthritis.Tezepelumab case: Yearly 2% price increases during the period of exclusivity and a post-LOE price decrease of 25% yielded an incremental cost per QALY gained that increased over the base case from $430,300 to $444,600 (+3.2%). Yearly 2% price increases followed by a steeper post-LOE price reduction of 40% resulted in a cost per QALY gained of $401,400 (6.8% reduction versus the base case). Rheumatoid arthritis case: Incorporating post-LOE price reductions for etanercept (intervention) and adalimumab (comparator) ranging from 25% to 40% yielded an incremental cost per QALY of $121,000 and $122,300, respectively (3% increase from the base case of $119,200/QALY). Including a 2% yearly price increase during the projected exclusivity periods of both intervention and comparator increased the cost per QALY gained by more than 60%.Two biologic treatment cases incorporating price dynamics in CEA had varied impacts on the cost-effectiveness ratio depending on the magnitude of pre-LOE price increase and post-LOE price decrease, and whether the LOE also affected the comparator. Yearly price increase magnitude during the period of exclusivity, among other factors, may counterbalance the effects of lower post-LOE intervention prices.

Scientific advancements, new US FDA approval pathways and limited competition have contributed to rapid growth in the number of approved rare disease treatments in recent years. While the rising numbers of orphan drug approvals are a sign of success, the rapid growth in approved rare disease treatments has created concerns about the pricing of orphan drugs and their cumulative affordability to the health system. To support efforts to build a policy and practice infrastructure that drives innovation within a platform that is affordable to patients and the health system, this paper provides an analysis of potential risks as well as advantages of reform options related to drug development, pricing and coverage.

This study aimed to estimate the cost-effectiveness of remdesivir, the first novel therapeutic to receive Emergency Use Authorization for the treatment of hospitalized patients with COVID-19, and identify key drivers of value to guide future pricing and reimbursement efforts.A Markov model evaluated the cost-effectiveness of remdesivir in patients hospitalized with COVID-19 from a US healthcare sector perspective. A lifetime time horizon captured potential long-term costs and outcomes. Model outcomes included discounted total costs, life-years, and quality-adjusted life-years (QALYs). Remdesivir was modeled as an addition to standard of care and compared with standard of care alone, including dexamethasone for patients requiring respiratory support. COVID-19 hospitalizations were assumed to be reimbursed through a single payment based on the respiratory support received alongside a remdesivir carveout payment in the base case. Sensitivity and scenario analyses identified key drivers.At a unit price of $520 per vial and assuming no survival benefit with remdesivir, the incremental cost-effectiveness was $298 200/QALY for patients with moderate to severe COVID-19 and $1 847 000/QALY for patients with mild COVID-19. Although current data do not support a survival benefit, if one was assumed, the cost-effectiveness estimate was $50 100/QALY for the moderate to severe population and $103 400/QALY for the mild population. Another key driver included the hospitalization payment structure (per diem vs bundled payment).With the current evidence available, remdesivir's price is too high to align with its expected health gains for hospitalized patients with COVID-19. Results from this study provide a rationale for iterative health technology assessment.

Mechanical ventilation is a lifesaving therapy for critically ill patients with respiratory failure, but like all treatments, it has the potential to cause harm if not administered appropriately. This review aims to give an overview of the basic principles of invasive and noninvasive mechanical ventilation. Topics covered include modes of mechanical ventilation, respiratory mechanics and ventilator waveform interpretation, strategies for initial ventilator settings, indications and contraindications for noninvasive ventilation, and the effect of the ventilator on kidney function.

