PERSPECTIVE Methodological issues in therapeutic trials
Bibliographic record
Abstract
replicated the findings of previous trials in chronic obstructive pulmonary disease (COPD) on the apparent effectiveness of inhaled corticosteroids (ICS) in reducing exacerbation rates, but not so for mortality. In the present article, the authors review methodological issues in the TORCH and previous trials, such as patients already receiving ICS before randomisation and the absence of follow-up after study drug discontinuation, using data from two trials. First, among previous ICS users in the Canadian Optimal Therapy of COPD Trial, the hazard ratio of the first exacerbation with ICS relative to bronchodilators was 0.71 (95 % confidence interval (CI) 0.53–0.96), while among those not using ICS prior to randomisation, it was 1.11 (95% CI 0.69–1.79). Secondly, the rate ratio of exacerbations with ICS was 0.78 (95 % CI 0.61–0.99) prior to drug discontinuation during follow-up and 1.23 (95 % CI 0.78–1.95) thereafter. Finally, a 262 factorial analysis of the TORCH data found a rate ratio of mortality for the salmeterol component to be 0.83 (95 % CI 0.74–0.95), while for the fluticasone component it was 1.00 (95 % CI 0.89–1.13). In conclusion, after proper consideration of the various methodological shortcomings in the design and analysis of randomised trials, the effectiveness of inhaled corticosteroids in treating chronic obstructive pulmonary disease remains doubtful, while the benefit observed with combination therapy may be due exclusively to the beneficial effects of the long-acting bronchodilator alone.
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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 | 0.753 | 0.874 |
| Meta-epidemiology (narrow) | 0.003 | 0.003 |
| Meta-epidemiology (broad) | 0.010 | 0.007 |
| Bibliometrics | 0.009 | 0.009 |
| Science and technology studies | 0.003 | 0.047 |
| Scholarly communication | 0.019 | 0.022 |
| Open science | 0.012 | 0.011 |
| Research integrity | 0.026 | 0.031 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
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".