Reshaping study design for faster extrapolation‐based drug approval in pediatric inflammatory bowel diseases: An ESPGHAN–NASPGHAN position paper
Bibliographic record
Abstract
Children with inflammatory bowel diseases (IBD) have limited access to the available advanced therapies, given the lengthy gap between adult and pediatric approval. We aimed to review key hurdles for pediatric trials and recommend practical solutions. This position paper was developed jointly by the European and North American Societies for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN and NASPGHAN), in consultation with patient representatives. A systematic review was performed for identified topics, and two voting rounds with two group meetings led to agreement on 24 statements. The systematic review (reviewing 4366 manuscripts, of which 123 were included in tables of evidence and 213 in support of 23 statements) found similar biologic pathogenesis, and similar or better effectiveness and safety in children older than 2 years compared to adults. Pharmacokinetics were similar in adolescents but dissimilar in younger children. The review also found sufficiently accurate noninvasive endpoints to reflect post-induction treatment response. There was no significant added benefit for ileocolonoscopy over sigmoidoscopy in ulcerative colitis. Drugs should be approved in children >12 years and ≥40 kg based on extrapolation from adult and real-world data. While efficacy may be extrapolated to children <40 kg, pharmacokinetics cannot and thus one open-label single-arm study should be performed to establish a dose that matches adult exposure-response from the adult trial in which adolescents may be enrolled if not exposed to placebo. Full colonoscopies should be minimized in the pediatric dosing trial. Efficacy in patients with infantile IBD cannot be extrapolated from adult data.
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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 | 0.550 | 0.669 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.007 | 0.013 |
| Bibliometrics | 0.004 | 0.005 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.008 | 0.009 |
| Open science | 0.005 | 0.007 |
| Research integrity | 0.008 | 0.009 |
| Insufficient payload (model declined to judge) | 0.021 | 0.004 |
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".