Shifting Patterns in the Interpretation of Phase III Clinical Trial Outcomes in Advanced Non–Small-Cell Lung Cancer: The Bar Is Dropping
Bibliographic record
Abstract
PURPOSE: Despite multiple trials of new agents in advanced non-small-cell lung cancer (NSCLC), outcomes remain poor. This study explores how the design and interpretation of randomized trials in advanced NSCLC has changed over time. METHODS: Phase III randomized controlled trials of systemic therapy for advanced NSCLC between 1980 and 2010 were identified, and their primary end point, outcome, statistical significance, and conclusions were recorded. RESULTS: Of 245 trials identified, 203 were eligible for study inclusion. Although overall survival remains the most common primary end point of phase III trials, more trials from the last decade have used progression-free survival instead (none in 1980 to 1990, 13% in 2001 to 2010; P = .002). The percentage of trials meeting their primary statistical end points remained stable over time; however, the percentage of trials reporting a positive outcome without meeting that end point increased (30% in 1980 to 1990, 53% in 2001 to 2010; P < .001). A trend toward decreasing magnitude of survival gain in positive trials was seen over time (3.9 months in 1980 to 1990, 2.5 months in 2001 to 2010; P = .11), with a concomitant increase in the sample size of clinical trials over the same time period (median: 152 patients in 1980 to 1990, 413 in 2001 to 2010; P < .001). Only studies predating 1990 reported negative results as a result of insufficient magnitude of survival benefit despite statistical significance. CONCLUSION: A significant shift has occurred over the past three decades in the design and interpretation of phase III trials in advanced NSCLC. The use of survival as the primary measure of benefit is declining, as is the magnitude of benefit deemed clinically relevant.
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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 | 0.742 | 0.847 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.005 |
| Bibliometrics | 0.010 | 0.010 |
| Science and technology studies | 0.002 | 0.014 |
| Scholarly communication | 0.012 | 0.013 |
| Open science | 0.005 | 0.008 |
| Research integrity | 0.004 | 0.008 |
| Insufficient payload (model declined to judge) | 0.002 | 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; 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".