Projecting the long‐term societal value of a disease‐modifying treatment for Alzheimer's disease in the United States

Prados, María José; Liu, Ying; Jun, Hankyung; Lam, Juan F.; Mattke, Soeren

doi:10.1002/alz.12578

Cited by 19 publications

(18 citation statements)

References 46 publications

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“…Third and most importantly, their estimated quality-adjusted life-year (QALY) gain from aducanumab is surprisingly low and inconsistent with prior research. We recently estimated a 0.75 per patient gain in QALYs, which is in line with other published estimates of QALY gains—summarized in our article—of 0.73, 0.65, and 0.23 assuming treatment effects of 25%, 31%, and 25%, respectively. Another recent study estimated 0.75 QALYs gained per patient as well.…”

supporting

confidence: 89%

Cost-effectiveness of Aducanumab and Donanemab for Early Alzheimer Disease—Estimating the True Value

Mattke

2022

JAMA Neurol

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To the Editor Alzheimer disease (AD) can be clinically devastating and costly, given its potential to profoundly impair quality of life and activities of daily living. Ross et al 1 sought to evaluate cost-effectiveness of controversial novel antiamyloid monoclonal antibodies aducanumab and donanemab, which aim to slow AD progression. The US Food and Drug Administration (FDA), despite dissent of its expert advisory committee, approved aducanumab under the accelerated approval pathway in 2021, based on the surrogate end point of reduction in cerebral amyloid-β plaque, and is currently considering donanemab for accelerated approval on similar grounds.Fundamentally, a drug that is not effective cannot be cost-effective. Thus, engaging in and publishing costeffectiveness analyses (CEAs) of an unproven class of drugs lends them undue legitimacy. In designing this model, the authors used clinical outcomes to calculate model efficacy, as described in quality-adjusted life-years. Dementia stages were assigned utility values and state transitions were based on changes in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) and Mini-Mental State Examination (MMSE) over the course of the trials. 1 However, the clinical outcomes from the 2 phase 3 aducanumab trials are discordant and statistically insignificant by meta-analysis, emphasizing that the efficacy of aducanumab remains unclear, as the FDA also acknowledges. 2 Similarly, the authors conclude that donanemab would be cost-effective at a price of $20 000 per year, based on a single, phase 2 trial that found a 3.2-point between-group difference in the integrated Alzheimer's Disease Rating Scale, a score out of 144 points. 3 However, this trial showed no difference between the donanemab and control groups in MMSE or CDR-SB. 3 The discordance between cognitive assessment tools seen with both drugs further undermines whether either drug is having a clinically significant effect. This uncertainty is not reflected in this model nor this cost-effective price of $20 000. The authors further comment that donanemab's timelimited dosing scheme may improve the cost-effectiveness of all antiamyloid drugs, yet this notion rests on the contested amyloid cascade hypothesis: that lowering amyloid will slow progression of AD. 4,5 Although decision-science approaches can be useful to determine the value of gathering further information, this is not formally quantified by the authors, although the US Centers for Medicare and Medicaid has already recognized the value of further information in their decision to fund aducanumab only for patients in clinical trials. We question the appropriateness of a cost-effectiveness analysis before demonstration of a therapy's effectiveness.

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supporting

confidence: 89%

Cost-effectiveness of Aducanumab and Donanemab for Early Alzheimer Disease—Estimating the True Value

Mattke

2022

JAMA Neurol

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“…A model of the effect of reduced nursing home use with effective treatments for AD projected billions of dollars saved for reduced nursing home placement [ 21 ]. Another study of societal benefits from a treatment that slowed disease progression by 30% projected a reduction in costs of $5 trillion over 20 years in the US [ 22 ].…”

Section: Impact Of Alzheimer’s Diseasementioning

confidence: 99%

The Case for a Novel Therapeutic Approach to Dementia: Small Molecule Hepatocyte Growth Factor (HGF/MET) Positive Modulators

Moebius

Church

2023

JAD

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An estimated 6.5 million Americans aged 65 years or older have Alzheimer’s disease (AD), which will grow to 13.8 million Americans by 2060. Despite the growing burden of dementia, no fundamental change in drug development for AD has been seen in > 20 years. Currently approved drugs for AD produce only modest symptomatic improvements in cognition with small effect sizes. A growing mismatch exists between the urgent need to develop effective drugs for symptomatic AD and the largely failed search for disease modification. The failure rate of clinical trials in AD is high overall, and in particular for disease-modifying therapies. Research efforts in AD have focused predominantly on amyloid-β and tau pathologies, but limiting clinical research to these “classical hallmarks” of the disease does not address the most urgent patient, caregiver, or societal needs. Rather, clinical research should consider the complex pathophysiology of AD. Innovative approaches are needed that provide outside-the-box thinking, and re-imagine trial design, interventions, and outcomes as well as progress in proteomics and fluid biomarker analytics for both diagnostics and disease monitoring. A new approach offering a highly specific, yet multi-pronged intervention that exerts positive modulation on the HGF/MET neurotrophic system is currently being tested in mid-to-late-stage clinical trials in mild to moderate AD. Findings from such trials may provide data to support novel approaches for development of innovative drugs for treating AD at various disease stages and may offer benefits for those already symptomatic and disease alteration in AD and other neurodegenerative diseases.

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“…25 Traditional costeffectiveness methods that are currently a cornerstone of these decisions may be particularly ill-suited to the ethical and empirical challenges of treatments for aging. 26,27 The example metric concept is a holistic view of value, including that of the patient and family, and could be assessed by examining the extent to which payers adopt broader perspectives and alternative payment models for dementia care.…”

Section: Awareness and Activationmentioning

confidence: 99%

A framework for addressing Alzheimer's disease: Without a frame, the work has no aim

Ball¹,

Mattke

Frank

et al. 2022

Alzheimer's & Dementia

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Confronting Alzheimer's disease (AD) involves patients, healthcare professionals, supportive services, caregivers, and government agencies interacting along a continuum from initial awareness to diagnosis, treatment, support, and care. This complex scope presents a challenge for health system transformation supporting individuals at risk for, or diagnosed with, AD. The AD systems preparedness framework was developed to help health systems identify specific opportunities to implement and evaluate focused improvement programs. The framework is purposely flexible to permit local adaptation across different health systems and countries. Health systems can develop solutions tailored to system-specific priorities considered within the context of the overall framework. Example metric concepts and initiatives are provided for each of ten areas of focus. Examples of funded projects focusing on screening and early detection are provided. It is our hope that stakeholders utilize the common framework to generate and share additional implementation evidence to benefit individuals with AD.

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Projecting the long‐term societal value of a disease‐modifying treatment for Alzheimer's disease in the United States

Cited by 19 publications

References 46 publications

Cost-effectiveness of Aducanumab and Donanemab for Early Alzheimer Disease—Estimating the True Value

Cost-effectiveness of Aducanumab and Donanemab for Early Alzheimer Disease—Estimating the True Value

The Case for a Novel Therapeutic Approach to Dementia: Small Molecule Hepatocyte Growth Factor (HGF/MET) Positive Modulators

A framework for addressing Alzheimer's disease: Without a frame, the work has no aim

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