Department of Statistics and Data Science, Cornell University, Ithaca, NY, US.
Schulich Heart Centre, Sunnybrook Health Science Centre, University of Toronto, Toronto, ON, Canada.
BMC Med Res Methodol. 2021 Nov 20;21(1):254. doi: 10.1186/s12874-021-01446-z.
Clinical trials routinely have patients lost to follow up. We propose a methodology to understand their possible effect on the results of statistical tests by altering the concept of the fragility index to treat the outcomes of observed patients as fixed but incorporate the potential outcomes of patients lost to follow up as random and subject to modification.
We reanalyse the statistical results of three clinical trials on coronary artery bypass grafting (CABG) to study the possible effect of patients lost to follow up on the treatment effect statistical significance. To do so, we introduce the LTFU-aware fragility indices as a measure of the robustness of a clinical trial's statistical results with respect to patients lost to follow up.
The analyses illustrate that clinical trials can either be completely robust to the outcomes of patients lost to follow up, extremely sensitive to the outcomes of patients lost to follow up, or in an intermediate state. When a clinical trial is in an intermediate state, the LTFU-aware fragility indices provide an interpretable measure to quantify the degree of fragility or robustness.
The LTFU-aware fragility indices allow researchers to rigorously explore the outcomes of patients who are lost to follow up, when their data is the appropriate kind. The LTFU-aware fragility indices are sensitivity measures in a way that the original fragility index is not.
临床试验通常会有患者失访。我们提出了一种方法，通过改变脆弱指数的概念，将观察到的患者的结果视为固定，同时将失访患者的潜在结果视为随机，并可进行修改，从而了解其对统计检验结果的可能影响。
我们重新分析了 3 项关于冠状动脉旁路移植术（CABG）的临床试验的统计结果，以研究失访患者对治疗效果统计显著性的可能影响。为此，我们引入了 LTFU 意识脆弱指数，作为衡量临床试验统计结果对失访患者结果的稳健性的指标。
分析表明，临床试验可以完全不受失访患者结果的影响，也可以非常敏感于失访患者的结果，或者处于中间状态。当临床试验处于中间状态时，LTFU 意识脆弱指数提供了一个可解释的衡量标准，以量化脆弱性或稳健性的程度。
LTFU 意识脆弱指数允许研究人员在适当的情况下，严格地研究失访患者的结果。LTFU 意识脆弱指数是一种敏感性指标，而原始脆弱指数不是。
