Letter: limitations of studies to evaluate the significance of anti-tumour necrosis factor serum levels in Crohn's disease - authors' reply
Bibliographic record
Abstract
In their review of our article,1 Drs Chaparro and Gisbert raise valid points regarding the trade-offs of cross-sectional study design in Crohn's disease (CD) including the choice of time-lines and outcome measures.2 However, it should be noted that the study represents a prospective evaluation of infliximab (IFX) pharmacokinetics and pharmacodynamics in a pragmatic sample of 327 patients with CD on maintenance therapy at 18 Canadian infusion centres. Specifically, we were interested in looking at a cross-section of patients on maintenance therapy to determine if there was a general relationship between the change in IFX trough concentrations between infusions and measures of disease activity. The fact that our final study population that was largely in remission presented significant challenges with regard to detecting these changes and relationships within the period of observation. We acknowledge the limitation of the Crohn's disease activity index (CDAI) as a measurement of CD inflammation.3 However, we took the opportunity to explore additional analyses that have clinical relevance [e.g. threshold trough IFX concentrations and C-reactive protein (CRP) concentrations, antibodies to infliximab (ATI) and IFX trough concentrations] and that were also possible given the constraints of the original study design. We focused our secondary analyses on cut-off levels for an IFX trough concentration that predict worsening disease activity because measuring mean changes in IFX trough concentrations may miss this relationship. Both receiver operator curve analyses and descriptive data support previous findings that trough concentrations less than 3 μg/mL are associated with increases in CDAI and CRP,4 and there was also a significant association between the presence of ATI and elevated CRP concentrations (>5 mg/L) at both visits. Despite these limitations, our data confirmed relationships between IFX trough concentration, ATI and changes in disease activity in patients receiving maintenance IFX infusions for CD in clinical practice. The authors' declarations of personal and financial interests are unchanged from those in the original article.1
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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 | 0.024 | 0.174 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.002 | 0.004 |
| Scholarly communication | 0.004 | 0.005 |
| Open science | 0.005 | 0.002 |
| Research integrity | 0.022 | 0.023 |
| Insufficient payload (model declined to judge) | 0.005 | 0.006 |
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".