Cure SMA, Chicago, IL, USA.
Cure SMA, Chicago, IL, USA.
Clin Ther. 2019 May;41(5):943-960.e4. doi: 10.1016/j.clinthera.2019.03.012. Epub 2019 May 3.
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.
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."
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.
With the approval of the first SMA treatment, these findings offer a unique opportunity to assess and characterize baseline risk-tolerance in SMA against which to evaluate future SMA treatment options. Although differences had been expected in risk tolerance among respondents based on disease baseline and certain patient attributes, this was not observed. Survey results should inform future SMA drug development and benefit-risk assessments.
患者对获益-风险的认知对于为监管流程提供信息以及评估潜在疗法的应用背景至关重要。为了将这一关键信息提供给监管机构，Cure SMA 首次针对脊髓性肌萎缩症（SMA）开展获益-风险调查，以描述与潜在疗法相关的 SMA 决策和获益-风险权衡。我们假设风险承受能力与 SMA 类型/严重程度和疾病进展相关。本文介绍获益-风险调查的结果，以增进对 SMA 患者及其照护者如何评估潜在疗法相关具体获益和风险的理解。
Cure SMA 数据库中所有类型（I-IV 型）的 SMA 受影响成人，以及各年龄段/类型 SMA 受影响个体的照护者，均通过电子邮件受邀参与调查。最佳最差标度法（Best-worst scaling，BWS）用于评估参与者对获益-风险权衡的优先级，因为其在测试属性中提供了更高的区分度和重要性标度。共测试了 12 种潜在的临床有意义的治疗获益和 11 种潜在风险（严重程度和紧急程度不一）。多种因素与个体反应相关，包括：SMA 类型/疾病严重程度、疾病阶段、受访者类型、性别和生活质量/独立性水平（当前和预期）。调查对象还进行了“风险承受态度”评估。
共评估了 298 份回复（28%受影响成人，72%照护者，多为父母）。大多数受访者诊断时间超过 5 年（67.3%），22.1%为 SMA 1 型，45.6%为 SMA 2 型，27.9%为 SMA 3 型。未发现风险承受能力与 SMA 类型、疾病进展阶段、受访者类型、性别、生活质量评估或评定的独立性水平之间存在强相关性。无论 SMA 类型如何，受访者始终将以下风险评定为“最不可容忍”：危及生命的过敏反应；有 1/1000 的风险出现危及生命的副作用，导致可能的器官衰竭；或生活质量恶化。此外，所有 SMA 类型的受访者均将以下风险评定为“最可容忍”：治疗管理的侵入性模式（包括需要全身麻醉）；头晕的副作用；以及其他常见副作用，如恶心、呕吐、食欲不振、头痛、背痛或疲劳。
随着首个 SMA 疗法的获批，这些发现为评估 SMA 潜在治疗方案提供了一个独特的机会，可借此评估并描述 SMA 背景下的基线风险承受能力。尽管基于疾病基线和某些患者特征，预计受访者的风险承受能力会存在差异，但并未观察到这一点。调查结果应能为未来的 SMA 药物开发和获益-风险评估提供信息。
