O-002 Evaluation of the Operating Properties of Candidate Patient Reported Outcomes for Use in Randomized Controlled Trials in Crohn’s Disease
Bibliographic record
Abstract
The Crohn’s Disease Activity Index (CDAI), the conventional composite outcome measure used in randomized controlled trials (RCTs), consists of 8 items that evaluate symptoms, signs and laboratory tests. Recently the US FDA has indicated that patient reported outcomes (PROs) should be utilized as, or incorporated into, the primary outcome measure in Crohn’s disease (CD) registration trials in preference to the CDAI. However no validated PROs currently exist. Development and validation of novel PRO instruments is a lengthy process. Therefore, we determined whether the outcomes reported by patients from the CDAI diary card (abdominal pain, stool frequency, general well-being) could be adapted to derive a PRO with favorable operating properties for use in RCTs. Development consisted of 2 phases. In Phase I, data from an RCT1 of rifaximin extended intestinal release therapy were used to identify cut-points that yielded optimum sensitivity and specificity for identification of CDAI –defined remission (score <150). Two item (abdominal pain, stool frequency) and 3 item (2 item plus general well-being) PRO instruments were generated. In Phase II, these instruments were assessed using data from an RCT2 of methotrexate (MTX) induction therapy in active CD for which the primary outcome measure was a CDAI score <150 without prednisone after 16 weeks of therapy. The magnitude of the treatment effect of MTX was estimated using the 2- and 3-item instruments and the CDAI in patients with and without objective evidence of inflammation at baseline (serum orosomucoid concentration >88 mg per deciliter). Figure 1 shows the Receiver Operator Characteristic (ROC) curves for the optimal cut-points for each of the daily average item scores (mean daily stool frequency ≤1.5, mean daily abdominal pain score ≤1, mean daily general well-being score ≤1). Table 1 shows the estimates of effect size of MTX for multiple outcome measures in the 2 patient populations. The estimates of MTX treatment effect were similar for the 2 and 3 item PROs and the CDAI—based outcomes. The largest estimates of the treatment effect were derived when 1) complete withdrawal of prednisone was included in the definition of outcome and 2) patients had objective evidence of inflammation as defined by the presence of an elevated baseline serum concentration of orosomucoid. These data indicate that readily available data derived from patients’ CDAI diary cards may be appropriate for use as a PRO in clinical trials for CD. 1. Prantera C, Lochs H, Grimaldi M, et al. Rifaximin-extended intestinal release induces remission in patients with moderately active Crohn's disease. Gastroenterology 2012;142:473–81 e4. 2. Feagan BG, Rochon J, Fedorak RN, et al. Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators. N Engl J Med 1995;332:292–7.
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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 | 0.301 | 0.483 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.007 |
| Bibliometrics | 0.003 | 0.004 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.004 | 0.004 |
| Open science | 0.001 | 0.003 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.028 | 0.003 |
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".