Table 2.
GRADE evidence profile question 2: what is the effect of naltrexone–bupropion (N‐B) on the frequency of adverse events in overweight and obese subjects?
| Quality assessment | No of patients | Effect | Quality | Comments | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No of studies | Design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | N‐B | Placebo | Relative (95% CI) | Absolute | ||
| Overall adverse events | ||||||||||||
| 4 | Randomised trials | seriousa | seriousb | No serious indirectness | No serious imprecision | None | 2631/3088 (85.2%) | 1080/1448 (74.6%) | RR 1.11 (1.05 to 1.18) | 82 more per 1000 (from 37 more to 134 more) | ⊕ ⊕ ΟΟ LOW | NNTH 12 (7 to 27) |
| Adverse events reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | Very seriousc | No serious indirectness | No serious imprecision | None | 1979/3088 (64.1%) | 522/1448 (36%) | RR 1.75 (1.48 to 2.06) | 270 more per 1000 (from 173 more to 382 more) | ⊕ΟΟΟ VERY LOW | NNTH 4 (3 to 6) |
| Nervous | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 1061/3088 (34.4%) | 269/1448 (18.6%) | RR 1.79 (1.57 to 2.05) | 147 more per 1000 (from 106 more to 195 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 7 (5 to 9) |
| Nervous events reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 777/3088 (25.2%) | 166/1448 (11.5%) | RR 2.15 (1.84 to 2.51) | 132 more per 1000 (from 96 more to 173 more) | ⊕ ⊕ ⊕ ⊕ HIGH | NNTH 8 (6 to 10) |
| Headache—nervous | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 529/3088 (17.1%) | 146/1448 (10.1%) | RR 1.63 (1.38 to 1.94) | 64 more per 1000 (from 38 more to 95 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 16 (11 to 26) |
| Headaches reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 373/3088 (12.1%) | 99/1448 (6.8%) | RR 1.71 (1.38 to 2.12) | 49 more per 1000 (from 26 more to 77 more) | ⊕ ⊕ ⊕ΟMODERATE | NNTH 21 (13 to 39) |
| Dizziness—nervous | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 290/3088 (9.4%) | 51/1448 (3.5%) | RR 2.53 (1.89 to 3.39) | 54 more per 1000 (from 31 more to 84 more) | ⊕ ⊕ ⊕ ⊕ HIGH | NNTH 19 (12 to 32) |
| Dizziness reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 236/3088 (7.6%) | 38/1448 (2.6%) | RR 2.76 (1.98 to 3.84) | 46 more per 1000 (from 26 more to 75 more) | ⊕ ⊕ ⊕ ⊕ HIGH | NNTH 22 (13 to 39) |
| Dysgeusia | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | seriouse | Strong associationd | 72/3088 (2.3%) | 8/1448 (0.6%) | RR 3.77 (1.85 to 7.68) | 15 more per 1000 (from 5 more to 37 more) | ⊕ ⊕ ⊕ΟMODERATE | NNTH 65 (27 to 213) |
| Dysgeusia reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | seriouse | Strong associationd | 55/3088 (1.8%) | 5/1448 (0.3%) | RR 3.65 (1.48 to 9.01) | 9 more per 1000 (from 2 more to 28 more) | ⊕ ⊕ ⊕Ο MODERATE |
NNTH 109 (36 to 603) |
| Lethargy | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 30/3088 (1%) | 4/1448 (0.3%) | RR 2.98 (1.1 to 8.06) | 5 more per 1000 (from 0 more to 20 more) | ⊕ ⊕ ⊕ ⊕ HIGH |
NNTH 183 (51 to 3620) |
| Lethargy reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 23/3088 (0.7%) | 3/1448 (0.2%) | RR 2.70 (0.93 to 7.86) | 4 more per 1000 (from 0 fewer to 14 more) | ⊕ ⊕ ⊕ ⊕ HIGH |
NNTH 284 (70 to 6895) |
| Parasthesia/hypoaesthesia—nervous | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 40/3088 (1.3%) | 20/1448 (1.4%) | RR 0.93 (0.54 to 1.59) | 1 fewer per 1000 (from 6 fewer to 8 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 1034 (−123 to 157) |
