Risk of bias assessment and fracture outcomes in RCTs of inhaled corticosteroids in COPD
| Source | Sequence generation | Allocation concealment | AE monitoring* | Drug (n) | Fracture events | Discontinued, n (%) | Loss to follow-up, n (%) |
| Anzueto SCO100250, 2009w1 w16 | Adequate, centrally generated block | Adequate | AEs and SAEs recorded after study medication but no later than last date after study medication | SFC (394) | 3 | 125 (32) | 6 (1.5) |
| Sal (403) | 0 | 156 (39) | 12 (3) | ||||
| Burge FLTB3054, 2000w2 w17 | Adequate, computer generated | Adequate | AEs and SAEs recorded throughout the study | Flu (n=376) | 4 | 160 (43) | 16 (4.3) |
| Placebo (n=375) | 7 | 195 (53) | 18 (4.9) | ||||
| Calverley SFCB3024, 2003w3 w18 | Adequate, computer generated | Adequate | AEs or SAEs occurring during treatment | SFC (358) | 3 | 89 (25) | 8 (2.2) |
| Sal (372) | 0 | 119 (32) | 8 (2.2) | ||||
| Flu (374) | 2 | 108 (29) | 8 (2.1) | ||||
| Placebo (361) | 1 | 140 (39) | 6 (1.7) | ||||
| Calverley SCO30003, 2007w4 w19 | Adequate, central allocation | Adequate | AEs reviewed at each visit. Prospectively specified data capture for fracture events and site of fracture | SFC (1546) | 78 | 522 (34) | 29 (1.9) |
| Sal (1542) | 61 | 561 (37) | 15 (1.0) | ||||
| Flu (1552) | 65 | 587 (38) | 24 (1.6) | ||||
| Placebo (1544) | 57 | 673 (44) | 21 (1.4) | ||||
| Ferguson SCO40043, 2008w5 w20 | Unclear | Unclear | AEs collected at start and end | SFC (394) | 3 | 117 (30) | 10 (2.5) |
| Sal (388) | 3 | 149 (38) | 10 (2.6) | ||||
| FLTA 3025, 2005w6 | Unclear | Unclear | AEs and SAEs recorded at each visit | Flu (434) | 3 | 147 (34) | NA |
| Placebo (206) | 0 | 79 (38) | NA | ||||
| Hanania SFCA3007, 2003w7 w21 | Unclear | Unclear | AE reporting at each visit | SFC (178) | 1 | 53 (30) | NA |
| Sal (177) | 0 | 57 (32) | NA | ||||
| Flu (183) | 0 | 49 (27) | NA | ||||
| Placebo (185) | 1 | 59 (32) | NA | ||||
| Johnell, 20026 w22 | Unclear | Unclear | Spine x-rays on 653 patients at beginning and end of trial | Bud (322) | 5 | NA | 0 |
| Placebo (331) | 3 | NA | 0 | ||||
| Kardos SCO30006, 2007w8 w23 | Adequate, centrally generated | Adequate | AEs and SAEs recorded during run in and follow-up | SFC (507) | 1 | 99 (20) | 4 (0.8) |
| Sal (487) | 1 | 103 (21) | 3 (0.6) | ||||
| Mahler SFCA3006, 2002w9 w24 | Unclear | Unclear | AEs and SAEs documented | SFC (165) | 0 | 52 (32) | NA |
| Sal (160) | 0 | 45 (28) | NA | ||||
| Flu (168) | 1 | 68 (41) | NA | ||||
| Placebo (181) | 0 | 69 (38) | NA | ||||
| Paggiaro FLIT97, 1998w10 w25 | Adequate, computer generated | Adequate | AE defined as untoward medical occurrence during treatment | Flu (142) | 1 | 19 (13) | 0 |
| Placebo (139) | 0 | 27 (19) | 2 (1.4) | ||||
| SCO100470, 2006w11 | Unclear | Unclear | AEs and SAEs recorded at each study visit | SFC (518) | 1 | 59 (11) | NA |
| Sal (532) | 0 | 74 (14) | NA | ||||
| SCO40041, 2008w12 | Unclear | Unclear | On therapy AEs and SAEs monitored | SFC (92) | 1 | 36 (39) | NA |
| Sal (94) | 1 | 39 (42) | NA | ||||
| SFCT 01/SCO30002, 2005w13 | Unclear | Unclear | All AEs occurring after subject consent until end of follow-up | Flu (131) | 1 | 34 (26) | NA |
| Placebo (125) | 0 | 40 (32) | NA | ||||
| Tashkin, 2008w14 | Computer generated in each centre | Unclear | AEs checked at each clinic visit, and during the final follow-up telephone call | Bud/For(845) | 1 | 125 (15) | 13 (1.5) |
| Bud (275) | 1 | 63 (23) | 4 (1.5) | ||||
| For (284) | 1 | 61 (22) | 1 (0.4) | ||||
| Placebo (300) | 0 | 77 (26) | 7 (2.3) | ||||
| Wouters SCO40002, 2005w15 w26 | Adequate | Adequate | AE collected at start and end of treatment | SFC (189) | 5 | 34 (18) | 0 |
| Sal (184) | 5 | 46 (25) | 0 |
↵* All RCTs were double-blinded.
AE, adverse event; Bud, budesonide; COPD, chronic obstructive pulmonary disease; Flu, fluticasone propionate; For, formoterol; For/Bud, combination of formoterol and budesonide; NA, not available; RCT, randomised controlled trial; SAE, serious adverse event; Sal, salmeterol xinafoate; SFC, combination of salmeterol and fluticasone.