Evidence map›Paper›PMID 37425214›Full record

ArticleJHEP reports : innovation in hepatology2023

Fragility index of positive phase II and III randomised clinical trials of treatments for hepatocellular carcinoma (2002-2022).

Sabrina Sidali, Nanthara Sritharan, Claudia Campani, Jules Gregory, François Durand, Nathalie Ganne-Carrié, Maxime Ronot, Vincent Lévy, Jean-Charles Nault

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JHEP reports : innovation in hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Sabrina SidaliUniversité de Paris, Service d'Hépatologie, DMU DIGEST, Hôpital Beaujon, APHP Nord, Clichy, France.
Nanthara SritharanDepartment of Clinical Research, Paris Seine Saint Denis Hospital, Sorbonne Paris University, APHP, Bobigny, France.
Claudia CampaniCentre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, Team 'Functional Genomics of Solid Tumors', Equipe Labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France.
Jules GregoryDepartment of Radiology, FHU MOSAIC, Hôpital Beaujon APHP Nord, Clichy, France.
François DurandUniversité de Paris, Service d'Hépatologie, DMU DIGEST, Hôpital Beaujon, APHP Nord, Clichy, France.
Nathalie Ganne-CarriéCentre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, Team 'Functional Genomics of Solid Tumors', Equipe Labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France.
Maxime RonotDepartment of Radiology, FHU MOSAIC, Hôpital Beaujon APHP Nord, Clichy, France.
Vincent LévyDepartment of Clinical Research, Paris Seine Saint Denis Hospital, Sorbonne Paris University, APHP, Bobigny, France.
Jean-Charles NaultCentre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, Team 'Functional Genomics of Solid Tumors', Equipe Labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France.
Inserm · FRAssistance Publique – Hôpitaux de Paris · FRUniversité Paris Cité · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background & Aims: The fragility index (FI), i.e., theminimum number of best survivors reassigned to the control group required to revert the statistically significant result of a clinical trial to non-significant, is a metric to evaluate the robustness of randomized controlled trials (RCTs). We aimed to assess the FI in the field of HCC. Methods: This is a retrospective analysis of phase 2 and 3 RCTs for the treatment of HCC published between 2002 and 2022. We included two-arm studies with 1:1 randomization and significant positive results for a primary time-to-event endpoint for the FI calculation, which involves the iterative addition of a best survivor from the experimental group to the control group, until positive significance ( Results: We identified 51 phase 2 and 3 positive RCTs, of which 29 (57%) were eligible for fragility index calculation. After reconstruction of the Kaplan-Meier curves, 25/29 studies remained significant, among which the analysis was performed. The median (interquartile range (IQR)) FI was 5 (2-10) and Fragility Quotient (FQ) was 3% (1%-6%). Ten trials (40%) had a FI of 2 or less. FI was positively correlated to the blind assessment of the primary endpoint (median FI 9 with blind assessment versus 2 without, Conclusions: Several phases 2 and 3 RCTs in HCC have a low fragility index, underlying the limited robustness on the conclusion of their superiority over control treatments. The fragility index might provide an additional tool to assess the robustness of clinical trial data in HCC. Impact and implications: The fragility index is a method to assess robustness of a clinical trial and is defined the minimum number of best survivors reassigned to the control group required to revert the statistically significant result of a clinical trial to non-significant. Among 25 randomised controlled trials in HCC, the median fragility index was 5, and 10 trials among 25 (40%) had a fragility index of 2 or less, indicating an important fragility.

Indexed as

Fragility indexFragility quotientHepatocellular carcinomap valueRandomised controlled clinical trial

Identifiers

PMID37425214
PMCPMC10326696
OpenAlexW4362696250

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.