Comparison 50. HA/hylan versus placebo.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Pain on weight bearing (0‐100 mm VAS)	27		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.1 1 to 4 weeks post‐injection	27	2542	Mean Difference (IV, Random, 95% CI)	‐7.70 [‐11.29, ‐4.10]
1.2 5 to 13 weeks post‐injection	21	2090	Mean Difference (IV, Random, 95% CI)	‐11.00 [‐17.77, ‐8.23]
1.3 14 to 26 weeks post‐injection	10	1491	Mean Difference (IV, Random, 95% CI)	‐9.04 [‐14.83, ‐3.24]
1.4 45 to 52 weeks post‐injection	3	527	Mean Difference (IV, Random, 95% CI)	‐2.60 [‐7.40, 2.19]
2 Pain at rest (0‐100 mm VAS)	12		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.1 1 to 4 weeks post‐injection	12	577	Mean Difference (IV, Random, 95% CI)	‐5.37 [‐9.90, ‐0.85]
3 WOMAC pain	9		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
3.1 1 to 4 weeks post‐injection	7	412	Std. Mean Difference (IV, Random, 95% CI)	‐1.22 [‐1.93, ‐0.52]
3.2 5 to 13 weeks post‐injection	7	639	Std. Mean Difference (IV, Random, 95% CI)	‐1.02 [‐1.57, ‐0.47]
3.3 14 to 26 weeks post‐injection	4	275	Std. Mean Difference (IV, Random, 95% CI)	‐1.04 [‐1.75, ‐0.32]
4 WOMAC physical function	9		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
4.1 1 to 4 weeks post‐injection	7	412	Std. Mean Difference (IV, Random, 95% CI)	‐1.02 [‐1.62, ‐0.42]
4.2 5 to 13 weeks post‐injection	7	639	Std. Mean Difference (IV, Random, 95% CI)	‐0.85 [‐1.31, ‐0.39]
4.3 14 to 26 weeks post‐injection	4	275	Std. Mean Difference (IV, Random, 95% CI)	‐0.80 [‐1.37, ‐0.24]
5 Lequesne Index (0‐24)	11		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
5.1 1 to 4 weeks post‐injection	7	495	Mean Difference (IV, Fixed, 95% CI)	‐0.82 [‐1.48, ‐0.16]
5.2 5 to 13 weeks post‐injection	7	506	Mean Difference (IV, Fixed, 95% CI)	‐1.38 [‐2.04, ‐0.73]
5.3 14 to 26 weeks post‐injection	4	566	Mean Difference (IV, Fixed, 95% CI)	0.06 [‐0.75, 0.87]
5.4 45 to 52 weeks post‐injection	1	94	Mean Difference (IV, Fixed, 95% CI)	‐1.11 [‐2.70, 0.48]
6 Patient global assessment (number of patients improved)	14		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
6.1 1 to 4 weeks post‐injection (much better/better or excellent/good)	6	594	Risk Ratio (M‐H, Random, 95% CI)	1.10 [0.89, 1.36]
6.2 5 to 13 weeks post‐injection (excellent/very good/good/better/somewhat better)	6	579	Risk Ratio (M‐H, Random, 95% CI)	1.09 [0.87, 1.37]
6.3 14 to 26 weeks post‐injection (better/somewhat/much)	4	552	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.73, 1.47]
6.4 45 to 52 weeks post‐injection (number of patients rating treatment effective or very good or good)	2	290	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.82, 1.23]
7 Flexion (degrees)	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
7.1 1 to 4 weeks post‐injection	3	174	Mean Difference (IV, Fixed, 95% CI)	3.87 [2.06, 5.68]
7.2 5 to 13 weeks post‐injection	1	35	Mean Difference (IV, Fixed, 95% CI)	7.60 [0.46, 14.74]
8 Safety: total withdrawals overall	25		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
8.1 1 to 4 weeks post‐injection	5	525	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.61, 2.15]
8.2 5 to 13 weeks post‐injection	8	858	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [0.73, 1.67]
8.3 14 to 26 weeks post‐injection	9	1489	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.83, 1.20]
8.4 45 to 52 weeks post‐injection	3	389	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.63, 2.08]
9 Safety: number of patients with local adverse reaction and study drug discontinued	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
10 Safety: number of patients with local adverse reaction but study drug continued	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
11 Safety: number of patients discontinued due to adverse events	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
11.1 14 to 26 weeks post‐injection	3	687	Risk Ratio (M‐H, Fixed, 95% CI)	1.42 [0.69, 2.93]
11.2 45 to 52 weeks post‐injection	1	216	Risk Ratio (M‐H, Fixed, 95% CI)	1.30 [0.24, 6.93]
12 Safety: withdrawals due to lack of efficacy	6		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
12.1 1 to 4 weeks post‐injection	1	41	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
12.2 14 to 26 weeks post‐injection	4	1005	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.63, 1.40]
12.3 45 to 52 weeks post‐injection	1	216	Risk Ratio (M‐H, Fixed, 95% CI)	0.32 [0.03, 3.52]
13 Safety: number of adverse events for injection site pain	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
13.1 14 to 26 weeks post‐injection	2	381	Risk Ratio (M‐H, Fixed, 95% CI)	1.70 [1.19, 2.44]
14 Safety: number of adverse events local skin rash	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
14.1 14 to 26 weeks post‐injection	2	558	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.55, 1.43]
15 Safety: number of patients with gastrointestinal complaints	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
15.1 14 to 26 weeks post‐injection	2	558	Risk Ratio (M‐H, Fixed, 95% CI)	1.42 [0.99, 2.03]
16 Safety: number of patients with treatment related adverse events	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
16.1 14 to 26 weeks post‐injection	4	464	Risk Ratio (M‐H, Fixed, 95% CI)	1.48 [0.91, 2.41]
17 Safety: number of patients with possible study medication related events	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
17.1 45 to 52 weeks post‐injection	1	63	Risk Ratio (M‐H, Fixed, 95% CI)	7.68 [0.41, 142.77]
18 Safety: number of serious adverse events	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
18.1 45 to 52 weeks post‐injection	2	392	Risk Ratio (M‐H, Fixed, 95% CI)	0.60 [0.34, 1.07]
19 Safety: number of adverse events probably or possibly related to treatment	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
19.1 45 to 52 weeks post‐injection	2	392	Risk Ratio (M‐H, Fixed, 95% CI)	0.49 [0.11, 2.20]
20 Safety: number of patients reporting adverse events	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
20.1 45 to 52 weeks post‐injection	2	308	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.91, 1.39]