Background and objectives: Despite existing therapies, people with lupus nephritis progress to kidney failure and have reduced life expectancy. Belimumab and voclosporin are two new disease-modifying therapies recently approved for the treatment of lupus nephritis.\ud \ud \ud \ud Design, setting, participants, & measurements: A de novo economic model was developed to estimate the cost-effectiveness of these therapies, including the following health states: “complete response,” “partial response,” and “active disease” defined by eGFR and proteinuria changes, kidney failure, and death. Short-term data and mean cohort characteristics were sourced from pivotal clinical trials of belimumab (the Belimumab International Study in Lupus Nephritis) and voclosporin (the Aurinia Urinary Protection Reduction Active–Lupus with Voclosporin trial and Aurinia Renal Response in Active Lupus With Voclosporin). Risk of mortality and kidney failure were on the basis of survival modeling using published Kaplan–Meier data. Each drug was compared with the standard of care as represented by the comparator arm in its respective pivotal trial(s) using US health care sector perspective, with a societal perspective also explored.\ud \ud \ud \ud Results: In the health care perspective probabilistic analysis, the incremental cost-effectiveness ratio for belimumab compared with its control arm was estimated to be approximately $95,000 per quality-adjusted life year. The corresponding incremental ratio for voclosporin compared with its control arm was approximately $150,000 per quality-adjusted life year. Compared with their respective standard care arms, the probabilities of belimumab and voclosporin being cost effective at a threshold of $150,000 per quality-adjusted life year were 69% and 49%, respectively. Cost-effectiveness was dependent on assumptions made regarding survival in response states, costs and utilities in active disease, and the utilities in response states. In the analysis from a societal perspective, the incremental ratio for belimumab was estimated to be approximately $66,000 per quality-adjusted life year, and the incremental ratio for voclosporin was estimated to be approximately $133,000 per quality-adjusted life year.\ud \ud \ud \ud Conclusions: Compared with their respective standard care arms, belimumab but not voclosporin met willingness-to-pay thresholds of $100,000 per quality-adjusted life year. Despite potential clinical superiority in the informing trials, there remains high uncertainty around the cost-effectiveness of voclosporin.

The accelerated approval pathway for new drugs in the United States is often praised but faces growing criticism of whether it is finding the appropriate balance between uncertainty, access and cost. To support efforts to strengthen the pathway, this paper provides an analysis of key concerns and the advantages and disadvantages of ten potential policy reforms - those achievable through the US FDA action alone, and those that would require a combination of government, payer and life science industry actions. Accelerated approval sits at the heart of many of the controversies regarding drug approvals and pricing, and this analysis provides perspectives on how best to strengthen the pathway within the broader landscape of an innovative US healthcare system.Tweetable abstract New ICER policy analysis evaluates ten potential policy reforms to strengthen FDA’s accelerated approval pathway for prescription drugs.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Sun Life Financial, uniQure, and United Healthcare. Whittington, Rind, and Pearson are employed by ICER. Through their affiliated institutions, Synnott and Lin received funding from ICER for the work described in this summary. In addition, Synnott reports support from Biogen for the Tufts Medical Center Cost-Effectiveness Analysis Registry, which is maintained by the Center for the Evaluation of Value and Risk in Health.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan ...

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Beinfeld, Fluetsch, and Pearson are employed by ICER. Ollendorf received funding from ICER for work on this summary and reports consulting and other personal fees from EMD Serono, Amgen, Analysis Group, Aspen Institute/University of Southern California, GalbraithWight, Cytokinetics, Executive Insight, Sunovion, University of Colorado, World Health Organization, and Eli Lilly, unrelated to this work. Lee and McQueen received funding from ICER for work on this summary.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Agboola, McKenna, and Pearson are employed by ICER. Lin and Kazi received funding from ICER for work on this report.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Beinfeld, McKenna, Rind, and Pearson are employed by ICER. Touchette received funding from ICER for work on this report and has also received fees from Monument Analytics and AstraZeneca, unrelated to this work. The University of Illinois at Chicago (UIC) and Touchette hold a patent for the model described in this report. The model is included in ICER's Interactive Modeler, for which a fee is paid to UIC and Touchette. Atlas also received funding from ICER for work on this report.

