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Figure.  Diagram of Estimated Range of Older US Adults With Mild Cognitive Impairment (MCI) and Dementia Because of Alzheimer Dementia in the 2016 Health and Retirement Study (HRS) Core Sample
Diagram of Estimated Range of Older US Adults With Mild Cognitive Impairment (MCI) and Dementia Because of Alzheimer Dementia in the 2016 Health and Retirement Study (HRS) Core Sample

We used data from the 2016 HRS, a nationally representative survey of adults older than 50 years that studies the health and economic changes of aging. The national sample was obtained biennially at the household level and used a multistage, national area-clustered probability sampling frame. We identified 8396 HRS participants who represented approximately 41.2 million (95% CI, 39.2-43.1 million) US adults 65 years or older with Medicare Part B coverage in 2016, including Medicare fee-for-service and Medicare Advantage beneficiaries (beneficiaries must enroll in Medicare Part A and Part B to join a Medicare Advantage plan). To identify eligible patients with MCI or dementia, we used a 27-point cognitive scaling score (including immediate and delayed 10-noun free recall testing, serial 7 subtraction testing, and a backward count from 20).4 This scale classified participants with scores ranging from 0 to 6 as having dementia and those with scores ranging from 7 to 11 as having MCI. For participants represented by a proxy, we used an 11-point scale that classified participants with scores ranging from 6 to 11 as having dementia and those with scores ranging from 3 to 5 as having MCI. Based on prior work, we also further subclassified dementia severity using the following threshold scores for the 27-point and 11-point scales, respectively: (1) mild dementia, 5 to 6 and 6; (2) moderate dementia, 3 to 4 and 7; and (3) severe dementia, 0 to 2 and 8 to 11. While these and similar measures have previously demonstrated strong validity,4,5 we performed an additional sensitivity analysis showing that these dementia stages showed a strong association with the presence of an informal caregiver, which is a proxy for functional status (eTable 1 in the Supplement).

Table.  Estimated Annual Spending on Treatment With Aducanumab Among Older US Adults With MCI or Mild Dementia Because of Alzheimer Disease in the 2016 HRS Core Samplea
Estimated Annual Spending on Treatment With Aducanumab Among Older US Adults With MCI or Mild Dementia Because of Alzheimer Disease in the 2016 HRS Core Samplea
1.
US Food and Drug Administration. Center for Drug Evaluation and Research clinical review of aducanumab. Accessed August 10, 2021. https://www.biogencdn.com/us/aduhelm-pi.pdf
2.
Lin  GA, Whittington  MD, Synnott  PG, McKenna  A, Campbell  J, Pearson  SD, Rind  DM. Aducanumab for Alzheimer’s disease: effectiveness and value; final evidence report and meeting summary. Accessed October 24, 2021. https://icer.org/assessment/alzheimers-disease-2021/.
3.
Kaiser Family Foundation. FDA’s approval of Biogen’s new Alzheimer’s drug has huge cost implications for Medicare and beneficiaries. Accessed August 10, 2021. https://www.kff.org/medicare/issue-brief/fdas-approval-of-biogens-new-alzheimers-drug-has-huge-cost-implications-for-medicare-and-beneficiaries/
4.
Crimmins  EM, Kim  JK, Langa  KM, Weir  DR.  Assessment of cognition using surveys and neuropsychological assessment: the Health and Retirement Study and the Aging, Demographics, and Memory Study.   J Gerontol B Psychol Sci Soc Sci. 2011;66(suppl 1):i162-i171. doi:10.1093/geronb/gbr048PubMedGoogle Scholar
5.
Langa  KM, Chernew  ME, Kabeto  MU,  et al.  National estimates of the quantity and cost of informal caregiving for the elderly with dementia.   J Gen Intern Med. 2001;16(11):770-778. doi:10.1111/j.1525-1497.2001.10123.xPubMedGoogle ScholarCrossref
6.
Doraiswamy  PM, Sperling  RA, Johnson  K,  et al; AV45-A11 Study Group.  Florbetapir F 18 amyloid PET and 36-month cognitive decline: a prospective multicenter study.   Mol Psychiatry. 2014;19(9):1044-1051. doi:10.1038/mp.2014.9PubMedGoogle ScholarCrossref
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    Total Addressable Market (TAM) vs Actual Anticipated Costs
    BRUCE QUINN, MD PhD | Physician and policy consultant
    The article moves back and forth between the framework of total addressable market (sometimes abbreviated TAM) and best expected costs. These are two quite different things.

    While the addressable population being carefully estimated here may vary from 1M to 6M, the uptake and hence the "expected" or "anticipated" costs may be lower. Many recommended programs and drugs and health interventions have much lower uptake than the addressable market.

