Olsen Hannah E, Kao Pei-Chi, Richmond Caleb, Shulman David S, London Wendy B, DuBois Steven G
Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA.
Cancer Med. 2024 Dec;13(24):e70356. doi: 10.1002/cam4.70356.
The fragility index (FI) is an adjunctive metric to facilitate the interpretation of p-values in clinical trials. The FI has not been studied in phase 3 trials in pediatric oncology.
PubMed was used to identify phase 3 pediatric oncology trials published between 1980 and 2020. We report trial characteristics and calculate the FI for trials with a binary outcome and survival-inferred fragility index (SIFI) for trials with a time-to-event outcome. FI/SIFI is the number of patients from one arm of a trial who would need to change groups for the statistical conclusion to change. We also report fragility quotients (FQ and SFQ) to normalize FI and SIFI relative to trial size.
One hundred and thirteen trials included sufficient data for analysis. The median FI for trials with a binary outcome (n = 40) was 4.5 (range: 1-33). The median SIFI for trials with a time-to-event outcome (n = 73) was 13 (range: 0-61). The FI or SIFI was less than the number of patients lost to follow-up in 25% of 36 trials. Median FQ and SFQ were 0.026 and 0.03, respectively, and did not significantly vary according to trial characteristics. While sample sizes increased over time, the FQ and SFQ remained stable.
The statistical conclusions of pediatric oncology phase 3 trials hinge on a relatively small number and proportion of patients. Despite the sample size limitations of low prevalence diseases, pediatric cancer trials are similarly or less fragile than adult oncology trials. Smaller trials do not appear more statistically fragile than larger trials. Statistical fragility appears to have remained constant over the four decades evaluated. We recommend reporting FI or SIFI, in conjunction with p-values, for all phase 3 pediatric oncology trials.
脆弱性指数（FI）是一种辅助指标，用于促进对临床试验中p值的解读。FI尚未在儿科肿瘤学的3期试验中进行研究。
使用PubMed检索1980年至2020年间发表的3期儿科肿瘤学试验。我们报告试验特征，并计算二元结局试验的FI以及事件发生时间结局试验的生存推断脆弱性指数（SIFI）。FI/SIFI是试验中一组患者需要改变分组以使统计结论改变的患者数量。我们还报告脆弱性商数（FQ和SFQ），以相对于试验规模对FI和SIFI进行标准化。
113项试验纳入了足够的数据进行分析。二元结局试验（n = 40）的FI中位数为4.5（范围：1 - 33）。事件发生时间结局试验（n = 73）的SIFI中位数为13（范围：0 - 61）。在36项试验中的25%中，FI或SIFI小于失访患者数量。FQ和SFQ中位数分别为0.026和0.03，且未根据试验特征有显著差异。虽然样本量随时间增加，但FQ和SFQ保持稳定。
儿科肿瘤学3期试验的统计结论取决于相对较少数量和比例的患者。尽管低患病率疾病的样本量有限，但儿科癌症试验与成人肿瘤学试验相比同样或更不易脆弱。较小的试验在统计学上似乎并不比较大的试验更脆弱。在评估的四十年中，统计脆弱性似乎一直保持不变。我们建议在所有儿科肿瘤学3期试验中报告FI或SIFI以及p值。
