Lackey Leila G, Ng Xinyi, Veldwijk Jorien, Thokala Praveen, Levitan Bennett, Payne Katherine, Ho Martin, Tervonen Tommi
Decision Support and Analysis Staff, Office of Program and Strategic Analysis, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Office of Biostatistics and Pharmacovigilance, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Value Health. 2023 Apr;26(4):519-527. doi: 10.1016/j.jval.2023.01.018. Epub 2023 Feb 9.
Quantitative benefit-risk assessment (qBRA) is a structured process to evaluate the benefit-risk balance of treatment options to support decision making. The ISPOR qBRA Task Force was recently established to provide recommendations for the design, conduct, and reporting of qBRA. This report presents a hypothetical case study illustrating how to apply the Task Force's recommendations toward a qBRA to inform the benefit-risk assessment of brodalumab at the time of initial marketing approval. The qBRA evaluated 2 dosing regimens of brodalumab (210 mg or 140 mg twice weekly) compared with weight-based dosing of ustekinumab and placebo.
We followed the 5 steps recommended by the Task Force. Attributes included treatment response (≥75% improvement in Psoriasis Area and Severity Index), suicidal ideation and behavior, and infections. Performance data were drawn from pivotal clinical trials of brodalumab. The qBRA used multicriteria decision analysis and preference weights from a hypothetical discrete choice experiment. Sensitivity analyses examined the robustness of benefit-risk ranking to uncertainty in clinical effect and preference estimates, consideration of a subgroup (nail psoriasis), and the maintenance phase of treatment (52 weeks instead of 12).
Results from this hypothetical qBRA suggest that brodalumab 210 mg had a more favorable benefit-risk profile compared with ustekinumab and placebo. Ranking of brodalumab compared with ustekinumab was dependent on brodalumab's dose. Sensitivity analyses demonstrated robustness of benefit-risk ranking to uncertainty in clinical effect and preference estimates, as well as choice of attributes and length of follow-up.
This case study demonstrates how to implement the ISPOR Task Force's good practice recommendations on qBRA.
定量效益-风险评估（qBRA）是一种评估治疗方案的效益-风险平衡以支持决策的结构化过程。国际药物经济学与结果研究协会（ISPOR）的qBRA特别工作组最近成立，旨在为qBRA的设计、实施和报告提供建议。本报告展示了一个假设的案例研究，说明如何将特别工作组的建议应用于qBRA，以在布罗达单抗首次上市批准时为其效益-风险评估提供信息。该qBRA评估了布罗达单抗的两种给药方案（每周两次，每次210毫克或140毫克），并与依奇珠单抗基于体重的给药方案及安慰剂进行比较。
我们遵循了特别工作组推荐的5个步骤。属性包括治疗反应（银屑病面积和严重程度指数改善≥75%）、自杀意念和行为以及感染。性能数据取自布罗达单抗的关键临床试验。qBRA使用多标准决策分析和来自假设的离散选择实验的偏好权重。敏感性分析检验了效益-风险排名对临床效果和偏好估计中的不确定性、亚组（甲银屑病）的考虑以及治疗维持阶段（52周而非12周）的稳健性。
这个假设的qBRA结果表明，与依奇珠单抗和安慰剂相比，210毫克的布罗达单抗具有更有利的效益-风险概况。布罗达单抗与依奇珠单抗相比的排名取决于布罗达单抗的剂量。敏感性分析表明，效益-风险排名对临床效果和偏好估计中的不确定性以及属性选择和随访时间具有稳健性。
本案例研究展示了如何实施ISPOR特别工作组关于qBRA的良好实践建议。