    For example, the total addressable market for sipuleucil (Provenge) was very large: all men in Medicare with metastatic prostate cancer. Yet despite
    an on-label national coverage determination (NCD), actual uptake was quite limited. The NCD was published in 2011; yearlong sales in 2012 and 2013 were circa $300M each, not multiples of billions of dollars, and roughly 3000 men per year. The prevalence for metastatic prostate cancer, and thus eligible men, had to be multiples of 35,000, the annual death rate from metastatic prostate cancer.

    For another example, many of the millions with dementia might qualify for a CSF exam, yet total Medicare CSF exams for all causes are only 28,000 services per year (codes 62270 + 62328).
    CONFLICT OF INTEREST: I have consulted for BIOGEN on diagnostic test policy for dementia.
    READ MORE
    Research Letter
    January 14, 2022

    Estimated Annual Spending on Aducanumab in the US Medicare Program

    Author Affiliations
    • 1Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine at UCLA, Los Angeles, California
    • 2RAND Corporation, Santa Monica, California
    • 3VA Greater Los Angeles Healthcare System, Los Angeles, California
    • 4Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
    • 5Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts
    JAMA Health Forum. 2022;3(1):e214495. doi:10.1001/jamahealthforum.2021.4495
    Introduction

    The US Food and Drug Administration’s June 2021 decision to approve aducanumab for treatment for Alzheimer dementia raised concerns that a drug with uncertain benefit and high cost could, in aggregate, threaten Medicare's solvency. In response to these concerns, Biogen recently announced a 50% annual drug price reduction from $56 000 to $28 200 per patient. Preliminary US spending estimates either used extrapolated Alzheimer dementia prevalence data from 2012 or did not explicitly quantify ancillary costs, such as additional diagnostic imaging to monitor the amyloid-associated imaging abnormalities (ARIAs) that occur in 41% of treated patients, and did not incorporate the recently announced price reduction.1-3 We estimated upper bound and lower bound annualized Medicare costs for administering aducanumab to beneficiaries with the approved indications of mild cognitive impairment (MCI) or mild dementia, focusing on the degree to which associated ancillary health services affect spending.1

    Methods

    For this cross-sectional study, we used validated cognitive measures from the 2016 Health and Retirement Study, a nationally representative survey of older adults, to identify Medicare Part B beneficiaries 65 years or older with MCI or mild dementia with either Medicare fee-for-service or Medicare Advantage coverage (Figure4,5). Institutional review board approval was provided by the University of California, Los Angeles, and informed consent was waived because of the study's design as a secondary analysis of publicly available, deidentified data. We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines for reporting cross-sectional studies.4,5

    The lower bound estimates of patients eligible for treatment with aducanumab assume prescribers would apply clinical trial inclusion criteria to adults with MCI or mild dementia with amyloid plaque on positron emission tomography imaging results. The upper bound estimate includes patients with MCI or mild dementia and plaque without age or comorbidity restrictions to reflect potential off-label prescribing.1 Between 37% to 68% of patients with MCI or dementia have plaque according to population studies (we used 37% for the lower bound and 68% for the upper bound estimate).6

    We quantified drug costs from patient weights and ancillary costs, such as additional magnetic resonance imaging scans, using amyloid-associated imaging abnormalities rates from clinical trials and US Food and Drug Administration recommendations (Table).1,2 We multiplied annualized per-person costs by lower bound and upper bound population estimates of MCI or mild dementia prevalence. Medicare would pay 80%, and the remaining 20% coinsurance would be paid by beneficiaries, private supplemental plans, and/or state Medicaid programs. While cost sharing may vary for Medicare Advantage beneficiaries, the total costs will remain the same regardless of the cost-sharing rules. The eAppendix and eTables 1 to 3 in the Supplement provide further details on dementia identification, weight-based drug cost estimates, and cost analysis assumptions.

    We analyzed data using SAS, version 9.4 (SAS Institute). We accounted for survey clustering and adjusted results by survey weights for the national representativeness and response rate.

    Results

    We identified 8396 participants representing approximately 41.2 million (95% CI, 39.2-43.1 million) US adults 65 years or older with Medicare Part B coverage in 2016. Total annualized per-person weight-based drug costs equaled $27 759.36; ancillary costs equaled $6563.94. For the lower bound estimate, if 25% of the 1 066 670 (95% CI, 0.95-1.2 million) eligible patients with MCI or mild dementia and plaque with clinical trial age and comorbidity restrictions received treatment with aducanumab, Medicare would pay $7.0 billion (95% CI, $6.2-$7.8 billion) each year. For the upper bound estimate, if 25% of the expanded population of 5 715 983 (95% CI, 5.3-6.2 million) eligible patients with MCI or mild dementia and plaque received treatment with aducanumab, Medicare would pay $37.4 billion (95% CI, $34.4-$40.3 billion). Ancillary health services comprised 19.4% of total population spending estimates.

