Effect of Group‐Based Outpatient Physical Therapy on Function After Total Knee Replacement: Results From a Multicenter Randomized Controlled Trial

Objective To evaluate the long‐term clinical effectiveness of a novel group‐based outpatient physical therapy (PT) following total knee replacement (TKR). Methods In this 2‐center, unblinded, superiority, randomized controlled trial, 180 patients on a waiting list for primary TKR due to osteoarthritis were randomized to a 6 session group‐based outpatient PT intervention and usual care (n = 89) or usual care alone (n = 91). The primary outcome was patient‐reported functional ability measured by the Lower Extremity Functional Scale at 12 months postoperative. Secondary outcomes included knee symptoms, depression, anxiety, and satisfaction. Questionnaires were completed preoperatively and at 3, 6, and 12 months postoperatively. Results The mean difference in function between groups was 4.47 (95% confidence interval [95% CI] 0.20, 8.75; P = 0.04) at 12 months postoperative, favoring the intervention. The mean difference in function between groups decreased over time, from 8.1 points at 3 months (95% CI 3.8, 12.4; P < 0.001) to 5.4 (95% CI 1.1, 9.8; P = 0.015) at 6 months postoperative. There were no clinically relevant differences in any secondary outcomes between groups, although patients in the intervention group were more likely to be satisfied with their PT. No serious adverse events related to the intervention were reported. Conclusion Supplementing usual care with this group‐based outpatient PT intervention led to improvements in function at 12 months after TKR, although the magnitude of the difference was below the minimum clinically important difference of 9 points. However, patient satisfaction was higher in the intervention group, and there was some evidence of clinically relevant improvements in function at 3 months.


INTRODUCTION
Total knee replacement (TKR) is a common opera tion, with ~100,000 TKRs performed annually in the NHS (1,2). The surgery is performed to reduce pain and im prove function for individuals with osteoarthritis; however, 20-30% of patients with TKR report long term disability (3), and 20% report chronic pain (4). These poor outcomes  can have a considerable negative impact on quality of life (5,6).
Physical therapy (PT) is often provided to patients under going TKR and aims to optimize physical function. PT can be provided before surgery, in the postoperative ward, or on an outpatient basis after surgery. There is conflicting evidence of the effectiveness of preoperative PT for improving postoperative functional outcome (7)(8)(9). Postoperative inpatient PT is focused on early functional recovery and independent mobilization to ensure safe hospital discharge rather than long term functional improvement. Outpatient PT has been shown to improve func tion up to 3 months after TKR, although there is insufficient evi dence to determine clinical effectiveness beyond 3 months after surgery (10).
In the UK, provision of PT after TKR is variable (11), and no definitive guidelines currently exist. Evidence is needed to guide the provision of effective PT services for patients with TKR. The primary aim of this randomized controlled trial (RCT) was to determine the clinical effectiveness of a novel group based outpatient PT intervention for improving long term function after primary TKR.

MATERIALS AND METHODS
Trial design. The Activity Orientated Rehabilitation Fol lowing Knee Arthroplasty (ARENA) study was a multicenter, pragmatic, unblinded, superiority RCT. Follow up assessments were performed at 3, 6, and 12 months postoperative, with a primary outcome of patient reported function at 12 months postoperatively. The trial was informed by a systematic review (10), survey of current practice (11), and feasibility study (12), and the protocol has been published previously (13). Reporting  Participants. NHS patients were recruited from preoper ative assessment clinics at 2 orthopedic centers in Bristol, UK: Southmead Hospital and Emersons Green Independent Treatment Centre. All patients provided informed written consent prior to par ticipation. Inclusion criteria were adults on the waiting list for pri mary TKR due to osteoarthritis. Exclusion criteria were as follows: the inability to participate in exercise for medical reasons; being unable/unwilling to attend PT classes postoperatively; being una ble/unwilling to provide informed consent; the inability to under stand English; and postoperative complications within the first 2 weeks of surgery that precluded participation in PT.

Randomization.
Participants were randomized with 1:1 treatment allocation to the intervention group or usual care group 2 weeks after TKR. Randomization with allocation con cealment was conducted by the trial manager or trial admin istrator (KL and WB) through the Bristol Clinical Trials and Evaluation Unit using a computer generated code that was administered centrally and communicated via the internet. Ran domization was stratified by preoperative function measured by the Lower Extremity Functional Scale (LEFS) (17) (categorized as high or low function based on mean scores from a previous study [18]) and recruitment center. Due to the nature of the intervention, it was not possible to blind participants and trial personnel.
