Operating Properties of Different Patient Reported Outcome Endpoints Combined With Endoscopic Evaluation: Data From EXTEND
Bibliographic record
Abstract
Introduction: Patient reported outcome (PRO) components of the Crohn's disease (CD) Activity Index (CDAI) are being explored as clinical remission (CR) endpoints,1 as are composite measures of endoscopic remission (ER) plus CR as outcome measures in CD trials. The aim is to explore the use of different definitions of CR, based on CDAI stool frequency (SF) and abdominal pain (AP) components, and composite endpoints on efficacy estimations in the mucosal healing study EXTEND.2 Methods: Three CR definitions were explored in patients (pts) from EXTEND: 1) CDAI 1 In EXTEND, adults with moderate to severe CD received induction ADA 160/80 mg at weeks (wks) 0/2. At wk 4, pts were randomized to ADA 40 mg every other wk or placebo (PBO) to wk 52. Pts (N=104) with BL avg daily SF ≥2.5 or AP score ≥2.0 and Simple Endoscopic Score for CD (SES-CD) ≥6 (or ≥4 for pts with isolated ileal disease) by central read were analyzed at wks 12 and 52. Endpoints assessed were the 3 CR definitions, ER (SES-CD ≤4 and at least 2 point reduction from BL, by central read), and composite ER and CR for each remission definition. Results: ER was achieved by 37.3% and 15.1% of ADA- and PBO-treated pts, respectively, at wk 12 (Δ22.2%, p=0.01); wk 52 values were 27.5% and 1.9% (Δ25.6%, pvs PBO at wks 12 and 52 (Table). Overall, composite endpoint effect sizes were similar to or slightly less than CR effect sizes. At wk 52, the SF/AP definition was associated with the lowest rates of remission in both PBO and ADA groups, and the lowest effect size of all CR definitions. Conclusion: Use of a composite endpoint (endoscopic plus symptomatic remission) led to diminished effect sizes compared to the endoscopic definition alone. Use of new endpoints should consider the ability of the endpoint to distinguish drug effect from PBO.Table 1: Effect size for various definitions of remission (NRI)
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.039 | 0.048 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.004 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".