Table 3 Comparison of methods for handling missing data for ITT analysis of the FREE trial

SF-36 PCS

1 month follow-up

8.00

1.3724

[5.31,10.69]

0.0000

5.24

1.0320

[3.22,7.27]

0.0000

5.32

1.1139

[3.14,7.51]

0.0000

5.09

1.1509

[2.83,7.34]

0.0000

3 months follow-up

5.60

1.3724

[2.91,8.29]

0.0000

4.52

1.0320

[2.50,6.54]

0.0000

4.13

1.1453

[1.89,6.38]

0.0003

4.06

1.1778

[1.75,6.37]

0.0006

6 months follow-up

4.16

1.3724

[1.47,6.85]

0.0025

4.06

1.0320

[2.04,6.08]

0.0001

3.39

1.1482

[1.13,5.64]

0.0032

3.39

1.1853

[1.06,5.71]

0.0043

12 months follow-up

2.07

1.3724

[-0.62,4.76]

0.1315

2.92

1.0320

[0.90,4.95]

0.0046

1.70

1.1647

[-0.59,3.98]

0.1451

2.42

1.2333

[0.00,4.84]

0.0499

24 months follow-up

2.49

1.3724

[-0.20,5.18]

0.0694

2.81

1.0320

[0.78,4.83]

0.0065

1.68

1.1757

[-0.63,3.98]

0.1538

2.40

1.2855

[-0.12,4.92]

0.0617

Overall treatment effect

4.47

1.1027

[2.30,6.63]

0.0001

3.91

0.8497

[2.24,5.58]

0.0000

3.24

0.8979

[1.48,5.00]

0.0003

3.47

0.9264

[1.66,5.29]

0.0002

EQ5D

1 month follow-up

0.20

0.0429

[0.12,0.28]

0.0000

0.18

0.0378

[0.10,0.25]

0.0000

0.17

0.0377

[0.10,0.24]

0.0000

0.16

0.0397

[0.09,0.24]

0.0000

3 months follow-up

0.10

0.0429

[0.02,0.18]

0.0195

0.15

0.0378

[0.07,0.22]

0.0001

0.11

0.0387

[0.03,0.18]

0.0054

0.10

0.0394

[0.03,0.18]

0.0090

6 months follow-up

0.11

0.0429

[0.02,0.19]

0.0130

0.17

0.0378

[0.09,0.24]

0.0000

0.12

0.0389

[0.04,0.20]

0.0019

0.11

0.0405

[0.03,0.19]

0.0065

12 months follow-up

0.11

0.0429

[0.02,0.19]

0.0125

0.15

0.0378

[0.08,0.23]

0.0000

0.10

0.0394

[0.02,0.18]

0.0097

0.10

0.0406

[0.02,0.18]

0.0131

24 months follow-up

0.09

0.0429

[0.00,0.17]

0.0451

0.13

0.0378

[0.05,0.20]

0.0007

0.08

0.0395

[0.00,0.16]

0.0497

0.07

0.0411

[-0.01,0.15]

0.0909

Overall treatment effect

0.12

0.0339

[0.05,0.19]

0.0004

0.15

0.0319

[0.09,0.22]

0.0000

0.12

0.0302

[0.06,0.18]

0.0001

0.11

0.0302

[0.05,0.17]

0.0003

RMD score

1 month follow-up

-4.45

0.8743

[-6.16, -2.74]

0.0000

-3.52

0.6573

[-4.81,-2.23]

0.0000

-4.22

0.6793

[-5.55,-2.89]

0.0000

-3.86

0.6845

[-5.20, -2.52]

0.0000

3 months follow-up

-2.86

0.8743

[-4.58,-1.15]

0.0011

-3.48

0.6573

[-4.77,-2.19]

0.0000

-3.64

0.7034

[-5.01,-2.26]

0.0000

-3.30

0.7319

[-4.74, -1.87]

0.0000

6 months follow-up

-2.04

0.8743

[-3.75,-0.32]

0.0198

-3.07

0.6573

[-4.36,-1.78]

0.0000

-2.96

0.7072

[-4.35,-1.58]

0.0000

-2.76

0.7258

[-4.19, -1.34]

0.0001

12 months follow-up

-1.95

0.8743

[-3.66,-0.24]

0.0258

-2.99

0.6573

[-4.28,-1.70]

0.0000

-2.81

0.7207

[-4.22,-1.40]

0.0001

-2.50

0.7409

[-3.95, -1.05]

0.0007

24 months follow-up

-0.60

0.8743

[-2.31,1.12]

0.4945

-2.34

0.6573

[-3.62,-1.05]

0.0004

-1.43

0.7327

[-2.87,0.00]

0.0506

-1.65

0.7431

[-3.10, -0.19]

0.0267

Overall treatment effect

-2.38

0.7355

[-3.82,-0.94]

0.0012

-3.08

0.5667

[-4.19,-1.97]

0.0000

-3.01

0.5716

[-4.13,-1.89]

0.0000

-2.81

0.5737

[-3.94, -1.69]

0.0000

VAS score

1 month follow-up

-1.92

0.3329

[-2.57,-1.27]

