Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Allen, 2016

computer-generated, stratified based on providers’ volume of female patients (< 15% versus ≥15%).

Unlikely, study team members involved in screening and consent were blinded to randomization.

Likely

(But: potential patient participants were blinded to their PCP’s randomization until after baseline assessments.)

Likely

Likely for patient-reported outcomes; outcomes assessors were blind to randomization.

Unlikely

Unlikely

Unlikely, analyses involved all randomly assigned participants using all data collected

Broderick, 2014

permuted blocking procedure using 2 block sizes (6 and 8)

Unlikely

Likely

Likely

Likely for patient-reported outcomes; The research team maintained assessor blinding, but patients sometimes revealed their experimental condition.

Unlikely

Likely

Unlikely; analyses were conducted in accordance with the intention-to-treat principle.

Coleman, 2012

Simple randomisation: a sealed envelope was drawn from a box by an independent person to determine group allocation.

Unlikely

Likely; blinding of participants

was not possible, owing to the nature of the intervention.

Likely; blinding of care providers was not possible.

Likely for patient-reported outcomes; the physiotherapists performing the assessments did not participate in the facilitation of the OAK program and thus were blind to group allocation.

Unlikely

Unlikely

Unlikely; the main comparisons between groups were performed using an intention-to-treat analysis.

De Rezende 2016

Randomization was performed by a computer-generated program

Unclear

Likely; although there was no difference in the information presented

between groups.

Likely

Likely for patient-reported outcomes; evaluators did not know the group to which each patient belonged.

Unlikely

Unclear

Helminen 2015

computer-generated code for randomization, administered via sequentially numbered sealed opaque envelopes

Unlikely

Likely; blinding not possible.

Unlikely

Likely for patient-reported outcomes

Unlikely

Unlikely; all analyses adhered to the intent-to-treat principle.

Hurley 2012

A randomization list was generated and held at a central site away from the research center by personnel not involved in the trial.

Unlikely

Likely; blinding of participants not possible, owing to the nature of the intervention.

Likely; blinding of care providers was not possible.

Likely for patient-reported outcomes; the assessors were blinded to a participant’s allocation.

Unlikely

Likely, as indicated by missing values analysis.

Unlikely

Murphy 2016

Randomization scheme was block stratified by age group (cut off was 62 years) and male/female sex with blocks of 3; randomization scheme developed by study statistician and implemented in statistical software

Unclear

Likely, blinding of participants not possible

Likely

Likely for patient-reported outcomes; assessors were blinded.

Unlikely

Unlikely

Unlikley, analyses used an Intent to Treat approach

Rini 2015

computer-generated permuted block randomization (with random block sizes varying from 2 to 12) stratified by sex and site; sequentially-numbered opaque envelopes used to conceal allocation

Unlikely

Unlikely

Likely for patient-reported outcomes

Schlenk 2011

adaptive randomization procedure of minimization to ensure groups were balanced in age (50–64 years, 65–74 years, and ≥ 75 years), gender, race (White and non-White), and recruitment site.

Unlikely

Unclear

Unclear

Likely for patient-reported outcomes

Unclear

Likely/unclear

Unclear

Somers, 2012

random allocation computer software program to assign participants in blocks

Unlikely

Unclear

Unclear

Likely for patient-reported outcomes

Unlikely

Likely

Unlikely; all randomized participants were included in the data analysis following the intent-to-treat principle.

Kao 2012

Participants living in two of four districts were assigned to an intervention group by ballot; while participants lived in the other two districts were assigned to a control group.

Likely

Likely

Likely

Likely for patient-reported outcomes; investigators remained blind to treatment groups

Unclear

Unclear

Unlikely

Farr 2010

Eligible participants were stratified by sex and randomly assigned via a random number table to 1 of the 3 treatment groups.

Unlikely; concealed allocation was accomplished using envelopes to conceal computer-generated

values.

Likely; manifest transparency of the treatments rendered blinding unfeasible

Likely

Likely for patient-reported outcomes

Unlikely

Unclear

Unclear

Rosemann 2007

Of 115 practices, 75 were randomly selected, stratified into rural or urban, and randomly assigned to either the control group or 1 of the 2 intervention groups

Unclear

Unclear

Likely

Likely for patient-reported outcomes

Unclear

Likely

Unlikely; all analyses were performed based on intent-to-treat, regardless of whether patients really received the intended treatment.

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Self-management programmes versus attention control

None found after Kroon (2014)

Self-management programmes versus usual care / no treatment

Allen, 2016

Type of study: cluster RCT

Setting: Ambulatory care service

Country: U.S.A.

Source of funding: National Institute of Arthritis and Musculoskeletal and Skin Disorders

Inclusion criteria:

- hip OA and / or knee OA (based on radiographic evidence - patient-reported joint symptoms that was present or for which patient used pain medications on most days during the last month

- overweight

- not currently meeting Department of Health and Human Services physical activity recommendations

Exclusion criteria:

See article Appendix A

N total at baseline: 300

Intervention: 151

Control: 149

Important prognostic factors²:

Age (SD):

I: 60 (9)

C: 62 (9)

Sex (n, % male)

I: 131 (87%)

C: 141 (95%)

Describe intervention (treatment/procedure/test):

A twelve-month intervention focusing on physical activity, weight management and cognitive behavioral pain management strategies. Telephone calls were scheduled twice per month for the first six months, then monthly for the last six months, and were delivered by one counselor with training in OA and behavior change.

Participants were given written patient educational materials corresponding to intervention topics, an exercise video for patients with OA, and an audio CD of relaxation exercises.

Describe control (treatment/procedure/test):

Usual care

Length of follow-up:

12 months (intermediate term)

Loss-to-follow-up:

Intervention:

N= 12 (8%)

Reasons for withdrawal: excluded, missed assessment, lost to follow-up.

Control:

N= 15 (10%)

Reasons: excluded, missed assessment, lost to follow-up.

Incomplete outcome data:

Intervention:

N (%)

Not reported

Control:

N (%)

Not reported

(Missing data were imputed)

Outcome measures and effect size (include 95%CI and p-value if available):

N in analysis:

I: 151

C:149

WOMAC subscale pain (treatment diff (95%CI)):

-0.5 (-1.2, 0.2)

SMD (SE): -0.16 (0.12), p=0.16

WOMAC subscale function:

Mean diff (95%CI):

-3.3 (1.0; 5.7)

SMD (SE): -0.31 (0.12), p=0.008

WOMAC total:

I: -4.0 (-6.2, -1.8)

C: 0.1 (-2.1, 2.3)

SMD (SE): -0.30 (0.12), p<0.01

Function performance (SPPB)

Mean diff (95%CI):

0.3 (-0.3, 0.9)

SMD (SE): 0.09 (0.12), p=0.43

Activities (hours per week)

3.6 (1.3, 5.9)

Adverse events

4, none associated with the OA intervention.

Health services utilization (N)

Physical therapy: I: 1; C: 2

Knee brace: I: 5; C: 3

MOVE! Program: I: 8; C: 2

Orthopedic visit: I: 4; C: 6

Joint injection: I: 8; C: 7

A patient and provider OA intervention improved total WOMAC and WOMAC function score at 12-months. No statistically significant or clinically relevant differences between arms for other secondary and process outcomes.

