Osteoarthritis and Cartilage 26 (2018) 383e396

Physical therapy vs internet-based exercise training for patients with

knee osteoarthritis: results of a randomized controlled trial
K.D. Allen y z x *, L. Arbeeva y z, L.F. Callahan y z, Y.M. Golightly y k ¶, A.P. Goode # yy,
B.C. Heiderscheit zz, K.M. Huffman xx kk, H.H. Severson ¶¶, T.A. Schwartz y ## yyy
y Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, 3300 Thurston Bldg., CB# 7280, Chapel Hill, NC 27599, USA
z Department of Medicine, University of North Carolina at Chapel Hill, 125 MacNider Hall, CB# 7005 Chapel Hill, NC 27599, USA
x Center for Health Services Research in Primary Care, Durham VA Medical Center, Durham, NC, USA
k Injury Prevention Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
¶ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
# Duke Clinical Research Institute, Durham, NC, USA
yy Department of Orthopedic Surgery, Division of Physical Therapy, Duke University Medical Center, USA
zz Department of Orthopedics and Rehabilitation, University of WisconsineMadison, Madison, WI, USA
xx Department of Medicine, Division of Rheumatology, Duke University Medical Center, Durham, NC, USA
kk Physical Medicine and Rehabilitation Service, Durham VA Medical Center, Durham, NC, USA
¶¶ Oregon Research Institute, Eugene, OR, USA
## Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
yyy School of Nursing, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

a r t i c l e i n f o s u m m a r y

Article history: Objective: To compare the effectiveness of physical therapy (PT, evidence-based approach) and internet-
Received 31 May 2017 based exercise training (IBET), each vs a wait list (WL) control, among individuals with knee osteoar-
Accepted 16 December 2017 thritis (OA).
Design: Randomized controlled trial of 350 participants with symptomatic knee OA, allocated to stan-
Keywords: dard PT, IBET and WL control in a 2:2:1 ratio, respectively. The PT group received up to eight individual
Osteoarthritis
visits within 4 months. The IBET program provided tailored exercises, video demonstrations, and
Knee
guidance on progression. The primary outcome was the Western Ontario and McMaster Universities
Physical therapy
Internet
Osteoarthritis Index (WOMAC, range 0 [no problems]e96 [extreme problems]), assessed at baseline, 4
Physical activity months (primary time point) and 12 months. General linear mixed effects modeling compared changes
in WOMAC among study groups, with superiority hypotheses testing differences between each inter-
vention group and WL and non-inferiority hypotheses comparing IBET with PT.
Results: At 4-months, improvements in WOMAC score did not differ significantly for either the IBET or PT
group compared with WL (IBET: 2.70, 95% Confidence Interval (CI) ¼ 6.24, 0.85, P ¼ 0.14; PT: 3.36,
95% (CI) ¼ 6.84, 0.12, P ¼ 0.06). Similarly, at 12-months mean differences compared to WL were not
statistically significant for either group (IBET: 2.63, 95% CI ¼ 6.37, 1.11, P ¼ 0.17; PT: 1.59, 95%
CI ¼ 5.26, 2.08, P ¼ 0.39). IBET was non-inferior to PT at both time points.
Conclusions: Improvements in WOMAC score following IBET and PT did not differ significantly from the
WL group. Additional research is needed to examine strategies for maximizing benefits of exercise-based
interventions for patients with knee OA.
Trial registration: NCT02312713.
Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.

* Address correspondence and reprint requests to: K.D. Allen, Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, 3300 Thurston Bldg., CB#
7280, Chapel Hill, NC 27599, USA.
E-mail addresses: kdallen@email.unc.edu (K.D. Allen), liubov_arbeeva@med.unc.edu (L. Arbeeva), leigh_callahan@med.unc.edu (L.F. Callahan), golight@email.unc.edu
(Y.M. Golightly), adam.goode@duke.edu (A.P. Goode), heiderscheit@ortho.wisc.edu (B.C. Heiderscheit), kim.huffman@duke.edu (K.M. Huffman), herb@ori.org
(H.H. Severson), Todd_Schwartz@unc.edu (T.A. Schwartz).

