Observational studyInternational journal of chronic obstructive pulmonary disease2025
Prompt versus Delayed Triple Therapy in COPD: Solutions to Time-Related Biases in Observational Studies.
Observational study in International journal of chronic obstructive pulmonary disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Triple Therapy in Routine Clinical Practice: Beyond Clinical Trials in COPD.Open respiratory archivesArticle
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Background: Recent observational studies have reported that prompt initiation of single-inhaler triple therapy after a COPD exacerbation is more effective than delayed initiation. We show that their study design, by "peeking into the future" to define the timing of treatment initiation, introduces time-related biases, particularly protopathic bias. These biases can be avoided using the "cloning" approach to emulate a randomized trial approach. Methods: We formed a cohort of patients with COPD who had an exacerbation (index) after September 2017, using the United Kingdom's Clinical Practice Research Datalink (CPRD). Using the "cloning" trial emulation technique, each subject was assigned to both the prompt and the delayed initiator arms as of the index date and censored according to their treatment over time. The Cox model was used to compare the incidence of the first exacerbation after the index exacerbation, over one year, after weighing by inverse probability of censoring. We also replicated the biased approach of the recent studies, based on peeking into the future. Results: The cohort included 91,958 eligible subjects who had an exacerbation, generating 91,958 prompt initiator clones and 91,958 delayed initiator clones. The hazard ratio (HR) of a moderate or severe exacerbation, comparing prompt versus delayed initiators, was 0.98 (95% CI: 0.80-1.19), while it was 1.26 (95% CI: 0.81-1.96) for severe exacerbation. The replication of the time-related biased approach comparing prompt with delayed initiation resulted, correspondingly, in HRs of 0.73 (95% CI: 0.65-0.81) and 0.58 (95% CI: 0.46-0.74). Conclusion: Using a trial emulation approach, prompt treatment with single-inhaler triple therapy after a COPD exacerbation was not more effective than delayed treatment at reducing the incidence of subsequent exacerbations. The method used by previous studies, suggesting significant effectiveness with prompt treatment initiation, was affected by time-related biases induced by peeking into the future. A randomized controlled trial can confirm these findings.
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