免疫性出版偏见及其对预测模型的影响:呼吁透明报告
Sophie Tascedda1, Zicheng Hu2, Hans Peter Grimm1
1Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Basel, Switzerland.
CPT: pharmacometrics & systems pharmacology
|January 28, 2026
概括
关于治疗性蛋白质中抗药抗体 (ADA) 发生率的已公布数据显示,其发生率低于实际情况. 早期试验数据,通常由于高免疫性而停止,经常被遗漏,扭曲预测并强调需要透明报告.
科学领域:
- 生物制药的发展.
- 免疫学 免疫学 免疫学
- 临床试验分析临床试验分析
背景情况:
- 治疗性蛋白质免疫性,特别是抗药抗体 (ADA) 的发展,是药物有效性和安全性的关键因素.
- 准确预测ADA发病率对于成功的药物开发和监管批准至关重要.
研究的目的:
- 调查针对治疗性蛋白质的已公布的抗药抗体 (ADA) 发病率数据中的偏差.
- 分析这种偏差对随时间推移的ADA发病率预测的影响.
- 强调生物制药行业透明数据报告的重要性.
主要方法:
- 对内部和批准的单克隆抗体的I-III期ADA发病率数据的比较分析.
- 开发一个经验模型来评估数据偏差对ADA发病率时间过程预测的影响.
主要成果:
- 发表的ADA发病率数据显示,与综合试验数据相比,报告率较低的偏见.
- 遗漏早期试验数据,特别是由于高免疫原性而中止的试验数据,对这种偏差有很大影响.
- 鉴定到的偏差导致了随着时间的推移对ADA发生率的不准确预测.
结论:
- 目前报告的ADA发病率数据可能低估了与治疗蛋白质相关的真实免疫性风险.
- 从所有临床试验阶段进行透明和完整的数据共享对于准确的风险评估和改善治疗蛋白质开发至关重要.
- 解决这种报告偏差对于提高免疫性可预测性和优化开发安全有效的基于蛋白质的治疗方法至关重要.
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