https://doi.org/10.1016/j.joca.2017.12.008
1063-4584/Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.
384 K.D. Allen et al. / Osteoarthritis and Cartilage 26 (2018) 383e396
Introduction
Exercise is a recommended component of treatment for knee
osteoarthritis (OA), based on studies showing improvements in
pain, function and other outcomes1e3. However, the majority of
adults with OA are inactive, highlighting the continued need for
increasing regular engagement in exercise4,5. Physical therapists
can play a key role in instructing patients with OA in an appro-
priate exercise program (as well as deliver other treatments such
as orthotics, braces, gait aids and manual therapy), and physical
therapy (PT) care is a recommended, evidence-based component
of knee OA treatment2,6. However, PT is underutilized for knee
OA7e9, partly due to health care access-related issues, particularly
for uninsured and under-insured patients and those in medically
underserved areas. Individuals with lower socioeconomic status
likely have the least access to a physical therapist or a supervised
exercise program, yet these individuals also bear a greater burden
of OA10,11.
Internet-based programs are an alternative, low-cost method
for providing instruction and support in appropriate exercise.
However, there has been little research on internet-based exer-
cise programs for patients with OA12e15 or older adults16,17.
Further, there have been no direct comparisons of internet-based
exercise programs with supervised exercise-based therapies for
knee OA. This study compared the effectiveness of an internet-
based exercise training (IBET) program to in-person PT among
individuals with symptomatic knee OA. Specifically, this study
tested whether PT or IBET were superior to a wait list (WL)
control group at 4-month (primary time point) and 12-month
follow-up. Additionally, analyses examined whether IBET was
non-inferior to PT.
Methods
This study was approved by the Institutional Review Boards of
the University of North Carolina at Chapel Hill (UNC) and Duke
University Medical Center. Detailed methods have been pub-
lished18. Recruitment occurred from November 2014 to February
2016, and follow-up assessments were completed in February 2017.
Study design
The PT vs IBET for Patients with Knee Osteoarthritis (PATH-IN)
study was a pragmatic randomized controlled trial with partici-
pants assigned to standard PT, IBET and WL control, with allocation
of 2:2:1, respectively. Randomization schedules were computer
generated by a statistician with stratification by recruitment source
(UNC Healthcare system, Johnston County Osteoarthritis Project19
and self-referral). Participants continued with usual medical care
for OA. Participants in the WL group did not receive PT or IBET
during the study but were offered two PT visits and access to IBET
following 12-month assessments.
Participants and recruitment
Study inclusion criteria were: (1) Radiographic evidence of knee
OA, physician diagnosis of knee OA in the medical record, or self-
report of physician diagnosis along with items based on the
American College of Rheumatology clinical criteria20. (2) Self-
report of pain, aching or stiffness in one or both knees on most
days of the week. Exclusion criteria are shown in Box 1. Participants
were recruited using two methods: (1) Active recruitment of pa-
tients with evidence of knee OA in the UNC medical record, as well
as participants with knee OA in the Johnston County Osteoarthritis
Box 1
Exclusion Criteria.
 No regular internet access
 Currently meeting Department of Health and Human
Services Guidelines for physical activity
 Currently completing series of PT visits for knee OA
 Diagnosis of gout in the knee, rheumatoid arthritis,
fibromyalgia, or other systemic rheumatic disease
 Severe dementia or other memory loss condition
 Active diagnosis of psychosis or current uncontrolled
substance abuse disorder
 On waiting list for arthroplasty
 Hospitalization for a stroke, heart attack, heart failure, or
had surgery for blocked arteries in the past 3 months
 Total joint replacement knee surgery, other knee surgery,
meniscus tear, or ACL tear in the past 6 months
 Severely impaired hearing or speech
 Unable to speak English
 Serious or terminal illness as indicated by referral to
hospice or palliative care
 Other health problem that would prohibit participation in
the study
 Nursing home residence
 Current participation in another OA intervention
 Fall history deemed by a study physical therapist
co-investigator to impose risk for potential injury with
participation in a home-based exercise program study
Project19; these individuals were mailed an introductory letter,
with telephone follow-up. (2) Advertisement within UNC and the
surrounding communities. All individuals who met eligibility
criteria based on telephone-based screening completed consent
and baseline assessments in person. Participants were then given
their randomization assignment via telephone by the study
coordinator.
IBET program
The IBET program was developed by Visual Health Information
and a multidisciplinary team, including physical therapists, phy-
sicians and patients; details have been described14. Features of the
IBET program include: (1) Tailored Exercises based on measures
regarding pain, function and current activity, along with an al-
gorithm that assigns participants to one of seven different exercise
levels. Exercise routines include strengthening, stretching and
aerobic activity recommendations. (2) Exercise Progression rec-
ommendations, based on serial measures of pain and function. (3)
Video Display of Exercises (and photographs) to demonstrate
proper exercise performance. (4) Automated Reminders to engage
with the website and remain active if participants have not logged
in for 7 days. (5) Progress Tracking, including graphs of pain,
function, and exercise over time. Participants were asked to access
the IBET site as soon as they were randomized and to continue
through the 12-month follow-up assessment. In accordance with
current Department of Health and Human Services and other
guidelines for physical activity21, participants were encouraged to
complete strengthening and stretching exercises at least 3 times
per week and to engage in aerobic exercises daily, or as often as
possible.
 K.D. Allen et al. / Osteoarthritis and Cartilage 26 (2018) 383e396
PT
Physical therapists (with experience in treating OA) at multiple
clinics administered the intervention following training by PT co-
investigators (YMG, APG), who also performed periodic fidelity
checks. The PT intervention, described in detail elsewhere18, was
modeled after recommended elements of care provided to patients
with knee OA22, including: (1) evaluation of strength, flexibility,
mobility, balance, function, knee alignment, and possible limb
length inequality; (2) evaluation of the need for assistive devices,
knee braces, patellar taping, heel lifts, shoe wedges and other
footwear modifications; (3) instruction in an appropriate home
exercise program (including strengthening, stretching/range of
motion, and aerobic exercises); (4) instruction in activity pacing
and joint protection; (5) manual therapy, if appropriate; (6) mo-
dalities for pain management, if appropriate. Emphasis was placed
on the home exercise program, which was initiated at the first visit.
To mirror standard clinical practice, physical therapists were
permitted to tailor visits to patients' needs and functional limita-
tions. Based on a typical range of outpatient PT visits for knee OA,
study participants could receive up to eight one-hour sessions. At
the first visit, physical therapists completed a standardized evalu-
ation form and documented treatment provided. At subsequent
visits, physical therapists completed progress notes including
documentation of treatment provided. The Appendix lists the
guidance given to physical therapists.
Measures
Baseline, 4-month and 12-month assessments were conducted
by trained research assistants blinded (via database restrictions) to
participants' randomization assignment. Assessments were typi-
cally conducted in person, though telephone-based follow-up as-
sessments were permitted in cases where participants are unable
to return to the study site. Participants were paid $30 for comple-
tion of assessments at each time point.
Primary outcome: Western Ontario and McMaster Universities
Osteoarthritis Index (WOMAC) total score
The WOMAC is a measure of lower extremity pain (five items),
stiffness (two items), and function (17 items)23,24. All items were
rated on a Likert scale of 0 (no symptoms)e4 (extreme symptoms),
with a total range of 0e96 and higher scores indicating worse
symptoms.
Secondary outcomes
We examined the WOMAC pain (range 0 [no pain]e20 [extreme
pain]) and function (range 0 [no difficulty]68 [extreme difficulty])
subscales separately. We also conducted four tests of physical
function: the 30-second chair stand25, the Timed Up and Go
Test (TUG)26,27, a two-minute step test28, and unilateral stand
time29,30. The latter was part of the Four-Stage Balance Test30, and
participants scored a “0” if they were unable to stand for 10 s in
side-by-side, semi-tandem or tandem positions. Self-reported
physical activity was assessed with the Physical Activity Scale for
the Elderly (PASE), which measures occupational, household, and
leisure activities during a 1-week period; the typical range for the
total PASE score is 0e400, with higher scores indicating greater
activity31. In addition, participants self-reported their current
minutes per week of stretching, strengthening and aerobic exercise.
Participants' Global Assessment of Change in right and left knee
(separately) pain, aching and stiffness was reported at follow-up
assessments. This scale ranged from 6 (a very great deal worse)
to þ6 (a very great deal better); data were coded as missing if
385
participants never had symptoms in that knee or responded “don't
know.”
Intervention delivery
We report the number of days on which participants in the IBET
group logged into the website and the number of PT visits attended.
For each participant in the PT group we calculated the proportion of
visits at which the therapist reported delivering specific
interventions.
Non-study PT visits
At 4-month and 12-month follow-up, we asked participants
whether they received PT care for knee OA outside the study since
their last visit. This informed per-protocol analyses described below.
Demographic and clinical characteristics
Self-reported participant characteristics included age, race/
ethnicity, gender, household financial state (with low income
defined as self-report of “just meeting basic expenses” or “don't even
have enough to meet basic expenses”), education level (bachelor's
degree vs less education), work status (employed vs not working),
marital status, joints affected by OA, duration of OA symptoms,
self-rated health (excellent, very good or good vs fair or poor),
and depressive symptoms (Patient Health Questionnaire-8)32.
Height and weight were measured at baseline to calculate body
mass index (BMI). Participants also self-reported use of other OA
treatments at both follow-up time points, including pain medication
use, knee injections, knee brace use, and topical creams.
Adverse event assessment
Adverse events were identified through regular reports of par-
ticipants' visits to the UNC healthcare system, as well as through
participants' reports to study team members.
Sample size
As detailed elsewhere1, the sample size estimate of N ¼ 350 was
based on the hypothesis of non-inferiority, which is the most
conservative33e35, and on the 2:2:1 randomization ratio36. A one-
sided, two-sample t test sample size calculation was used at the
0.025 significance level for the difference in mean WOMAC be-
tween IBET and PT to be less than five points at 4-month follow-up,
with an adjustment to the variance to account for repeated mea-
sures37 and potential 10% attrition.
Data analyses
We tested four hypotheses: H1: Participants who receive either
IBET or standard PT will have clinically relevant improvements in
WOMAC at 4-month follow-up, compared with WL control group.
H2: IBET will be non-inferior to PT (an intervention with established
evidence6) at 4-month follow-up, indicated by a mean WOMAC
score less than five points higher (worse) than PT. For total WOMAC
scores, a five point non-inferiority margin was selected because it is
on the border of what would be considered a clinically important
effect in this context38,39. H3 and H4 mirrored H1 and H2 but at the
12-month follow-up time point. For the superiority hypotheses (H1,
H3), primary conclusions were based on intention-to-treat (ITT)
analyses, with participants assigned to the arm to which they were
randomized, regardless of adherence, using all available follow-up
data40. For non-inferiority hypotheses (H2, H4), the ITT analysis
would not necessarily be the conservative approach41. We therefore
performed analyses on both an ITT and per-protocol basis35,42. For
the latter we excluded individuals who did not adhere to their
386 K.D. Allen et al. / Osteoarthritis and Cartilage 26 (2018) 383e396
assigned study group, including those in the PT group (N ¼ 9) who
attended no visits, those in the IBET group who did not log on to the
website (N ¼ 28), and those in the IBET (N ¼ 5) and WL (N ¼ 4)
groups who received PT outside the study.
A general linear mixed effects model was fitted with changes
from baseline in WOMAC scores as the dependent variables with an
unstructured covariance matrix to account for the two follow-up
repeated measures. Fixed effects included follow-up time, inter-
vention group, their interaction, baseline WOMAC score, and
enrollment source. The SAS MIXED procedure (Cary, NC) was used
to fit these models and to test linear contrasts corresponding to
each hypothesis. Participants missing either follow-up measure-
ment were still included in the model under a ‘missing at random'
paradigm. Sensitivity analyses were also conducted through mul-
tiple imputation of missing values (see below).
To test the null hypothesis of non-inferiority of IBET vs standard
PT at 4 months in management of OA symptoms, the 95% confi-
dence interval (CI) of the appropriate linear contrast was con-
structed; non-inferiority was concluded if the upper limit of the
interval was less than the non-inferiority margin of five points42.
Superiority hypotheses involved two comparisons vs WL control, so
each was conducted at the two-sided 0.025 significance level. The
non-inferiority hypotheses involve only one comparison and were
tested at the full one-sided 0.025 significance level.
We had several strategies for handling missing data. When
individual items were missing from self-report scales, we followed
guidelines regarding when to impute scores43. When guidelines
were unavailable, we treated the scale as missing if >1 item was
missing; when one item was missing we substituted with the
mean of available items. When participants declined or could not
complete function tests they were assigned the lowest value for
that test; when participants ran out of time to complete function
tests or assessments were completed via telephone, data were
treated as missing. In some cases (four at 4-months, five at 12-
months), our data coding scheme did not allow us to differen-
tiate between these two situations; these were treated as missing.
For sensitivity analysis for the ITT approach, we performed mul-
tiple imputation to deal with missing data at follow-up assess-
ments via the SAS MI and MIANALYZE procedures, specifying 30
imputations. First, three missing race values were imputed based
on other participant characteristics. Then we identified baseline
characteristics that differed between completers and non-
completers at follow-up at the P  0.25 level. These characteris-
tics were used to impute missing baseline WOMAC values. Next,
missing 4-month WOMAC scores were imputed as a function of
these baseline characteristics, baseline WOMAC score, and treat-
ment group; imputation of 12-month WOMAC score also included
4-month WOMAC scores. The same imputation process was fol-
lowed for secondary outcomes.
Corresponding analytic strategies were used for secondary
outcomes, though there was insufficient information in the litera-
ture to define a non-inferiority margin for these measures. Addi-
tionally, as the Global Assessment of Change variables do not have
baseline values, the actual values (rather than change from base-
line) were managed as the response variable, with no baseline score
as a covariate. A square root transformation was used for the
weekly minutes of exercise variables to improve the residuals with
respect to the normality assumption. To provide comparison with
prior studies, we calculated standardized mean differences (SMDs)
for WOMAC total and subscale scores for both intervention groups
compared to WL (ratio of model-predicted mean group differences
to their pooled standard deviation (SD)).
Results
Participants and retention
We identified 11,274 potential participants from all recruitment
sources (Fig. 1). Of 683 who completed telephone screening, 350
(51%) were eligible, enrolled and randomized. Because randomi-
zation was stratified by enrollment source, allocation across groups
was slightly different than the 2:2:1 ratio, with 142 participants
assigned to the IBET group, 140 to the PT group and 68 to the WL
group. At both 4-month and 12-month follow-up, 86% of partici-
pants completed primary outcomes (Fig. 1). Compared with par-
ticipants who completed follow-up assessments for the primary
outcome at 12-months, non-completers had a higher baseline
mean WOMAC total score (31.2, SD ¼ 17.6 vs 37.6, SD ¼ 19.1,
respectively). Participant characteristics are shown in Table I. Par-
ticipants' use of other OA treatments at follow-up was similar
across groups (Appendix Table I).
Adverse events
There were four non-serious study-related events in the PT
group (one fall, three increased knee pain) and four in the IBET
group (two increased knee pain, one shoulder pain, one ankle pain).
Intervention delivery
Between baseline and 4-month follow-up, 114 (80%) of partici-
pants in the IBET group logged onto the website; the mean (SD)
number of days logged on was 20.7 (24.6), median ¼ 9.5. Between
baseline and 12-month follow-up, 115 (81%) of participants in the
IBET group logged onto the website with a mean (SD) number of
days logged on of 40.5 (59.8) median ¼ 10.5. The mean number of
days logged onto the website between 4-month and 12-month
follow-up was 19.8 (37.7), median ¼ 0. Seven physical therapists
contributed to intervention delivery, with numbers of participants
treated by each PT ranging from 2 to 40; this wide range was pri-
marily due to participants' geographic proximity to the different
study PT clinics. Among participants in the PT group, 131 (94%)
attended at least one visit; 51% attended 6e8 visits. The mean (SD)
number of visits was 5.7 (2.5), with a median of 7.0 visits. The mean
proportions of visits per patient at which therapists reported
delivering specific intervention components were: Therapeutic
Exercise e 94%; Balance/Neuromuscular Education e 38%; Manual
Therapy e 43%; Gait/Strength Training e 44%; Modalities e 29%;
and Shoes/Wedges e 20%.
Primary outcome: WOMAC total score
ITT analyses
Superiority hypotheses. Neither IBET nor PT were superior to WL at
4 months or 12 months at the specified P < 0.025 (Table II, Fig. 2).
Multiple imputation analyses showed similar results for both in-
terventions (Appendix Table II). At 4-months, the SMDs for PT and
IBET group, respectively were 0.26 (0.53, 0.00) and 0.20
(0.48, 0.07), compared to the WL group (Table III). At 12-months,
the SMDs for PT and IBET group, respectively were 0.12 (0.40,
0.16) and 0.19 (0.46, 0.09), compared to the WL group.
Non-inferiority hypotheses. Compared to PT, IBET effects were
within the pre-specified non-inferiority limit of five points on the
WOMAC total score at both 4-months (estimate ¼ 0.67, 95%
 K.D. Allen et al. / Osteoarthritis and Cartilage 26 (2018) 383e396 387