Objectives To evaluate alternative methods to calculate and/or attribute economic surplus in the cost-effectiveness analysis of single or short-term therapies. Methods We performed a systematic literature review of articles describing alternative methods for cost-effectiveness analysis of potentially curative therapies whose assessment using traditional methods may suggest unaffordable valuations owing to the magnitude of estimated long-term quality-adjusted life-year (QALY) gains or cost offsets. Through internal deliberation and discussion with staff at the Health Technology Assessment bodies in England and Canada, we developed the following 3 alternative methods for further evaluation: (1) capping annual costs in the comparator arm at $150 000 per year; (2) “sharing” the economic surplus with the health sector by apportioning only 50% of cost offsets or 50% of cost offsets and QALY gains to the value of the therapy; and (3) crediting the therapy with only 12 years of the average annual cost offsets or cost offsets and QALY gains over the lifetime horizon. The impact of each alternative method was evaluated by applying it in an economic model of 3 hypothetical condition-treatment scenarios meant to reflect a diversity of chronicity and background healthcare costs. Results The alternative with greatest impact on threshold price for the fatal pediatric condition spinal muscular atrophy type 1 was the 12-year cutoff scenario. For a hypothetical one-time treatment for hemophilia A, capping cost offsets at $150 000 per year had the greatest impact. For chimeric antigen receptor T-cell treatment of non-Hodgkin’s lymphoma, capping cost offsets or using 12-year threshold had little impact, whereas 50% sharing of surplus including QALY gains and cost offsets greatly reduced threshold pricing. Conclusions Health Technology Assessment bodies and policy makers will wrestle with how to evaluate single or short-term potentially curative therapies and establish pricing and payment mechanisms to ensure sustainability. Scenario analyses using alternative methods for calculating and apportioning economic surplus can provide starkly different assessment results. These methods may stimulate important societal dialogue on fair pricing for these novel treatments.

At the heart of all health insurance programs lies ethical tension between maximizing the freedom of patients and clinicians to tailor care for the individual and the need to make healthcare affordable. Nowhere is this tension more fiercely debated than in benefit design and coverage policy for pharmaceuticals. This paper focuses on three areas over which there is the most controversy about how to judge whether drug coverage is appropriate: cost-sharing provisions, clinical eligibility criteria, and economic-step therapy and required switching. In each of these domains we present ‘ethical goals for access’ followed by a series of ‘fair design criteria’ that can be used by stakeholders to drive more transparent and accountable drug coverage.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Agboola, Rind, Herron-Smith, and Pearson are employed by ICER. Walton and Quach, through the University of Illinois at Chicago, received funding from ICER for development of the economic model described in this report.

BACKGROUND: Oral semaglutide is the first oral formulation of a glucagon-like peptide 1 (GLP-1) receptor agonist to be approved in the United States for glycemic control in people with type 2 diabetes mellitus (T2DM). While oral semaglutide is not indicated for reduction of cardiovascular event risk, its label does include evidence of no increase in cardiovascular risk in people who received oral semaglutide. OBJECTIVE: To estimate the incremental value of oral semaglutide added to existing antihyperglycemic treatment for people with T2DM with additional risk for cardiovascular disease. METHODS: We estimated the lifetime cost-effectiveness of oral semaglutide added to current antihyperglycemic treatment for T2DM using a microsimulation model based primarily on the UK Prospective Diabetes Study (UKPDS) Outcomes Model 2 (OM2) equations. Oral semaglutide added to current antihyperglycemic treatment was separately compared with (a) ongoing background antihyperglycemic treatment, (b) sitagliptin, (c) empagliflozin, and (d) liraglutide. Comparators sitagliptin, empagliflozin, and liraglutide were added to ongoing antihyperglycemic treatment. We applied hazard ratios derived from a network meta-analysis for cardiovascular and renal outcomes to the UKPDS OM2 estimated baseline rates. Health state utilities and costs were derived from the published literature. We estimated total costs, life-years (LYs), quality-adjusted life-years (QALYs), clinical events, and cost per major adverse cardiovascular event (MACE) avoided, over a lifetime time horizon using discount rates of 3% for costs and outcomes. RESULTS: The lifetime total cost for people treated with oral semaglutide was $311,300, with costs for the other comparators ranging from $262,800 (background treatment alone) to $287,800 (liraglutide). Oral semaglutide resulted in the fewest MACE, including the fewest cardiovascular deaths. Among the 5 modeled treatment strategies, oral semaglutide had the highest LYs gained (8.43 vs. 7.76 [background treatment alone] to 8.29 [empagliflozin and liraglutide]) and the highest QALYs gained (4.11 vs. 3.70 [background treatment alone] to 4.03 [empagliflozin]). Oral semaglutide would likely be considered cost-effective compared with liraglutide (incremental cost-effectiveness ratio [ICER] = $40,100), and moderately cost-effective versus background treatment alone ([ICER] = $117,500/QALY) and sitagliptin (ICER = $145,200/QALY). The ICER for oral semaglutide compared with empagliflozin was approximately $458,400 per QALY. CONCLUSIONS: As modeled, oral semaglutide as an add-on therapy to background antihyperglycemic treatment produced incremental benefits in MACE avoided, along with greater QALYs compared with background antihyperglycemic treatment alone. Oral semaglutide use resulted in better outcomes than background treatment alone or sitagliptin, and similar outcomes to liraglutide or empagliflozin with overlapping 95% confidence ranges for QALYs. Oral semaglutide was estimated to be cost-effective compared with liraglutide and to have incremental cost-effectiveness ratios between $100,000 and $150,000 per QALY versus sitagliptin and background therapy alone, but it did not meet these thresholds compared with empagliflozin. DISCLOSURES: Funding for this study was provided by the Institute for Clinical and Economic Review, an independent organization that evaluates the evidence on the value of health care interventions. ICER reports grants from Laura and John Arnold Foundation, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Rind, Fazioli, Chapman, and Pearson are employed by ICER. Guzauskas and Hansen have nothing to disclose. Study results were presented at the New England Comparative Effectiveness Public Advisory Council (New England CEPAC), November 14, 2019, at Brown University, Providence, RI.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan ...

