Benefit–Harm Analysis of Earlier Initiation of Triple Therapy for Prevention of Acute Exacerbation in Patients with Chronic Obstructive Pulmonary Disease
Bibliographic record
Abstract
Abstract Rationale Reducing the risk of exacerbation is a fundamental goal in managing stable chronic obstructive pulmonary disease (COPD). Guidelines recommend triple therapy (inhaled corticosteroids, long-acting muscarinic antagonists, and long-acting β-agonists) only as a stepup from dual therapy (long-acting muscarinic antagonists and long-acting β-agonists) for patients at continued high risk of exacerbation, because of the trade-off of an increased risk of pneumonia associated with inhaled corticosteroid–containing therapies. However, there is little evidence on the optimum timing of initiating triple therapy. Objectives To perform a benefit–harm analysis to evaluate the net benefit of earlier initiation of triple therapy for the prevention of acute exacerbations in patients with COPD compared with standard timing recommended in current guidelines. Methods We used a validated whole-disease microsimulation model of COPD in the Canadian general population aged ⩾40 years to determine the benefit versus harm of earlier initiation of triple therapy over a 20-year time horizon compared with standard care. We assessed net change in quality-adjusted life-years (QALYs) from the reduction in risk of acute exacerbations and the increased risk of treatment-related pneumonia in subgroups of patients with COPD defined by exacerbation history, symptoms, and disease severity. Model parameters were determined from clinical trials and other published literature. Key parameters were varied in one-way sensitivity analysis. Results In patients at high risk of acute exacerbation (54.7% female; mean age, 74.0 yr; 68% Global Initiative for Chronic Obstructive Lung Disease grades I and II), earlier initiation of triple therapy was associated with a net QALY gain of 4.8 per 100 patients with COPD over 20 years compared with standard care. The net QALY gain increased to 5.9 per 100 patients in the subgroup of patients with a high symptom burden (modified Medical Research Council dyspnea scale score, >1). Earlier initiation remained net beneficial in all subgroup and sensitivity analysis scenarios. Conclusions Modeling suggests that earlier initiation of triple therapy is likely to be net beneficial for patients at high risk of acute exacerbation, with an even greater benefit to patients with a high symptom burden. Further clinical research is needed to verify these findings in empirical studies.
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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 | 0.013 | 0.017 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.008 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".