0.0000

-1.87

0.2807

[-2.42,-1.32]

0.0000

-1.89

0.2872

[-2.46,-1.33]

0.0000

-1.76

0.3064

[-2.36,-1.16]

0.0000

3 months follow-up

-1.51

0.3329

[-2.16,-0.86]

0.0000

-1.71

0.2807

[-2.26,-1.16]

0.0000

-1.53

0.2958

[-2.11,-0.95]

0.0000

-1.35

0.3120

[-1.96,-0.74]

0.0000

6 months follow-up

-1.53

0.3329

[-2.18,-0.88]

0.0000

-1.76

0.2807

[-2.31,-1.21]

0.0000

-1.56

0.2980

[-2.15,-0.98]

0.0000

-1.43

0.3181

[-2.05,-0.80]

0.0000

12 months follow-up

-0.77

0.3329

[-1.42,-0.11]

0.0214

-1.31

0.2807

[-1.86,-0.76]

0.0000

-0.93

0.3055

[-1.53,-0.33]

0.0023

-0.85

0.3153

[-1.47,-0.23]

0.0071

24 months follow-up

-0.77

0.3329

[-1.42,-0.12]

0.0203

-1.14

0.2807

[-1.69,-0.59]

0.0000

-0.80

0.3043

[-1.39,-0.20]

0.0089

-0.61

0.3408

[-1.28,0.06]

0.0725

Overall treatment effect

-1.42

0.2316

[-1.87,-0.96]

0.0000

-1.65

0.2123

[-2.07,-1.23]

0.0000

-1.49

0.2000

[-1.88,-1.10]

0.0000

-1.20

0.2248

[-1.64,-0.76]

0.0000

Resticted activity

1 month follow-up

-4.44

0.9193

[-6.24,-2.63]

0.0000

-2.95

0.6979

[-4.31,-1.58]

0.0000

-3.46

0.7466

[-4.93,-2.00]

0.0000

-3.13

0.7356

[-4.57,-1.69]

0.0000

3 months follow-up

-3.79

0.9193

[-5.59,-1.98]

0.0000

-3.82

0.6979

[-5.19,-2.45]

0.0000

-3.94

0.7649

[-5.44,-2.44]

0.0000

-3.59

0.7542

[-5.07,-2.11]

0.0000

6 months follow-up

-3.00

0.9193

[-4.80,-1.19]

0.0011

-2.96

0.6979

[-4.32,-1.59]

0.0000

-2.43

0.7647

[-3.93,-0.93]

0.0015

-2.64

0.7804

[-4.17,-1.11]

0.0007

12 months follow-up

-1.48

0.9193

[-3.28,0.32]

0.1067

-2.64

0.6979

[-4.00,-1.27]

0.0002

-2.04

0.7788

[-3.56,-0.51]

0.0089

-1.86

0.7766

[-3.38,-0.34]

0.0167

24 months follow-up

-1.56

0.9193

[-3.36,0.24]

0.0896

-2.17

0.6979

[-3.54,-0.80]

0.0019

-1.24

0.7905

[-2.79,0.31]

0.1156

-1.62

0.7800

[-3.15,-0.09]

0.0378

Overall treatment effect

-2.85

0.6589

[-4.14,-1.56]

0.0000

-2.90

0.5328

[-3.95,-1.86]

0.0000

-2.62

0.5357

[-3.67,-1.57]

0.0000

-2.57

0.5189

[-3.59,-1.55]

0.0000

Days in bed

1 month follow-up

-2.71

0.4710

[-3.63,-1.78]

0.0000

-2.53

0.4897

[-3.49,-1.57]

0.0000

-2.55

0.4418

[-3.42,-1.69]

0.0000

-2.45

0.5682

[-3.56,-1.34]

0.0000

3 months follow-up

-0.86

0.4710

[-1.78,0.07]

0.0693

-1.39

0.4897

[-2.35,-0.43]

0.0044

-0.96

0.4557

[-1.86,-0.07]

0.0342

-1.48

0.5809

[-2.62,-0.34]

0.0109

6 months follow-up

-0.31

0.4710

[-1.23,0.62]

0.5155

-0.87

0.4897

[-1.83,0.09]

0.0757

-0.30

0.4565

[-1.19,0.60]

0.5143

-0.83

0.5929

[-1.99,0.33]

0.1606

12 months follow-up

-0.08

0.4710

[-1.00,0.85]

0.8701

-0.67

0.4897

[-1.63,0.29]

0.1741

0.17

0.4672

[-0.74,1.09]

0.7113

-0.35

0.6261

[-1.57,0.88]

0.5800

24 months follow-up

-0.64

0.4710

[-1.57,0.28]

0.1718

-0.83

0.4897

[-1.79,0.13]

0.0899

-0.70

0.4739

[-1.63,0.23]

0.1393

-1.21

0.6211

[-2.42,0.01]

0.0521

Overall treatment effect

-0.92

0.3002

[-1.51,-0.33]

0.0022

-1.26

0.3894

[-2.02,-0.49]

0.0012

-0.87

0.2908

[-1.44,-0.30]

0.0028

-1.26

0.3629

[-1.97,-0.55]

0.0005