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan ...

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clin...

The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine, in a 3- to 4-year recurring cycle of topics. These topics will be presented at the 2020 International Conference. Below is the adult critical care medicine core including complications of chemotherapy, acute-on-chronic liver failure, alcohol withdrawal syndrome, mechanical circulatory support, direct oral anticoagulants, upper gastrointestinal hemorrhage, and vasopressor selection.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clin...

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM), New England St...

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM), New England St...

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM), New England St...

PURPOSES OF REVIEW: Critically ill patients frequently require mechanical ventilation as part of their care. Administration of analgesia and sedation to ensure patient comfort and facilitate mechanical ventilation must be balanced against the known negative consequences of excessive sedation. The present review focuses on the current evidence for sedation management during mechanical ventilation, including choice of sedatives, sedation strategies, and special considerations for acute respiratory distress syndrome (ARDS). RECENT FINDINGS: The Society of Critical Care Medicine recently published their updated clinical practice guidelines for analgesia, agitation, sedation, delirium, immobility, and sleep in adult patients in the ICU. Deep sedation, especially early in the course of mechanical ventilation, is associated with prolonged time to liberation from mechanical ventilation, longer ICU stays, longer hospital stays, and increased mortality. Dexmedetomidine may prevent ICU delirium when administered nocturnally at low doses; however, it was not shown to improve mortality when used as the primary sedative early in the course of mechanical ventilation, though the majority of patients in the informing study failed to achieve the prescribed light level of sedation. In a follow up to the ACURASYS trial, deep sedation with neuromuscular blockade did not result in improved mortality compared to light sedation in patients with severe ARDS. SUMMARY: Light sedation should be targeted early in the course of mechanical ventilation utilizing daily interruptions of sedation and/or nursing protocol-based algorithms, even in severe ARDS.

DISCLOSURES: Funding for this summary was contributed by the Laura and John Arnold Foundation, National Institute for Health Care Management, California Health Care Foundation, Blue Cross Blue Shie...

