Fixed Triple Therapy in Chronic Obstructive Pulmonary Disease and Survival. Living Better, Longer, or Both?
Bibliographic record
Abstract
Fixed Triple Therapy in Chronic Obstructive Pulmonary Disease and SurvivalLiving Better, Longer, or Both?Does regular pharmacological treatment including inhaled corticosteroids (ICS) reduce mortality in patients with chronic obstructive pulmonary disease (COPD)?Few questions have attracted more attention in COPD, and the number of commentaries, editorials, and reviews on this topic by far exceeds the limited number of original papers addressing the topic.However, here is one more.In this issue of the Journal, Lipson and colleagues (pp.1508-1516) report findings from a post hoc analysis of the IMPACT (Informing the Pathway of COPD Treatment) trial (1).The trial was enriched for exacerbators, and the primary outcome was the annual rate of on-treatment moderate and severe exacerbations comparing a fixed combination of fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) with fixed combinations of UMEC/VI and FF/VI.Mortality was listed among "other efficacy outcomes" (2), and the article presents an expanded analysis of mortality compared with the one reported in their primary report (3).By obtaining information on vital status at end of the trial for an additional 574 patients, the authors had information on vital status for 10,313 of the 10,355 patients included in the trial.The authors compared mortality in patients randomized to FF/UMEC/VI with those randomized to either a fixed combination of FF/VI or a fixed combination of UMEC/VI.After 1 year, there were significantly fewer deaths in the triple-combination group (FF/UMEC/VI) than in the UMEC/VI group (absolute risk reduction [ARR], 0.83%; relative risk reduction [RRR], 28%; P = 0.042) but not when comparing the FF/VI group with the UMEC/VI group (ARR, 0.55%; RRR, 18%; P = 0.190).When analyses were restricted to on-treatment mortality, both these group analyses were statistically significant.The authors convincingly showed that missing outcome data on the 0.4% of the patient population were very unlikely to have had an impact on the reported estimates.Only a few previous trials of an ICS-containing treatment have had mortality as a primary outcome.The TORCH (Toward a Revolution in COPD Health) study (4) found a 2.6% ARR and a 17.5% RRR in deaths when comparing the combination of salmeterol and fluticasone propionate with placebo.However, the P value was adjusted from 0.041 to 0.052 to take a late interim analysis into account, and the study has since been referred to as "negative."The SUMMIT (Study to Understand Mortality and Morbidity) (5) compared a combination of vilanterol and fluticasone furoate with placebo in patients with moderate COPD
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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 | 0.008 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 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 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".