稀缺确诊性PET测量的分配：A4/LEARN中的目标对齐验证
Spending Scarce Confirmatory PET Measurements: Target-Aligned Validation in A4/LEARN
- Clinical Functional Service Provider (cFSP)（临床功能服务提供商（cFSP））
- Kuntuo, an IQVIA company（昆图公司（IQVIA旗下））
- University of California, Los Angeles（加州大学洛杉矶分校）
机构由 AI 辅助整理，请以论文原文为准。
AI总结：
该研究针对阿尔茨海默病检查中稀缺的确诊性PET测量分配问题，提出按待验证主张的目标对齐验证方法，实验显示其在特定场景下可提升置信区间精度，优于通用不确定性采样与随机验证。
AI中文摘要：
抗淀粉样蛋白疗法和基于血液的生物标志物正将阿尔茨海默病检查转变为两阶段测量工作流程：先用低成本信息进行广泛筛查，再将稀缺的确诊性淀粉样蛋白测量分配到支持最终报告决策的场景中。淀粉样蛋白正电子发射断层扫描（PET）仍是评估淀粉样蛋白负荷的此类方案测量手段之一，但PET检查名额、试验预算及面向付款方的证据包均有限。本文提出一个明确的操作性问题：何时采用简单透明的PET验证就足够，何时拟合的残差不确定性评分值得增加的复杂度？对于加权方案目标，受试者i的验证一阶价值为目标影响与残差方案不确定性的乘积。通用不确定性采样仅使用第二个因子，可能将PET测量分配到难以预测但对科学、临床或商业主张作用较弱的受试者。我们将该规则应用于A4/LEARN PET档案，将观测到的PET视为稀缺确认研究的设计实验室。针对Centiloid 24及以上PET阳性中APOE4携带者与非携带者的主要对比，简单的APOE4平衡验证可恢复几乎所有目标特定增益：在PET预算为200时，相对于随机验证的置信区间宽度比，APOE4平衡为0.923，目标特定评分为0.914，而通用不确定性采样为0.980。其他目标表现不同：目标特定评分在年龄斜率分析和 cutoff 索引PET阳性分析中带来更大增益。实际结论明确：应根据待验证的主张而非仅预测不确定性来分配稀缺的方案测量资源。
英文摘要：
Anti-amyloid therapies and blood-based biomarkers are changing Alzheimer disease workups into a two-stage measurement workflow: screen broadly with cheaper information, then spend scarce confirmatory amyloid measurements where they support the decision that will be reported. Amyloid positron-emission tomography (PET) remains one such protocol measurement for amyloid burden, but PET slots, trial budgets, and payer-facing evidence packages are finite. This paper asks a deliberately operational question: when is simple transparent PET validation enough, and when is a fitted residual-uncertainty score worth the added complexity? For a weighted protocol target, the first-order value of validating subject i is the product of target influence and residual protocol uncertainty. Generic uncertainty sampling uses only the second factor and can spend PET measurements on subjects that are hard to predict but weak for the scientific, clinical, or commercial claim. We apply this rule to the A4/LEARN PET archive, treating observed PET as a design laboratory for scarce-confirmation studies. For the primary APOE4 carrier versus non-carrier contrast in Centiloid 24-or-higher PET positivity, simple APOE4-balanced validation recovers nearly all of the target-specific gain: at PET budget 200, the confidence-interval width ratio relative to random validation is 0.923 for APOE4 balancing and 0.914 for target-specific scoring, while generic uncertainty sampling is 0.980. Other targets behave differently: target-specific scoring gives larger gains for an age-slope analysis and for cutoff-indexed PET positivity. The practical message is simple: spend scarce protocol measurements according to the claim being validated, not only according to prediction uncertainty.
