Analysis of low frequency bleeding data: the association of joint bleeds according to baseline FVIII activity levels
Analysis of low frequency bleeding data: the association of joint bleeds according to baseline FVIII activity levels
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DOI：
10.1111/j.1365-2516.2010.02383.x
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发表时间：
2011-01-01
期刊：
影响因子：
3.9
通讯作者：
Plug, I.
中科院分区：
文献类型：
--
作者：
den Uijl, I. E. M.;Fischer, K.;Plug, I.
血友病和其他凝血缺陷领域的许多研究需要分析出血频率。在血友病中，出血频率与凝血因子VIII（FVIII）活性水平的相关性是已知的，但缺乏显著的结果。血友病的出血频率是高度偏斜的计数数据，零的比例很大。偏度和大量的零点都对标准（线性）建模技术造成了问题。本研究通过使用按需治疗的中度和轻度患者中残留凝血因子水平与关节出血次数的相关性作为示例，研究了出血数据的最佳分析策略。本研究共纳入了433例按需治疗的中度（27%）和轻度（73%）A型血友病患者。使用泊松分布、负二项分布、零膨胀泊松分布和零膨胀负二项分布分析了关节出血频率和基线凝血因子活性的1年自我报告数据。采用负二项分布的多元回归分析提供了最佳的数据分析策略。该模型显示，残留FVIII活性每增加1 IU/dL（-1），出血频率降低18%[率比（RR）0.82; 95%置信区间（CI）0.77-0.86]。由于排除了（463例患者中的30例）接受预防性治疗的患者（基线FVIII水平0.01-0.06 IU mL（-1）），预计实际相关性更高。分析低频出血数据的最佳方法是使用负二项分布。
Many studies in the field of haemophilia and other coagulation deficiencies require analyses of bleeding frequencies. In haemophilia, the association of bleeding frequency with factor VIII (FVIII) activity levels is known from experience, but significant results are lacking. Bleeding frequencies in haemophilia are highly skewed count data, with large proportions of zeros. Both the skewness and the high amount of zeros pose a problem for standard (linear) modelling techniques. This study investigated the optimal analysing strategy for bleeding data by using the association of residual clotting factor level and number of joint bleeds in moderate and mild patients treated on demand as example. In total, 433 patients with moderate (27%) and mild (73%) haemophilia A treated on demand were included in this study. One year of self-reported data on joint bleed frequency and baseline clotting factor activity were analysed using Poisson, negative binomial, zero-inflated Poisson, and zero-inflated negative binomial distributions. Multivariate regression analysis using negative binomial distribution provided the optimum data analytical strategy. This model showed 18% reduction [Rate ratio (RR) 0.82; 95% confidence interval (CI) 0.77-0.86] of bleeding frequency with every IU dL(-1) increase in residual FVIII activity. The actual association is expected to be higher because of exclusion (30 out of 463 patients) of patients on prophylaxis (baseline FVIII levels 0.01-0.06 IU mL(-1)). The best way to analyse low frequency bleeding data is using a negative binomial distribution.