Dantzer Jennifer A, Shaker Marcus S, Greenhawt Matthew
Division of Pediatric Allergy, Immunology, and Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Md.
Dartmouth Hitchcock Medical Center, Section of Allergy and Clinical Immunology, Lebanon, NH; Department of Pediatrics, Geisel School of Medicine at Dartmouth, Hanover, NH.
J Allergy Clin Immunol Pract. 2025 Apr;13(4):763-772. doi: 10.1016/j.jaip.2024.11.027. Epub 2024 Dec 19.
The current US Food and Drug Administration (FDA) paradigm may not fully capture important patient-centered outcomes or measure a primary outcome that is truly meaningful to patients. Patient-reported outcome measures (PROMs) are standardized tools measuring the patient's experience in food allergy clinical trials, which can help support shared decision-making (SDM) and further our understanding of treatment impact. Food allergy PROMs include quality of life (QoL), health state utility (HSU), severity, and self-efficacy measures. Currently, FDA registration trials for product approval only consider a fixed increase in allergen threshold from pre-to-post intervention as a primary outcome (vs a more flexible "X-fold" increase not accounting for an upper and lower specific threshold), though many use QoL as a secondary outcome for patient-centered assessment of treatment impact. Currently used QoL PROMs were not designed to measure change on therapy nor measure HSU (eg, quantitative risk a patient may be willing to take to improve their current health), which can be used to determine therapy value. Although the current paradigm for primary and secondary outcomes in food allergy clinical trials was appropriate at the early stages of food allergy therapy development when conceived in the late 2000s and early 2010s, in the 2020s, these outcome choices risk being stagnant and outdated. As such, the current paradigm for food allergy outcomes should evolve to incorporate more patient-centered primary outcome measures that patient data indicate are meaningful, so outcomes more realistically reflect a therapy's impact. This evolution will better support SDM discussions as patients consider their therapy options and can inform new product development.
美国食品药品监督管理局(FDA)目前的模式可能无法全面涵盖重要的以患者为中心的结果,也无法衡量对患者真正有意义的主要结果。患者报告结果测量(PROMs)是用于衡量食物过敏临床试验中患者体验的标准化工具,有助于支持共同决策(SDM)并加深我们对治疗效果的理解。食物过敏PROMs包括生活质量(QoL)、健康状态效用(HSU)、严重程度和自我效能测量。目前,FDA用于产品批准的注册试验仅将干预前后过敏原阈值的固定增加作为主要结果(与更灵活的“X倍”增加不同,后者不考虑特定的上下阈值),尽管许多试验将QoL作为以患者为中心评估治疗效果的次要结果。目前使用的QoL PROMs并非设计用于测量治疗变化,也无法测量HSU(例如,患者为改善当前健康状况可能愿意承担的定量风险),而HSU可用于确定治疗价值。尽管食物过敏临床试验中主要和次要结果的当前模式在21世纪末和2010年代初构思时,在食物过敏治疗发展的早期阶段是合适的,但在2020年代,这些结果选择有可能停滞不前且过时。因此,食物过敏结果的当前模式应发展,纳入更多患者数据表明有意义的以患者为中心的主要结果测量,以便结果更现实地反映治疗的影响。这种演变将更好地支持共同决策讨论,因为患者在考虑治疗选择时,并可为新产品开发提供信息。