Comparison 2. LABA/LAMA versus placebo < 6 months.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐cause mortality	16	7708	Odds Ratio (M‐H, Fixed, 95% CI)	1.86 [0.75, 4.60]
1.1 IND/GLY 110/50	3	976	Odds Ratio (M‐H, Fixed, 95% CI)	2.97 [0.47, 18.97]
1.2 UMEC/VI 62.5/25	5	1921	Odds Ratio (M‐H, Fixed, 95% CI)	3.12 [0.68, 14.36]
1.3 UMEC/VI 125/25	4	1401	Odds Ratio (M‐H, Fixed, 95% CI)	0.14 [0.01, 2.83]
1.4 UMEC/VI 500/25	1	51	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.5 TIO/OLO 2.5/5	6	1670	Odds Ratio (M‐H, Fixed, 95% CI)	2.53 [0.12, 53.43]
1.6 TIO/OLO 5/5	6	1689	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 SAEs	19	8682	Odds Ratio (M‐H, Fixed, 95% CI)	1.02 [0.80, 1.29]
2.1 IND/GLY 110/50	3	976	Odds Ratio (M‐H, Fixed, 95% CI)	1.35 [0.54, 3.40]
2.2 UMEC/VI 62.5/25	6	2317	Odds Ratio (M‐H, Fixed, 95% CI)	1.29 [0.86, 1.93]
2.3 UMEC/VI 125/25	4	1403	Odds Ratio (M‐H, Fixed, 95% CI)	0.75 [0.46, 1.22]
2.4 UMEC/VI 500/25	1	51	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.5 TIO/OLO 2.5/5	6	1670	Odds Ratio (M‐H, Fixed, 95% CI)	0.90 [0.49, 1.68]
2.6 TIO/OLO 5/5	7	1840	Odds Ratio (M‐H, Fixed, 95% CI)	0.97 [0.55, 1.73]
2.7 ACM/FOR 200/6	1	141	Odds Ratio (M‐H, Fixed, 95% CI)	0.51 [0.02, 12.96]
2.8 ACM/FOR 200/12	1	140	Odds Ratio (M‐H, Fixed, 95% CI)	0.51 [0.02, 13.07]
2.9 ACM/FOR 200/18	1	144	Odds Ratio (M‐H, Fixed, 95% CI)	1.11 [0.06, 22.41]
3 AECOPD	3	1127	Odds Ratio (M‐H, Fixed, 95% CI)	0.53 [0.36, 0.78]
3.1 UMEC/VI 62.5/25	2	786	Odds Ratio (M‐H, Fixed, 95% CI)	0.58 [0.37, 0.93]
3.2 UMEC/VI 125/25	1	290	Odds Ratio (M‐H, Fixed, 95% CI)	0.37 [0.17, 0.78]
3.3 UMEC/VI 500/25	1	51	Odds Ratio (M‐H, Fixed, 95% CI)	1.68 [0.08, 35.43]
4 Time to first AECOPD	2		Hazard Ratio (Fixed, 95% CI)	0.44 [0.31, 0.63]
4.1 UMEC/VI 125/25	2		Hazard Ratio (Fixed, 95% CI)	0.44 [0.31, 0.63]
5 Difference vs placebo in adjusted SGRQ score (HRQoL)	6		Mean Difference (Fixed, 95% CI)	‐4.15 [‐4.99, ‐3.32]
5.1 UMEC/VI 62.5/25	3		Mean Difference (Fixed, 95% CI)	‐4.25 [‐5.73, ‐2.77]
5.2 UMEC/VI 125/25	2		Mean Difference (Fixed, 95% CI)	‐3.64 [‐5.48, ‐1.80]
5.3 TIO/OLO 2.5/5	2		Mean Difference (Fixed, 95% CI)	‐3.89 [‐5.60, ‐2.17]
5.4 TIO/OLO 5/5	2		Mean Difference (Fixed, 95% CI)	‐4.72 [‐6.43, ‐3.01]
6 SGRQ responder analysis	6	3552	Odds Ratio (M‐H, Fixed, 95% CI)	1.84 [1.59, 2.12]
6.1 TIO/OLO 2.5/5	2	579	Odds Ratio (M‐H, Fixed, 95% CI)	1.87 [1.30, 2.70]
6.2 TIO/OLO 5/5	2	578	Odds Ratio (M‐H, Fixed, 95% CI)	2.35 [1.63, 3.40]
6.3 UMEC/VI 62.5/25	3	1441	Odds Ratio (M‐H, Fixed, 95% CI)	1.70 [1.37, 2.12]
6.4 UMEC/VI 125/25	2	954	Odds Ratio (M‐H, Fixed, 95% CI)	1.78 [1.35, 2.34]