Table 2 Placebo response of improvement and subgroup analyses.
|  | No. of trials | No. of participants (placebo arm) | Pooled placebo response rate (%) | 95% CI | I2 (%) | P value for I2 †| Q | P value‡ |
|---|---|---|---|---|---|---|---|---|
All trials | 9 | 309 | 28.2 | 16.6–39.9 | 88 | <0.01 | – | – |
Trial ___location | ||||||||
 North America | 4 | 94 | 30.8 | 8.1–53.4 | 93 | <0.01 | 2.48 | 0.48 |
 Europe | 3 | 87 | 26.7 | 3.5–49.9 | 89 | <0.01 | ||
 Asia | 1 | 69 | 21.7 | 12.7–33.3 | – | – | ||
 Mixed continent | 1 | 59 | 33.9 | 22.1–47.4 | – | – | ||
Study design | ||||||||
 Parallel | 8 | 250 | 27.7 | 14.6–40.7 | 88 | <0.01 | 0.47 | 0.49 |
 Crossover | 1 | 59 | 33.9 | 22.1–47.4 | – | – | ||
 Number of centers | ||||||||
 Single | 4 | 91 | 17.8 | 0–36.6 | 85 | <0.01 | 2.76 | 0.10 |
 Multi | 5 | 218 | 35.9 | 25.8–45.9 | 60 | 0.04 | ||
Diagnostic criteria | ||||||||
 RomeII | 6 | 189 | 31.6 | 16.6–46.5 | 91 | <0.01 | 5.45 | 0.07 |
 RomeIII | 2 | 99 | 14.1 | 0–28.8 | 80 | 0.03 | ||
 Other | 1 | 21 | 42.9 | 21.8–66.0 | – | – | ||
Mode of administration | ||||||||
 Capsule | 5 | 113 | 30.6 | 12.5–48.8 | 91 | <0.01 | 21.45 | <0.01 |
 Powder | 2 | 97 | 38.1 | 27.7–48.4 | 12 | 0.29 | ||
 Liquid | 1 | 30 | 6.7 | 0.8–22.1 | – | – | ||
 Chewable tablet | 1 | 69 | 21.7 | 12.7–33.3 | – | – | ||
Dosing schedule | ||||||||
 Three times a day | 1 | 21 | 42.9 | 21.8–66.0 | – | – | 17.76 | <0.01 |
 Twice a day | 4 | 113 | 41.3 | 32.3–50.4 | 0 | 0.75 | ||
 Once a day | 3 | 116 | 9.2 | 0–21.8 | 83 | <0.01 | ||
 Once/Twice a day | 1 | 59 | 33.9 | 22.1–47.4 | – | – | ||
Run-in period | ||||||||
 No | 3 | 76 | 28.3 | 4.2–52.4 | 88 | <0.01 | 2.08 | 0.35 |
 2 weeks | 4 | 176 | 24.3 | 5.3–43.2 | 92 | <0.01 | ||
 4 weeks | 2 | 57 | 39.9 | 27.3–52.6 | 0 | 0.33 | ||
Duration of therapy | ||||||||
 2–4 weeks | 3 | 70 | 25.2 | 3.0–47.5 | 84 | <.01 | 2.84 | 0.24 |
 5–8 weeks | 5 | 208 | 27 | 10.8–43.2 | 91 | <.01 | ||
 >8 weeks | 1 | 31 | 45.2 | 27.3–64.0 | - | - | ||
Proportion of participants assigned to placebo | ||||||||
 50% | 8 | 278 | 26.3 | 14–38.5 | 88 | <0.01 | 3.01 | 0.08 |
 25% | 1 | 31 | 45.2 | 27.3–64.0 | – | – | ||
Sex | ||||||||
 Female% ≤50% | 4 | 197 | 34.9 | 23.5–46.3 | 67 | 0.03 | 1.02 | 0.6 |
 Female% ≥50% | 2 | 55 | 22.2 | 0–54.8 | 89 | <0.01 | ||
 NR | 3 | 57 | 23.3 | 0–49.6 | 90 | <0.01 | ||
Clinical outcome assessor | ||||||||
 Physician | 1 | 21 | 42.9 | 21.8–66.0 | – | – | 8.08 | 0.04 |
 Patient | 4 | 91 | 17.8 | 0–36.6 | 85 | <0.01 | ||
 Parent | 2 | 69 | 44.9 | 33.2–56.7 | 0 | 0.97 | ||
 Patient or parent | 2 | 128 | 27.3 | 15.4–39.1 | 58 | 0.12 | ||
Allocation concealment | ||||||||
 Unclear | 5 | 146 | 21.5 | 4.8–38.1 | 89 | <0.01 | 1.98 | 0.16 |
 Low risk of bias | 4 | 163 | 36.5 | 23.8–49.1 | 69 | 0.02 | ||