Usual care. At hospital discharge following TKR, patients at both centers were assessed on an individual basis by the inpa tient PT team. All patients received advice on knee specific and functional exercises. Referral for outpatient PT was on a need only basis, with patients with poor range of motion or muscular weak ness being further referred for outpatient PT. Criteria for referral differed between the centers and are described in Supplementary

SIGNIFICANCE & INNOVATIONS
• This trial found that supplementing usual care with a novel group-based outpatient physical therapy (PT) intervention led to an improvement in patient-reported function. While there was some evidence that the short-term improvements were clinically important, the magnitude of the benefit was not sustained in the longer term after total knee replacement. • Patients randomized to the group-based outpatient PT intervention were more satisfied with their PT treatment than patients in the usual care group, and the group format was considered beneficial because it provided peer support, motivation, and increased confidence.
General practitioners could also refer patients for outpatient PT as appropriate.
Intervention. Participants who were allocated to the intervention group received the intervention in addition to usual care. The intervention was a novel 1 hour group based PT class, starting at 6 weeks after surgery and delivered on a weekly basis over 6 consecutive weeks (see Supplementary Material 2). The classes were in an NHS outpatient gymnasium and included individualized exercises within a group based task orientated exercise circuit. Classes were run on a rolling system with a max imum of 12 patients and supervised by 2 physical therapists or a physical therapist (NA) and PT technician. Delivery was in a group based setting, which is common in the NHS (11) and has been shown to be a cost effective way to deliver rehabilitation without compromising effectiveness (19).
Classes began with a short warm up, after which patients followed an exercise circuit consisting of 12 exercise stations. Ten stations were designed to increase leg strength, balance, func tion, and confidence using task related activities. Two stations were dedicated to individualized exercises, which were developed in the first class to help participants achieve their functional goals. Individualized exercises aimed to improve patients' ability to par ticipate in valued activities (20), to empower patients to take an active role in rehabilitation, and to increase self efficacy (21,22).
Graded exercises were provided at each station to enable the patients to exercise at an intensity level suitable to their ability. Exercises progressed on an individual basis through discussion with the physical therapists (see Supplementary Material 5, avail able on the Arthritis Care & Research web site at http://onlin elibr ary.wiley.com/doi/10.1002/acr.23909/ abstract). Participants were given an exercise booklet in which they recorded details about their weekly progress in the class. At the end of the intervention, participants were provided with an individualized home exercise plan. Attendance at sessions was recorded, and adherence to the intervention was predefined as attendance at ≥4 sessions.
Outcomes. Postal questionnaires were administered pre operatively and at 3, 6, and 12 months after TKR. Participants completed additional preoperative questions on demographics, socioeconomic status, and medical comorbidities (23).
Primary outcome. The primary outcome was functional ability measured by the LEFS (17) at 12 months postoperative. Twelve months was the primary end point because functional outcomes after TKR start to plateau around this time (24). The LEFS is a validated 20 item questionnaire assessing lower ex tremity function and difficulty in performing everyday tasks, with scores ranging from 0-80 (worst to best). Secondary outcomes. The LEFS was collected at 3 and 6 months to assess lower extremity function. Knee pain, symptoms, function in daily living, function in sports and rec reation, and knee related quality of life were assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) (25), with each subscale score ranging from 0 to 100 (worst to best). Depression and anxiety were assessed using the Hos pital Anxiety and Depression Scale (HADS) (26), with subscale scores ranging from 0 to 21 (best to worst). Patient satisfac tion was assessed using the Patient Satisfaction Scale (27), with scores ranging from 25 to 100 (worst to best). Satisfac tion with PT was assessed using a 5 point Likert type scale (ranging from very satisfied to very dissatisfied). Self reported use of PT services was also captured. Health care resource use data, including data from the EuroQol 5 domain question naire (28), were collected for the cost effectiveness analysis and will be reported separately.
Safety data. Participants self reported adverse events, and these were verified through medical records review. Serious adverse events (SAEs) were defined as any unto ward medical occurrence that resulted in death, was life threatening, required inpatient hospitalization/prolongation of existing hospitalization, or resulted in persistent or significant disability/incapacity. Process evaluation. Intervention. Participants who at tended the classes were telephoned by a researcher 1 month after the classes and asked about their experiences of the in tervention. Questions focused on satisfaction with the class es, which aspects were helpful or unhelpful, adherence to the home exercise plan, and any barriers to performing the exer cises. Responses were recorded on a standardized proforma, and free text data were analyzed using a descriptive content analysis.
Trial participation. After completion of the final questionnaire, all participants were telephoned and asked about their reasons for and experiences of participation and any perceived benefits or negative aspects to participation.
