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P-106 Examination of an Alternative Definition for Clinical Remission in UC

2016· article· en· W2331412141 on OpenAlexaff
William J. Sandborn, Brian G. Feagan, Geert D’Haens, Douglas C. Wolf, Séverine Vermeire, Stephen B. Hanauer, Subrata Ghosh, Heather Smith, Matthew Cravets, Paul Frohna, Richard Aranda, Sheila Gujrathi, Allan Olson

Bibliographic record

VenueInflammatory Bowel Diseases · 2016
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunodeficiency and Autoimmune Disorders
Canadian institutionsUniversity of CalgaryRobarts Clinical Trials
Fundersnot available
KeywordsMedicineInternal medicinePlaceboClinical trialRandomized controlled trialPost-hoc analysisGastroenterologyInfliximabSurgeryDiseasePathology

Abstract

fetched live from OpenAlex

The Mayo score has been used to assess UC disease activity and to establish the efficacy of medications approved for the treatment of UC for over 2 decades. The definition of clinical remission used for approval of biologic agents since infliximab has been a Mayo score ≤2 with no subscore >1, which is being scrutinized by the FDA due to its lack of formal validation and inclusion of the poorly-defined physician global assessment subscore (PGA). An alternative definition of clinical remission using the Mayo scoring system without the PGA, has been proposed that requires a rectal bleeding subscore (RBS) = 0, an endoscopy subscore (ES) of ≤1 and a stool frequency subscore (SFS) ≤1 with improvement ≥1. We have explored this alternative definition of remission in a post hoc analysis of the data from the TOUCHSTONE study. TOUCHSTONE was a randomized, double-blind, placebo-controlled trial designed to evaluate efficacy and safety of 0.5 mg (low dose, LD) and 1 mg (high dose, HD) ozanimod, an oral, selective sphingosine 1-phosphate (S1P) 1 and 5 receptor modulator, in comparison to placebo (PBO), in patients with moderate to severe UC. A total of 197 patients were randomized (1:1:1) and treated once daily with PBO (n = 65), LD (n = 65) or HD (n = 67). The patients who achieved clinical response at week 8 continued into the maintenance period (MP) with their original treatment for an additional 24 weeks. Using the data from TOUCHSTONE, we calculated clinical remission rates at weeks 8 and 32 applying the alternative definition of clinical remission, which excludes the PGA. Of 197 patients in the IP, 103 (52.3%) continued in the MP and 91/103 (88.3%) completed. At week 8 using the original definition (Mayo score ≤2 with no subscore >1) clinical remission occurred in 16.4% for HD (P = 0.0482 versus PBO), 13.8% for LD (P = 0.1422), and 6.2% for PBO while the alternate definition (RBS = 0, SFS ≤1 with improvement ≥1, ES ≤1), clinical remission occurred in 23.9%, HD (P = 0.0154 versus PBO), 16.9%, LD (P = 0.2099), and 9.2%, PBO. At week 32, using the original definition, clinical remission occurred in 20.9%, HD (P = 0.0108 versus PBO), 26.2%, LD (P = 0.0021), and 6.2%, PBO while using the alternative definition clinical remission occurred in 26.9%, HD (P = 0.0025 versus PBO), 26.2%, LD (P = 0.0053), and 7.7%, PBO. Using this alternative definition of clinical remission, a greater difference between HD and PBO was observed. An endpoint that excludes the PGA but maintains the other components of the Mayo score (RBS, ES, SFS) is able to demonstrate a treatment effect and could be one of the endpoints in clinical trials of UC. Further, the analysis confirms that patients with moderate to severe UC treated with ozanimod HD were more likely to both achieve and maintain clinical remission.

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)0.026
metaresearch head score (Gemma)0.032
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch
Consensus categoriesnone
DomainCandidate signal: Methods · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.974
Threshold uncertainty score0.139

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0260.032
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0010.002
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0070.001

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 head0.031
GPT teacher head0.300
Teacher spread0.269 · 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.

Study designObservational
DomainMethods
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

Citations0
Published2016
Admission routes1
Has abstractyes

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