Broderick, 2014

Type of study: RCT

Setting:

Primary care and rheumatology practices

Country: U.S.A.

Source of funding: National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health

Inclusion criteria:

- physician-confirmed diagnosis

of hip or knee OA;

- 21 years of age or older;

- usual pain ≥4 on a 10-point scale for a duration of at least 6 months;

- no cognitive/ mental impairment that would interfere with participation;

- no expected joint replacement surgery in the next 2 years.

Exclusion criteria:

none reported

N total at baseline: 256

Intervention: 129

Control: 127

Important prognostic factors²:

Age (SD):

I: 68 (8.7)

C: 66 (10)

Sex (F)

I: 78.9

C: 74.4

No significant group differences were found on demographic or clinical variables, except for employment (p = .001), with control group participants more likely to be employed.

Describe intervention (treatment/procedure/test):

Pain coping skills training interventions teach patients cognitive and behavioral skills to manage their pain and enhance their perception of pain control. Four broad coping skills were taught across ten 30- to 45-minute sessions:

Describe control (treatment/procedure/test):

Usual care: patients in both conditions were provided with an OA informational brochure from the Arthritis Foundation

and information on programs (support groups, arthritis education, and aquatic exercise classes) offered in the community.

Length of follow-up:

12 months (intermediate term)

Loss-to-follow-up:

Intervention:

N= 38 (29%)

Reasons for withdrawal: not reported

Control:

N= 36 (28%)

Reasons for withdrawal: not reported

Retention rates did not differ between treatment and control groups.

Incomplete outcome data:

Intervention:

N (%)

Not reported

Control:

N (%)

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

N total in analysis: 256

Intervention: 129

Control: 127

Pain intensity (composite of BPI pain, AIMS2 pain, and WOMAC pain)

mean diff (SE): -0.21 (0.11), p=0.047

SMD (SE): 0.21 (unknown)

Physical functioning (composite AIMS2 physical and WOMAC difficulties performing activities)

mean diff (SE): -0.17 (0.08) p=0.036

SMD (SE): 0.17 (unknown)

AIMS2 social activities

mean diff (SE): 0.12 (0.21), p=0.557

SMD (SE): -0.07 (unknown)

Daily pain medication

mean diff (SE): −0.10 (0.05), p<0.05

This NP-delivered PCST protocol produced significant improvements in a range of pain-related variables including pain intensity, coping with pain, self-efficacy for controlling pain, activity interference due to pain, and the use of pain medication when compared with usual care.

Coleman, 2012

Type of study: RCT

Setting: primary care

Country: Australia

Source of funding: Arthritis Western

Australia. The research undertaken was independent

from the funding body.

Inclusion criteria:

- Diagnosis of OA (X-ray or clinical diagnosis)

- Referral from general practitioner or specialist

- Able to meet program requirements

Exclusion criteria:

- Coexisting inflammatory arthritis

- Serious comorbidity

- Knee replacement scheduled in < 6 months

N total at baseline: 146

Intervention: 71

Control: 75

Important prognostic factors²:

Age ± SD:

I: 65 ± 7.9

C: 65 ± 8.7

Sex, M:F

I: 14:57

C: 23:52

Despite randomisation, there were between group differences in severity at baseline. Therefore, baseline values were used as covariates in the analyses

Describe intervention (treatment/procedure/test):

Disease-specific SM program for people with osteoarthritis of

the knee (OAK) for delivery by health care professionals.

Six weekly sessions of 2.5 hours each

Describe control (treatment/procedure/test):

Waiting list

Length of follow-up:

6 months (intermediate term)

Loss-to-follow-up:

Intervention:

N=3 (4%)

Control:

N=7 (9%)

Reasons for withdrawal (describe): overseas relocation; work, family and time commitments; and not having been randomised to the OAK group

Incomplete outcome data:

Intervention: not reported

N (%)

Reasons (describe)

Control: not reported

N (%)

Reasons (describe)

Outcome measures and effect size (include 95%CI and p-value if available):

N total in analysis:136

Intervention: 68

Control: 68

WOMAC subscale Pain (mean (SE)):

I: 6.1 (0.3)

C: 6.7 (0.3)

SMD (SE)= -0.24 (0.17), p=0.16

mean diff in change: -0.49 (-1.26 to 0.28)

WOMAC total (mean (SE)):

I: 29.2 (1.2)

C: 33.3 (1.2)

SMD (SE): -0.41 (0.17), p=0.02)

mean diff in change: -4.08 (-7.47 to –0.68)

WOMAC subscale function (mean (SE)):

I: 19.9 (1)

C: 23.4 (0.9), p<0.05

SMD (SE): -0.44 (0.17), p=0.01

mean diff in change: -4.35 (-6.20 to -0.91

OARSI Responder index

I: 22 (33%)

C: 14 (20%), p=0.123

Function performance: Timed Up and Go test (mean (SE)):

I: 10 (0.2)

C: 11 (0.2), p<0.05

SMD (SE): -0.60 (0.18, p<0.001)

mean diff in change: -0.72 (-1.35 to -0.08)

Withdrawal (proportion):

I: 3/71

C: 7/75

In the OAK group, a significantly greater proportion of responders* were observed at 8 weeks compared with the control group, though by 6 months this proportion did not differ significantly between groups.

(* responders defined as: an improvement of ≥ 50% and an absolute change of ≥ 20 points on a 100-point scale in pain or function or an improvement in at least two of the following: an improvement of ≥ 20% and an absolute change of ≥ 10 points in two of the three parameters pain, function and

global health)

Helminen, 2015

Type of study: cluster RCT

Setting: primary healthcare

Country: Finland

Source of funding: an EVO and a VTR grant from Kuopio University Hospital

Inclusion criteria:

- aged between 35 and 75 years with clinical symptoms and radiographic grading of knee osteoarthritis

Exclusion criteria:

- Severe psychiatric or psychological disorders that had led to hospitalization or an inability to work;

- previous or planned lower extremity joint surgery;

- other back or lower limb pain symptoms that had been more aggravating than the knee pain.

N total at baseline: 111

Intervention: 55

Control: 56

Important prognostic factors²:

Age (min-max):

I: 65 (7)

C: 63 (7)

Sex (female)

I: 39 (71%)

C: 38 (68%)

No statistical differences were noted in the baseline characteristics between the two groups

Describe intervention (treatment/procedure/test):

Cognitive– behavioural intervention on knee osteoarthritis pain.

Six weekly sessions supervised by an experienced psychologist and a physiotherapist. The sessions took place in a group of 7−13 persons according to the model presented by Linton. Each session lasted for two hours.

Describe control (treatment/procedure/test):

Care as usual: both the intervention and the control group continued side by side with the usual GP care that patients might have received in primary care throughout the study

Length of follow-up:

12 months (intermediate term)

N at follow-up analyses:

Intervention: 55

Control: 48

Loss-to-follow-up:

Intervention:

N= 2 (3%)

Reasons for withdrawal: no response.

