494 The Fragility of Randomized Placebo-Controlled Trials for Irritable Bowel Syndrome Management
Bibliographic record
Abstract
INTRODUCTION: Fragility indices (FI) are a novel method to measure the robustness of results in clinical trials. The FI represents the number of participants whose status in a clinical trial would have to change from a non-event (not experiencing the primary endpoint) to an event (experiencing the primary endpoint) to turn a statistically significant result into a non-significant result. The aim of this study was to evaluate the robustness of trials for irritable bowel syndrome (IBS) including IBS-mixed, IBS-constipation, and IBS-diarrhea. METHODS: Trials published in high impact journals comparing the efficacy of therapies for IBS were identified from Medline. Trials had to be in adults, randomized, parallel-armed, with at least one statistically significant ( P < 0.05) binary outcome, and a positive result (i.e. primary endpoint met). Only primary endpoints of therapeutic efficacy were considered. Only trials comparing Rifaximin, Eluxadoline, fecal microbiota transplant (FMT), probiotics, Ramosetron, Alosetron, physical activity, Cimetropium and Pinaverium to placebo met the inclusion criteria. FI and correlation coefficients were calculated and regression modeling was also used to identify predictors of a high FI. RESULTS: Thirteen trials meeting the inclusion criteria were analyzed. The impact factor of the journals in which they were published ranged from 3.5-79. The median FI was 6 (range 1-38). The median sample size in all trials was 427 (range: 44-1280). The trial publication year ( P = 0.60), journal impact factor ( P = 0.16), time point in weeks when the primary outcome was assessed ( P = 0.45), duration of the study ( P = 0.89), and number needed to treat [NNT] ( P = 0.06) were not predictive of a high FI. However, a larger sample size was predictive of a higher FI ( P = 0.01). The highest FI was seen in a Ramosetron trial (FI = 38) for IBS-D published in Gastroenterology. No correlation was seen between FI and journal impact factor (R = 0.19, P = 0.55), trial publication year (R = 0.09, P = 0.77), duration of trial (R = -0.45, P = 0.12), time point at which the primary endpoint was assessed (R = -0.12, P = 0.70), NNT (R = -0.34, P = 0.26), and sample size (R = 0.22, P = 0.47) CONCLUSION: Our results suggest that a median of six participants is needed to nullify efficacy outcomes in the included IBS therapy trials. A larger sample size was predictive of a high FI. Some trials used in the formation of evidence-based guidelines are fragile suggesting how easily statistical significance based on a threshold P -value may be overturned.
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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 | 0.334 | 0.649 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.008 | 0.012 |
| Bibliometrics | 0.011 | 0.012 |
| Science and technology studies | 0.001 | 0.004 |
| Scholarly communication | 0.007 | 0.006 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.003 | 0.003 |
| 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".