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Defining Remission Using Patient-reported Outcome Components of the Crohnʼs Disease Activity Index: Post-hoc Analyses of Vedolizumab Data from the GEMINI 2 Study

2015· article· en· W2520265660 on OpenAlexaff
William J. Sandborn, Séverine Vermeire, Bruce E. Sands, Brian Feagan, Michael A. Shetzline, Jing Xu, Reema Mody, Asit Parikh, Brihad Abhyankar

Bibliographic record

VenueThe American Journal of Gastroenterology · 2015
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsRobarts Clinical TrialsWestern University
Fundersnot available
KeywordsMedicineVedolizumabPost-hoc analysisPlaceboInternal medicinePost hocClinical trialGastroenterologyExtended releasePhysical therapyCrohn's diseaseDiseasePathologyPharmacologyAlternative medicine

Abstract

fetched live from OpenAlex

Introduction: Clinical trials in Crohn's disease (CD) are evolving toward including patient (pt)-reported outcomes (PROs) to evaluate drug efficacy; however, no validated PROs are available. In post hoc analyses of data from the GEMINI 2 study,1 we evaluated different definitions of vedolizumab (VDZ)-induced remission using PRO components of the CD Activity Index (CDAI).Table 1: Definitions of RemissionMethods: Pts with moderately to severely active CD (CDAI 220-450) who responded to 6 weeks (wks) of VDZ induction therapy were re-randomized to maintenance therapy with placebo (PBO) or VDZ for 46 wks. CDAI stool frequency (SF), abdominal pain (AP), and general well-being (GWB) subscores were evaluated alone and in combination (PRO-2 [SF + AP] and PRO-3 [SF + AP + GWB]) at wks 0, 6, and 52, and their contributions to baseline and mean change from baseline CDAI total scores were analyzed. The sensitivity of PRO-based remission—defined by unweighted combined daily (PRO-2 [SF ≤3 + AP ≤1]) and weighted 7-day (PRO-2 ≤75 or PRO-3 ≤80) mean scores—to detect clinical remission (CDAI =150), their agreement with CDAI ≤150, and the percentage of GEMINI 2 pts who met PRO-based entry criteria (SF ≥4 and/or AP ≥2) were evaluated. Results: The SF, AP, and GWB subscores contributed 25%, 21%, and 31%, respectively, to the mean baseline CDAI score. PRO-2 and PRO-3 accounted for, respectively, 53% and 91% of the mean change from baseline CDAI score at wk 6, and 47% and 82% at wk 52. The PRO-based definition with the best agreement with CDAI remission at wk 6 was PRO-3 ≤80 and at wk 52 was PRO-2 ≤75 (Table). PRObased entry criteria of SF ≥4 and/or AP ≥2 were met by 86% of GEMINI 2 pts; 42% of patients had both SF ≥4 and AP ≥2. Conclusion: Of CDAI components, the PROs contributed most to baseline and treatment-induced changes in CDAI score. Different PRO-based definitions of remission (PRO-2 ≤75 or PRO-3 ≤80) had the best agreement with clinical remission at wks 6 and 52. Interpretations of these post hoc analyses are limited, but applying cutoffs used here to other data sets could clarify the reliability and clinical meaningfulness of PROs as outcome measures.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.016
metaresearch head score (Gemma)0.010
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.016
Threshold uncertainty score0.085

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0160.010
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.003
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0000.002
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.083
GPT teacher head0.348
Teacher spread0.265 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2015
Admission routes1
Has abstractyes

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