Control:

N= 11 (20%)

Reasons: Reasons for withdrawal: dead, dropped out, no response.

Incomplete outcome data:

Intervention: 2 (3%)

Control: 11 (20%)

Outcome measures and effect size (include 95%CI and p-value if available):

N total at follow-up: 103

Intervention: 55

Control: 48

Age, gender, and disease severity were included in all models based on their associations with the study outcomes in prior research.

No adverse events were recorded in either of the study groups.

WOMAC subscale Pain

Mean diff (95% CI):

-3.9 (-11.8 to 4.0)

Mean (95% CI):

I: 35.6 (30.0 tot 41.1)

C: 39.5 (33.7 tot 45.2)

SMD (SE): -0.19 (0.20), P=0.34

WOMAC subscale function mean diff (95% CI):

-0.3 (-8.3, 7.8)

I: 36.5 (30.6 tot 42.3)

C: 36.7 (31.0 tot 42.4)

SMD (SE): -0.010 (0.20), p=0.96

HRQoL, 15D

Mean diff (95% CI):

−0.03 (−0.06, 0.00)

I: 0.82 (0.80 tot 0.85)

C: 0.85 (0.83 tot 0.88)

SMD (SE): -0.42 (0.20), p =0.04

RAND-36 Social Functioning Mean diff (95% CI):

−7.8 (−16.4, 0.81), p=0.08

I: 75.0 (68.2−81.8)

C: 82.8 (77.6−88.0)

SMD (95%CI): -0.35 (-0.74-0.04)

No significant differences between the groups at any assessment point in the use of pain medication, the number of doctor appointments, physiotherapist appointments, or sick-leave days owing to osteoarthritis.

This single-blinded RCT could not confirm the hypothesized advantage of a group-based cognitive–behavioural training programme over ordinary GP care in knee osteoarthritis pain patients. On the contrary, our findings indicated a negative impact of the intervention on pain self-efficacy in knee osteoarthritis patients.

Hurley, 2012

Type of study: cluster RCT

Setting: primary care surgeries

Country: Great Britain

Source of funding:

Inclusion criteria:

- 50 years or over

- mild, moderate, or severe knee pain of more than 6 months’ duration

Exclusion criteria:

Leg arthroplasty, physiotherapy for knee pain in the preceding 12 months, intraarticular injections in the preceding 6 months, unstable medical conditions, inability/unwillingness to exercise, severe lack of mobility,

N total at baseline: 418

Intervention:

• Individuals: 146
• Small groups: 132

Control: 178

Important prognostic factors²:

Age (min-max):

I: 67 (50-91)

C: 67 (51-89)

Sex, M:F

I: 80:198

C: 44:96

All of the participants in the trial received interventions their primary care physicians considered appropriate. For the majority, this consisted of prolonged medication (analgesia and nonsteroidal anti-inflammatory drugs). There were no between-group differences in the interventions received.

Describe intervention (treatment/procedure/test):

ESCAPE-knee pain program: In addition to care as usual, the intervention group participated in an exercise-based rehabilitation program designed to improve function by integrating exercise, education, and self-management strategies to dispel inappropriate health beliefs, alter behavior, and encourage regular

physical activity.

12 supervised sessions twice weekly for 6 weeks.

Describe control (treatment/procedure/test):

Care as usual: whatever services or interventions their physicians considered appropriate

Length of follow-up:

6 months (intermediate term);

18 and 30 months (long term)

Loss-to-follow-up @ 30 months:

Intervention:

N= 89 (32%)

Reasons for withdrawal: not reported

Control:

N= 46 (33%)

Reasons: not reported

Incomplete outcome data:

Intervention:

N (%)

Not reported

Control:

N (%)

Not reported

The decline in WOMAC function for usual care participants may, in part, be due to loss to followup rather than improvements in functioning for individual participants. Participants who were lost to followup had poorer functioning at baseline than those who were assessed on at least 1 followup occasion (WOMAC function score 29.0 versus 26.9; P = 0.41). In particular, participants who were lost to followup from the usual care arm had poorer baseline functioning than participants lost to followup from the ESCAPE-knee pain arm (mean WOMAC function score 32.2 versus 28.0; P = 0.49).

Outcome measures and effect size (include 95%CI and p-value if available):

N at 6 months:

I: 229

C: 113

N at 30 months:

I: 189

C: 94

WOMAC subscale Pain

Mean (SD):

6 months

I: 5.7 (1.9)

C: 6.5 (2.1), p=0.18

SMD (SE): -0.41 (0.12), p<0.001

30 months

I: 5.9 (2.6)

C: 6.4 (2.0), p=0.46

SMD (SE): -0.21 (0.13), p=0.10

WOMAC subscale function (mean (SD)):

6 months

I: 21.7 (6.7)

C: 23.4 (7.5), p=0.42

NNT: 7.3 (4.1 to 42.0)

Adjusted for missings:

mean diff: -4.44 (-6.54 to -2.33), p<0.0001

SMD (SE): -0.24 (0.12), p=0.04

30 months

I: 22.3 (8.7)

C: 23.8 (6.3), p=0.53

NNT: 6.7 (3.8 to 39.5)

Adjusted for missings:

mean diff: -2.78 (-5.32 to -0.23), p=0.032

SMD (SE): -0.19 (0.13), p=0.14

Costs

Over 30 months there were no differences in discounted total health and social costs (£-1,177; 95% CI £-3,609 to £313)

Imputing missing data did suggest that ESCAPE-knee pain participants had lower

costs: £ -1,118; 95% CI £-2,566 to £-221.

Adjusting for baseline differences in functioning had little impact on the treatment effects. Overall, physical functioning of usual care participants did not change during the 30-month followup

The unadjusted data analysis, which ignores baseline values and missing data, suggests little or no between-group

differences. However, this was greatly influenced by the differential withdrawal from usual care of participants with the highest health and social care costs and poorest function. This differential attrition reduced betweengroup treatment differences and masked the program’s greater and sustained clinical and cost benefits compared to usual primary care.

Kao, 2012

Type of study: RCT

Setting: Hospital

Country: Taiwan

Source of funding: Department of Health, Taipei City Government

Inclusion criteria:

- 50 years or older

- Knee pain complaints or muscle weakness in lower extremity confirmed by a clinical examination as having OA affecting their knees.

Exclusion criteria:

Had knee replacement or surgery; unable to maintain balance while standing independently; having medical conditions that could be exacerbated by the protocol.

N total at baseline: 259

Intervention: 134

Control: 125

Important prognostic factors²:

Age (SD):

I: 67.3 (10.1

C: 68.2 (11.2)

Sex (Male)

I: 22 (19%)

C: 26 (29%)

Describe intervention (treatment/procedure/test):

Taipei Osteoarthritis Program: Four 80-min classes held once a week, each with 10–15 participants led by a physical therapist trained in leading small groups and in self-management

basic principles.;

Describe control (treatment/procedure/test):

Standard care

Length of follow-up:

8 weeks (intermediate term)

Loss-to-follow-up:

Intervention:

N= 20 (15%)

Reasons for withdrawal: no contact, busy, withdraw, much better.

