A 4-Year Trial of Tiotropium in Chronic Obstructive Pulmonary Disease
2008 · paper · Clinical trials
A four-year randomized trial of tiotropium versus placebo in 5,993 patients with COPD. Tiotropium improved lung function, quality of life and exacerbations but did not significantly slow the rate of decline in lung function.
1 finding
Substance Fig. 2A prints "Hazard ratio, 0.89 (95% CI, 0.85–0.94)" for discontinuation. This is hard to reconcile with the curve values (36.2% vs 44.6% at 45 months), the numbers at risk (1970/2986 vs 1723/3006 at 42 months) and the 1099 vs 1358 events.
- p. 7 Figure 2A legend inside panel
Hazard ratio, 0.89 (95% CI, 0.85–0.94)
- p. 4 Results, Study Population
months of treatment in the placebo group (44.6%) than in the tiotropium group (36.2%, P<0.001)
- p. 4 Study Population
placebo group (44.6%) than in the tiotropium group (36.2%, P<0.001)
Only the authors can say what is right here.
Judge's note: Read on the p7 image. Under proportional hazards, the cumulative hazard ratio from the 45-month proportions is about 0.76, and the ratio from the numbers at risk at 42 months is about 0.75. With about 2457 events, SE(log HR) is about 0.041. That gives a CI wider than the printed 0.85–0.94, whose log width implies an SE of about 0.026. The value 0.89 is also the all-cause mortality HR. The authors should confirm which model produced the printed HR and CI.
Second check: another model agreed
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5 minor (typos and the like; most checked by the judge only)
Wording Table 2 footnote: "Values were measured from day 30 until the end of the study (including 30 days after the discontinuation of treatment)". Methods: "from day 30 (steady state) until completion of double-blind treatment". Results: "from day 30 to the end of study-drug treatment (Table 2".
- p. 8 Table 2 footnote *
Values were measured from day 30 until the end of the study (including 30 days after the discon-
- p. 2 Methods, Study Design
from day 30 (steady state) until completion of double-blind treatment
- p. 4 Results, Rate of Decline in Lung Function
from day 30 to the end of study-drug treatment (Table 2
Only the authors can say what is right here.
Judge's note: Footnote seen in the p8 image. The Methods also describe a separate analysis "from baseline to 30 days after the discontinuation" using the Wilcoxon test. It is unclear whether the Table 2 slopes include the post-treatment visit.
Second check: another model agreed
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Wording "as compared with 38 to 90% in other studies.3-6": reference 4 (EUROSCOP) is a trial of persons with COPD "who continue smoking".
- p. 10 Discussion, right column, second paragraph
as compared with 38 to 90% in other studies.3-6
- p. 12 Reference 4
budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: that EUROSCOP enrolled only current smokers (100%). The p10 text and the title of reference 4 on p12 suggest the upper bound might be 100%, but the cited papers are not in the files, so only the authors can confirm.
Second check: another model agreed
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Typo The same drug is called "albuterol" in the Methods ("400 μg of albuterol") and "salbutamol" in the Discussion ("maximal doses of salbu-tamol").
- p. 3 Procedures
400 μg of albuterol
- p. 11 Discussion, paragraph 2
serial administration of maximal doses of salbu-
Judge's note: Seen in the p3 and p11 crops. The two names are synonyms, so either is legitimate; the point is only that the paper is inconsistent.
Second check: none (judge only)
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Typo Reference 6 reads "Decramer M. Rutten-van Mölken M,", with a period where a comma should separate the authors.
- p. 12 Reference 6
Decramer M. Rutten-van Mölken M,
Judge's note: The period is visible in the p12 image; all other author lists use commas.
Second check: none (judge only)
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Typo Disclosures read "grant support from Boehringer Ingelheim, Forrest, and GlaxoSmithKline".
- p. 12 Disclosures, Dr. Celli
Forrest, and GlaxoSmithKline
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: the company is Forest Laboratories, spelled with one 'r'. The page image shows "Forrest".
Second check: none (judge only)