Identified from
Identified from
Self-Referrals Johnston County
UNC Medical
(SR) Osteoarthritis Project
Records
n=158 (JoCo) Database
n=10,860
n=256

Not Screened: n=4 Ineligible per Med Record

Ineligible per Not Screened: n=12
Review: n=304
Screener*: Ineligible per
Bad Contact Info: n=232
n=33 Screener*:
Not Screened: n=8595
Refused: n=33 n=77
Ineligible per Screener*: n=158
Refused: n=102
Refused: n=1309

Reasons for Ineligibility at

Screener (Total = 268)
No Knee OA = 88
No Internet Access = 64
Exclusionary Health
Condition = 48
Meeting Physical Activity
Total Screened Eligible: n=415
(SR: n=88, UNC: n=262, JoCo: n=65) Refused n=65
Recommendations = 13
Had Joint Replacement
Surgery = 10
Not English Speaker = 10
Deceased = 10
Receiving PT for OA = 7 Total Enrolled and Randomized: n=350
Moved Out of Area = 6 (SR: n=72, UNC: n=224, JoCo: n=54)
In Another OA Study = 5
Missing Data = 7

PT Group: IBET Group: Waitlist Control:

n=140 n=142 n=68

Dropped: n=4 Dropped: n=5 Dropped: n=0

Withdrew: n=0 Withdrew: n=13 Withdrew: n=1
Missed Visit: n=6 Missed Visit: n=8 Missed Visit: n=3
Lost to Follow Up: Lost to Follow Up: Lost to Follow Up:
n=0 n=2 n=3

4 Month Follow - 4 Month Follow - 4 Month Follow -

Up Completed: Up Completed: Up Completed:
n=130 n=114 n=61

Dropped: n=3 Dropped: n=5 Dropped: n=1

Withdrew: n=0 Withdrew: n=1 Withdrew: n=0
Missed Visit: n=0 Missed Visit: n=0 Missed Visit: n=0
Lost to Follow Up: Lost to Follow Up: Lost to Follow Up:
n=3 n=5 n=0

12 Month Follow 12 Month Follow 12 Month Follow

Up Completed: Up Completed: Up Completed:
n=129 n=112 n=63

Fig. 1. CONSORT diagram.