Control:

N= 31 (27%)

Reasons: no contact, busy, withdraw,

There was no statistically significant difference between non-completers and completers in terms of demographics and outcome measures at baseline.

Incomplete outcome data:

Intervention:

N (%)

Not reported

Control:

N (%)

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

N total at follow-up:

Intervention: 114

Control: 91

WOMAC total

Mean (SD)

I: 41.2 (31.2)

C: 33.4 (27.2)

SMD (95% CI): 0.26 (-0.01; 0.54), p=0.06

SF36 pain index

Mean (SD)

I: 70.0 (16.7)

C: 60.5 (18.5)

SMD (95% CI): 0.54 (0.26; 0.82), p<0.001

SF36 physical functioning Mean (SD)

I: 65.1 (10.0)

C: 65.3 (10.0)

mean diff: -0.02 (-0.30;0.26), p=0.89

The study showed at an 8-week follow-up an impact on the psychological well being of participants, in particular the participants’ GH perception and mental subscales of the SF-36. Other outcomes, including disability level by WOMAC showed no significant effect.

Murphy, 2016

Type of study: RCT

Setting: Occupational therapy

Country: U.S.A.

Source of funding: Rehabilitation and Research Branch of the Veterans Affairs Office of Research Development

Inclusion criteria:

- age 50 and older;

- pain for at least 3 months duration;

- at least mild to moderate pain severity overall;

- radiographic evidence of osteoarthritis in a corresponding knee or hip joint.

Exclusion criteria:

- non-ambulatory;

- changed any medications within the past 2 weeks;

- medical conditions that could interfere with symptom ratings or accelerometer data

- knee joint injection within the previous 3 months or knee arthroscopic procedure within the previous 2 months, or knee replacement within the previous 6 months;

- in the last 12 months physical or occupational therapy for OA symptoms for knee or hip problems or participated in a cognitive behavioral program or other self-management program.

N total at baseline: 193

Intervention-1: n=64

Intervention-2: n=66

Control: n=63

Important prognostic factors²:

Age (years (SD)):

I-1: 64 (8)

I-2: 64 (8)

C: 66 (9)

Sex (Female

I-1: 39 (61%)

I-2: 41 (62%)

C: 39 (62%)

Describe intervention (treatment/procedure/test):

Intervention 1:Tailored activity pacing

Interverntion 2: General activity pacing

Describe control (treatment/procedure/test):

Care as usual.

Length of follow-up:

6 months (intermediate term)

Loss-to-follow-up:

I-1: 18 (28%)

I-2: 17 (26%)

Reasons for withdrawal: unable to follow instructions, started new treatment, lost to follow-up, medical conditions.

Control:

N=8 (13%)

Reasons: lost to follow-up

Incomplete outcome data:

Intervention:

N (%)

Not reported

Control:

N (%)

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

I-2 (N=64) vs C (N=63)

WOMAC pain

Mean (SE)

I: 7.93 (0.45)

C: 6.78 (0.43)

Mean diff (95%CI):

0.13 (-0.21, 0.48)

SMD (SE): 0.33 (0.18), p=0.07

Physical function

Six minute walk (feet)

Mean (SE)

I: 1223.39 (32.93)

C: 1208.63 (32.54)

SMD (95%CI): 0.06 (-0.29, 0.41)

We did not find that activity pacing as a singular behavioral strategy was sufficient for improving pain, fatigue, or physical function for participants in this sample.

Rini, 2015

Type of study: RCT

Setting: Recruitment through medical and surgical clinics

Country: U.S.A.

Source of funding: National Institute of Arthritis and Musculoskeletal and Skin Diseases

Inclusion criteria:

- ≥18 years old with knee or hip OA, confirmed radiographically or by physician;

- frequent OA pain

Exclusion criteria:

- significant cognitive impairment;

- less than 7th grade reading proficiency;

- medical comorbidities that interfered with their ability to complete the intervention or that indicated they had a pain-related condition in addition to OA

N total at baseline: 113

Intervention: n=58

Control: n=55

Important prognostic factors²:

Age (years (SD)):

I: 68 (8)

C: 67 (11)

Sex (Female

I: 46 (79%)

C: 45 (82%)

Participants in the two treatment conditions did not differ at baseline in terms of sociodemographic, medical, or study outcome variables

Describe intervention (treatment/procedure/test):

PainCOACH, an in-person Pain Coping Skills Training (PCST) protocol for delivery via the Internet.

Eight modules, to be completed in a self-directed manner (i.e., without therapist contact) at the rate of one per week. Each module took 35-45 minutes to complete and provided interactive training in a cognitive or behavioral pain coping skill

Describe control (treatment/procedure/test):

Care as usual.

Length of follow-up:

11 weeks (intermediate term)

Loss-to-follow-up:

I: 1/58 (2%)

Reasons for withdrawal: not reported

Control:

N=3/55 (5%)

Reasons for withdrawal: not reported

Incomplete outcome data:

Intervention:

N (%)

Not reported

Control:

N (%)

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

N total at follow-up: 109

Intervention: 57

Control: 52

AIMS2 Pain subscale

Mean (SD):

I: 4.07 (1.99)

C: 4.62 (1.79)

SMD (SE): -0.29 (0.19), p=0.14

AIMS2 Functioning subscale Mean (SD)

I: 1.62 (1.19)

C: 1.75 (1.24)

SMD (SE): -0.11 (0.19)

Results showed a significant sex by treatment interaction, F(1,107)=12.96; p<.001.

Women in the PainCOACH condition had significant reductions in pain from baseline (M=4.02; Tukey adjusted p=.036).

There were no corresponding significant reductions in pain for women in the control condition.

Rosemann, 2007

Type of study: cluster-RCT

Setting: General Practice

Country: Germany

Source of funding: not reported

Inclusion criteria:

- ≥18 years;

- diagnosed with OA in the knee or the hip according to the American College of Rheumatology criteria.

Exclusion criteria:

None reported

N total at baseline: 1,021

Intervention-1: n=345

Intervention-2: n=344

Control: n=332

Important prognostic factors²:

Age (years (SD)):

I-1: 66 (15)

I-2: 66 (15)

C: 66 (15)

Sex (Female

I-1: 214 (62%)

I-2: 231 (67%)

C: 229 (69%)

No significant differences between the control group versus intervention group 1 and intervention group 2.

Describe intervention (treatment/procedure/test):

Intervention 1: only GPs providing information on arthritis self-management.

Intervention 2: additional case management conducted via telephone by a practice nurse. (used for comparison in meta-analysis)

GPs in intervention group 1 and 2 participated in 2 interactive peer group meetings of 8 hours each. In addition to the meetings, GPs received a written summary of evidence-based treatments for OA in a primary care setting. Furthermore, GPs received written material for patients: a leaflet providing information about the cause and the treatment possibilities as well as coping strategies. GPs also received booklets and audio CDs with a detailed exercise program, similar to some ASMPs, and were asked to provide these materials to every included patient.

Practice nurses from intervention group II also participated in a course. Telephone calls with the patients were conducted at least every 4 weeks.