Sample size. The minimum clinically important difference (MCID) for the LEFS is 9 scale points (17). In our feasibility study (12), the pooled SD on the LEFS score at 6 months postoperative was 18.4 points. For the purposes of the sample size calculation, a similar SD for the LEFS at 12 months after TKR was assumed. To account for the uncertainty induced by estimating parameters from a small feasibility study, the assessed sample was adjusted by an inflation factor of 1.122, a value derived from the 80% upper confidence limit of the SD estimate (29). A sample of 166 (83 par ticipants per arm) would allow the detection of an MCID in the LEFS between trial arms at 12 months postoperatively, assuming a power of 80%, a 2 sided 5% significance level, and account ing for an inflation factor of 1.122. In our feasibility study, the rate of missing LEFS scores at 6 months postoperative was 9% in the intervention group and 35% in the usual care group. Assuming a 35% loss to follow up, 256 patients would need to be recruited to include data from 166 participants in the primary analysis. Statistical analysis. Analyses were performed accord ing to the statistical analysis plan (30). Baseline characteristics were reported by trial arm using percentages, means and SDs, or medians and interquartile ranges (IQRs), as appropriate. The repeated measures of primary and secondary outcomes were plotted by trial arm.
The analyses were conducted on an intent to treat basis. The main analysis consisted of a linear mixed regression (with random intercept for patient to control for the repeated follow up measures) with an interaction between the intervention effect and the assessment time, adjusted for stratification varia bles, preoperative function, and center (with fixed effects). The use of these interaction terms allowed the estimation of time specific effect of the intervention on the LEFS at 3, 6, and 12 months postoperative (primary outcome). Four separate sensitivity analy ses were conducted. First, the effect of clustering at surgeon level was investigated by adding an additional level to the previ ous linear mixed regression. Then, the analysis was adjusted for imbalanced individual characteristics between arms at baseline, followed by adjustment for whether additional PT was received. Finally, the primary outcome treatment effect was estimated using a per protocol approach. Given the differences in sex in TKR out comes (31), exploratory analysis was undertaken to investigate and compare the intervention effect by sex using interaction terms. An additional analysis was conducted to investigate the effect of class size on 12 month LEFS scores using linear regression.
The analyses were conducted with and without imputation of missing primary outcome data. Missing data were imputed using multiple imputation by chained equations under a miss ing at random assumption stratified by randomization (32). In a sensitivity analysis of the imputation method, missing data were also imputed using the value 10% greater than the mean and 10% smaller than the mean value of the observations for each outcome. The same modeling strategy was used to investigate the intervention effect on secondary outcomes. A similar strategy was used to impute the secondary outcomes.   Table 1. Some differences in anxiety levels, education level, and working status between groups were observed and adjusted for in      There was no evidence of differences in the mean total KOOS score, KOOS subscales, HADS anxiety or depression subscales, or in Patient Satisfaction Scale scores between groups at 3, 6, or 12 (Table 4 and Supplementary Material 11.3-11.11, available at http://onlin elibr ary.wiley.com/doi/10.1002/acr.23909/ abstract). However, patients in the intervention group were more likely to have high satisfaction with their PT than patients in the usual care group throughout the postoperative period (Table 4 and Supple Intervention evaluation. Sixty eight participants completed a structured telephone survey. Participants were generally satisfied with both the task orientated and individualized exercises. Most thought that the class length was appropriate, although 50% of participants would have liked more classes. Participants found it helpful to have 1:1 time with a physical therapist during the classes for individualized advice and support. The group format was considered beneficial be cause it provided peer support, motivation, and increased confidence. While some task related exercises were particularly helpful to some participants, they were too easy for other patients, highlighting the dif ficulty in delivering an intervention catering for individuals with different levels of functional ability.
Participants found the home exercise plan useful, and most reported that they were performing their home exercises 1 month after their final class. Reasons given for discontinuation were that patients were participating in other exercises or that they felt they had good functional ability. The most common challenges in adhering to the home exercises were a lack of access to gym equipment and difficulty fitting the exercises into daily routines.
Trial participation. A structured telephone survey was com pleted by 142 participants. Altruism was the most common reason for participation, with many eager to help future patients and be involved in generating evidence to inform improvements to health care. The potential for personal benefit was also a key motivation, with participants perceiving that allocation to the classes would be beneficial. The majority of participants had a positive experience of the trial, finding it enjoyable and easy to take part in. The main suggestions for improvements included shorter questionnaires that avoided questions that were per ceived to be irrelevant and repetitive.

