Clinical remission in paired phase two and three studies in inflammatory bowel disease: a systematic review with meta-analysis
Bibliographic record
Abstract
Discrepancies in phase two and three studies can result in significant patient and financial burden, as well as the nonapproval of potentially efficacious drugs. We aimed to determine whether this discrepancy exists for clinical trials in inflammatory bowel disease (IBD). Electronic databases (MEDLINE and Embase) and clinical trial repositories were searched from 1 January 1946 to 12 March 2021, for paired phase two and three studies of advanced therapies for Crohn's disease and ulcerative colitis. The primary outcome was to compare clinical remission rates between paired phase two and three studies for Crohn's disease and ulcerative colitis. Multivariable mixed-model meta-analysis was performed to calculate odds ratios (OR) with 95% confidence intervals (CI). The Cochrane risk-of-bias tool was used to grade the risk of bias. Of 2642 studies, 29 were included. Fifteen were phase three, 11 were phase two, one was phase one/two, and two were phase two/three. There were no differences in clinical remission rates between phase two and three studies for Crohn's disease (OR, 1.07; 95% CI, 0.86-1.34; P = 0.54) and ulcerative colitis (OR, 0.81; 95% CI, 0.48-1.36; P = 0.43). Furthermore, there was a lack of any appreciable differences in study characteristics, inclusion criteria and patient demographics among paired phase two and three studies. Most studies were considered low risk of bias. Overall, paired phase two and three studies demonstrate similar clinical remission rates for advanced therapies in IBD. Whether this applies to newer outcomes, such as endoscopic and mucosal healing remains to be determined.
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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 | 0.037 | 0.071 |
| Meta-epidemiology (narrow) | 0.004 | 0.002 |
| Meta-epidemiology (broad) | 0.029 | 0.064 |
| Bibliometrics | 0.013 | 0.012 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.005 | 0.003 |
| Open science | 0.003 | 0.003 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
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.
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".