Describe control (treatment/procedure/test):

Not described – Assumption: care as usual.

Length of follow-up:

9 months (intermediate term)

Loss-to-follow-up:

I-1: 84 (24%)

I-2: 68 (20%)

Reasons for withdrawal: did not return questionnaires

Control:

N=74 (22%)

Reasons: did not return questionnaires

No statistically significant differences were found between the dropouts and the remaining subjects on baseline factors.

Incomplete outcome data:

Intervention:

N (%)

Not reported

Control:

N (%)

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

N total at follow-up:

I-1: 261

I-2: 276

C: 258

IPAQ score physical activity Mean (95% CI):

I-1: 131.5 (104.3, 157.2), p=0.78

I-2: 133.4 (118.6, 148.2), p=0.67

C: 125.2 (103.8, 146.6)

SMD (SE) I-2 vs C: 0.05 (0.09), p=0.53

Health services utilization Mean (95% CI)

GP contacts

I-1: 0.12 (-0.24, 0.36), p=0.34

I-2: 0.11 (-0.23, 0.34), p=0.82

C: 0.22 (-0.21, 0.45)

SMD (SE) I-2 vs C: -0.03 (-0.09)

Referrals to orthopaedics

Mean (95% CI)

I-1: 0.09 (0.02, 0.15), p=0.15

I-2: 0.24 (-0.16, 0.31), p=0.04

C: 0.01 (-0.05, 0.06)

Radiographs

Mean (95% CI)I

-1: 0.07 (-0.01, 0.15), p=0.05

I-2: 0.09 (0.02, 0.16), p=0.03

C: -0.06 (-0.13, 0.01)

Physiotherapy

Mean (95% CI)I

-1: 0.07 (-.04, 0.18), p=0.24

I-2: 0.14 (0.02, 0.23), p=0.13

C: 0.04 (-0.05, 0.12)

Prescriptions (Mean (95% CI))

Paracetamol:

I-1: 7.43 (3.33, 11.53), p<0.001

I-2: 6.89 (2.93, 10.70), p<0.001)

C: 1.31 (-3.01, 0.39)

Opioids

I-1: 4.33 (3.32, 5.34), p<0.08

I-2: 8.80 (5.02, 12.58), p<0.001)

C: 0.98 (-1.32, 3.28)

NSAID

I-1: 4.30 (2.82, 5.78)<0.08

I-2: 6.54 (4.54, 8.54), p<0.02)

C: 2.31 (0.91, 3.71)

Multifaceted educational interventions with GPs provided through quality circles had no impact on patients’ QOL or physical activity. However, the interventions seemed to reduce certain aspects of health service utilization, such as radiographs, and to change prescription patterns

Somers, 2012

Type of study: RCT

Setting: outpatient section of Clinic at a university medical center

Country: U.S.A.

Source of funding: National Institutes of Health

Inclusion criteria:

1) Knee pain on most days of the month for at least the prior 6 months; 2) over the age of 18; 3) overweight or obese; 4) met the American College of Rheumatology criteria for OA and had radiographic evidence of OA affecting one or both

knees (knee x-rays were graded by an experienced reader) on the basis of the Kellgren-Lawrence grading system; 5) no other major weight bearing joint affected by OA; 6) OA of the knee(s) was considered the medical condition that contributed most to limitations in their daily function as assessed by the healthcare provider.

Exclusion criteria:

1) medical condition that increased risk of a significant adverse health event during physical activity; 2) another known organic disease that would contraindicate safe participation in the study; 3) a non-OA inflammatory arthropathy or another arthritic disorder; 4) used oral corticosteroids regularly; or 5) were participating in a regular exercise or weight loss program

N total at baseline: 232

Intervention: n=62

Control:

PCST only: n=60

BWM only: n=59

Standard care: n=51

Important prognostic factors²:

Age (years) (SD):

Intervention: 57 (9)

Control:

PCST only: 58 (11)

BWM only: 58 (11)

Standard care: 58 (10)

Sex (Male)

Intervention: 5 (8%)

Control:

PCST only: 20 (33%))

BWM only: 12 (20%)

Standard care: 11 (22%)

Describe intervention (treatment/procedure/test):

Combined pain coping skills training (PCST) and lifestyle behavioral weight management BWM

intervention.

Program of 24 weeks.

PCST: During the first 12 weeks, 60-minute group sessions were held weekly. For the last 12 weeks, 60-minute group sessions were held every other week. PCST was delivered by clinical psychologists with prior PCST experience.

BMW: During the first 12 weeks, 60 minute group sessions were held weekly. Additionally, three 90-minute supervised exercises sessions were held each week of the first 12 weeks. During the last 12 weeks, 60-minute group sessions were held every other week; there were no supervised exercise sessions. BWM was delivered by psychologists with a specialty in behavioral medicine and prior experience in behavioral weight management protocols.

Participants in all treatment conditions received six monthly maintenance calls focused on reinforcing the use of skills learned during the program.

Describe control (treatment/procedure/test):

- PCST-only;

- BWM-only;

- standard care

Length of follow-up:

24 months (long term)

N at Follow-up:

Intervention: n=47 (76%)

Control:

PCST only: n=39 (65%)

BWM only: n=40 (68%

Standard care: n=51 (37 (73%)

Reasons for withdrawal: no time, lost to contact, health concerns, moved, family reasons, dissatisfied.

Dropout rates did not vary significantly across treatment conditions (chi-square = 2.0; p = 0.57).

Participants who dropped out had higher baseline pain scores (p = 0.02) and weight (p = 0.03).

Incomplete outcome data:

Intervention:

N (%)

Not reported

Control:

N (%)

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

WOMAC subscale pain:

I: 27.2 (23.9 tot 30.4)

PCST only: 34.5 (30.8 tot 38.2)

mean diff: 7.3(1.3 tot 13.3)

BWM only: 35.5 (31.9 tot 39.0)

mean diff: 8.3(2.5 tot 14.1)

standard care: 38.0 (34.1 tot 41.8)

mean diff: 10.8 (4.6 tot 16.9)

WOMAC subscale function:

I: 25.1 (22.1 tot 28.3)

PCST only: 35.2 (31.8 tot 38.6)

mean diff: 10.0 (4.4 tot 15.6)

BWM only: 36.0 (32.6 tot 39.3)

mean diff: 10.8 (5.3 tot 16.2)

standard care: 37.5 (33.9 tot 41.2)

mean diff: 12.4 (6.5 tot 18.2)

Function performance

Normal gait velocity

I: 1.2 (1.1–1.2)

PCST only: 1.1 (1.1 to 1.2)

mean diff: −.04 (−.10 to .01)

BWM only: 1.2 (1.1 to 1.2)

mean diff: −.01 (−.06 to .03)

standard care: 1.2 (1.1 to 1.2)

mean diff: −.01(−.05 to .04)

A behavioral intervention that simultaneously addresses pain and weight is more effective in improving pain and other outcomes than behavioral interventions that address pain or weight alone.