| Parasthesia/hypoesthesia reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 19/3088 (0.6%) | 5/1448 (0.3%) | RR 1.49 (0.55 to 4.02) | 2 more per 1000 (from 2 fewer to 10 more) | ⊕ ⊕ ⊕Ο MODERATE |
NNTH 591 (−96 to 644) |
| Tremors—nervous | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | seriouse | Strong associationd | 125/3088 (4%) | 10/1448 (0.7%) | RR 4.92 (2.57 to 9.39) | 27 more per 1000 (from 11 more to 58 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 37 (17 to 92) |
| Tremors reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | Very seriousf | Very strong associationg | 87/3088 (2.8%) | 5/1448 (0.3%) | RR 6.67 (2.82 to 15.76) | 20 more per 1000 (from 6 more to 51 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 51 (20 to 159) |
| Psychiatric | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 586/3088 (19%) | 202/1448 (14%) | RR 1.32 (1.11 to 1.57) | 45 more per 1000 (from 15 more to 80 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 22 (13 to 65) |
| Psychiatric events reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 481/2779 (17.3%) | 129/1448 (8.9%) | RR 1.95 (1.49 to 2.56) | 85 more per 1000 (from 44 more to 139 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 12 (7 to 23) |
| Insomnia—psychiatric | ||||||||||||
| 4 | Randomised trials | seriousa | seriousb | No serious indirectness | No serious imprecision | None | 383/3088 (12.4%) | 96/1448 (6.6%) | RR 1.80 (1.23 to 2.64) | 53 more per 1000 (from 15 more to 109 more) | ⊕ ⊕ ΟΟLOW | NNTH 19 (9 to 66) |
| Insomnia reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 281/3088 (9.1%) | 74/1448 (5.1%) | RR 1.78 (1.28 to 2.47) | 40 more per 1000 (from 14 more to 75 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 25 (13 to 70) |
| Depression—psychiatric | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | seriouse | None | 57/3088 (1.8%) | 41/1448 (2.8%) | RR 0.62 (0.4 to 0.96) | 11 fewer per 1000 (from 1 fewer to 17 fewer) | ⊕ ⊕ ΟΟ LOW | NNTB 93 (59 to 883) |
| Depression reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 29/3088 (0.9%) | 20/1448 (1.4%) | RR 0.68 (0.38 to 1.2) | 4 fewer per 1000 (from 9 fewer to 3 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTB 93 (−362 to 117) |
| Cardiac | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 121/3088 (3.9%) | 36/1448 (2.5%) | RR 1.52 (0.88 to 2.62) | 13 more per 1000 (from 3 fewer to 40 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 77 (−25 to 335) |
| Cardiac defined as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 74/3088 (2.4%) | 15/1448 (1%) | RR 2.02 (1.12 to 3.63) | 11 more per 1000 (from 1 more to 27 more) | ⊕ ⊕ ⊕ ⊕ HIGH | NNTH 95 (37 to 804) |
| Palpitation—cardiac | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 82/3088 (2.7%) | 15/1448 (1%) | RR 2.17 (1.2 to 3.94) | 12 more per 1000 (from 2 more to 30 more) | ⊕ ⊕ ⊕ ⊕ HIGH | NNTH 83 (33 to 483) |
| Palpitation reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 37/3088 (1.2%) | 6/1448 (0.4%) | RR 2.41 (1.03 to 5.63) | 6 more per 1000 (from 0 more to 19 more) | ⊕ ⊕ ⊕ ⊕ HIGH |
NNTH 171 (52 to 8044) |
| Vascular | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 277/3088 (9%) | 74/1448 (5.1%) | RR 1.77 (1.38 to 2.27) | 39 more per 1000 (from 19 more to 65 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 25 (15 to 52) |
