Table 1. Percentage of male patients enrolled in clinical studies estimated using random effects meta-analysis.
| Indian sub-continent | Eastern Africa | |||||||
|---|---|---|---|---|---|---|---|---|
| Age range | k | n | Males enrolled [95% CI] | I2 | k | n | Males enrolled [95% CI] | I2 |
| Less than 15 years | 6 | 418 | 61.2% [56.5–65.8] | 0.0% | 2 | 59 | 71.2% [58.4–81.3] | 0.0% |
| Adults | 6 | 295 | 70.4% [62.7–77.1] | 17.9% | 2 | 81 | 97.5% [90.7–99.4] | 0.0% |
| All ages | 73 | 22563 | 67.7% [65.2–69.9] | 92.3% | 20 | 6576 | 71.5% [66.3–76.2] | 92.7% |
| Not clear | 6 | 942 | 68.7% [60.8–75.6] | 78.2% | - | - | - | - |
| Time period | ||||||||
| Before 1990 | 4 | 1257 | 80.1% [74.0–85.1] | 70.2% | 3 | 99 | 69.7% [60.0–77.9] | 0.0% |
| 1990 through 1999 | 35 | 5472 | 72.8% [70.2–75.2] | 68.7% | 7 | 501 | 68.1% [54.5–79.1] | 85.1% |
| 2000 through 2009 | 28 | 7188 | 65.7% [61.5–69.7] | 91.7% | 6 | 1349 | 72.7% [62.1–81.3] | 92.6% |
| On or after 2010 | 24 | 10301 | 61.3% [59.8–62.7] | 45.1% | 8 | 4767 | 79.9% [71.6–86.2] | 95.7% |
| Inclusion of pregnant and lactating mothers | ||||||||
| Included | 6 | 3600 | 68.9% [60.6–76.2] | 94.6% | 5 | 3502 | 63.9% [56.5–70.7] | 76.3% |
| Excluded | 41 | 10570 | 65.1% [63.1–67.0] | 70.7% | 10 | 1804 | 79.1% [72.5–84.4] | 83.1% |
| Unclear | 44 | 10048 | 69.5% [65.8–72.9] | 92.2% | 9 | 1410 | 73.2% [62.2–81.9] | 92.7% |
| Inclusion of women of child bearing age | ||||||||
| Excluded | - | - | - | 1 | 151 | 81.5% [74.5–86.9] | - | |
| Included | 5 | 1839 | 70.8% [61.5–78.6] | 91.8% | 5 | 3502 | 63.9% [56.5–70.7] | 76.3% |
| Conditional inclusion upon agreeing to contraception usage | 13 | 6365 | 63.1% [60.8–65.3] | 59.6% | 1 | 58 | 98.3% [88.7–99.8] | - |
| Unclear | 73 | 16014 | 68.2% [65.6–70.6] | 89.7% | 17 | 3005 | 73.9% [68.1–79.0] | 88.9% |
| Inclusion of HIV co-infected patients | ||||||||
| Included | 1 | 120 | 61.7% [52.7–69.9] | 7 | 4706 | 83.4% [68.2–92.2] | 98.8% | |
| Excluded | 50 | 16172 | 63.5% [60.8–66.0] | 90.0% | 5 | 444 | 79.5% [75.5–83.0] | 0.0% |
| Not clear | 40 | 7926 | 72.9% [70.2–75.4] | 81.0% | 12 | 1566 | 65.4% [59.8–70.7] | 72.7% |
| FDA risk category (pregnant and lactating women) of the drugs studied | ||||||||
| Category B drugs a | 38 | 8342 | 68.5% [65.7–71.3] | 82.7% | 3 | 237 | 67.5% [51.2–80.5] | 81.7% |
| Category C drugs a | 28 | 6594 | 69.8% [64.9–74.3] | 93.5% | 15 | 6094 | 71.7% [65.3–77.4] | 94.6% |
| Category D drugs a | 19 | 8503 | 62.4% [60.9–63.9] | 39.8% | 3 | 239 | 88.4% [66.3–96.7] | 86.0% |
| Unclear/Unassigned a | 6 | 779 | 64.8% [58.3–70.8] | 38.1% | 3 | 146 | 76.0% [68.4–82.3] | 0.0% |
| Study design | ||||||||
| Randomised | 41 | 9314 | 69.4% [66.8–71.8] | 82.7% | 8 | 1750 | 78.9% [67.9–86.8] | 94.0% |
| Non-randomised | 43 | 13202 | 65.6% [63.1–68.0] | 84.2% | 14 | 4848 | 71.0% [63.6–77.5] | 93.2% |
| Unclear | 7 | 1702 | 65.7% [49.7–78.7] | 96.7% | 2 | 118 | 74.6% [66.0–81.6] | 0.0% |
|
Overall (adjusted for small study-effects)b |
91 | 24218 | 67.6% [65.5–69.7] (62.5% [59.9–65.0]) |
90.5% | 24 | 6716 | 74.1% [68.4–79.1] (67.1% [60.7–72.9]) |
94.4% |
k = number of studies combined; n = total number of patients; CI = confidence interval
a Category B drugs include amphotericin B deoxycholate and liposomal amphotericin B; Category C drugs include pentavalent antimony and pentamidine; Category D drugs include miltefosine. The categories were extracted from published literature (reviewed in [38, 39]). In multi-armed trials, the study is assigned the worst of the known categories.
b Small study effects were evaluated using linear regression test for funnel plot asymmetry (P = 0.128 for Eastern Africa, P = 0.008 for Indian sub-continent, P = 0.0285 for overall dataset). Bias-adjusted estimate was derived using trim-and-fill method with an estimate of 63.5% [95% CI: 61.1%–65.7%] obtained for overall dataset (135 studies).