    Discussion

    In this nationally representative analysis, we identified between 1.1 to 5.7 million Medicare beneficiaries who are potentially eligible to receive treatment with aducanumab. Ancillary health services comprised nearly 20% of total population spending estimates, suggesting that prior analyses underestimated the anticipated costs of aducanumab.3

    This study has limitations. We used plaque rates from population studies rather than actual scans on Health and Retirement Study participants.6 Our validated approach of identifying dementia prevalence may have misclassified some cases.4 Surveys may be less reliable among participants with dementia, although participants’ proxies were frequently available.4 Furthermore, we did not account for potential future changes to drug acquisition costs or for societal costs, such as caregiver burden or health system capacity limitations.

    Conclusions

    The findings of this cross-sectional study suggest that the drug and ancillary costs of aducanumab could seriously strain Medicare’s budget, raising questions of how to maximize the value of public dollars, particularly for a drug with unknown benefit and known risk of patient harm.

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    Article Information

    Accepted for Publication: November 4, 2021.

    Published: January 14, 2022. doi:10.1001/jamahealthforum.2021.4495

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Mafi JN et al. JAMA Health Forum.

    Correction: This article was corrected on February 18, 2022, to fix errors in the text and Figure.

    Corresponding Author: John N. Mafi, MD, MPH, Division of General Medicine and Health Services Research, Department of Medicine, David Geffen School of Medicine at UCLA, 1100 Glendon Ave, #908, Los Angeles, CA 90024 (jmafi@mednet.ucla.edu).

    Author Contributions: Dr Mafi (principal investigator) had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Mafi, Arbanas, Damberg, Sarkisian, Landon.

    Acquisition, analysis, or interpretation of data: Mafi, Leng, Arbanas, Tseng.

    Drafting of the manuscript: Mafi.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Mafi, Leng, Tseng.

    Obtained funding: Mafi, Sarkisian.

    Administrative, technical, or material support: Mafi, Arbanas.

    Supervision: Mafi, Sarkisian, Landon.

    Conflict of Interest Disclosures: Dr Mafi reported grants from the National Institute on Aging (NIA) during the conduct of the study, as well as nonfinancial support from Milliman MedInsight and grants from Arnold Ventures. Ms Arbanas reported grants from the NIA during the conduct of the study. Dr Sarkisian reported grants from the National Institutes of Health (NIH) during the conduct of the study. No other disclosures were reported.

    Funding/Support: This work was supported by NIH/NIA award R01AG070017-01. Dr Mafi was also supported by a NIH/NIA Beeson Emerging Leaders in Aging Research Career Development Award (grant K76AG064392-01A1).

    Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

    Additional Contributions: We thank Kenneth Langa, MD, PhD, University of Michigan, for his technical assistance in our methods to identify patients with mild cognitive impairment and mild, moderate, and severe dementia. He was compensated for his contributions.

    References
    1.
    US Food and Drug Administration. Center for Drug Evaluation and Research clinical review of aducanumab. Accessed August 10, 2021. https://www.biogencdn.com/us/aduhelm-pi.pdf
    2.
    Lin  GA, Whittington  MD, Synnott  PG, McKenna  A, Campbell  J, Pearson  SD, Rind  DM. Aducanumab for Alzheimer’s disease: effectiveness and value; final evidence report and meeting summary. Accessed October 24, 2021. https://icer.org/assessment/alzheimers-disease-2021/.
    3.
    Kaiser Family Foundation. FDA’s approval of Biogen’s new Alzheimer’s drug has huge cost implications for Medicare and beneficiaries. Accessed August 10, 2021. https://www.kff.org/medicare/issue-brief/fdas-approval-of-biogens-new-alzheimers-drug-has-huge-cost-implications-for-medicare-and-beneficiaries/
    4.
    Crimmins  EM, Kim  JK, Langa  KM, Weir  DR.  Assessment of cognition using surveys and neuropsychological assessment: the Health and Retirement Study and the Aging, Demographics, and Memory Study.   J Gerontol B Psychol Sci Soc Sci. 2011;66(suppl 1):i162-i171. doi:10.1093/geronb/gbr048PubMedGoogle Scholar
    5.
    Langa  KM, Chernew  ME, Kabeto  MU,  et al.  National estimates of the quantity and cost of informal caregiving for the elderly with dementia.   J Gen Intern Med. 2001;16(11):770-778. doi:10.1111/j.1525-1497.2001.10123.xPubMedGoogle ScholarCrossref
    6.
    Doraiswamy  PM, Sperling  RA, Johnson  K,  et al; AV45-A11 Study Group.  Florbetapir F 18 amyloid PET and 36-month cognitive decline: a prospective multicenter study.   Mol Psychiatry. 2014;19(9):1044-1051. doi:10.1038/mp.2014.9PubMedGoogle ScholarCrossref
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