Work

Estimated wasteful spending on aducanumab dispensing in the U.S. Medicare population: A cross‐sectional analysis

Year: 2022

Type: article

Abstract: Aducanumab, a weight-dosed Alzheimer's drug with uncertain benefits and high cost, could strain Medicare's budget if approved for widespread use.1 In April 2022, Medicare issued a final determination restricting aducanumab's use to clinical trials. However, Medicare's coverage decision may still be overturned by legal challenges, potentially leading to much higher uptake.2 Moreover, several other Alzheimer's infusion drugs similar to aducanumab are currently in the development pipeline.3 Because aducanumab is available in two fixed-dose vial sizes, its use may result in large amounts of discarded drug and wasteful spending.4, 5 To quantify the amount of discarded drug and potential savings that could be generated from more efficient aducanumab vial sizes, we analyzed patient weight distributions from a nationally representative sample of Medicare beneficiaries with mild cognitive impairment (MCI) or mild dementia. We used nationally representative data from the 2016 Health and Retirement Study (HRS), focusing on participants aged ≥65 years with Medicare Part B insurance. Using validated cognitive measures to identify patients with MCI or mild dementia and self/proxy-reported patient weights, we estimated a lower and upper bound of potentially eligible patients to receive aducanumab (Figure S1, Tables S1 and S2, and Appendix S1).6, 7 The manufacturer created two vial sizes: 170 mg/1.7 ml and 300 mg/3.0 ml. Assuming a 10 mg/kg monthly dose, we counted the number of vials needed for each patient weight category, and multiplied the per-vial costs by the survey-weighted population (e.g., 7.96% of the upper-bound survey-weighted population weighing 85–90 kg required three 300 mg/3 ml vials, or $2538 × 0.0796 per month, Table 1), and summarized across categories to derive a weighted average for drug spending. To estimate annualized per-patient discarded drug, we subtracted the milligrams of the patient weight-based dose needed for each patient in the non-survey-weighted sample from the total dose provided in the most cost-efficient combination of vials. For example, an 85 kg patient requires 850 mg of drug provided by three 300 mg/3.0 ml vials (900 mg total), with 50 mg of discarded drug per month. We multiplied monthly discarded drug (mg) for each survey participant by the survey-weighted population (e.g., for the same 85 kg patient, multiply 50 mg of discarded drug per month by the survey-weighted population of 10,707 patients representing the 85 kg HRS survey participant), multiplied by 12 months to annualize estimates. We accounted for expected amyloid plaque rates7, 8 in the lower (37%) and upper-bound (68%) populations (Figure 1). We tabulated costs using the 300 mg/3.0 ml vial price. Hypothesizing that smaller vials could reduce the amount of discarded drug, we simulated three alternative size combinations (100 and 170 mg; 170 and 250 mg; and 80 mg, 170, and 300 mg), retaining at least one original vial size, and quantified potential savings. We used SAS version 9.4, accounting for clustering, survey weights, and non-response to generate nationally representative estimates. The University of California, Los Angeles Institutional Review Board approved this study, which follows Strengthening the Reporting of Observational Studies in Epidemiology guidelines. We identified lower and upper estimates of 737–2035 participants, representing approximately 2,882,893 (95% CI 2.6–3.2 million) to 8,405,858 (95% CI 7.7–9.1 million) Medicare Part B beneficiaries aged ≥65 years with MCI or mild dementia. Conservatively assuming a 10% drug uptake, the equivalent of between 132,398 (95% CI 115,220–149,655) and 694,258 (95% CI 628,458-760,059) 300 mg/3.0 ml vials of aducanumab would be discarded annually (Figure 1), costing between $115.4 (95% CI $100.4–$130.4) million and $604.9 (95% CI $547.6–$662.3) million each year. If the 300 mg/3.0 ml vial was reduced to 100 mg/1.0 ml, savings would range between $70.9 (95% CI $60.8–$81.1) and $369.0 (95% CI $331.1–$406.9) million per year. In this nationally representative analysis, a 10% drug uptake would waste hundreds of thousands of aducanumab vials annually, burdening Medicare with $115–$605 million in wasteful spending each year. While Medicare set limits on aducanumab's use, Medicare's decision may still be overturned.2 With several other Alzheimer's infusion drugs in the development pipeline, aducanumab will not be the last Part B infusion drug to threaten Medicare's solvency. Given Medicare's 15% premium increase in 2022 due in part to anticipated aducanumab uptake, greater attention to efficient vial packaging has the potential to improve the value of future of Part B spending, constrain Part B premium growth, and limit beneficiaries' out-of-pocket spending. This study has limitations. While self/proxy-reported cognitive measures and weights were previously validated,6 surveys may misclassify some cases. We used plaque prevalence rates from population studies rather than PET scans on HRS participants.7, 8 We assumed patient weights would be randomly distributed by plaque presence and by aducanumab uptake, that changing vial size would have negligible cost and that drug pricing would not change. Reducing vial size could decrease wasteful spending from discarded vials by over 60%, with policy implications for all weight-based infusion drugs. Carlos Irwin A. Oronce wrote the initial draft of the manuscript. Carlos Irwin A. Oronce, Julia Cave Arbanas, and John N. Mafi conceived the idea and design of the study. Cheryl L. Damberg, Bruce E. Landon, and Catherine Sarkisian provided input on the conceptualization of the study. Mei Leng performed the initial construction of the cohort. Carlos Irwin A. Oronce, Julia Cave Arbanas, and Mei Leng performed the analyses. Julia Cave Arbanas created the tables and figures. All authors provided critical feedback and revisions to the manuscript. The authors have no conflicts of interest to declare. This work was supported by a National Institutes of Health (NIH)/National Institute on Aging (NIA) R01 Award (R01AG070017-01). Dr. Carlos Irwin A. Oronce was supported by the VA Office of Academic Affiliations through the VA Advanced Health Services Research Fellowship. Dr. John N. Mafi was supported by a National Institute on Aging award (K76AG064392-01A1) and reported nonfinancial support from Milliman MedInsight and grants from Arnold Ventures. Ms. Julia Cave Arbanas reported grants from the NIA during the conduct of the study. Dr. Bruce E. Landon was supported by a National Institute on Aging award (R01AG058878-03) and an Agency for Healthcare Research and Quality award (R01HS026498-04) during the conduct of the study. Dr. Catherine Sarkisian was supported by a National Institute on Aging award (1K24AG047899-01), the UCLA CTSI NIH/National Center for Advanced Translational Science Grant (L1TR001881), and the U.S. Deprescribing Research Network (NIA 2R24AG064025) during the conduct of the study. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. No other disclosures were reported. The funders had no role in the design and conduct of the study; no role in the collection, management, analysis, and interpretation of the data; no role in the preparation, review, or approval of the manuscript; and no role in the decision to submit the manuscript for publication. Appendix S1. Detailed description of methods, including cohort design, weight-based dosing assumptions, and weight-based calculations. Figure S1. Flow Diagram of Cohort Design Using the 2016 Health and Retirement Study (HRS) CORE Sample. Table S1. STROBE Checklist for Cross-Sectional Studies. Table S2. Presence of Reported Informal Caregivers Stratified by Dementia Stage. Table S3. Comparison of Measured Weight and Self-Reported Weight Distributions Among HRS Participants in 2016. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Source: Journal of the American Geriatrics Society

DOI: 10.1111/jgs.17891