Medical Research Institute of New Zealand, Wellington, New Zealand.
Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
Crit Care. 2017 Jun 5;21(1):132. doi: 10.1186/s13054-017-1726-x.
An important limitation of many critical care trial designs is that they hypothesize large, and potentially implausible, reductions in mortality. Interpretation of trial results could be improved by systematic assessment of the plausibility of trial hypotheses; however, such assessment has not been attempted in the field of critical care medicine. The purpose of this study was to determine clinicians' views about prior probabilities and plausible effect sizes for ongoing critical care trials where the primary endpoint is landmark mortality.
We conducted a systematic review of clinical trial registries in September 2015 to identify ongoing critical care medicine trials where landmark mortality was the primary outcome, followed by a clinician survey to obtain opinions about ten large trials. Clinicians were asked to estimate the probability that each trial would demonstrate a mortality effect equal to or larger than that used in its sample size calculations.
Estimates provided by individual clinicians varied from 0% to 100% for most trials, with a median estimate of 15% (IQR 10-20%). The median largest absolute mortality reduction considered plausible was 4.5% (IQR 3.5-5%), compared with a median absolute mortality reduction used in sample size calculations of 5% (IQR 3.6-10%) (P = 0.27).
For some of the largest ongoing critical care trials, many clinicians regard prior probabilities as low and consider that plausible effects on absolute mortality are less than 5%. Further work is needed to determine whether pooled estimates obtained by surveying clinicians are replicable and accurate or whether other methods of estimating prior probability are preferred.
许多重症监护试验设计的一个重要局限性是，它们假设死亡率会大幅降低，而且这种降低幅度可能不切实际。如果系统评估试验假设的合理性，那么对试验结果的解释可能会得到改善；然而，在重症监护医学领域，尚未尝试过这种评估。本研究的目的是确定临床医生对正在进行的以主要终点为里程碑死亡率的重症监护试验的先验概率和合理的效应大小的看法。
我们在 2015 年 9 月对临床试验登记处进行了系统回顾，以确定正在进行的以里程碑死亡率为主要结局的重症监护医学试验，随后对临床医生进行了一项调查，以获取关于 10 项大型试验的意见。临床医生被要求估计每个试验展示与样本量计算中使用的死亡率效应相等或更大的可能性。
大多数试验的个体临床医生提供的估计值在 0%到 100%之间，中位数估计值为 15%（IQR 10-20%）。认为合理的最大绝对死亡率降低中位数为 4.5%（IQR 3.5-5%），而样本量计算中使用的绝对死亡率降低中位数为 5%（IQR 3.6-10%）（P=0.27）。
对于一些最大的正在进行的重症监护试验，许多临床医生认为先验概率较低，认为对绝对死亡率的合理影响小于 5%。需要进一步的工作来确定通过调查临床医生获得的汇总估计值是否可复制和准确，或者是否更倾向于使用其他估计先验概率的方法。
