International Drug Development Institute, Avenue Provinciale 30, 1340, Louvain-la-Neuve, Belgium.
Interuniversity Institute for Biostatistics and Statistical Bioinformatics (I-BioStat), Hasselt University, Diepenbeek, Belgium.
Orphanet J Rare Dis. 2023 Oct 12;18(1):321. doi: 10.1186/s13023-023-02943-8.
Generalized pairwise comparisons (GPC) can be used to assess the net benefit of new treatments for rare diseases. We show the potential of GPC through simulations based on data from a natural history study in mucopolysaccharidosis type IIIA (MPS IIIA).
Using data from a historical series of untreated children with MPS IIIA aged 2 to 9 years at the time of enrolment and followed for 2 years, we performed simulations to assess the operating characteristics of GPC to detect potential (simulated) treatment effects on a multi-domain symptom assessment. Two approaches were used for GPC: one in which the various domains were prioritized, the other with all domains weighted equally. The net benefit was used as a measure of treatment effect. We used increasing thresholds of clinical relevance to reflect the magnitude of the desired treatment effects, relative to the standard deviation of the measurements in each domain.
GPC were shown to have adequate statistical power (80% or more), even with small sample sizes, to detect treatment effects considered to be clinically worthwhile on a symptom assessment covering five domains (expressive language, daily living skills, and gross-motor, sleep and pain). The prioritized approach generally led to higher power as compared with the non-prioritized approach.
GPC of prioritized outcomes is a statistically powerful as well as a patient-centric approach for the analysis of multi-domain scores in MPS IIIA and could be applied to other heterogeneous rare diseases.
广义成对比较（GPC）可用于评估新疗法治疗罕见病的净效益。我们通过基于黏多糖贮积症 IIIA（MPS IIIA）自然史研究数据的模拟，展示了 GPC 的潜力。
利用在纳入时年龄为 2 至 9 岁且随访 2 年的未经治疗的 MPS IIIA 儿童的历史系列数据，我们进行了模拟以评估 GPC 的操作特性，以检测在多领域症状评估中潜在（模拟）的治疗效果。使用了两种 GPC 方法：一种是对各个领域进行优先排序，另一种是对所有领域进行平等加权。净效益被用作治疗效果的衡量标准。我们使用不断增加的临床相关性阈值来反映相对于每个领域测量的标准差的所需治疗效果的幅度。
即使样本量较小，GPC 也显示出足够的统计效力（80%或更高），以检测被认为在涵盖五个领域（表达性语言、日常生活技能以及大运动、睡眠和疼痛）的症状评估中有临床价值的治疗效果。优先方法通常比非优先方法具有更高的效力。
优先考虑结局的 GPC 是一种统计上强大且以患者为中心的分析 MPS IIIA 多领域评分的方法，并且可以应用于其他异质性罕见疾病。
