Table 1. Large Bronchodilator Trials According to Factors For Interpreting Good Clinical Practice on Design, Results, and Translation

Study (trial registry; funding)	Characteristics				Medication Protocol				Effect			Focus^*
Study (trial registry; funding)	Patients (n)	Length of Follow-up	Selection Criteria (Part)	Population	Interventions	Rescue	Prohibited medication	Allowed bias medication	Primary outcome	Results	Significance	Focus^*
Calverley, 2007⁶ (registered; funding from GSK)	6112	3 years	40–80 years old, COPD diagnosis FEV₁: <60% FER: <0.70 before BD Reversibility: <10% No respiratory disease, use of oxygen	65 years 75% male 43% smoker FEV₁ 44% predicated value	Salmeterol/Fluticason Salmeterol Fluticason Placebo	Albuterol	Long-acting BD, steroids	Short-acting and other BD	Mortality	12.6% vs 13.5% vs 16.0% vs 15.2%	NS	A
Calverley et al,⁴ 2003 (not registered; funding from GSK)	1465	1 year	FEV₁: 25% to 70% before BD FER: <0.70 before BD Reversibility: <10% ≥1 exac/year 3 years No respiratory disease, use of oxygen	63.5 years 72.5% male 51% smoker FEV₁ 49% predicted value	Salmeterol/ Fluticason Salmeterol Fluticason Placebo	Albuterol	Long-acting β-agonist, steroids	Anticholinergics and theophillin	FEV₁ before BD	10% vs 2% vs 2% vs −3%	P < .01	B
Tashkin et al,⁷ 2008 (registered; funded by BI and Pfizer)	5993	4 years	>40 years FEV₁: <70%, FER: <0.70 No respiratory disease, use of oxygen Myocardial infarction during last 6 months, unstable arrhythmia	64.5 years 75% male 30% smoker FEV₁ 48% predicted value	Spiriva Placebo	—	Short-acting anticholinergics	All nonanticholinergics	FEV₁ decline before and after BD	Before BD: 30 vs 30 mL/yr After BD: 40 vs 42 mL/yr	NS	C
Niewoehner et al,⁵ 2005 (not registered; funded by BI and Pfizer)	1829	6 months	>40 years COPD diagnosis FEV₁: <60% FER: <0.70 No asthma Myocardial infarction during past 6 months, cardiac hospital during past year	67.8 years 99% male 30% smoker FEV₁ 36% predicted value 29% oxygen	Spiriva Placebo	—	Short-acting anticholinergics	All nonanticholinergics	%Exacerbation	32.3% vs 27.9%	P = .037	D
									%Exacerbation hospitalization	9.5% vs 7.0%	NS
Vogelmeier et al,⁸ 2011 (registered; funded by BI and Pfizer)	7376	1 year	>40 years FEV₁: <70%, FER: <0.70 ≥1 exacerbation during past year No asthma CVD	62.9 years 74.7% male 48% smoker FEV₁ 49% predicted value	Spiriva Salmeterol	Albuterol	Anticholinergics, long-acting β-agonist	Short-acting β-agonist	Time to first exacerbation	187 vs 145 days (first fourth of patients)	P < .001	E

↵* A: Acknowledge statistically nonsignificant results for primary outcome, but the focus is on beneficial effect and secondary outcome in main text discussion and conclusion. They claim the study is underpowered. B: Focus is on secondary outcomes in main text discussion. C: Focus is on secondary outcome in result and discussion section of both abstract and main text. Of many nonsignificant post hoc subgroup analyses, they only state the significant one. D: Acknowledge statistically nonsignificant results for the primary outcome (called “borderline significant”), but focus is on beneficial effect in the abstract and main text results. E: Focus is on an exaggerated effect on one fourth of all patients (a third had an exacerbation), which is not stated in the abstract. Focus is on inaccurate description of population in main text discussion and conclusion.
BD, bronchodilator; BI, Boehringer Ingelheim; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease; FER, forced expiratory ratio; FEV₁, forced expiratory volume in first second; GSK, GlaxoSmithKline; NS, not significant.