Khormaee Sariah, Choe Judy, Ruzbarsky Joseph J, Agarwal Kunal N, Blanco John S, Doyle Shevaun M, Dodwell Emily R
Hospital for Special Surgery.
New York Presbyterian, University Hospitals of Columbia and Cornell, New York, NY.
J Pediatr Orthop. 2018 Sep;38(8):e418-e423. doi: 10.1097/BPO.0000000000001201.
The randomized controlled trial (RCT) is the gold standard study design allowing critical comparison of clinical outcomes while minimizing bias. Traditionally clinical trials are evaluated through statistical significance, expressed by P-values and confidence intervals. However, until recently, the robustness of a study's conclusions has been given little attention. A new metric, the fragility index, quantifies the number of patients theoretically required to switch outcomes in order to reverse the study conclusions. The primary aim of our work was to determine the fragility index of RCTs in the pediatric orthopaedic literature. The secondary aim was to determine study factors associated with lower fragility index.
Pubmed and Embase were systematically searched for pediatric orthopaedic RCTs published September 1, 2006 to September 1, 2016. Two independent reviewers screened titles, abstracts, and manuscripts to identify studies published in English involving 2 treatment arms. Trials without dichotomous primary or secondary outcomes or with patients >18 years were excluded. Data were extracted from each eligible article in duplicate and the fragility index was determined using Fisher exact test, with previously published methods. Univariate analysis was used to determine factors associated with lower fragility index.
Seventeen trials were eligible for inclusion. The median treatment arm size was 58 and overall sample size was 116 patients. The median fragility index was 3 (range, 0 to 18). A fragility index of 3 means that just 3 patients would need to switch treatment outcomes in order for the trial results to become statistically nonsignificant. In 1 study, the number of patients lost to follow-up exceeded the fragility index, such that the study conclusions could be completely reversed purely depending on the outcomes of the patients lost to follow-up. Lower fragility index was associated with smaller patient sample sizes and greater P-values.
The fragility index is a useful adjunct metric to the P-value and confidence intervals, allowing analysis of the robustness of study conclusions. RCTs in pediatric orthopaedics often have small sample sizes, many with low fragility indices. Future efforts could focus on encouraging institutional collaboration and patient recruitment with the ultimate goal of improving RCT sample sizes, and potentially improving the robustness of RCT results.
Level I.
随机对照试验（RCT）是黄金标准的研究设计，能在最大限度减少偏倚的同时对临床结果进行关键比较。传统上，临床试验通过统计学显著性进行评估，用P值和置信区间表示。然而，直到最近，研究结论的稳健性很少受到关注。一个新的指标——脆弱性指数，量化了理论上为了逆转研究结论而需要改变结果的患者数量。我们这项工作的主要目的是确定儿科骨科文献中RCT的脆弱性指数。次要目的是确定与较低脆弱性指数相关的研究因素。
系统检索了2006年9月1日至2016年9月1日发表的儿科骨科RCT的PubMed和Embase数据库。两名独立的评审员筛选标题、摘要和手稿，以确定以英文发表的涉及两个治疗组的研究。排除没有二分法主要或次要结局的试验或患者年龄>18岁的试验。从每篇符合条件的文章中重复提取数据，并使用Fisher精确检验和先前发表的方法确定脆弱性指数。采用单因素分析来确定与较低脆弱性指数相关的因素。
17项试验符合纳入标准。治疗组的中位样本量为58，总体样本量为116例患者。脆弱性指数的中位数为3（范围为0至18）。脆弱性指数为3意味着只需3名患者改变治疗结果，试验结果就会在统计学上变得无显著性差异。在1项研究中，失访患者的数量超过了脆弱性指数，以至于研究结论可能完全取决于失访患者的结局而被逆转。较低的脆弱性指数与较小的患者样本量和较大的P值相关。
脆弱性指数是P值和置信区间的一个有用的辅助指标，可用于分析研究结论的稳健性。儿科骨科的RCT样本量通常较小，许多脆弱性指数较低。未来的努力可以集中在鼓励机构间合作和患者招募上，最终目标是增加RCT的样本量，并可能提高RCT结果的稳健性。
I级。
