Röver Christian, Nicholas Richard, Straube Sebastian, Friede Tim
Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany.
Imperial College Healthcare NHS Trust, London, United Kingdom.
PLoS One. 2015 Sep 1;10(9):e0137052. doi: 10.1371/journal.pone.0137052. eCollection 2015.
Recent systematic reviews of randomised controlled trials (RCTs) in relapsing multiple sclerosis (RMS) revealed a decrease in placebo annualized relapse rates (ARR) over the past two decades. Furthermore, regression to the mean effects were observed in ARR and MRI lesion counts. It is unclear whether disease progression measured by the expanded disability status scale (EDSS) exhibits similar features.
A systematic review of RCTs in RMS was conducted extracting data on EDSS and baseline characteristics. The logarithmic odds of disease progression were modelled to investigate time trends. Random-effects models were used to account for between-study variability; all investigated models included trial duration as a predictor to correct for unequal study durations. Meta-regressions were conducted to assess the prognostic value of a number of study-level baseline variables.
The systematic literature search identified 39 studies, including a total of 19,714 patients. The proportion of patients in placebo controls experiencing a disease progression decreased over the years (p<0.001). Meta-regression identified associated covariates including the size of the study and its duration that in part explained the time trend. Progression probabilities tended to be lower in the second year of a study compared to the first year with a reduction of 28% in progression odds from year 1 to year 2 (p = 0.017).
EDSS disease progression exhibits similar behaviour over time as the ARR and point to changes in trial characteristics over the years. This needs to be considered in comparisons between historical and recent trials.
近期对复发型多发性硬化症（RMS）随机对照试验（RCT）的系统评价显示，在过去二十年中，安慰剂年化复发率（ARR）有所下降。此外，在ARR和MRI病灶计数中观察到了均值回归效应。尚不清楚通过扩展残疾状态量表（EDSS）衡量的疾病进展是否具有类似特征。
对RMS的RCT进行系统评价，提取关于EDSS和基线特征的数据。对疾病进展的对数优势进行建模以研究时间趋势。采用随机效应模型来考虑研究间的变异性；所有研究模型均将试验持续时间作为预测因子，以校正研究持续时间的不平等。进行Meta回归以评估一些研究水平基线变量的预后价值。
系统文献检索确定了39项研究，共纳入19714例患者。安慰剂对照组中经历疾病进展的患者比例多年来有所下降（p<0.001）。Meta回归确定了相关协变量，包括研究规模及其持续时间，这些部分解释了时间趋势。与第一年相比，研究第二年的进展概率往往较低，从第1年到第2年进展优势降低了28%（p = 0.017）。
EDSS疾病进展随时间呈现出与ARR相似的行为，并表明多年来试验特征发生了变化。在历史试验和近期试验的比较中需要考虑这一点。
