Wilson Leslie, Kwok Tiffany, Ma Yanlei, Wong Jenise, Ho Martin, Ionova Yelena, McGrath Maureen, Mueller Monica M, Gitelman Stephen E, Irony Telba
Department of Clinical Pharmacy, University of California San Francisco, San Francisco, CA.
Cornell University Department of Medicine, Ithaca, New York.
Transplantation. 2022 Aug 1;106(8):e368-e379. doi: 10.1097/TP.0000000000004189. Epub 2022 Jun 3.
The advisory panel for US Food and Drug Administration (FDA) recently endorsed pancreatic islet cell transplantation (ICT) therapy for suboptimally controlled type 1 diabetes (T1D), and FDA approval is under consideration. An important part of regulatory approval includes the patient perspective, through discrete choice. We developed a discrete-choice instrument and used it to determine how 90 people with T1D weigh the risks and benefits of ICT to inform regulatory decisions.
Sawtooth software created a random, full-profile, balanced-overlap experimental design for a measure with 8 attributes of ICT risks/benefits, each with 3 to 5 levels. We asked 18 random task pairs, sociodemographics, diabetes management, and hypoglycemia questions. Analysis was performed using random parameters logistic regression technique.
The strongest preference was for avoiding the highest chance (15%) of serious procedure-related complications (β = -2.03, P < 0.001). The strongest positive preference was for gaining 5-y insulin independence (β = 1.75, P < 0.001). The desire for 5-y HbA1C-defined clinical treatment success was also strong (β = 1.39, P < 0.001). Subgroup analysis suggested strong gender differences with women showing much higher preferences for all benefits (68% higher for 5-y insulin independence), and men were generally more risk averse than women. Those with high versus low diabetes distress showed 3 times stronger preference for 5-y insulin independence but also twice preference to avoid risks of serious complications.
Despite showing the most preference for avoiding serious ICT complications, people with T1D had a strong preference for achieving ICT benefits, especially insulin independence. We identified important attributes of ICT and demonstrated that patients are willing to make these trade-offs, showing support for the introduction of ICT.
美国食品药品监督管理局（FDA）的咨询小组最近批准了胰岛细胞移植（ICT）疗法用于控制不佳的1型糖尿病（T1D），FDA正在考虑批准该疗法。监管批准的一个重要部分包括从患者角度出发，通过离散选择来考量。我们开发了一种离散选择工具，并使用它来确定90名1型糖尿病患者如何权衡ICT的风险和益处，以为监管决策提供参考。
锯齿软件为一项包含ICT风险/益处8个属性、每个属性有3至5个水平的测量创建了随机、全轮廓、平衡重叠的实验设计。我们询问了18对随机任务、社会人口统计学、糖尿病管理和低血糖问题。使用随机参数逻辑回归技术进行分析。
最强烈的偏好是避免严重手术相关并发症的最高几率（15%）（β = -2.03，P < 0.001）。最强烈的积极偏好是实现5年胰岛素独立（β = 1.75，P < 0.001）。对5年糖化血红蛋白定义的临床治疗成功的渴望也很强烈（β = 1.39，P < 0.001）。亚组分析表明存在强烈的性别差异，女性对所有益处的偏好更高（5年胰岛素独立方面高68%），男性通常比女性更厌恶风险。糖尿病痛苦程度高与低的人群对5年胰岛素独立的偏好强度高出3倍，但避免严重并发症风险的偏好也高出两倍。
尽管1型糖尿病患者最倾向于避免ICT严重并发症，但他们对实现ICT益处，尤其是胰岛素独立，有强烈偏好。我们确定了ICT的重要属性，并证明患者愿意做出这些权衡，表明对引入ICT的支持。