Self-management programmes versus information only

De Rezende, 2016

Type of study: RCT

Setting: Department of Orthopedics and Traumatology in a tertiary hospital

Country: Brazil

Source of funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.

Inclusion criteria:

- outpatient aged 45 years or older with knee OA according to the American

College of Rheumatology clinical and radiological definition;

- had received standard care for OA in the past 6 months; - no other rheumatologic disease;

- knee pain rated above 30 mm on a numerical scale and necessitating drug treatment.

Exclusion criteria:

- Participating in another program with nutritional education, engaging in another clinical trial, or undergoing surgery during the study not related to knee OA that would prevent daily regular exercises.

N total at baseline: 228

Intervention: 150, divided in 6 groups

Control: 48

All groups were similar in gender, race, age, affected side, and OA severity.

Describe intervention (treatment/procedure/test):

3 groups: according to the intervals of 1, 2, and 3 months between the 2 days of lectures and 2 subgroups (A and B, according to the use of bimonthly telephone calls or no telephone calls, respectively) of 28 or 29 participants. All groups received a booklet on OA and a video with all of the lectures.

Patients in groups 1 to 3 were asked to come to the hospital on 2 specific

Saturdays according to the intervals of each group.

Describe control (treatment/procedure/test):

Control group watched the video once at the hospital and only then received the take-home material.

Length of follow-up:

12 months (intermediate term)

Loss-to-follow-up:

Intervention:

N=

Control:

N= (%)

Reasons: not reported

Reasons for withdrawal: weather conditions that prevented access to the hospital, being unable to attend classes when they were scheduled, not interested, living too far away.

Incomplete outcome data:

Intervention:

N (%)

Not reported

Control:

N (%)

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

Outcomes not reported for interventions vs control, but across 8 different groups.

- Interval between

classes (1, 2, or 3 months) is not an important issue.

- Telephone calls did not

significantly improve the results

Schlenk, 2011

Type of study: RCT (feasibility)

Setting: outpatient section of Clinical Research Center at a university medical center

Country: U.S.A.

Source of funding: not reported

Inclusion criteria:

- age 50 years or

older

- a physician-confirmed diagnosis of OA of the knee

- overweight or obese

Exclusion criteria:

Currently doing lower-extremity exercise ≥ 2 times per week; currently fitness walking ≥ 90 minutes per week; having current knee conditions such as meniscus tears, knee ligament ruptures, or previous unilateral knee replacement surgery; scheduled to undergo a major surgical procedure in the next 6 months; currently participating in a drug or psychoeducational trial.

N total at baseline: 26

Intervention: 13

Control: 13

Important prognostic factors²:

Age (SD):

63.2 (9.8)

Sex, M:F

1:25

Describe intervention (treatment/procedure/test):

The first session consisted of a standardized educational program on sedentary lifestyles and obesity as risk factors for cardiovascular disease, and OA of the knee and its treatment plus distribution of educational brochures followed by a physical therapy evaluation. Subjects then completed five weekly sessions of lower-extremity flexibility and strengthening exercise guided by a physical therapist. Subjects also received a lower extremity exercise videotape (Schlenk et al., 1999; University of Pittsburgh Medical Center

Health System, 1999), written exercise guide, and diagrams of the exercise for a modelling strategy based on self-efficacy.

During weeks 8–24, subjects received nine biweekly telephone calls by a registered nurse to monitor progress

Describe control (treatment/procedure/test):

Usual care initially, and at the end of the 6-month intervention period controls met with the physical therapist for a physical therapy evaluation, brief one-time instruction on lower-extremity exercise, and educational materials. The group received no self-efficacy-based adherence counseling.

Length of follow-up:

6 months (intermediate term)

Loss-to-follow-up:

Intervention:

N= 2 (15%)

Reasons for withdrawal: not reported

Control:

N= 3 (23%)

Reasons: not reported

No statistically significant differences were found between the dropouts and the remaining subjects on baseline factors.

Incomplete outcome data:

Intervention:

N (%)

Not reported

Control:

N (%)

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

N in analysis:

I: 11

C: 10

WOMAC subscale function Mean (SD):

I: 18.9 (13.2)

C: 21.6 (10.3), n.s.

SMD (SE): -0.22 (0.44), p=0.62

Function performance

6-minute walk (yards):

Mean (SD):

I: 480.0 (94.9)

C: 502.3 (104.3), n.s.

SMD (SE): -22.3 (43.7), p=0.61

SPPB:

Mean (SD):

I: 11.6 (1.4)

C: 11.5 (2.2), n.s.

Self-management programmes versus alternate interventions

Farr, 2010

Type of study: RCT

Setting: university campus

Country: U.S.A.

Source of funding: National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases

Inclusion criteria:

1) age between 35 and 68 years; 2) pain on 4 or more days of the week in one or both knees for at least 4 months during the previous year; 3) less than 5 years' symptom duration; 4) radiographic status of grade II OA (and no higher) in at least one knee; 5) disability due to knee OA

Exclusion criteria:

None reported

N total at baseline: 293

Intervention: n=98

Control:

RT only: n=95

RT + SM: n=100

Important prognostic factors²:

Age (years) (SD):

55 (7)

Sex (M:F):

26:74

No significant (p>.05) difference among groups or between completers (n=171) and noncompleters (n=83) at baseline for any variables.

Describe intervention (treatment/procedure/test):

The 9-month program began with 12 weekly, 90-minute classroom

sessions in which participants completed SM education modules. Classroom sessions were followed by 24 weeks of a structured telephone intervention program that reinforced SM skills

Describe control (treatment/procedure/test):

Alternative interventions:

RT only (used for comparison in meta-analysis)

RT + SM

Resistance training (RT): participants met with certified physical trainers 3 times per week for 9 months, with a minimum of 1 day of rest between training sessions, to complete a 1-hour exercise regimen that emphasized RT.

The RT groups were combined because both groups of participants engaged in the RT intervention and no significant (p>.05) group differences using independent t tests were observed for any variables at any time point.

Length of follow-up:

9 months (intermediate term)

Loss-to-follow-up:

Intervention: n=25 (26%)

Control:

RT only: n=23 (24%)

RT + SM: n=24 (24%)

Reasons for withdrawal: not interested, lost to follow-up, health problems, time commitment, personal, leaving local area, did not receive allocated intervention.

Incomplete outcome data:

Intervention:

Intervention: n=16/73 (22%)

Control:

RT only: n=20/72 (28%)

RT + SM: n=14/76 (18%)

Outcome measures and effect size (include 95%CI and p-value if available):

WOMAC Pain (mean (SD)):

I: 62.9 (81.0)

RT only: 48.6 (61.3)

RT + SM: 56.2 (75.3)

SMD (SE): 0.19 (0.29), p=0.50

Level of moderate- and vigorous-intensity physical activity (min/day (SD)):

I: 24.8 (18.7)

Control:

RT only: 27.7 (20.0)

RT + SM: 31.8 (16.8)

SMD (SE): -0.15 (0.29)

No significant (p>.05) differences in VPA among the intervention groups at any time interval.

The SM group participants increased their MVPA by 22% at 3 months (P=.023, effect size (d)=0.25) and by 2% at 9 months (P=.80, effect size (d)=0.03) compared with baseline levels.

