Table 2—

Risk of bias assessment of included randomised controlled trials of inhaled corticosteroids in chronic obstructive pulmonary disease(COPD)#

Study [Ref.]Sequence generationAllocation concealmentAE monitoringDrugWithdrawal ratesLost to follow-up
Aaron 15Adequate, central allocationAdequateAE captured by monthly telephone questionnaire and checklistSalmeterol/fluticasone combination = 14515 (10.3)2 (1.3)
Salmeterol xinafoate = 14820 (13.5)2 (1.3)
Burge 16Adequate, computer generated, stratified by centreAdequateAEs and SAEs recorded throughout the studyFluticasone propionate = 372160 (43.0)16 (4.3)
Placebo = 370195 (52.7)18 (4.9)
Calverley 17Adequate, computer generatedAdequateAE or SAE occurring during therapySalmeterol/fluticasone combination = 35889 (24.9)8 (2.2)
Salmeterol xinafoate = 372119 (32.0)8 (2.2)
Fluticasone propionate = 374108 (29.0)8 (2.1)
Placebo = 361140 (38.8)6 (1.7)
Calverley 19UnclearUnclearAEs recorded at 1, 2, 3, 6, 9 and 12 months of treatmentFormoterol/budesonide = 25474 (29)4 (1.6)
Formoterol = 255111 (44)4 (1.6)
Budesonide = 257102 (40)4 (1.6)
Placebo = 256106 (41)6 (2.3)
Calverley 18Adequate, schedule central allocationAdequateAEs reviewed at each visitSalmeterol/fluticasone combination = 1533522 (34.1)29 (1.9)
Salmeterol xinafoate = 1521561 (36.9)15 (1.0)
Fluticasone propionate = 1534587 (38.3)24 (1.6)
Placebo = 1524673 (44.2)21 (1.4)
Ferguson 20UnclearUnclearAE collected at start and endSalmeterol/fluticasone combination = 394117 (29.7)10 (2.5)
Salmeterol xinafoate = 388149 (38.4)10 (2.6)
FLTA3025 21UnclearUnclearAEs and SAEs recorded at each visitFluticasone propionate = 434147 (33.9)NA
Placebo = 20679 (38.3)NA
Hanania 26UnclearUnclearAE reporting at each visitSalmeterol/fluticasone combination = 17853 (30)NA
Salmeterol xinafoate = 17757 (32)NA
Fluticasone propionate = 18349 (27)NA
Placebo = 18559 (32)NA
Kardos 27Adequate, centrally generated blockAdequateAEs and SAEs recorded during run in and follow-upSalmeterol/fluticasone combination = 50799 (19.5)4 (0.8)
Salmeterol xinafoate = 487103 (21.1)3 (0.6)
Lofdahl 28UnclearUnclearAngina pectoris, MI, CAD and myocardial ischaemia reported as AE and SAEBudesonide = 634176 (27.7)NA
Placebo = 643189 (29.4)NA
Lung Health Study 29UnclearUnclearAEs every 3 monthsTriamcinolone = 55928 (5.0)NA
Reviewed deaths to determine cause of deathPlacebo = 55738 (6.8)NA
Mahler 30UnclearUnclearAEs and SAEs documentedSalmeterol/fluticasone combination = 16552 (31.5)NA
Salmeterol xinafoate = 16045 (28.2)NA
Fluticasone propionate = 16868 (40.5)NA
Placebo = 18169 (38.1)NA
Paggiaro 31Adequate, computer generatedAdequateAE defined as untoward medical occurrence during treatmentFluticasone propionate = 14219 (13.3)0
Placebo = 13927 (19.4)2 (1.4)
Rennard 32UnclearUnclearAEs, vital signs and ECGs at study visitBudesonide 320 μg/formoterol 9 μg b.i.d. = 494134 (27.1)9 (1.8)
Budesonide 160μg/formoterol 9 μg b.i.d. = 494143 (28.9)12 (2.4)
Formoterol = 495157 (31.7)12 (2.4)
Placebo = 481175 (36.3)13 (2.7)
SCO100250 22UnclearUnclearAEs and SAEs recorded after study medication but no later than last date after study medicationSalmeterol/fluticasone combination = 394125 (31.7)NA
Salmeterol xinafoate = 403156 (38.7)NA
SCO100470 24UnclearUnclearAEs and SAEs recorded at each study visitSalmeterol/fluticasone combination = 51859 (11.4)NA
Salmeterol xinafoate = 53274 (13.9)NA
SCO40041 23UnclearUnclearOn therapy AEs and SAEs monitoredSalmeterol/fluticasone combination = 9236 (39.1)NA
Salmeterol xinafoate = 9439 (41.5)NA
SFCT01/SCO30002 25UnclearUnclearAll AEs occurring after subject consented to participate until end of follow-upFluticasone propionate = 13134 (26.0)NA
Placebo = 12540 (32.0)NA
Szafranski 33UnclearUnclearAEs detected at visits 2–8, with ECGs at visits 1, 6 and 8Budesonide/formoterol = 20859 (28)NA
Formoterol = 20164 (32)NA
Budesonide = 19862 (31)NA
Placebo = 20590 (44)NA
Tashkin 34UnclearUnclearAEs, vital signs and ECGs at study visitBudesonide 160 μg/formoterol 4.5 μg b.i.d. = 277NANA
Budesonide/formoterol = 281NANA
Budesonide + formoterol = 287NANA
Budesonide = 275NANA
Formoterol = 284NANA
Placebo = 300NANA
van der Valk 35Adequate, permuted blocks, stratifiedAdequate3- and 6-month follow-upFluticasone propionate = 1231 (0.8)0
Placebo = 1211 (0.8)0
Vestbo 36Adequate, computer generatedAdequateParticipants seen every 3 monthsBudesonide = 14536 (24.8)0
Placebo = 14551 (35.2)0
Wouters 37AdequateAdequateAE collected at start and end of treatmentSalmeterol/fluticasone combination = 18934 (18.0)0
Salmeterol xinafoate = 18446 (25.0)0
  • Data are presented as n or n (%). AE: adverse event; SAE: serious adverse event; NA: not available; MI: myocardial infarction; CAD: coronary artery disease; ECG: electrocardiogram. #: all randomised controlled trials were double blinded.