| Vascular events reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 123/3088 (4%) | 20/1448 (1.4%) | RR 2.82 (1.77 to 4.51) | 25 more per 1000 (from 11 more to 48 more) | ⊕ ⊕ ⊕ ⊕ HIGH | NNTH 40 (21 to 94) |
| Hypertension | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 72/3088 (2.3%) | 19/1448 (1.3%) | RR 1.64 (1 to 2.7) | 8 more per 1000 (from 0 more to 22 more) | ⊕ ⊕ ⊕Ο MODERATE |
NNTH 120 (45 to 76211) |
| Hypertension reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 45/3088 (1.5%) | 12/1448 (0.8%) | RR 1.63 (0.86 to 3.09) | 5 more per 1000 (from 1 fewer to 17 more) | ⊕ ⊕ ⊕ΟMODERATE |
NNTH 192 (−58 to 862) |
| Hot flushes | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | seriouse | Strong associationd | 84/3088 (2.7%) | 10/1448 (0.7%) | RR 3.28 (1.01 to 10.61) | 16 more per 1000 (from 0 more to 66 more) | ⊕ ⊕ ⊕ΟMODERATE | NNTH 64 (15 to 14480) |
| Hot flushes reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | Very seriousf | Very strong associationg | 73/3088 (2.4%) | 3/1448 (0.2%) | RR 6.70 (1.93 to 23.26) | 12 more per 1000 (from 2 more to 46 more) | ⊕ ⊕ ⊕ΟMODERATE | NNTH 85 (22 to 519) |
| Musculoskeletal | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 384/3088 (12.4%) | 211/1448 (14.6%) | RR 0.83 (0.71 to 0.96) | 25 fewer per 1000 (from 6 fewer to 42 fewer) | ⊕ ⊕ ⊕Ο MODERATE | NNTB 40 (24 to 172) |
| Musculoskeletal events reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 42/3088 (1.4%) | 12/1448 (0.8%) | RR 1.38 (0.72 to 2.66) | 3 more per 1000 (from 2 fewer to 14 more) | ⊕ ⊕ ⊕ΟMODERATE |
NNTH 318 (−73 to 431) |
| Gastrointestinal | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 1699/3088 (55%) | 398/1448 (27.5%) | RR 1.95 (1.76 to 2.17) | 261 more per 1000 (from 209 more to 322 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 4 (3 to 5) |
| Gastrointestinal events reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | seriousb | No serious indirectness | No serious imprecision | Strong associationd | 1405/3088 (45.5%) | 245/1448 (16.9%) | RR 2.59 (2.05 to 3.26) | 269 more per 1000 (from 178 more to 382 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 4 (3 to 6) |
| Abdominal pain | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 226/3088 (7.3%) | 55/1448 (3.8%) | RR 1.91 (1.26 to 2.91) | 35 more per 1000 (from 10 more to 73 more) | ⊕ ⊕ ⊕Ο MODERATE |
NNTH 72 (35 to 253) |
| Abdominal pain reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 62/3088 (2%) | 10/1448 (0.7%) | RR 2.63 (1.36 to 5.06) | 11 more per 1000 (from 2 more to 28 more) | ⊕ ⊕ ⊕ ⊕ HIGH |
NNTH 89 (36 to 402) |
| Dry mouth—gastrointestinal | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 249/3088 (8.1%) | 36/1448 (2.5%) | RR 3.20 (2.27 to 4.52) | 55 more per 1000 (from 32 more to 88 more) | ⊕ ⊕ ⊕ ⊕ HIGH |
NNTH 18 (11 to 32) |
| Dry mouth reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 243/3088 (7.9%) | 35/1448 (2.4%) | RR 3.20 (2.26 to 4.54) | 53 more per 1000 (from 30 more to 86 more) | ⊕ ⊕ ⊕ ⊕ HIGH |
NNTH 19 (12 to 33) |
| Constipation | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 569/3088 (18.4%) | 107/1448 (7.4%) | RR 2.38 (1.88 to 3.02) | 102 more per 1000 (from 65 more to 149 more) | ⊕ ⊕ ⊕ ⊕ HIGH |
NNTH 10 (7 to 15) |