Self-management programmes versus acupuncture

Excluded from the literature review in the guideline

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Messier 2004

random assignments computer-generated with blocks

Unlikely

Likely, it was not possible to blind participants

Likely, not possible to blind care providers

Likely for patient-reported outcomes

Unlikely

Unclear

Unlikely

Miller 2006

no details available ‘participants were randomized’

Unclear

Likely, it was not possible to blind participants

Likely, not possible to blind care providers

Likely for patient-reported outcomes

Unlikely

Unlikely

Likely, ‘’the number of participants tested for each dependent variable, varies’’; not all randomized participants were included in the analysis

Messier 2013

A stratified-block randomization method, stratified by BMI and sex

Unlikely

Likely, it was not possible to blind participants

Likely, not possible to blind care providers

Likely for patient-reported outcomes

Unlikely

Unclear

Unlikely

Christensen 2005

randomization was done in a stratified way, according to gender, BMI and age

Unlikely

Likely, it was not possible to blind participants

Likely, not possible to blind care providers

Likely for patient-reported outcomes

Unlikely

Unclear, based on completers only (~10% drop-outs in both groups)

Unclear, no ITT but based on completers

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Miller, 2006

Type of study:

RCT

Setting: ‘Treatment center’

Country:

USA

Source of funding:

This project was funded by SlimFast

Nutrition Institute, the Wake Forest University, Claude D.

Pepper Older American Independence Center,

and the Wake Forest University General

Clinical Research Center

Inclusion criteria:

-BMI ≥30.0 kg/m2

-≥60 years of age

-symptomatic knee OA

-self-reported difficulty, attributed to knee pain, in performing at least one of the following activities: lifting and carrying groceries, walking one-quarter mile, getting in and out of a chair, or going up and down stairs.

Exclusion criteria:

-unstable

medical condition

-condition where rapid weight loss or

exercise is contraindicated (e.g., unstable angina, frailty, advanced osteoporosis).

-individuals who were unwilling to modify diet or physical activity patterns or would not be able to comply with the intervention because of food allergies or reactions to the meal replacements, - individuals living>50 miles from the treatment center,

- individuals with known

excessive alcohol consumption

N total at baseline:

Intervention: 44

Control: 43

Important prognostic factors²:

Age ± SD:

I:69.3 (0.9)

C: 69.7 (0.9)

Sex:

I: 36.4% M

C: 39.5% M

Weight Loss group (WL)

The weight loss goal was 10% loss during 6 months of trial: partial meal replacements, nutrition education, and lifestyle behaviour modifications; providing daily energy deficit of 1000 kcal of dietary intake predicted energy expenditure (predicted resting metabolism X 1.2 activity factor); lowest levels 1100 kcal for women and 1200 kcal for men. The calorie distribution goal for each individual was~20% from protein, ~25% from fat, and ~55% from carbohydrates. A maximum of two meal replacements per day (shakes and bars; SlimFast Foods Co., Englewood, NJ) were provided based on the participant’s tolerance for the product. For the third meal, a weekly menu plan with recipes was given

for participants to follow. They were free to choose the meal they preferred that allowed them to stay within the daily calorie goals. This meal of traditional foods was typically consumed in the evening, contained 500 to 750 kcal, and was low in fat and high in vegetables. Recommended snacks

included fruits or vegetables providing ~100 to 120 kcal.

The food plan was tailored to allow for individual preferences for various food items.

Behavioral and educational sessions were held on a weekly basis for those in the WL group. These sessions were conducted for 60 minutes in a group (n = 6 to 12 per group) and individual format and were led by a registered dietitian and exercise physiologist with expertise in behavior therapy with older adults. All participants were instructed in behavior modification with advice on food selection, meal portion, dietary fat control, relapse prevention, and self-monitoring techniques. Throughout the duration of the study, body weight was monitored and recorded in these weekly sessions. If an individual was not meeting weight loss goals, energy intake was individually modified accordingly

to produce the desired rate of weight loss. All participants in the WL group were taught self-monitoring

techniques for diet and body weight.

Weight Stable group (WS)

Participants randomized to this arm of the study were the attention control group and met bimonthly in a group format that included presentations on general health, including OA and exercise. Individuals

were weighed at these meetings and encouraged to maintain their weight throughout the 6-month study. Bimonthly newsletters were sent to participants in months 1, 3, and 5 describing other health facts on topics such as nutrition, pertinent disease topics, aging, and other health issues in older adults. At the close of the study, individuals in the WS control group were provided with weight loss information on diet and exercise, a 2-month supply of meal replacements and snack food provisions, a personalized exercise consultation, and 1 month of the facility-based exercise program as an incentive and reward for participation in the study

Length of follow-up:

6 months

Loss-to-follow-up:

Total: 8 (9%)

Intervention: 2/43

Reasons: moving from area, medical condition unrelated to study intervention, transportation issues, and undisclosed personal reasons.

Control:

N (%): 6/44

Most common reason: participants wanted to be randomized to the WL group.

Incomplete outcome data:

Intervention: 10/43

Control: 2/44

Outcome measures and effect size (include 95%CI and p-value if available):

N in analysis:

I: 33; C: 41

Baseline vs follow-up

WOMAC subscale pain (lower score is better)

I: 6.5 (0.5) vs 4.1 (0.4)

C: 6.3 (0.5) vs 6.1 (0.5); p<0.05

WOMAC function (lower score is better)

I: 24.0 (1.5) vs 15.2 (1.5)

C: 26.7 (1.9) vs 23.8 (2.0); p<0.05

WOMAC total (lower score is better)

I: 33.9 (2.0) vs 22.3 (1.9)

C: 36.6 (2.5) vs 33.0 (2.6); p<0.05

Physical performance

Stair-climb time

I: 10.7 (0.8) vs 11.2 (1.2)

C: 9.2 (0.5) vs 9.37 (0.76)

6-min walk (m)

I: 426 (11) vs 430 (13)

C: 435 (11) vs 430 (13)

Authors’ conclusions: the WL group obtained a mean weight loss of 8.5% and showed higher physical function assessed by self-reported and performance tasks compared with WS controls.

Correlation analysis showed that greater weight loss was associated with better improvements in function (r~0.3-0.5)

Messier, 2004

Type of study: RCT (ADAPT)

Setting: Claude D. Pepper Older Americans Independence Center of Wake Forest University

Country: U.S.A.

Source of funding: NIH

Inclusion criteria:

1) age ≥60 years; 2) body mass index ≥28 kg/m2; 3) knee pain on most days of the month; 4) sedentary activity pattern with 20 minutes of formal exercise once weekly for the past 6 months; 5) selfreported difficulty in at least one of the g activities ascribed to knee pain; 6) radiographic evidence of grade I–III tibiofemoral or patellofemoral OA based on weight-bearing anteroposterior and sunrise view radiographs

Exclusion criteria:

1) serious medical condition that prevented safe participation in an exercise program; 2) a Mini-Mental State Examination score

of ≥24; 3) inability to finish the 18-month study or unlikely to be compliant; 4) inability to walk without a cane or other assistive device; 5) participation in another research study; 6) reported alcohol consumption of>14 drinks per week; 7) ST segment depression of at least 2 mm at an exercise level of 4 METS or less, hypotension, or complex arrhythmias during a graded exercise test; 8) inability to complete the protocol, in the opinion of the clinical staff, because of frailty, illness, or other reasons.

