Shklyar Irina, Pasternak Amy, Kapur Kush, Darras Basil T, Rutkove Seward B
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Pediatr Neurol. 2015 Feb;52(2):202-5. doi: 10.1016/j.pediatrneurol.2014.09.014. Epub 2014 Oct 7.
Compared with individual parameters, composite biomarkers may provide a more effective means for monitoring disease progression and the effects of therapy in clinical trials than single measures. In this study, we built composite biomarkers for use in Duchenne muscular dystrophy by combining values from two objective measures of disease severity: electrical impedance myography and quantitative ultrasound and evaluating how well they correlated to standard functional measures.
Using data from an ongoing study of electrical impedance myography and quantitative ultrasound in 31 Duchenne muscular dystrophy and 26 healthy boys aged 2-14 years, we combined data sets by first creating z scores based on the normal subject data and then using simple mathematical operations (addition and multiplication) to create composite measures. These composite scores were then correlated to age and standard measures of function including the 6-minute walk test, the North Star Ambulatory Assessment, and handheld dynamometry.
Combining data sets resulted in stronger correlations with all four outcomes than for either electrical impedance myography or quantitative ultrasound alone in six of eight instances. These improvements reached statistical significance (P < 0.05) in several cases. For example, the correlation coefficient for the composite measure with the North Star Ambulatory Assessment was 0.79 but was only 0.66 and 0.67 (respectively) for gray scale level and electrical impedance myography separately.
Arithmetically derived composite scores can provide stronger correlations to functional measures than isolated biomarkers. Longitudinal study of such composite markers in Duchenne muscular dystrophy clinical trials is warranted.
与单个参数相比，在临床试验中，复合生物标志物可能比单一指标提供更有效的手段来监测疾病进展和治疗效果。在本研究中，我们通过结合疾病严重程度的两项客观测量指标（电阻抗肌电图和定量超声）的值，并评估它们与标准功能测量指标的相关性，构建了用于杜氏肌营养不良症的复合生物标志物。
利用一项正在进行的针对31名杜氏肌营养不良症男孩和26名2至14岁健康男孩的电阻抗肌电图和定量超声研究数据，我们首先根据正常受试者数据创建z分数，然后通过简单的数学运算（加法和乘法）合并数据集以创建复合测量指标。然后将这些复合分数与年龄以及包括6分钟步行试验、北极星动态评估和手持测力计在内的标准功能测量指标进行相关性分析。
在八个实例中的六个实例中，合并数据集所得到的结果与所有四项结果的相关性都比单独使用电阻抗肌电图或定量超声更强。在一些情况下，这些改善具有统计学意义（P < 0.05）。例如，复合测量指标与北极星动态评估的相关系数为0.79，但灰度水平和电阻抗肌电图单独与该评估的相关系数分别仅为0.66和0.67。
通过算术推导得出的复合分数与功能测量指标的相关性比单独的生物标志物更强。有必要在杜氏肌营养不良症临床试验中对这类复合标志物进行纵向研究。
