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When stratified by comparator groups, the pooled estimate was most favorable in monotherapy trials versus placebo (SMD 2.41, 95% CI 4.43 to 0.39), whereas the add-on designs versus the same background treatment (SMD 0.65, 95% CI 1.85 to 0.55), head-to-head comparisons versus another drug (SMD 0.19, 95% CI 0.84 to 0.45), and add-on designs versus placebo (SMD 0.65, 95% CI 1.35 to 0.06) showed more modest estimates and did not provide clear evidence of a between-group difference overall (p=0.21)