CI ¼ 2.23, 3.56; P ¼ 0.65) and 12-months (estimate ¼ 1.04, 95%
CI ¼ 5.26, 2.08; P ¼ 0.39), Fig. 3.
Per-protocol analyses. Per-protocol analyses yielded similar results
(Appendix Table III): The greatest difference was between PT and
WL at 4 months (3.65, 95% CI ¼ 7.34, 0.03, P ¼ 0.05). Differ-
ences between IBET and PT were within the pre-specified non-
inferiority limit at both time points.
Secondary outcomes
WOMAC subscales
In ITT analyses, changes in WOMAC pain and function did not
differ significantly between either intervention group and WL at 4
or 12 months (Table II). There were also no statistically significant
differences between PT and IBET (Appendix Table IV). Results were
similar in multiple imputation and per-protocol analyses for both
388 K.D. Allen et al. / Osteoarthritis and Cartilage 26 (2018) 383e396

Table I
Participant characteristics at baseline*

Characteristic All participants (N ¼ 350) IBET group (N ¼ 142) PT group (N ¼ 140) WL control (N ¼ 68)

Age, years 65.3 (11.1) 65.3 (11.5) 65.7 (10.3) 64.3 (12.2)
Women N (%) 251 (71.7%) 98 (69%) 100 (71.4%) 53 (77.9%)
Non-white race N (%) 95 (27.4%) 48 (33.8%) 29 (21%) 18 (26.9%)
Married or living with partner N (%) 215 (61.4%) 93 (65.5%) 80 (57.1%) 42 (61.8%)
Bachelors degree N (%) 208 (59.4%) 80 (56.3%) 86 (61.4%) 42 (61.8%)
Employed N (%) 141 (40.3%) 51 (35.9%) 59 (42.1%) 31 (45.6%)
Household financial status: low income N (%) 62 (17.8%) 29 (20.6%) 20 (14.3%) 13 (19.1%)
Fair or poor health N (%) 48 (13.7%) 22 (15.5%) 14 (10%) 12 (17.6%)
BMI, kg/m2 31.4 (8) 31.5 (7.8) 31.9 (8.6) 30.1 (7.3)
Joints with OA symptoms 5.4 (3.2) 5.2 (3.1) 5.5 (3) 5.5 (3.9)
Duration of OA symptoms, years 13.1 (11.7) 11.6 (11) 14.1 (11.6) 14.2 (13)
PHQ-8 score 3.8 (4.1) 3.7 (4.1) 4 (4.5) 3.6 (3.5)
WOMAC total 32.0 (17.9) 31.3 (17.5) 32 (17.7) 33.6 (19.2)
WOMAC pain subscale 6.1 (3.8) 6.0 (3.9) 6.1 (3.5) 6.2 (4.0)
WOMAC function subscale 22.5 (13.0) 21.8 (12.7) 22.6 (12.9) 23.9 (13.8)
PASE total score 126.9 (72.7) 132.3 (71.2) 121.4 (72) 126.9 (77.2)
PASE household score 75.2 (40.7) 81.6 (41.3) 70.4 (40.4) 71.8 (38.8)
PASE leisure score 21.6 (21.9) 22.4 (21.9) 20.9 (23.2) 21.5 (19.7)
PASE work score 30.7 (51.1) 30.5 (51.5) 29.1 (48.4) 34.2 (55.9)
Timed Up and Go, seconds 11.9 (4.3) 12 (4.6) 11.9 (4.2) 11.6 (3.7)
Unilateral stand test, seconds 7.2 (3.6) 7.3 (3.5) 7.3 (3.6) 6.7 (3.7)
30 s chair stand 9.5 (3.9) 9.5 (3.8) 9.5 (4.2) 9.6 (3.5)

Missing Data: non-white race ¼ 3, household financial status ¼ 1, WOMAC ¼ 2, Timed Up and Go ¼ 4, PASE total ¼ 10, PASE Household ¼ 5, PASE work ¼ 1, PASE Leisure ¼ 6.
PHQ ¼ Patient Health Questionnaire; WOMAC ¼ Western Ontario and McMaster Universities Osteoarthritis Index; PASE ¼ Physical Activity Scale for the Elderly.
*
Values are Mean (SD) unless otherwise specified.

WOMAC subscales (Appendix Tables II and III). Table III shows
SMDs for both interventions compared to WL.
PASE and weekly minutes of exercise
At 4 months there were no significant differences in PASE sub-
scale scores across groups (Table II). At 12 months the PT group had
significantly greater improvement in PASE Leisure subscale score
compared to WL (P ¼ 0.02). There were no notable differences in
multiple imputation or per-protocol analyses of PASE scores
(Appendix Tables II and III). There were no significant differences in
weekly minutes of strengthening or aerobic exercise across groups
at either time point (Table II). The PT group reported greater weekly
minutes of stretching than WL at both 4 and 12 months, and the
IBET reported greater minutes than WL at 12 months. Results were
similar in multiple imputation analyses. In per protocol analyses,
the PT group reported greater minutes of strengthening at 4
months and aerobic activity at 12 months compared to WL; the
IBET group reported greater minutes of aerobic activity at 4 and 12
months.
Functional tests
For both unilateral stand time and the 30 s chair stand test,
there were minimal within-group changes over time and no
between-group differences when using ITT (Table II), multiple
imputation or per-protocol analyses (Appendix Tables II and III).
For the 2-minute march test, the largest difference was between
the PT and WL groups at 4 months (ITT estimate ¼ 7.75, 95%
CI ¼ 0.43, 15.07, P ¼ 0.04), favoring the PT group; using multiple
imputation, this difference was 8.97 (95% CI ¼ 1.68, 16.26,
P ¼ 0.02). There were no statistically significant differences in the
TUG test for the PT or IBET groups compared to the WL group
(Appendix Table II).
Global assessment of knee symptom change
In ITT analyses for the right knee, the PT group reported greater
improvement than WL at 4 and 12 months, and the IBET group
reported greater improvement than WL at 12 months (Table II). At 4
months, IBET reported less improvement than the PT group. For the
left knee, the PT group reported more improvement than WL at 4
months, and the IBET group reported more improvement than WL
at 12 months. Results were similar for multiple imputed and per
protocol analyses.
Discussion
In this study there were no statistically significant nor clinically
meaningful differences in most study outcomes, including total
WOMAC score, between intervention groups and the WL group.
IBET was non-inferior to PT at both 4 and 12 months for the primary
outcome.
Given prior studies on the effectiveness of exercise and PT care
for knee OA3,6,44, it is unclear why the PT intervention was not su-
perior to WL for most outcomes. It is challenging to compare effects
across PT-based interventions due to heterogeneity in dose (e.g.,
number and duration of sessions), type and duration. However, a
meta-analysis of PT-related interventions for knee OA found that
with respect to pain, SMDs were 0.21 (0.35, 0.08) and 0.69
(1.24, 0.14) for programs focusing on aerobic and strengthening
exercise, respectively6. The SMD for pain immediately following our
PT intervention was smaller than these (0.14) and declined at 12
months. The meta-analysis found that with respect to disability/
function, SMDs were 0.21 (0.37, 0.04) and 0.16 (0.48, 0.16),
for programs focusing on aerobic and strengthening exercise,
respectively. The SMD for function immediately after our PT inter-
vention was somewhat larger than these (0.27), but declined to
0.19 at 12 months. Therefore, our PT intervention was comparable to
pooled estimates of prior PT-related studies regarding function but
less effective with respect to pain; overall these effect sizes were
small. We aimed for the PT intervention to mirror standard practice,
but effects may have been more robust with a greater exercise dose.
Recent meta-analyses of OA studies indicate that exercise-based
interventions adhering to American College of Sports Medicine
 K.D. Allen et al. / Osteoarthritis and Cartilage 26 (2018) 383e396 389

