5018A phase 3 study in an enriched population of pulmonary arterial hypertension patients with long term oxygen use demonstrating improved exercise tolerance with use of ambulatory inhaled nitric oxide
Bibliographic record
Abstract
Background: Typical large clinical trials in a rare disease like pulmonary arterial hypertension (PAH) are less practical due to patient scarcity. Regulatory health authorities have advocated using an enriched population in randomized withdrawal clinical trials in PAH. Randomized withdrawal studies (RWS) represent empiric enrichment. In this RWS study, patients demonstrating a defined apparent response to treatment are eligible for the RWS. Precedence exists with a RWS in a PAH population. Patients stable on IV Epoprostenol therapy were transitioned to SC Trepostinil or Placebo. Subjects withdrawn to placebo, 88% had clinical deterioration, while only 7% withdrawn to SC Trepostinil had clinical deterioration (p=0.00023). Using the RWS design in 22 patients, the outcome was identified during a short duration. Purpose: The FDA agreed to an accelerated Phase 3 clinical development program of inhaled NO (iNO) with the 1st pivotal trial assessing impact on 6MWD and 2nd pivotal trial RWS to verify this effect by evaluating Time To Clinical Worsening (TTCW).
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 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; 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".