Importance The possibility of widespread use of a novel effective therapy for Alzheimer disease (AD) will present important clinical, policy, and financial challenges. Objective To describe how including different patient, caregiver, and societal treatment-related factors affects estimates of the cost-effectiveness of a hypothetical disease-modifying AD treatment. Design, setting, and participants In this economic evaluation, the Alzheimer Disease Archimedes Condition Event Simulator was used to simulate the prognosis of a hypothetical cohort of patients selected from the Alzheimer Disease Neuroimaging Initiative database who received the diagnosis of mild cognitive impairment (MCI). Scenario analyses that varied costs and quality of life inputs relevant to patients and caregivers were conducted. The analysis was designed and conducted from June 15, 2019, to September 30, 2020. Exposures A hypothetical drug that would delay progression to dementia in individuals with MCI compared with usual care. Main outcomes and measures Incremental cost-effectiveness ratio (ICER), measured by cost per quality-adjusted life-year (QALY) gained. Results The model included a simulated cohort of patients who scored between 24 and 30 on the Mini-Mental State Examination and had a global Clinical Dementia Rating scale of 0.5, with a required memory box score of 0.5 or higher, at baseline. Using a health care sector perspective, which included only individual patient health care costs, the ICER for the hypothetical treatment was $192 000 per QALY gained. The result decreased to $183 000 per QALY gained in a traditional societal perspective analysis with the inclusion of patient non-health care costs. The inclusion of estimated caregiver health care costs produced almost no change in the ICER, but the inclusion of QALYs gained by caregivers led to a substantial reduction in the ICER for the hypothetical treatment, to $107 000 per QALY gained in the health sector perspective. In the societal perspective scenario, with the broadest inclusion of patient and caregiver factors, the ICER decreased to $74 000 per added QALY. Conclusions and relevance The findings of this economic evaluation suggest that policy makers should be aware that efforts to estimate and include the effects of AD treatments outside those on patients themselves can affect the results of the cost-effectiveness analyses that often underpin assessments of the value of new treatments. Further research and debate on including these factors in assessments that will inform discussions on fair pricing for new treatments are needed.

Background and ObjectivesAducanumab was granted accelerated approval with a conflicting evidence base, near-unanimous Food and Drug Administration Advisory Committee vote to reject approval, and a widely criticized launch price of $56,000 per year. The objective of this analysis was to estimate its cost-effectiveness.MethodsWe developed a Markov model to compare aducanumab in addition to supportive care to supportive care alone over a lifetime horizon. Results were presented from both the health system and modified societal perspective. The model tracked the severity of disease and the care setting. Incremental cost-effectiveness ratios were calculated and a threshold analysis was conducted to estimate at what price aducanumab would meet commonly used cost-effectiveness thresholds.ResultsUsing estimates of effectiveness based on pooling of data from both pivotal trials, patients treated with aducanumab spent 4 more months in earlier stages of Alzheimer disease. Over the lifetime time horizon, treating a patient with aducanumab results in 0.154 more quality-adjusted life-years (QALYs) gained per patient and 0.201 equal value of life-years gained (evLYG) per patient from the health care system perspective, with additional costs of approximately $204,000 per patient. The incremental outcomes were similar for the modified societal perspective. At the launch price of $56,000 per year, the cost-effectiveness ranged from $1.02 million per evLYG to $1.33 million per QALY gained from the health care system perspective and from $938,000 per evLYG to $1.27 million per QALY gained in the modified societal perspective. The annual price to meet commonly used cost-effectiveness thresholds ranged from $2,950 to $8,360, which represents a discount of 85%–95% off from the annual launch price set by the manufacturer. Using estimates of effectiveness based only on the trial that suggested a benefit, the mean incremental cost was greater than $400,000 per QALY gained.ConclusionPatients treated with aducanumab received minimal improvements in health outcomes at considerable cost. This resulted in incremental cost-effectiveness ratios that far exceeded commonly used value thresholds, even under optimistic treatment effectiveness assumptions. These findings are subject to the substantial uncertainty regarding whether aducanumab provides any true net health benefit, but evidence available currently suggests that an annual price of aducanumab of $56,000 is not in reasonable alignment with its clinical benefits.

The purpose of this article is to describe the process and the methods of cost-effectiveness analysis for clinicians interested in joining or leading aspects of this branch of evidence-based research. Cost-effectiveness is a useful tool for policymakers and is considered a starting point for discussions of fair pricing. Clinicians are important members of teams conducting cost-effectiveness analyses, particularly as it relates to integrating their clinical expertise into the decisions around the design and conduct of the analysis. Their input is essential in assuring that models adequately reflect clinical practice and are informed by expert judgments of how existing data can best be interpreted to build a comprehensive analysis of the clinical and economic outcomes of different treatment options. We illustrate specific contributions that clinicians are well positioned to make in these teams using a recent cost-effectiveness analysis of aducanumab that was conducted to support fair drug pricing. While discussing these contributions, we explain key components of a cost-effectiveness analysis, such as time horizon, health states, and perspective, to support understanding of the methods of cost-effectiveness by the clinical researchers and to promote a common dialogue among these multidisciplinary teams.