Table 1. Large Bronchodilator Trials According to Factors For Interpreting Good Clinical Practice on Design, Results, and Translation
Study (trial registry; funding)CharacteristicsMedication ProtocolEffectFocus*
Patients (n)Length of Follow-upSelection Criteria (Part)PopulationInterventionsRescueProhibited medicationAllowed bias medicationPrimary outcomeResultsSignificance
Calverley, 20076 (registered; funding from GSK)61123 years40–80 years old, COPD diagnosis FEV1: <60% FER: <0.70 before BD Reversibility: <10% No respiratory disease, use of oxygen65 years 75% male 43% smoker FEV1 44% predicated valueSalmeterol/Fluticason Salmeterol Fluticason PlaceboAlbuterolLong-acting BD, steroidsShort-acting and other BDMortality12.6% vs 13.5% vs 16.0% vs 15.2%NSA
Calverley et al,4 2003 (not registered; funding from GSK)14651 yearFEV1: 25% to 70% before BD FER: <0.70 before BD Reversibility: <10% ≥1 exac/year 3 years No respiratory disease, use of oxygen63.5 years 72.5% male 51% smoker FEV1 49% predicted valueSalmeterol/ Fluticason Salmeterol Fluticason PlaceboAlbuterolLong-acting β-agonist, steroidsAnticholinergics and theophillinFEV1 before BD10% vs 2% vs 2% vs −3%P < .01B
Tashkin et al,7 2008 (registered; funded by BI and Pfizer)59934 years>40 years FEV1: <70%, FER: <0.70 No respiratory disease, use of oxygen Myocardial infarction during last 6 months, unstable arrhythmia64.5 years 75% male 30% smoker FEV1 48% predicted valueSpiriva PlaceboShort-acting anticholinergicsAll nonanticholinergicsFEV1 decline before and after BDBefore BD: 30 vs 30 mL/yr After BD: 40 vs 42 mL/yrNSC
Niewoehner et al,5 2005 (not registered; funded by BI and Pfizer)18296 months>40 years COPD diagnosis FEV1: <60% FER: <0.70 No asthma Myocardial infarction during past 6 months, cardiac hospital during past year67.8 years 99% male 30% smoker FEV1 36% predicted value 29% oxygenSpiriva PlaceboShort-acting anticholinergicsAll nonanticholinergics%Exacerbation32.3% vs 27.9%P = .037D
%Exacerbation hospitalization9.5% vs 7.0%NS
Vogelmeier et al,8 2011 (registered; funded by BI and Pfizer)73761 year>40 years FEV1: <70%, FER: <0.70 ≥1 exacerbation during past year No asthma CVD62.9 years 74.7% male 48% smoker FEV1 49% predicted valueSpiriva SalmeterolAlbuterolAnticholinergics, long-acting β-agonistShort-acting β-agonistTime to first exacerbation187 vs 145 days (first fourth of patients)P < .001E
  • * 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.