DISCUSSION
This is the first trial to evaluate whether group based outpa tient PT can improve patient reported function up to 12 months after TKR in an NHS setting. Supplementing usual care with a novel group based outpatient PT intervention resulted in better patient reported function at 3, 6, and 12 months after TKR. How ever, the difference in function at 12 months was below the MCID, suggesting the intervention may not result in a clinically impor tant improvement in function. However, the intervention was safe, associated with higher patient satisfaction, and there was some evidence of a clinically important short term benefit at 3 months postoperatively.
This project was informed by a robust series of projects, including a feasibility study (12), in line with Medical Research Council guidance on complex interventions (33). PPI activities guided the design and management of the trial to ensure that the research was relevant and acceptable to patients. Patients were recruited from an NHS independent treatment center and an elec tive orthopedic center, thereby increasing the generalizability of the results. This was a pragmatic trial with patient eligibility criteria, intervention delivery, and nonstandardized usual care designed to reflect how the intervention would be delivered if implemented within usual NHS care. However, limitations of the trial should also be acknowledged when interpreting the results. As with many PT trials (34), blinding of the intervention was not possible, which could have led to an overestimation of the treatment effect (35). While this risk of bias may have influenced the positive short term effects, the decrease in treatment effect over time would have ren dered this bias less meaningful.
Another potential limitation is our use of the MCID threshold of the LEFS. Using the MCID allows a more meaningful evalua tion of the clinical relevance of the results rather than simply inter preting the results based on statistical significance. However, the MCID for the LEFS was derived from patients with a variety of lower extremity musculoskeletal conditions (17), which may limit the applicability to patients with TKR. It should also be acknowl edged that findings from our trial only relate to the specific PT intervention that we evaluated. However, other trials have reported similar findings. Since the publication of a systematic review that found insufficient evidence to evaluate the long term effectiveness of postdischarge PT (10), relevant trials have been published. An Australian trial found that an outpatient exercise program did not improve patient reported outcomes at 1 year after TKR compared to usual care (36). Another Australian trial found that 10 days of postdischarge inpatient PT and a monitored home exercise pro gram did not improve walking ability at 6 months after TKR com pared with a home exercise program only (37).
There are a number of potential reasons why our interven tion was only associated with a small improvement in function at 12 months after TKR. First, we limited the treatment to 6 classes to optimize the feasibility of the intervention being implemented into usual NHS practice if found to be effective. It is possible that a more intensive intervention may have had a beneficial effect; however, previous studies that have evaluated more inten sive interventions have found similar results (36)(37)(38). Also, no follow up support was provided to participants for their home exercise program, which may have resulted in participants not continuing an adequate amount of home exercises and con tributed to the short term benefits not being sustained in the longer term. Second, both groups had access to usual care and private PT because we wanted to assess the effectiveness of the intervention as implemented within the NHS setting. Very few trials compare a PT intervention to no care (10,39), and the purpose of our trial was to evaluate if the addition of group based PT to usual care could improve patient outcomes. This resulted in approximately one half of participants in both arms using usual care or private PT during the follow up, although PT usage was balanced between trial arms, and adjustment in sensitivity analyses produced similar results. Third, adherence to rehabilitation interventions is a common issue (40). Similar to a previous study (36), only one half of participants randomized to the intervention group attended all the classes. Per protocol analysis of the 78% of participants who met the prespecified adherence criteria found a larger treatment effect, and the 95% CIs suggest that the true difference at 12 months could reach a clinically meaningful level. This suggests a possible dose effect, which has been found previously (41), and that attending <6 sessions may not provide patients with an adequate interven tion level to change outcomes. Higher dose PT is unlikely to be pragmatic in the NHS; however, supplementing weekly classes with guidance on home exercises could be beneficial and war rants further research. Fourth, we used a patient reported out come measure to capture patients' experiences of their function, rather than objective measures or performance tests to evaluate their actual functional ability, because performance tests may not capture limitations experienced during important daily activ ities (42). However, self reported function is strongly influenced by pain (43,44), and the small difference in outcomes between groups may be because the intervention was not designed to reduce pain. The intervention may have shown a larger effect on objective outcomes or performance measures, which are less influenced by pain and more sensitive to changes in function (43,44). Further research is warranted.
In conclusion, addition of group based outpatient PT to usual NHS care led to improvements in function at 12 months after TKR, although the magnitude of the difference did not reach a clinically meaningful level. However, patient satisfaction was higher in the intervention group, and there were clinically relevant improvements in function at 3 months. This suggests that there is early benefit from PT with the potential for longer term bene fit. Recommendations for future research include evaluating the optimal mode of PT delivery to maximize patient benefit, including intensity, duration, progression, and support with home exercises. Our findings add to the evidence on the effectiveness of group based outpatient PT to guide decisions by clinicians and patients and to inform commissioning of services to ensure that patients receive optimal PT after TKR.