Table II
Within- and between-group mean changes in outcomes and 95% CIs: Results of ITT analyses

Outcome Baseline to 4-month Difference in baseline to Baseline to 12-month Difference in baseline to

difference (95% CI) 4-month vs WL (95% CI), P-value difference (95% CI) 12-month vs WL (95% CI), P-value

WOMAC total (N ¼ 348)*

WL 3.37 (6.33, 0.41) e 2.83 (5.93, 0.27) e
PT 6.73 (8.86, 4.6) 3.36 (6.84, 0.12), 0.06 4.42 (6.66, 2.17) 1.59 (5.26, 2.08), 0.39
IBET 6.06 (8.29, 3.84) 2.70 (6.24, 0.85), 0.14 5.46 (7.82, 3.09) 2.63 (6.37, 1.11), 0.17
WOMAC function (N ¼ 348)
WL 2.3 (4.46, 0.14) e 1.51 (3.76, 0.74) e
PT 4.77 (6.32, 3.23) 2.48 (5.02, 0.07), 0.06 3.3 (4.91, 1.68) 1.79 (4.45, 0.87), 0.19
IBET 3.74 (5.36, 2.12) 1.44 (4.03, 1.15), 0.27 3.4 (5.11, 1.7) 1.90 (4.61, 0.82), 0.17
WOMAC pain (N ¼ 350)
WL 0.66 (1.41, 0.09) e 0.64 (1.38, 0.09) e
PT 1.11 (1.65, 0.58) 0.45 (1.33, 0.42), 0.31 0.7 (1.23, 0.16) 0.05 (0.92, 0.81), 0.90
IBET 1.59 (2.15, 1.02) 0.93 (1.82, 0.03), 0.04 1.15 (1.71, 0.59) 0.51 (1.39, 0.38), 0.26
PASE total (N ¼ 340)
WL 4.7 (21.04, 11.64) e 1.17 (13.11, 15.45) e
PT 2.25 (9.18, 13.68) 6.95 (12.31, 26.22) , 0.48 8.28 (2.01, 18.56) 7.11 (9.69, 23.91), 0.41
IBET 11.52 (23.79, 0.74) 6.82 (26.55, 12.91), 0.50 8.19 (2.99, 19.37) 7.02 (10.31, 24.35), 0.43
PASE leisure (N ¼ 344)
WL 2.41 (7.49, 2.66) e 0.11 (6.25, 6.04) e
PT 3.27 (0.28, 6.82) 5.68 (0.25, 11.62), 0.06 8.68 (4.3, 13.05) 8.78 (1.46, 16.1), 0.02
IBET 1.34 (5.14, 2.46) 1.07 (5.70, 0.14), 0.73 7.66 (2.94, 12.39) 7.77 (0.25, 15.29), 0.04
PASE household (N ¼ 345)
WL 5.32 (14.49, 3.84) e 3.42 (11.59, 4.75) e
PT 1.07 (7.50, 5.36) 4.25 (6.59, 15.09), 0.44 2.3 (3.61, 8.21) 5.72 (3.94, 15.38), 0.25
IBET 9.16 (16.11, 2.21) 3.84 (14.99, 7.31), 0.50 3.72 (10.13, 2.69) 0.3 (10.26, 9.67), 0.95
PASE Work (N ¼ 349)
WL 2.35 (8.45, 13.15) e 5.24 (4.49, 14.98) e
PT 0.98 (6.53, 8.48) 1.37 (14.12, 11.37), 0.83 2.62 (9.58, 4.34) 7.86 (19.36, 3.63), 0.18
IBET 2.00 (10.01, 6) 4.35 (17.39, 8.69), 0.51 5.25 (2.2, 12.69) 0.00 (11.78, 11.79), 1.00
Unilateral stand time (N ¼ 350)
WL 0.04 (0.75, 0.82) e 0.09 (0.88, 0.69) e
PT 0.59 (1.15, 0.03) 0.63 (1.56, 0.30), 0.19 0.05 (0.6, 0.50) 0.04 (0.89, 0.98), 0.93
IBET 0.02 (0.57, 0.61) 0.02 (0.97, 0.93), 0.97 0.05 (0.64, 0.53) 0.04 (0.91, 1.00), 0.93
30 s chair stand (N ¼ 350)
WL 0.18 (0.87, 1.23) e 0.66 (0.27, 1.58) e
PT 0.13 (0.87, 0.61) 0.31 (1.55, 0.94), 0.63 0.16 (0.49, 0.82) 0.49 (1.58, 0.60), 0.37
IBET 0.50 (0.29, 1.28) 0.32 (0.95, 1.59), 0.62 0.90 (0.20, 1.60) 0.24 (0.87, 1.35), 0.67
2 m march test (N ¼ 350)
WL 8.43 (14.61, 2.24) e 0.00 (6.49, 6.48) e
PT 0.68 (5.07, 3.71) 7.75 (0.43, 15.07), 0.04 1.11 (3.45, 5.67) 1.12 (6.59, 8.82), 0.78
IBET 3.54 (8.20, 1.11) 4.88 (2.56, 12.33), 0.20 1.12 (3.76, 6) 1.13 (6.74, 8.99), 0.78
Timed Up and Go (N ¼ 346)
WL 0.23 (1.24, 0.78) e 0.26 (1.4, 0.87) e
PT 0.62 (1.34, 0.09) 0.39 (1.58, 0.8), 0.52 0.77 (1.57, 0.04) 0.5 (1.86, 0.85), 0.46
IBET 0.87 (1.63, 0.11) 0.64 (1.85, 0.58), 0.30 1.49 (2.35, 0.63) 1.22 (2.61, 0.16), 0.08
Weekly minutes of aerobic activity**
WL 0.09 (1.53, 1.35) e 1.59 (3.21, 0.04) e
PT 1 (0.02, 2.02) 1.09 (0.61, 2.8), 0.21 0.48 (0.67, 1.63) 2.07 (0.13, 4), 0.04
IBET 1.79 (0.71, 2.88) 1.89 (0.15, 3.62), 0.03 0.41 (0.82, 1.63) 1.99 (0.01, 3.97), 0.05
Weekly minutes of stretching**
WL 0.4 (1.39, 0.6) e 1.34 (2.24, 0.44) e
PT 1.45 (0.76, 2.15) 1.85 (0.67, 3.03), 0.00 0.27 (0.37, 0.92) 1.62 (0.55, 2.68), 0.00
IBET 0.97 (0.23, 1.72) 1.37 (0.16, 2.57), 0.03 0.72 (0.04, 1.41) 2.07 (0.98, 3.16), 0.00
Weekly minutes of strengthening**
WL 0.43 (0.69, 1.54) e 0.14 (1.32, 1.04) e
PT 1.78 (0.99, 2.57) 1.36 (0.05, 2.66), 0.04 1.07 (0.23, 1.91) 1.21 (0.18, 2.6), 0.09
IBET 1.27 (0.44, 2.11) 0.85 (0.49, 2.19), 0.22 1.21 (0.32, 2.1) 1.35 (0.08, 2.78), 0.06
Patient global assessment of change e right Knee
WL 0.15 (0.36, 0.66) e 0.18 (0.69, 0.33) e
PT 1.36 (0.99, 1.73) 1.21 (0.6, 1.81), 0.00 0.58 (0.2, 0.96) 0.76 (0.15, 1.37), 0.01
IBET 0.42 (0.03, 0.82) 0.27 (0.35, 0.89), 0.39 0.53 (0.12, 0.94) 0.71 (0.08, 1.33), 0.03
Patient global assessment of change e left Knee
WL 0.09 (0.64, 0.45) e 0.38 (0.95, 0.19) e
PT 0.93 (0.56, 1.31) 1.03 (0.39, 1.66), 0.00 0.17 (0.24, 0.59) 0.56 (0.12, 1.23), 0.11
IBET 0.46 (0.06, 0.86) 0.56 (0.1, 1.21), 0.09 0.57 (0.13, 1.01) 0.95 (0.26, 1.64), 0.01

