建立多变量预测模型的最小样本量:第二部分 - 二分类和生存数据。
Minimum sample size for developing a multivariable prediction model: PART II - binary and time-to-event outcomes.
机构信息
Centre for Prognosis Research, Research Institute for Primary Care and Health Sciences, Keele University, Staffordshire, UK.
Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee.
出版信息
Stat Med. 2019 Mar 30;38(7):1276-1296. doi: 10.1002/sim.7992. Epub 2018 Oct 24.
When designing a study to develop a new prediction model with binary or time-to-event outcomes, researchers should ensure their sample size is adequate in terms of the number of participants (n) and outcome events (E) relative to the number of predictor parameters (p) considered for inclusion. We propose that the minimum values of n and E (and subsequently the minimum number of events per predictor parameter, EPP) should be calculated to meet the following three criteria: (i) small optimism in predictor effect estimates as defined by a global shrinkage factor of ≥0.9, (ii) small absolute difference of ≤ 0.05 in the model's apparent and adjusted Nagelkerke's R , and (iii) precise estimation of the overall risk in the population. Criteria (i) and (ii) aim to reduce overfitting conditional on a chosen p, and require prespecification of the model's anticipated Cox-Snell R , which we show can be obtained from previous studies. The values of n and E that meet all three criteria provides the minimum sample size required for model development. Upon application of our approach, a new diagnostic model for Chagas disease requires an EPP of at least 4.8 and a new prognostic model for recurrent venous thromboembolism requires an EPP of at least 23. This reinforces why rules of thumb (eg, 10 EPP) should be avoided. Researchers might additionally ensure the sample size gives precise estimates of key predictor effects; this is especially important when key categorical predictors have few events in some categories, as this may substantially increase the numbers required.
在设计用于开发具有二项或时间至事件结局的新预测模型的研究时,研究人员应确保其样本量在参与者数量(n)和结局事件(E)方面相对于纳入的预测参数数量(p)足够大。我们建议,应计算 n 和 E 的最小值(以及随后的每个预测参数的最小事件数,EPP),以满足以下三个标准:(i)预测效果估计的小乐观性,定义为全局收缩因子≥0.9,(ii)模型的表观和调整后的 Nagelkerke R 的差异≤0.05,(iii)人群中总体风险的精确估计。标准(i)和(ii)旨在根据所选 p 减少过度拟合,并需要预先指定模型预期的 Cox-Snell R,我们表明可以从先前的研究中获得该 R。满足所有三个标准的 n 和 E 值提供了模型开发所需的最小样本量。在应用我们的方法时,用于 Chagas 病的新诊断模型需要至少 4.8 的 EPP,用于复发性静脉血栓栓塞的新预后模型需要至少 23 的 EPP。这再次证明了为什么应该避免经验法则(例如 10 个 EPP)。研究人员还可能确保样本量能够对关键预测因素的效果进行精确估计;当关键分类预测因素在某些类别中事件较少时,这一点尤为重要,因为这可能会大大增加所需的数量。