Table 2 Results from random-effect meta-analysis and meta-regression analysis

Overall (REML)

186

16,655

0.54 (0.46 to 0.64)

1.027

93.6

Overall (REML, sensitivity analysis)

168

15,765

0.72 (0.67 to 0.79)

0.208

85.7

Overall (D-L random)

186

16,655

0.59 (0.54 to 0.65)

0.253

Overall (Fixed)

186

16,655

0.82 (0.80 to 0.83)

0.253

Allocation concealment

1.005

93.6

0.024

 Clearly concealed

28

4322

0.82 (0.55 to 1.21)

 Not clearly concealed

158

12,333

0.50 (0.41 to 0.59)

Blinding of patients and providers

1.034

93.6

0.451

 Clearly a double-blind design

59

6477

0.62 (0.46 to 0.84)

 Clearly not a double-blind design

97

8275

0.49 (0.39 to 0.62)

 Unclear

30

1903

0.55 (0.37 to 0.82)

Blinding of outcome assessor

0.967

93.5

0.002

 Clearly stated that outcome assessor was blinded

81

7614

0.72 (0.56 to 0.91)

 Not stated that outcome assessor was blinded

105

9041

0.43 (0.34 to 0.54)

Low risk of bias

1.016

93.6

0.084

 Clearly concealed allocation, dropout rate ≤15%, sample size > 49

16

3360

0.83 (0.50 to 1.40)

 Criteria not fulfilled

170

13,295

0.51 (0.43 to 0.61)

Information to participants

1.029

93.6

0.477

 Not informed that trial involved placebo

22

2150

0.64 (0.39 to 1.03)

 Informed that trial involved placebo or not stated

164

14,505

0.53 (0.44 to 0.63)

Time of outcome measurement

1.029

93.6

0.578

 < 4 weeks

83

6422

0.60 (0.47 to 0.76)

 4–8 weeks

44

2614

0.55 (0.38 to 0.78)

 > 8–12 weeks

27

2597

0.42 (0.27 to 0.65)

 > 12 weeks

32

5022

0.50 (0.34 to 0.75)

Type of intervention

1.005

93.4

0.026

 Pharmacological

56

6523

0.61 (0.45 to 0.82)

 Physical

68

6649

0.64 (0.50 to 0.83)

 Psychological

62

3483

0.38 (0.28 to 0.52)

Type of outcome

1.029

93.7

0.523

 Patient-reported outcomes that are observable

42

3605

0.59 (0.41 to 0.84)

 Patient-reported outcomes that are non-observable

88

7987

0.57 (0.45 to 0.72)

 Observer-reported outcomes dependent on patient cooperation

25

1143

0.53 (0.34 to 0.83)

Observer-reported outcomes that were not dependent on patient cooperation

22

1314

0.42 (0.24 to 0.74)

 Laboratory outcomes

9

2606

0.31 (0.14 to 0.68)

Settings

1.041

93.6

0.890

 Single center

97

5268

0.54 (0.42 to 0.68)

 Multicenter

33

7394

0.51 (0.35 to 0.73)

 Unclear

56

3993

0.57 (0.42 to 0.78)

Patient´s condition

0.996

93.4

0.028

 Chronic condition

119

9771

0.47 (0.38 to 0.58)

 Non-chronic condition

67

6884

0.68 (0.52 to 0.88)

Type of outcome

1.015

93.6

0.083

 Binary outcome

39

5654

0.71 (0.50 to 1.01)

 Continuous outcome

147

11,001

0.50 (0.42 to 0.60)

Sample size^a

1.028

93.6

0.199

 ≤ 70 participants

93

2893

0.48 (0.37 to 0.61)

 ≥ 71 participants

93

13,762

0.60 (0.48 to 0.74)

Publication year

1.02

93.5

0.116

 Published before 2000

120

8961

0.49 (0.39 to 0.60)

 Published in 2000 or later

66

7694

0.64 (0.49 to 0.83)

Meta-regression of continuous variables

Trials (k)

Patients (n)

Slope (95% CI)

τ²

I²

P

Publication year

186

16,655

1.00 (0.98 to 1.02)

1.035

93.58

0.989

Sample size

186

16,655

1.00 (1.00 to 1.00)

1.026

93.54

0.162

Mean age

175

15,538

0.99 (0.98 to 0.99)

1.048

93.86

0.004

Percentage of females

163

15,259

1.01 (1.00 to 1.01)

0.8824

92.54

0.044

Placebo effect (SMD)

186

16,655

1.55 (1.07 to 2.24)

1.005

93.51

0.027