Evaluating Benefit-risk Decision-making in Spinal Muscular Atrophy: A First-ever Study to Assess Risk Tolerance in the SMA Patient Community
Evaluating Benefit-risk Decision-making in Spinal Muscular Atrophy: A First-ever Study to Assess Risk Tolerance in the SMA Patient Community
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DOI：
10.1016/j.clinthera.2019.03.012
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发表时间：
2019-05-01
影响因子：
3.2
通讯作者：
Jarecki, Jill
中科院分区：
文献类型：
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作者：
Cruz, Rosangel;Belter, Lisa;Jarecki, Jill
目的：患者对益处-风险的认知对于告知调节过程和评估潜在疗法的背景是必不可少的。为了将这些关键信息提交给监管机构，Cure SMA发起了有史以来第一次脊髓性肌萎缩症(SMA)益处-风险调查，以表征与潜在疗法相关的SMA的决策和益处-风险权衡。我们假设风险耐受性与SMA类型/严重程度和疾病进展相关。本文介绍了一项利益-风险调查的结果，以加强对SMA患者和照顾者如何评估与潜在治疗相关的具体好处和风险的了解。方法：通过电子邮件邀请代表Cure SMA数据库中所有SMA类型(I-IV)的受影响成年人和受影响个人的照顾者参与。最佳-最差标度(BWS)被用来评估参与者在利益-风险权衡上的优先顺序，因为它在被测试的属性中提供了更高的区分度和重要性标度。测试了12项可能具有临床意义的治疗益处和11项潜在风险(严重性和即时性)。多个因素与个体反应相关，包括：SMA类型/疾病严重程度、疾病阶段、被调查者类型、性别和生活质量/独立性水平(当前和预期)。调查对象还被评估了“冒险态度”。结果：总共评估了298个回答(28%受影响的成年人和72%的照顾者，主要是父母)。大多数受访者被诊断为5年前(67.3%)，其中22.1%的SMA为I型，45.6%的SMA为II型，27.9%的SMA为III型。风险容忍度与SMA类型、疾病进展阶段、受试者类型、性别、生活质量评估或评定的独立性水平之间没有明显的相关性。无论SMA的类型如何，受访者始终将与潜在治疗相关的以下风险评为“最不能容忍”：威胁生命的过敏反应；1/1000的威胁生命的副作用导致可能的器官衰竭；或生活质量恶化。此外，所有SMA类型的受访者都将这些风险评为“最可容忍的”：侵入性给药模式(包括需要全身麻醉)；头晕的副作用；以及其他常见的副作用，如恶心、呕吐、食欲不振、头痛、背痛或疲劳。(C)2019年提交人。由爱思唯尔公司出版。
Purpose: Patients' perceptions of benefit-risk are essential to informing the regulatory process and the context in which potential therapies are evaluated. To bring this critical information to regulators, Cure SMA launched a first-ever Benefit-Risk Survey for spinal muscular atrophy (SMA) to characterize decision-making and benefit-risk trade-offs in SMA associated with a potential therapy. We hypothesized that risk tolerance would be correlated with SMA type/severity and disease progression. This article presents the results of a benefit-risk survey to enhance understanding of how patients with SMA and caregivers evaluate specific benefits and risks associated with potential therapies.Methods: Affected adults, representing all SMA types (I-IV) within the Cure SMA database, and caregivers of affected individuals of all ages/types were invited via e-mail to participate. Best-worst scaling (BWS) was used to assess participants' priorities on benefit-risk trade-offs, as it provides higher discrimination and importance scaling among tested attributes. Twelve potentially clinically meaningful treatment benefits and 11 potential risks (ranging in severity and immediacy) were tested. Multiple factors were correlated with individual responses, including: SMA type/disease severity, stage of disease, respondent type, sex, and quality of life/level of independence (current and expected). Survey respondents were also evaluated for "risk-taking attitudes."Findings: A total of 298 responses were evaluated (28% affected adults and 72% caregivers, mostly parents). Most respondents were diagnosed >5 years ago (67.3%), with 22.1% SMA type I, 45.6% SMA type II, and 27.9% SMA type III. No strong correlation was found between risk tolerance and SMA type, stage of disease progression, respondent type, sex, quality of life assessment, or rated levels of independence. Irrespective of SMA type, respondents consistently rated the following risks, associated with a potential treatment, as "least tolerable": life-threatening allergic reactions; 1 in 1000 risk of life-threatening side effects leading to possible organ failure; or worsening quality of life. Furthermore, all SMA type respondents rated these risks as "most tolerable": invasive mode of treatment administration (including need for general anesthesia); side effect of dizziness; and other common side effects such as nausea, vomiting, loss of appetite, headaches, back pain, or fatigue. (C) 2019 The Authors. Published by Elsevier Inc.