Therapeutic preference for Alzheimer’s disease treatments: a discrete choice experiment with caregivers and neurologists

Dranitsaris et al. Alzheimer’s Research & Therapy (2023) 15:60 https://doi.org/10.1186/s13195-023-01207-8 Alzheimer’s Research & Therapy Open Access RESEARCH Therapeutic preference for Alzheimer’s disease treatments: a discrete choice experiment with caregivers and neurologists George Dranitsaris1*, Quanwu Zhang2, Lin Mu3, Christopher Weyrer3, Erik Drysdale3, Peter Neumann4, Alireza Atri5,6 and Amir Abbas Tahami Monfared2,7 Abstract Background Alzheimer’s disease (AD) is a major global health crisis in need of more effective therapies. However, difficult choices to optimize value-based care will need to be made. While identifying preferred therapeutic attributes of new AD therapies is necessary, few studies have explored how preferences may vary between the stakeholders. In this study, the trade-offs among key attributes of amyloid plaque-lowering therapies for AD were assessed using a discrete choice experiment (DCE) and compared between caregivers and neurologists. Methods An initial pilot study was conducted to identify the potentially relevant features of a new therapy. The DCE evaluated seven drug attributes: clinical effects in terms of delay in AD progression over the standard of care (SOC), variation in clinical effects, biomarker response (achieving amyloid plaque clearance on PET scan), amyloid-related imaging abnormalities-edema (ARIA-E), duration of therapy, need for treatment titration as well as route, and frequency of drug administration. Respondents were then randomly presented with 12 choice sets of treatment options and asked to select their preferred option in each choice set. Hierarchical Bayesian regression modeling was used to estimate weighted preference attributes, which were presented as mean partial utility scores (pUS), with higher scores suggesting an increased preference. Results Both caregivers (n = 137) and neurologists (n = 161) considered clinical effects (mean pUS = 0.47 and 0.82) and a 5% incremental in ARIA-E (mean pUS =  − 0.26 and − 0.52) to be highly impactful determinants of therapeutic choice. In contrast, variation in clinical effects (mean pUS = 0.12 and 0.14) and treatment duration (mean pUS =  − 0.02 and − 0.13) were the least important characteristics of any new treatment. Neurologists’ also indicated that subcutaneous drug delivery (mean pUS = 0.42 vs. 0.07) and administration every 4 weeks (mean pUS = 1.0 vs. 0.20) are highly desirable therapeutic features. Respondents were willing to accept up to a 9% increment in ARIA-E for one additional year of delayed progression. Conclusions Caregivers and neurologists considered incremental clinical benefit over SOC and safety to be highly desirable qualities for a new drug that could clear amyloid plaques and delay clinical progression and indicated a willingness to accept incremental ARIA-E to achieve additional clinical benefits. Keywords Alzheimer’s disease, Caregiver preference, Physician preference, Discrete choice experiment *Correspondence: George Dranitsaris Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Dranitsaris et al. Alzheimer’s Research & Therapy (2023) 15:60 Introduction Dementia is a clinical condition characterized by the progressive deterioration of at least two cognitive domains such as memory, language, personality, behavior, or visuospatial and executive function [1]. Alzheimer’s disease (AD) is the most common type of dementia, accounting for approximately 80% of all new diagnoses [2]. AD is a disease primarily diagnosed in the elderly, and the prevalence is expected to increase with the aging global population [2]. Indeed, the incidence of AD is expected to rise twofold every 5 years in people 65 years and older [3]. In the United States of America (USA) alone, approximately 5.8 million Americans above 65 years of age have AD [4]. Furthermore, the number of cases in the USA is expected to rise to 13 million by 2050 as the elderly population increases to 88 million [4]. This represents a major concern for health policy decision-makers and for the allocation of societal resources. In the USA, the direct costs of AD medical management and the indirect costs of lost productivity are estimated to be $305 billion annually [5]. Similar prevalence and cost estimates have also been reported for Europe [6]. The natural history of clinical progression in AD is characterized by a gradual decline, within and across multiple domains, as the disease advances through mild, moderate, and severe stages [1]. Impairment is higher with moderate to severe disease with patients demonstrating a decline in physical functioning (e.g., apraxia; impaired body coordination with frequent falls and uncontrolled sphincters) and in cognitive functioning (e.g., memory loss, speech difficulties, and disorientation in space and time) [1, 7]. Such declines severely impact patient quality of life (QOL) and well-being [8]. There is also a tremendous burden on the caregiver [7]. One study from Portugal evaluated depression, anxiety, and stress in 102 caregivers of AD patients using validated instruments [9]. The investigators determined that number of days of care and duration of daily care for AD patients severely impacted caregivers’ QOL. Furthermore, caregivers supporting a patient with more memory and behavioral problems reported greater stress, depression, and anxiety compared to those who were supporting patients with less advanced disease [9]. To mitigate clinical decline and support QOL, the current standard of care in AD is to augment behavioral, environmental, and lifestyle management strategies (a.k.a. non-pharmacological management) and management of co-morbidities (e.g., hypertension, sleep apnea), with stage-dependent symptomatic pharmacotherapy using FDA-approved anti-AD medications. The two main classes of drugs first used to manage AD were the cholinesterase inhibitors (i.e., done (...truncated)