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.