Pfister Isabel B, Zandi Souska, Gerhardt Christin, Spindler Jan, Reichen Natalie, Garweg Justus G
Swiss Eye Institute, Rotkreuz, and Berner Augenklinik am Lindenhofspital, Bern, Switzerland.
Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Transl Vis Sci Technol. 2020 Jun 24;9(7):27. doi: 10.1167/tvst.9.7.27. eCollection 2020 Jun.
To determine the inherent risks of handling results below the lowest detectable value in the analysis of multiple cytokines in the aqueous humor of patients with retinal diseases by comparing possible statistical strategies to lower the risk of mis interpretation or over interpretation of results. Furthermore, in analyzing multiple cytokines simultaneously, the challenge of multiple comparison arises.
The analyses were based on parallel testing of 43 cytokines in 58 aqueous humor samples from patients with macular hole or epiretinal membrane. Substitution of values below the detection limit with 0.1 ×, 0.5 ×, or 1.0× of the lowest level of quantitation was compared with handling as missing value. The impact of correction for multiple comparisons was assessed using the Holm correction.
When comparing macular hole with epiretinal membrane, not substituting the missing data revealed a difference ( < 0.05) for five compared with wight cytokines after their substitution, indicating an increased risk for under-estimating group differences (type II error). Correcting for multiple comparisons revealed a relevant risk of over estimating group differences (type I error).
Physiologic cytokine concentrations in ocular fluids typically range at or below the lowest level of quantitation. Handling of results below this cutoff as missing leads to increased type II errors. Not correcting for multiple comparisons increases the risk of a type I error. Taken together, both harbor a systematic inherent risk of misinterpretation of the results.
Ignoring the inherent risks of data misinterpretation in analyses of ocular fluid samples may result in mis leading conclusions regarding their biological relevance.
通过比较降低结果错误解读或过度解读风险的可能统计策略，确定在分析视网膜疾病患者房水中多种细胞因子时处理低于最低检测值结果的固有风险。此外，在同时分析多种细胞因子时，会出现多重比较的挑战。
分析基于对58例黄斑裂孔或视网膜前膜患者房水样本中43种细胞因子的平行检测。将低于检测限的值分别用最低定量水平的0.1倍、0.5倍或1.0倍替代，并与作为缺失值处理进行比较。使用霍尔姆校正评估多重比较校正的影响。
在比较黄斑裂孔与视网膜前膜时，不替代缺失数据显示有5种细胞因子存在差异（<0.05），而替代后为8种细胞因子，这表明低估组间差异的风险增加（II类错误）。对多重比较进行校正显示存在高估组间差异的相关风险（I类错误）。
眼内液中生理细胞因子浓度通常处于或低于最低定量水平。将低于此临界值的结果作为缺失值处理会导致II类错误增加。不对多重比较进行校正会增加I类错误的风险。综上所述，两者都存在结果错误解读的系统性固有风险。
在眼内液样本分析中忽略数据错误解读的固有风险可能会导致关于其生物学相关性的误导性结论。
