Successful Trial Design and Planning in Systemic Sclerosis: Does It Take a Village?
Bibliographic record
Abstract
Negative trial reporting, especially in rare diseases, provides essential information. The design and analysis of a “negative” trial, in diseases for which few potential treatments and no cure exist, warrants particular scrutiny to determine whether the trial was truly negative, or rather a “failed” trial owing to other design, financial, planning, or recruitment impediments1. A trial that is discontinued early warrants the label negative if an unbiased, independent data safety monitoring board identified either a harm signal (excessive intolerance or drug-related adverse events) or a clear worsening of the disease state in comparison to placebo. In an article by Hsu, et al , in this issue of The Journal , the authors describe a 52-week randomized double-blind placebo-controlled multicenter phase II study of pomalidomide2. The sponsors have conceded to the reviewers that the study was discontinued early because of poor recruitment. Yet the article’s discussion section persists in stating that discontinuation by the sponsor was due to lack of drug efficacy. To be clear, there exists no statistical application capable of calculating a reliable result in any of the study variables between the 4 treatment and the 7 placebo cases completing a study that was powered for a sample of 88. Thus, the study results carry similar statistical weight to the initial anecdotal case reports of perceived efficacy of pomalidomide by systemic sclerosis (SSc) specialists — cases that likely inspired moving the drug to trial. SSc disease behavior remains complex and challenging to the most seasoned SSc clinician researchers who are well-acclimated to a cautious approach to data interpretation in this “rare” and exceptionally complex disease. In a journal less cognizant of the humbling landscape in SSc clinical trial design, this study would have slipped by as a negative study, generating an inaccurate interpretation of the … Address correspondence to Dr. L.A. Saketkoo, MD, MPH, Associate Professor of Medicine, Tulane University School of Medicine, Division of Pulmonary Medicine and Critical Care, 1430 Tulane Ave., New Orleans, Louisiana 70112, USA. E-mail: lsaketk{at}tulane.edu
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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 | 0.608 | 0.754 |
| Meta-epidemiology (narrow) | 0.003 | 0.003 |
| Meta-epidemiology (broad) | 0.009 | 0.006 |
| Bibliometrics | 0.005 | 0.005 |
| Science and technology studies | 0.010 | 0.036 |
| Scholarly communication | 0.030 | 0.038 |
| Open science | 0.013 | 0.013 |
| Research integrity | 0.043 | 0.056 |
| Insufficient payload (model declined to judge) | 0.008 | 0.007 |
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".