P643 Generalizability of Crohn’s disease randomized controlled trials compared to clinical practice
Bibliographic record
Abstract
Abstract Background There are no curative medical therapies for Crohn’s disease (CD). However, multiple novel treatment options are currently being evaluated in randomized controlled trials (RCTs). Historically, CD populations enrolled in RCTs have not reflected the heterogeneity of patients observed in clinical practice due to strict inclusion/exclusion criteria and protocolized trial procedures do not reflect day-to-day care. These factors have raised concerns that results from pivotal RCTs required for drug approval are poorly generalizable. The aim of this study is to assess the generalizability of CD RCTs. We evaluated the proportion of CD patients initiating ustekinumab or vedolizumab in clinical care who would have been eligible for enrolment in the corresponding phase 3 registrational induction trial, and the factors impacting trial eligibility. Methods This is a retrospective cohort study using data from two ambulatory IBD clinics in Calgary, AB. Our study population included consecutive adult (>=18 years) patients with a confirmed diagnosis of CD, newly initiated on ustekinumab or vedolizumab between January 1, 2018 and January 1, 2020. We then applied the inclusion/exclusion criteria from the phase 3 GEMINI II/III and UNITI I/II induction trials to determine the proportion of patients who would have been trial-eligible. We then tabulated the indications for trial exclusion to determine the characteristics of patients who would not have been reflected in the trial population. Results A total of 50 patients were included. The results are outlined in Table 1. The median age was 42.5 years. Most patients had non-stricturing non-penetrating disease (44%, 22/50) and ileocolonic disease distribution (48%, 24/50). A total of 66% (33/50) would have been eligible for inclusion in GEMINI II/III and (30/50) 60% would be eligible for inclusion in UNITI I/II. The most common reasons for trial exclusion included extensive surgery (total colectomy/subtotal colectomy) with short bowel or ileostomy (n=12) and surgery within 6 months of enrolment (n=3), multiple previous resections (n=2). Four patients were excluded based on intra-abdominal abscess. A total of 13 patients (26%) were temporarily ineligible due to recent biologic switch and would have required an 8-week washout prior to trial enrolment. Only two patients were excluded based on age (>80 years). Conclusion Although most patients on ustekinumab or vedolizumab would have been eligible for the respective pivotal trials, patients who have complications of disease, extensive surgery, or altered anatomy are not reflected in current RCTs.
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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 | 0.547 | 0.807 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.009 |
| Bibliometrics | 0.007 | 0.009 |
| Science and technology studies | 0.001 | 0.009 |
| Scholarly communication | 0.008 | 0.007 |
| Open science | 0.004 | 0.006 |
| Research integrity | 0.004 | 0.004 |
| Insufficient payload (model declined to judge) | 0.011 | 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; the direct Gemma label and the distilled Codex classifier agree on what is shown here.
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".