Transportability of patient outcomes from a US clinical trial to real-world populations - a case study using Lung-MAP S1400I (NCT02785952)
Bibliographic record
Abstract
2. Abstract Background The external validity of results from clinical trials to routine clinical practice is often questioned. This is sometimes because certain real world patient groups are excluded or underrepresented in clinical trials, or because standards of care in trials are different from those in real-world populations globally. This lack of external validity of trial results manifests as an efficacy-effectiveness gap. In this study, we aim to address the question of whether it is possible to extend results from a clinical trial to real-world populations across different countries. To do this, we use the Lung-MAP nonmatch sub-study S1400I trial ( NCT02785952 ) as a case study. Setting Squamous cell lung carcinoma is a subtype of non-small cell lung cancer (NSCLC) accounting for 25-30% of cases. Compared to other NSCLC subtypes such as adenocarcinoma, the presence of actionable genetic variants is less common and there are fewer targeted therapies available for advanced/metastatic NSCLC (aNSCLC) of squamous subtype. Patients with squamous aNSCLC who progress on front-line chemotherapy commonly receive immunotherapy using immune checkpoint inhibitors such as nivolumab. The Lung-MAP nonmatch sub-study S1400I ( NCT02785952 ) compared overall survival (OS) in patients with recurrent/stage IV squamous NSCLC randomized to receive either nivolumab monotherapy or nivolumab + ipilimumab combination therapy and found no significant difference in mortality rates between these groups. The trial included patients from the United States only. Objectives The goal of this study is to evaluate the transportability of results from NCT02785952 in United States patients to real-world populations in the United States, Germany, France, England and Japan. Using individual-level data for OS from NCT02785952 , we will adjust for baseline characteristics from published studies of real-world populations in these countries and benchmark the predicted OS against Kaplan-Meier estimates reported by these studies for patients with squamous cell aNSCLC treated with nivolumab. Sensitivity analyses for unmeasured prognostic variables will be performed.
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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 | 0.292 | 0.528 |
| Meta-epidemiology (narrow) | 0.001 | 0.002 |
| Meta-epidemiology (broad) | 0.003 | 0.008 |
| Bibliometrics | 0.002 | 0.006 |
| Science and technology studies | 0.002 | 0.005 |
| Scholarly communication | 0.007 | 0.005 |
| Open science | 0.004 | 0.006 |
| Research integrity | 0.005 | 0.005 |
| Insufficient payload (model declined to judge) | 0.016 | 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; 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".