| Constipation reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 453/3088 (14.7%) | 78/1448 (5.4%) | RR 2.58 (1.95 to 3.41) | 85 more per 1000 (from 51 more to 130 more) | ⊕ ⊕ ⊕ ⊕ HIGH | NNTH 12 (8 to 20) |
| Nausea | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 956/3088 (31%) | 97/1448 (6.7%) | RR 4.50 (3.51 to 5.78) | 234 more per 1000 (from 168 more to 320 more) | ⊕ ⊕ ⊕ ⊕ HIGH | NNTH 4 (3 to 6) |
| Nausea reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Very strong associationg | 838/3088 (27.1%) | 74/1448 (5.1%) | RR 5.14 (3.84 to 6.86) | 212 more per 1000 (from 145 more to 299 more) | ⊕ ⊕ ⊕ ⊕ HIGH | NNTH 5 (3 to 7) |
| Vomiting | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 301/3088 (9.7%) | 43/1448 (3%) | RR 3.17 (1.96 to 5.11) | 64 more per 1000 (from 29 more to 122 more) | ⊕ ⊕ ⊕ ⊕ HIGH | NNTH 16 (8 to 35) |
| Vomiting reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | Very seriousf | Very strong associationg | 199/3088 (6.4%) | 10/1448 (0.7%) | RR 7.69 (3.2 to 18.49) | 46 more per 1000 (from 15 more to 121 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 22 (8 to 66) |
| Ear and labyrinth | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 145/3088 (4.7%) | 15/1448 (1%) | RR 4.20 (2.47 to 7.13) | 33 more per 1000 (from 15 more to 64 more) | ⊕ ⊕ ⊕ ⊕ HIGH | NNTH 30 (16 to 66) |
| Ear and labyrinth reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | Very seriousf | Very strong associationg | 109/3088 (3.5%) | 6/1448 (0.4%) | RR 6.12 (2.75 to 13.62) | 21 more per 1000 (from 7 more to 52 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 47 (19 to 138) |
| Tinnitus | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | Very seriousf | Very strong associationg | 88/3088 (2.8%) | 6/1448 (0.4%) | RR 5.48 (2.37 to 12.68) | 19 more per 1000 (from 6 more to 48 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 54 (21 to 176) |
| Tinnitus reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | Very seriousf | Strong associationd | 83/3088 (2.7%) | 5/1448 (0.3%) | RR 4.86 (1.96 to 12.04) | 13 more per 1000 (from 3 more to 38 more) | ⊕ ⊕ ΟΟ LOW | NNTH 75 (25 to 302) |
| Vertigo | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | Strong associationd | 27/3088 (0.9%) | 3/1448 (0.2%) | RR 3.05 (1.07 to 8.73) | 4 more per 1000 (from 0 more to 16 more) | ⊕ ⊕ ⊕ ⊕ HIGH | NNTH 235 (62 to 6895) |
| Vertigo reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | Very seriousf | None | 22/3088 (0.7%) | 1/1448 (0.1%) | RR 3.45 (0.91 to 13.14) | 2 more per 1000 (from 0 fewer to 8 more) | ⊕ΟΟΟ VERY LOW | NNTH 591 (−119 to 16089) |
| General disorders | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 378/3088 (12.2%) | 139/1448 (9.6%) | RR 1.21 (0.96 to 1.53) | 20 more per 1000 (from 4 fewer to 51 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 50 (−20 to 260) |
| General disorders reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 243/3088 (7.9%) | 67/1448 (4.6%) | RR 1.64 (1.26 to 2.13) | 30 more per 1000 (from 12 more to 52 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 34 (19 to 83) |
| Fatigue | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 126/3088 (4.1%) | 39/1448 (2.7%) | RR 1.51 (0.89 to 2.54) | 14 more per 1000 (from 3 fewer to 41 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 73 (−24 to 338) |