Notes: Between-group comparisons refer to changes from baseline for each intervention group relative to the WL group. Results are least-squares means and mean differences
(and corresponding 95% CIs) from separate general linear mixed effects models, as described in the Methods.
WOMAC ¼ Western Ontario and McMaster Universities Osteoarthritis Index; PASE ¼ Physical Activity Scale for the Elderly.
*
Indicates number included in the statistical model for that outcome.
**
A square root transformation was applied due to superior diagnostics in statistical models.
390 K.D. Allen et al. / Osteoarthritis and Cartilage 26 (2018) 383e396

Although IBET was non-inferior to PT for most outcomes, these

results should be interpreted in light of the small, non-significant
effects of the PT intervention. Effect sizes for the IBET interven-
tion were also small. There has been little research on internet-
based exercise programs for knee OA, but in two prior studies,
effects were somewhat greater than in our study14,15. Both of those
prior studies recruited participants via self-referral or opt-in after
clinician referral, which may have resulted in more highly moti-
vated samples with greater “readiness to change” compared to our
participants, who recruited participants proactively by the study
team18. Engagement with the IBET program was relatively low,
highlighting the need for strategies to facilitate use of these types
of programs and identify patients who may be most likely to
benefit.
There are several limitations to our study. First, we did not
confirm OA diagnosis with standardized de novo radiographs or
independent physician assessments. However, all participants had
either a prior radiographic or physician diagnosis of OA (in the
medical record or self-reported), so it is very unlikely there were
Fig. 2. Estimated mean WOMAC Total Scores and 95% CIs by Group and Time Point.
participants without either radiographic or symptomatic OA. Sec-
ond, self-reported physical activity is often over-reported. However,
it is unlikely that this differed among study groups. Third, we did
not assess adherence to home exercise. Fourth, because this was a
pragmatic study, physical therapists were permitted to vary the
Table III intervention in terms of specific exercises assigned and intensity,
SMDs and 95% CIs for IBET and PT vs WL control group based on participant needs; this approach has advantages
regarding the study of real-world PT practice but presents chal-
Outcome 4 Months 12 Months
lenges in evaluating effects of a specific exercise dose. Fifth, this
WOMAC total study was conducted in one geographic region and only included
PT 0.26 (0.53, 0.00) 0.12 (0.40, 0.16)
IBET 0.20 (0.48, 0.07) 0.19 (0.46, 0.09)
participants with regular internet access, which may limit gener-
WOMAC function alizability of findings. Sixth, this sample was relatively well
PT 0.27 (0.52, 0.01) 0.19 (0.45, 0.08) educated, and results may not generalize to patient groups with
IBET 0.15 (0.43, 0.13) 0.19 (0.45, 0.08) lower education levels.
WOMAC pain
In conclusion, in this pragmatic study neither the PT nor IBET
PT 0.14 (0.39, 0.11) 0.02 (0.31, 0.27)
IBET 0.28 (0.41, 0.15) 0.15 (0.39, 0.09) intervention resulted in statistically significant or clinically relevant
improvement in most outcomes, compared to a WL control group.
Effects of both interventions may have been robust if the dose had
been greater44,45. In agreement with a recent systematic review46,
dose recommendations resulted in larger improvements44,45. results of this study suggest additional research is needed to
Additional work is needed to develop strategies for standardizing develop strategies for maximizing the effectiveness of PT in-
and implementing these recommendations within the structure and terventions, including understanding which PT treatments work
limited number of visits typically allowed for routine PT care for best for which patients and optimizing intervention dose in the
knee OA. context of real-world clinical settings.

Fig. 3. Comparison of change in WOMAC total scores between IBET and PT group (non-inferiority hypotheses): Results of intent-to-treat analyses.
 K.D. Allen et al. / Osteoarthritis and Cartilage 26 (2018) 383e396 391

Competing interests Appendix. Guidance for structure and content of PT visits

Visual Health Information, Inc (VHI) owns the website used in the
current manuscript. Heiderscheit and Seversen have received 1. Programs, both in the clinic and at home, should be compre-
consulting fees from VHI. A patent related to the website described hensive and functional, focusing on core and lower body func-
in this manuscript is currently under review. tion, but can be tailored to meet the functional abilities, needs
and deficits of each participant.
Role of the funding 2. Each visit should emphasize therapeutic exercise and include
This study was funded through a Patient-Centered Outcomes muscle strengthening, stretching/flexibility/range of motion,
Research Institute Award (CER-1306-02043). The statements, and aerobic exercise.
opinions presented in this manuscript are solely the responsibility 3. Education on activity pacing, joint protection and pain
of the authors and do not necessarily represent the views of the management.
Patient-Centered Outcomes Research Institute, its Board of Gover- 4. A home program should be recommended during the first visit
nors or Methodology Committee. KDA, LA, LFC, YMG, APG, and TAS and should be progressed over the course of treatment.
receive support from National Institute of Arthritis and Musculo- 5. Home programs should emphasize the following:
skeletal and Skin Diseases Multidisciplinary Clinical Research a. Strengthening Exercises
Center P60 AR062760. KDA receives support from the Center for i. Recommend performing strengthening exercises 2e3
Health Services Research in Primary Care, Durham VA Health Care times per week
System (CIN 13-410). ii. Include functional exercises, such as gait or stair training
and neuromuscular education
b. Stretching/flexibility/range of motion Exercises
Authors contributions
i. Recommend performing range of motion exercises daily
KDA, LA, LFC, YMG, APG, BCH, KMH, HS and TAS contributed to the
c. Aerobic Exercises
study design and protocol and helped draft the manuscript. HS and
i. Promote “lifestyle” physical activity
BCH contributed to the original design and evaluation of the exer-
ii. Encourage moderate intensity exercise
cise website. TS and LA contributed to plans for and conduct of
iii. Episodes of activity should last at least 10 min, if the
statistical analyses. All authors read and approved the final
participant is able
manuscript. YMG and APG oversaw design and fidelity checks for
iv. Episodes should be spread out throughout the week with
the PT intervention.
a long-term goal of working up to a total of 150 min of
activity per week
Acknowledgements v. Aerobic exercise can be weight-bearing, reduced weight-
bearing or non-weight-bearing.
The study team thanks all of the study participants, without 6. Modalities for pain management can be included during the
whom this work would not be possible. We also thank the clinic visit and as part of the home program. Modalities should
following team members for their contributions to the research: be used conservatively, taking no more than 25% of the time of
Caroline Nagle, Kimberlea Grimm, Ashley Gwyn, Bernadette each clinic visit.
Benas, Alex Gunn, Leah Schrubbe, and Quinn Williams. The study 7. If appropriate, manual therapy and/or patellar taping can be
team also expresses gratitude to the Stakeholder Panel for this provided during the clinic visit.
project: Ms Sandy Walker LPN (Chapel Hill Children's Clinic), 8. Shoes should be assessed during the first visit, and shoe rec-
Ms Susan Pedersen RN BSN, Ms Sally Langdon Thomas, Mr Ralph ommendations should be provided, if appropriate.
B. Brown, Ms Frances Talton CDA RHS Retired, Dr Katrina 9. If limb length inequality or frontal plane knee malalignment is
Donahue, MD, MPH (Department of Family Medicine at the suspected, treatment with shoe lifts or shoe wedges, respec-
University of North Carolina at Chapel Hill), Dr Alison Brooks, tively, should be attempted.
MD, MPH (Department of Orthopedics & Rehabilitation at the
University of Wisconsin-Madison), Dr Anita Bemis-Dougherty,
PT, DPT, MAS (American Physical Therapy Association), Appendix Table 1
Dr Teresa J. Brady, PhD (Centers for Disease Control and Pre- Proportions of participants reporting use of specific OA treatments by group and
follow-up time point
vention), Ms Laura Marrow (Arthritis Foundation National Of-
fice), Ms Megan Simmons Skidmore (American Institute of % of Participants self-reporting IBET PT WL
Healthcare and Fitness), and Dr Maura Daly Iversen, PT, DPT, SD, use of treatment
MPH, FNAP, FAPTA (Department of Physical Therapy, Movement Pain medications for osteoarthritis
and Rehabilitation Sciences Northeastern University). The study 4-Month follow-up 65% 55% 60%
team thanks study physical therapists and physical therapy as- 12-Month follow-up 59% 57% 52%
Knee injection since baseline
sistants: Jennifer Cooke, PT, DPT, Jyotsna Gupta, PT, PhD and
4-Month follow-up 7% 7% 12%
Carla Hill, PT, DPT, OCS, Cert MDT (Division of Physical Therapy, 12-Month Follow-Up 14% 12% 21%
University of North Carolina at Chapel Hill), Bruce Buley, Andrew PT (non-study) for knee OA
Genova, and Ami Pathak (Comprehensive Physical Therapy, since last study visit
4-Month follow-up 5% 1% 7%
Chapel Hill, NC), Chris Gridley and Aaron Kline (Pivot Physical
12-Month follow-up 12% 7% 11%
Therapy, Smithfield, NC). Knee brace (current)
4-Month follow-up 19% 19% 20%
Supplementary data 12-Month follow-up 19% 20% 17%
Topical creams (current)
4-Month follow-up 24% 23% 22%
Supplementary data related to this article can be found at 12-Month follow-up 29% 28% 24%
https://doi.org/10.1016/j.joca.2017.12.008.
392 K.D. Allen et al. / Osteoarthritis and Cartilage 26 (2018) 383e396