N total at baseline:

Intervention: 82

Control: 78

Important prognostic factors²:

Age ± SD:

I: 68 (0.7)

C: 69 (0.1)

Sex:

I: 28% M

C: 32% M

Dietary intervention with the aim to produce and maintain an average weight loss of 5% during the 18-month intervention period.

Based on principles from the group dynamics literature and social cognitive theory and was divided into 3 phases: intensive (months 1–4), transition (months 5–6), and maintenance (months 7–18).

Healthy lifestyle control group (‘a usual-care comparison group). Designed to provide attention, social interaction, and health education.

Length of follow-up:

18 months

Loss-to-follow-up:

Intervention: 19/82

Reasons not reported

Control: 11/78

Reasons not reported

Incomplete outcome data:

Intervention:

not reported

Control:

not reported

Retention of participants was not significantly different between the groups (for healthy lifestyle, 86%; for diet only, 77%.

Outcome measures and effect size (include 95%CI and p-value if available):

N in analysis:

I: 63; C: 67

Baseline vs follow-up

WOMAC subscale pain (lower score is better)

I: 6.58 (0.40) vs 5.51 (0.45)

C: 7.25 (0.39) vs 6.02 (0.45)

Physical performance

Stair-climb time

I: 9.74 (0.65) vs 8.43 (0.78)

C: 9.59 (0.64) vs 9.37 (0.76)

6-min walk (m)

I: 426 (11) vs 430 (13)

C: 435 (11) vs 430 (13)

Adherence

I: 72% (defined as attendance at nutrition classes)

C: 77% for the first 3 months (defined as attendance at the 3 healthy lifestyle classes) and 73% for months 4–18 (defined as the percentage of follow-up calls that were successfully completed).

Messier, 2013

Type of study: RCT

Setting: University

Country: U.S.A.

Source of funding: National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute on Aging, National Center for Research Resources—and by General Nutrition Centers

Inclusion criteria:

Kellgren-Lawrence14 grade 2 or 3 (mild or moderate) radiographic tibiofemoral OA or tibiofemoral plus patellofemoral OA of one or both knees, pain on most days due to knee OA, a body mass index (BMI) from 27 through 41 (calculated as weight in kilograms divided by height in meters squared), and a sedentary lifestyle (< 30 minutes per week of formal exercise for the past 6 months)

Exclusion criteria:

Reported elsewhere, see article for details.

N total at baseline:

Intervention: 152

Control: 150

Important prognostic factors²:

Age ± SD:

I: 66 (6)

C: 66 (6)

Sex:

I: 29% M

C: 28% M

Weight loss intervention

A mean group loss of at least 10% of baseline weight, with a desired range between 10% and 15%.

The diet was based on partial meal replacements, including up to 2 meal-replacement shakes per day (Lean Shake; General Nutrition Centers). For the third meal, participants followed a weekly menu plan and recipes that were 500 to 750 kcal, low in fat, and high in vegetables.

As follow-up progressed, fewer meal replacements were consumed.

Exercise intervention

1 hour on 3 days/ week for 18 months.

Length of follow-up:

18 months

Loss-to-follow-up:

Intervention: N= 23/152

Reasons: cancellations, no contact, unhappy with group, personal or health issues, moved, no longer interested

Control: N= 22/150

Reasons: cancellations, no contact, unhappy with group, personal or health issues, moved, no longer interested

Incomplete outcome data:

Intervention: 5/129

Control: 6/134

Retention did not differ significantly among the groups and noncompleters did not differ significantly from completers in terms of age, sex, race, number of comorbidities, initial radiographic score, knee pain, or physical function.

Outcome measures and effect size (include 95%CI and p-value if available):

N in analysis:

I: 124; C: 128

Baseline vs follow-up

WOMAC subscale pain (lower score is better)

I: 6.6 vs 4.8

C: 6.1 vs 4.4

WOMAC function (lower score is better)

I: 24.8 vs 17.7

C: 23.1 vs 17.6

Physical performance

6-min walk (m)

I: 475 vs 502

C: 480 vs 525

Adherence

I: (number of individual and class sessions attended/number scheduled) was 61%.

C: (number of sessions I: completed/ number scheduled) was 66% for the first 6 months and 54% for 18months.

Christensen 2005

RCT

Outpatient clinic Dept Rheumatology; Denmark

Inclusion: Overweight, age>18 age, primary knee OA (ACR criteria), KL-grade 2 or 3, BMI>28; clear, unequivocal motivation for weight

loss

Exclusion: history or active presence of other rheumatic diseases that might be responsible for secondary OA; diabetes mellitus; other endocrine disorders or substantial abnormalities in hematological, hepatic, renal or cardiac functions

N total at baseline:

96 patients

Intervention: 44

Control: 45

9 dropouts: 4/5 in intervention and control

Analytic sample:

96 patients

Intervention: 40

Control: 40

Important prognostic factors²:

Age ± SD:

I: 60.5 (11.6)

C: 64.6 (10.4)

Sex:

I: 12% M

C: 10% M

BMI

I: 36.3

C: 35.5

Weight (kg)

I: 96.4

C: 97.1

LED (low-energy diet)

3.4 MJ/day

n=40

LED: nutrition powder in water, taken as six daily meals, meeting all recommendations for daily intake of high quality protein; 37 energy percent from protein, 47% from carbohydrate, 16% from vegetable fat, and fibers from oat-bran (15 g/day); nutritional instruction and behavioral therapy by experienced dietician at weekly sessions (1.5 h/week)

conventional diet

5 MJ/day

n=40

conventional diet: nutritional advice 2-h session at baseline, recommending ordinary foods in amounts, which would provide patients with approximately 5 MJ/day; patients received ideas for diet plans in a booklet; no contact with the dietician after the dietary consultation at baseline

Length of follow-up:

2 months (8 weeks)

Loss-to-follow-up:

Intervention: N= 4/44

Control: N= 5/45

analyses based on completers

Outcome measures and effect size (include 95%CI and p-value if available):

N in analysis:

I: 40; C: 40

WOMAC pain (lower = better)

change from baseline (SD)

Diff (95%CI)

I/C: -57.0 (16.9) vs -29.8 (17.7)

Diff= -27.2 (-64.0; 9.7)

p= 0.15 (NS)

WOMAC funct (lower = better)

change from baseline (SD)

Diff (95%CI)

I/C: -252.5 (49.6) vs -85.6 (51.9)

Diff= -166.9 (-274.5; -59.3) p=0.003

WOMAC stiffn (lower = better)

change from baseline (SD)

Diff (95%CI)

I/C: -22.6 (7.2) vs -10.2 (7.4)

Diff= -12.4 (-27.7; 2.8)

p= 0.11 (NS)