The time toxicity efficacy-effectiveness gap: A population-based study of stage III/IV non-small cell lung cancer (NSCLC) in Ontario, Canada.
Bibliographic record
Abstract
133 Background: While patients enrolled in clinical trials tend to have superior cancer-specific outcomes relative to those in routine practice (the ‘’efficacy-effectiveness gap’’), it is unknown if this gap extends to time toxicity. While trial protocols can impose additional contact days, trial participants also tend to be healthier, perhaps needing fewer contact days. We sought to evaluate the time toxicity efficacy-effectiveness gap among patients with stage III/IV NSCLC. Methods: We created a population-based, retrospective cohort with health administrative data covering the population of Ontario, Canada (15.5 million), of adults aged ≥20 years diagnosed with stage III/IV NSCLC in 2014-2017 and died in 2014-2019, receiving palliative systemic anti-cancer drug(s) as part of a trial. We matched patients 1:1 to those who received the same drug(s) in the real world (post-approval) in the same line of treatment, and received the same total lines of therapy. We calculated contact days (days with healthcare contact outside the home) from diagnosis to death and measured overall survival. We plotted, normalized, and fitted with cubic splines the weekly percentage of contact days to obtain trajectories over the disease course. Results: We identified and matched 55 trial participants to 55 patients in routine practice. Trial participants were younger (median age, 62 vs 66 years), had fewer co-morbidities (hypertension, 35% vs 53%), and more often had de novo metastatic disease (82% vs 67%). Median lines of therapy were 2. Systemic therapy regimens most commonly included immunotherapy (n=41, 75%). Trial participants initiated systemic therapy sooner than in routine practice (median 2.0 vs 2.4 months). Trial participants had a longer overall survival (median 13.8 vs 11.6 months) and a similar number of contact days (median 79 vs 78 days). The percentage of contact days was lower in trial participants due to longer survival (median 19% vs 22%). Trial participants had similar acute/assisted institutional care contact days (median 19 vs 18 days), but more days with laboratory tests (median 23 vs 17 days), systemic therapy (median 9 vs 6 days), and radiotherapy visits (median 15 vs 11 days). Normalized trajectories for both cohorts followed a ‘’U-shape’’; the difference between the maximal peak and trough was smaller in trial participants. Conclusions: We describe a novel efficacy-effectiveness gap in time toxicity, in addition to the previously established efficacy-effectiveness gap in overall survival. Encouragingly, trial participants did not experience delays in treatment, and initiated treatments sooner than in routine practice. Among trial participants, the higher number of contact days for tests, and the shallower U-shaped curve (indicating frequent visits even when relatively well) indicate potential opportunities to decrease trial-related time toxicity.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".