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治疗阿尔茨海默病的治疗偏好:对护理人员和神经科医生的离散选择实验。

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

机构信息

Department of Public Health, Falk College, Syracuse University, 150 Crouse Dr., Syracuse, NY, 13244, USA.

Eisai, Inc., Nutley, NJ, USA.

出版信息

Alzheimers Res Ther. 2023 Mar 24;15(1):60. doi: 10.1186/s13195-023-01207-8.

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.

摘要

背景

阿尔茨海默病(AD)是一个全球性的健康危机,需要更有效的治疗方法。然而,需要做出优化基于价值的护理的艰难选择。虽然确定新 AD 疗法的首选治疗属性是必要的,但很少有研究探讨利益相关者之间的偏好可能如何变化。在这项研究中,使用离散选择实验(DCE)评估了 AD 淀粉样斑块降低疗法的关键属性之间的权衡,并在护理人员和神经科医生之间进行了比较。

方法

进行了初步的试点研究,以确定新疗法的潜在相关特征。DCE 评估了七种药物属性:与标准治疗(SOC)相比,在 AD 进展方面的临床效果(延迟)、临床效果的变化、生物标志物反应(在 PET 扫描上实现淀粉样斑块清除)、淀粉样相关成像异常-水肿(ARIA-E)、治疗持续时间、需要进行治疗滴定以及治疗途径和药物给药频率。然后,受访者会随机收到 12 组治疗选择的选择集,并要求他们在每个选择集中选择首选选项。使用分层贝叶斯回归模型估计加权偏好属性,这些属性表示为平均部分效用得分(pUS),得分越高表示偏好增加。

结果

护理人员(n=137)和神经科医生(n=161)都认为临床效果(平均 pUS=0.47 和 0.82)和 5%的 ARIA-E 增量(平均 pUS=-0.26 和-0.52)是治疗选择的高度决定性因素。相比之下,临床效果的变化(平均 pUS=0.12 和 0.14)和治疗持续时间(平均 pUS=-0.02 和-0.13)是任何新治疗的最不重要的特征。神经科医生还表示,皮下给药(平均 pUS=0.42 与 0.07)和每 4 周给药一次(平均 pUS=1.0 与 0.20)是非常理想的治疗特征。受访者愿意接受高达 9%的 ARIA-E 增量,以换取额外一年的延迟进展。

结论

护理人员和神经科医生认为,与 SOC 相比,新药物具有额外的临床获益和安全性是高度理想的品质,这种药物可以清除淀粉样斑块并延缓临床进展,并表示愿意接受额外的 ARIA-E 以获得额外的临床获益。

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