Appendix Table 2
Within- and between-group mean changes in outcomes and 95% CIs: Results of ITT analyses with multiple imputation

Outcome Baseline to 4-month Difference in baseline to Baseline to 12-month Difference in baseline to

difference (95% CI) 4-month vs WL (95% CI), P-value difference (95% CI) 12-month vs WL (95% CI), P-value

WOMAC total
WL 3.29 (6.29, 0.29) e 2.95 (6.04, 0.15) e
PT 6.85 (9.01, 4.69) 3.56 (7.16, 0.04), 0.05 4.72 (6.96, 2.48) 1.77 (5.38, 1.84), 0.34
IBET 6.00 (8.19, 3.82) 2.71 (6.28, 0.86), 0.14 5.68 (8.03, 3.32) 2.73 (6.50, 1.04), 0.16
WOMAC function
WL 2.31 (4.45, 0.17) e 1.63 (3.95, 0.68) e
PT 4.97 (6.50, 3.43) 2.66 (5.20, 0.11), 0.04 3.39 (5.04, 1.75) 1.76 (4.48, 0.96), 0.21
IBET 3.97 (5.57, 2.37) 1.66 (4.29, 0.97), 0.22 3.75 (5.41, 2.10) 2.12 (4.85, 0.62), 0.13
WOMAC pain
WL 0.65 (1.4, 0.10) e 0.65 (1.39, 0.09) e
PT 1.12 (1.66, 0.58) 0.47 (1.36, 0.41), 0.29 0.71 (1.26, 0.17) 0.06 (0.94, 0.81), 0.89
IBET 1.53 (2.12, 0.95) 0.89 (1.8, 0.03), 0.06 1.12 (1.65, 0.58) 0.47 (1.33, 0.40), 0.29
PASE total
WL 2.72 (19.05, 13.61) e 1.96 (12.93, 16.85) e
PT 2.49 (9.08, 14.07) 5.21 (13.91, 24.33), 0.59 7.91 (2.86, 18.69) 5.95 (11.31, 23.22), 0.50
IBET 11.25 (24.37, 1.88) 8.53 (27.33, 10.26), 0.37 9.43 (2.12, 20.99) 7.47 (10.23, 25.18), 0.41
PASE leisure
WL 2.73 (8.15, 2.69) e 0.23 (6.49, 6.03) e
PT 4.01 (0.44, 7.58) 6.74 (0.56, 12.92), 0.03 8.81 (4.45, 13.16) 9.04 (1.67, 16.40), 0.02
IBET 1.00 (4.91, 2.91) 1.74 (4.59, 8.06), 0.59 7.69 (3.09, 12.28) 7.92 (0.55, 15.29), 0.04
PASE household
WL 5.65 (14.68, 3.37) e 4.05 (12.07, 3.97) e
PT 2.05 (8.34, 4.24) 3.60 (7.05, 14.25), 0.51 2.02 (3.85, 7.88) 6.07 (3.55, 15.68), 0.22
IBET 8.83 (15.61, 2.05) 3.18 (14.04, 7.69), 0.57 4.12 (10.69, 2.44) 0.07 (10.06, 9.92), 0.99
PASE work
WL 4.38 (6.81, 15.56) e 5.67 (4.10, 15.44) e
PT 1.45 (6.01, 8.91) 2.93 (15.79, 9.93), 0.66 2.76 (9.64, 4.11) 8.43 (19.85, 2.98), 0.15
IBET 1.32 (9.51, 6.87) 5.70 (19.48, 8.08), 0.42 5.87 (1.30, 13.04) 0.20 (11.46, 11.86), 0.97
Unilateral stand time
WL 0.12 (0.90, 0.66) e 0.14 (0.94, 0.65) e
PT 0.53 (1.08, 0.02) 0.41 (1.32, 0.50), 0.38 0.02 (0.55, 0.52) 0.13 (0.81, 1.06), 0.79
IBET 0.08 (0.53, 0.70) 0.20 (0.77, 1.18), 0.68 0.02 (0.54, 0.58) 0.16 (0.78, 1.11), 0.73
30 s chair stand
WL 0.10 (0.95, 1.16) e 0.55 (0.38, 1.49) e
PT 0.06 (0.80, 0.68) 0.16 (1.41, 1.09), 0.80 0.13 (0.54, 0.80) 0.43 (1.54, 0.69), 0.45
IBET 0.67 (0.10, 1.43) 0.56 (0.72, 1.85), 0.39 0.86 (0.18, 1.55) 0.31 (0.84, 1.45), 0.60
2 m march test
WL 8.83 (14.99, 2.67) e 0.09 (6.67, 6.50) e
PT 0.14 (4.20, 4.48) 8.97 (1.68, 16.26), 0.02 1.06 (3.68, 5.79) 1.14 (6.69, 8.98), 0.77
IBET 2.38 (6.88, 2.11) 6.45 (0.99, 13.88), 0.09 1.35 (3.51, 6.20) 1.43 (6.80, 9.67), 0.73
Timed Up and Go
WL 0.11 (1.14, 0.91) e 0.31 (1.43, 0.80) e
PT 0.56 (1.30, 0.17) 0.45 (1.63, 0.73), 0.45 0.94 (1.75, 0.13) 0.62 (1.98, 0.73), 0.37
IBET 0.90 (1.74, 0.06) 0.79 (2.08, 0.50), 0.23 1.47 (2.36, 0.58) 1.16 (2.58, 0.27), 0.11
Weekly minutes of aerobic activity*
WL 0.05 (1.48, 1.38) e 1.68 (3.32, 0.05) e
PT 0.98 (0.03, 1.99) 1.03 (0.67, 2.73), 0.23 0.51 (0.65, 1.66) 2.19 (0.24, 4.13), 0.03
IBET 1.88 (0.76, 3) 1.93 (0.25, 3.62), 0.02 0.49 (0.77, 1.74) 2.17 (0.15, 4.18), 0.03
Weekly minutes of stretching*
WL 0.36 (1.38, 0.65) e 1.29 (2.19, 0.38) e
PT 1.45 (0.76, 2.15) 1.81 (0.62, 3), 0.00 0.36 (0.28, 1) 1.65 (0.58, 2.72), 0.00
IBET 1.08 (0.31, 1.85) 1.44 (0.22, 2.67), 0.02 0.8 (0.09, 1.51) 2.09 (1, 3.17), 0.00
Weekly minutes of strengthening*
WL 0.43 (0.69, 1.55) e 0.1 (1.28, 1.08) e
PT 1.85 (1.04, 2.65) 1.42 (0.11, 2.72), 0.03 1.17 (0.33, 2.02) 1.27 (0.12, 2.67), 0.07
IBET 1.47 (0.63, 2.32) 1.04 (0.31, 2.39), 0.13 1.32 (0.38, 2.26) 1.42 (0.03, 2.87), 0.05
Patient global assessment of change e right Knee
WL 0.14 (0.39, 0.67) e 0.17 (0.69, 0.36) e
PT 1.36 (0.97, 1.74) 1.22 (0.58, 1.86), 0.00 0.60 (0.2, 1.01) 0.77 (0.14, 1.4), 0.02
IBET 0.43 (0.04, 0.83) 0.30 (0.33, 0.92), 0.35 0.53 (0.13, 0.94) 0.70 (0.04, 1.36), 0.04
Patient global assessment of change e left Knee
WL 0.1 (0.66, 0.45) e 0.39 (0.96, 0.17) e
PT 0.94 (0.56, 1.33) 1.05 (0.4, 1.7), 0.00 0.16 (0.27, 0.59) 0.55 (0.14, 1.24), 0.11
IBET 0.50 (0.1, 0.9) 0.60 (0.07, 1.27), 0.08 0.58 (0.15, 1.02) 0.98 (0.28, 1.68), 0.00
*
A square root transformation was applied due to superior diagnostics in statistical models.
 K.D. Allen et al. / Osteoarthritis and Cartilage 26 (2018) 383e396 393