| Fatigue reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 94/3088 (3%) | 22/1448 (1.5%) | RR 1.89 (1.19 to 3) | 14 more per 1000 (from 3 more to 30 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 74 (33 to 346) |
| Jitteryness | ||||||||||||
| 4 | Randomised trials | seriousg | No serious inconsistency | No serious indirectness | seriouse | Strong associationd | 39/3088 (1.3%) | 4/1448 (0.3%) | RR 2.87 (1.11 to 7.42) | 5 more per 1000 (from 0 more to 18 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 194 (56 to 3291) |
| Jitteryness reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | seriouse | Strong associationd | 37/3088 (1.2%) | 4/1448 (0.3%) | RR 2.67 (1.02 to 6.98) | 5 more per 1000 (from 0 more to 17 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 217 (61 to 18100) |
| Skin and subcut | ||||||||||||
| 4 | Randomised trials | seriousa | seriousb | No serious indirectness | No serious imprecision | None | 307/3088 (9.9%) | 109/1448 (7.5%) | RR 1.39 (0.88 to 2.19) | 29 more per 1000 (from 9 fewer to 90 more) | ⊕ ⊕ ΟΟ LOW | NNTH 34 (−11 to 111) |
| Skin and subcut reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 194/3088 (6.3%) | 47/1448 (3.2%) | RR 1.78 (1.21 to 2.63) | 25 more per 1000 (from 7 more to 53 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 40 (19 to 147) |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 311/3088 (10.1%) | 191/1448 (13.2%) | RR 0.75 (0.63 to 0.88) | 33 fewer per 1000 (from 16 fewer to 49 fewer) | ⊕ ⊕ ⊕Ο MODERATE | NNTB 30 (21 to 63) |
| Respiratory, thoracic and mediastinal disorders reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 24/3088 (0.8%) | 8/1448 (0.6%) | RR 1.33 (0.59 to 2.99) | 2 more per 1000 (from 2 fewer to 11 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 549 (−91 to 442) |
| Metabolism and nutrition disorders | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 126/3088 (4.1%) | 80/1448 (5.5%) | RR 0.75 (0.58 to 0.98) | 14 fewer per 1000 (from 1 fewer to 23 fewer) | ⊕ ⊕ ⊕Ο MODERATE | NNTB 72 (43 to 905) |
| Metabolism and nutrition disorders reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 50/3088 (1.6%) | 18/1448 (1.2%) | RR 1.21 (0.7 to 2.09) | 3 more per 1000 (from 4 fewer to 14 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 383 (−74 to 268) |
| Reproductive and breast disorders | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 163/3088 (5.3%) | 41/1448 (2.8%) | RR 1.69 (1.05 to 2.72) | 20 more per 1000 (from 1 more to 49 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 51 (21 to 706) |
| Reproductive and breast disorders reported as related or possibly related to intervention | ||||||||||||
| 4 | Randomised trials | seriousa | No serious inconsistency | No serious indirectness | No serious imprecision | None | 19/3088 (0.6%) | 4/1448 (0.3%) | RR 1.56 (0.56 to 4.35) | 2 more per 1000 (from 1 fewer to 9 more) | ⊕ ⊕ ⊕Ο MODERATE | NNTH 646 (−108 to 823) |
Settings: Academic and primary care centres; academic medical centres; private or institutional practices; research centres
a
High drop‐out rates; several investigators have financial ties to the study sponsor;
b
moderate to severe heterogeneity;
c
substantial heterogeneity;
d
RR > 2;
e
wide confidence interval;
f
very wide confidence interval;
g
RR > 5.
CI: confidence interval; NNTB: number needed to treat to benefit; NNTH: number needed to treat to harm; RR: risk ratio.