{
  "abstract": "Background: Conventional measures such as p-values and hazard ratios (HRs) do not directly quantify the sensitivity of time-to-event outcomes to small changes in individual outcomes. The Survival-Inferred Fragility Index (SIFI) evaluates the minimum number of survival-outcome changes required to reverse trial conclusions and provides complementary information on result robustness. Methods: This systematic review (PROSPERO: CRD420251182325) identified phase III colorectal cancer randomized controlled trials (RCTs) published from 2015 to 2025 via PubMed, Embase, and Cochrane. SIFI was calculated using Bomze’s framework with the “flip best” strategy. The fragility quotient (FQ) and the relationship between SIFI and withdrawals or losses to follow-up (WCLFU) were assessed. Analyses used R version 4.5.1. Results: SIFI was calculated for 50 phase III colorectal cancer RCTs, including 9 three-arm trials, resulting in 59 pairwise comparisons. Among positive results, median SIFI values for colorectal, colon, and rectal cancer were 6.0 (interquartile range [IQR]: 2.0 to 11.0), 19.0 (IQR: 15.5 to 22.5), and 4.0 (IQR: 4.0 to 4.0). Higher SIFI was observed in trials with HR < 0.75 than in those with HR 0.75–0.94 (median SIFI: 9.0 vs. 1.0; p = 0.035) and in trials with power > 85% than in those with power ≤ 85% (median SIFI: 8.5 vs. 2.0; p = 0.028). For negative results, median SIFI values were −4.5 (IQR: −7.2 to −3.0), −30.5 (IQR: −43.5 to −18.0), and −10.5 (IQR: −11.0 to −5.5). Greater absolute SIFI values were associated with adjuvant therapy, sample size ≥ 500, disease-free survival as the primary endpoint, and HR ≥ 0.95 (all p ≤ 0.005). Overall, 44.07% of pairwise comparisons had an absolute SIFI < 5. Conclusions: SIFI shows some phase III colorectal cancer RCT conclusions were sensitive to small outcome changes. It complements conventional statistics by illuminating result robustness.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Clinical Research Management, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou 450008, China",
    "Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou 450001, China",
    "Clinical Trials Center, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, 17 South Panjiayuan Lane, Beijing 100021, China",
    "IRB Office, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Shenzhen Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 113, Baohe Avenue, Shenzhen 518116, China"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Lanwei Guo",
      "orcid": "0000-0002-0822-2578"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiani Yuan"
    },
    {
      "affs": [
        2
      ],
      "name": "Xuejing Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lin Cai"
    },
    {
      "affs": [
        3
      ],
      "name": "Xinxin Yan"
    },
    {
      "affs": [
        1
      ],
      "name": "Huamei Luan"
    },
    {
      "affs": [
        0
      ],
      "name": "Chenxin Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yan Zheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanyan Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Huiyao Huang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4kp3c217z7n42.bib",
  "cited_by": 0,
  "doi": "10.3390/cancers18203394",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702729/?tool=EBI",
  "id": "4kp3c217z7n42",
  "issns": [
    "2072-6694"
  ],
  "landing_url": "https://www.mdpi.com/2072-6694/18/20/3394",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2613|Statistical Methods in Clinical Trials"
    ]
  ],
  "openalex": "W7223039845",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702729/pdf/?tool=EBI",
  "pmcid": "PMC13702729",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/4kp3c217z7n42.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:58Z",
      "native_id": "10.3390/cancers18203394",
      "source": "crossref",
      "url": "https://www.mdpi.com/2072-6694/18/20/3394"
    },
    {
      "first_seen": "2026-10-30T12:21:34Z",
      "native_id": "PMC:PMC13702729",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13702729"
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  "subjects": [
    {
      "field": "mathematics",
      "origin": "openalex:2613|Statistical Methods in Clinical Trials",
      "subfield": "statistics"
    }
  ],
  "title": "Survival-Inferred Fragility Index in Phase III Colorectal Cancer Trials: A Systematic Review",
  "title_text": "Survival-Inferred Fragility Index in Phase III Colorectal Cancer Trials: A Systematic Review",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:34Z",
  "url": "https://research.draconitic.com/paper/4kp3c217z7n42",
  "venue": "Cancers",
  "versions": []
}