Appendix Table 3
Within- and between-group mean changes in outcomes and 95% CIs: Results of per protocol analyses

Outcome Baseline to 4-month Difference in baseline to Baseline to 12-month Difference in baseline to

difference (95% CI) 4-month vs WL (95% CI), P-value difference (95% CI) 12-month vs WL (95% CI), P-value

WOMAC total
WL 3.64 (6.8, 0.48) e 2.74 (6, 0.53) e
PT 7.29 (9.56, 5.03) 3.65 (7.34, 0.03), 0.05 4.71 (7.07, 2.35) 1.97 (5.81, 1.86), 0.31
IBET 6 (8.53, 3.46) 2.36 (6.23, 1.51), 0.23 5.84 (8.48, 3.19) 3.1 (7.13, 0.93), 0.13
WOMAC function
WL 2.48 (4.79, 0.18) e 1.37 (3.72, 0.97) e
PT 5.2 (6.83, 3.56) 2.71 (5.4, 0.02), 0.05 3.58 (5.26, 1.9) 2.21 (4.96, 0.55), 0.11
IBET 3.79 (5.63, 1.95) 1.31 (4.13, 1.52), 0.36 3.75 (5.65, 1.86) 2.38 (5.27, 0.51), 0.11
WOMAC pain
WL 0.7 (1.49, 0.09) e 0.68 (1.46, 0.1) e
PT 1.19 (1.75, 0.62) 0.49 (1.41, 0.43), 0.29 0.69 (1.25, 0.13) 0.01 (0.92, 0.9), 0.98
IBET 1.59 (2.22, 0.95) 0.89 (1.86, 0.08), 0.07 1.16 (1.79, 0.53) 0.49 (1.44, 0.47), 0.32
PASE total
WL 2.95 (20.41, 14.51) e 2.36 (12.43, 17.15) e
PT 2.39 (9.73, 14.51) 5.34 (15.13, 25.81), 0.61 8.33 (2.3, 18.96) 5.97 (11.29, 23.23), 0.50
IBET 8.85 (22.92, 5.22) 5.9 (27.55, 15.75), 0.59 7.94 (4.41, 20.29) 5.58 (12.77, 23.93), 0.55
PASE leisure
WL 2.7 (8.17, 2.77) e 0.79 (7.26, 5.68) e
PT 3.39 (0.42, 7.19) 6.08 (0.26, 12.42), 0.06 7.93 (3.34, 12.52) 8.72 (1.07, 16.37), 0.02
IBET 1.19 (5.56, 3.18) 1.51 (5.18, 8.2), 0.66 7.54 (2.24, 12.84) 8.33 (0.24, 16.42), 0.04
PASE household
WL 3.48 (13.05, 6.1) e 1.79 (10.37, 6.78) e
PT 0.57 (7.24, 6.1) 2.9 (8.35, 14.16), 0.61 3.4 (2.78, 9.58) 5.19 (4.9, 15.28), 0.31
IBET 8.55 (16.33, 0.76) 5.07 (17.02, 6.88), 0.40 3.1 (10.25, 4.05) 1.3 (12.02, 9.41), 0.81
PASE work
WL 2.27 (9.4, 13.93) e 5.25 (4.77, 15.26) e
PT 0.42 (7.61, 8.46) 1.84 (15.53, 11.84), 0.79 2.93 (10.07, 4.21) 8.18 (19.91, 3.55), 0.17
IBET 0.95 (10.18, 8.28) 3.22 (17.64, 11.2), 0.66 4.18 (3.94, 12.3) 1.07 (13.41, 11.28), 0.86
Unilateral stand time
WL 0.03 (0.81, 0.76) e 0.21 (1.04, 0.62) e
PT 0.6 (1.15, 0.04) 0.57 (1.49, 0.35), 0.22 0.09 (0.66, 0.48) 0.12 (0.86, 1.1), 0.80
IBET 0.19 (0.43, 0.81) 0.22 (0.75, 1.18), 0.66 0.01 (0.65, 0.66) 0.21 (0.81, 1.24), 0.68
30 s chair stand
WL 0.06 (1.05, 1.17) e 0.56 (0.43, 1.55) e
PT 0.2 (0.98, 0.58) 0.26 (1.57, 1.05), 0.70 0.12 (0.57, 0.81) 0.44 (1.6, 0.71), 0.45
IBET 0.62 (0.26, 1.5) 0.57 (0.81, 1.94), 0.42 0.95 (0.16, 1.73) 0.38 (0.83, 1.6), 0.53
2 m march test
WL 8.51 (14.94, 2.08) e 0.5 (7.28, 6.28) e
PT 0.33 (4.88, 4.22) 8.18 (0.62, 15.74), 0.03 1.73 (2.94, 6.4) 2.23 (5.72, 10.18), 0.58
IBET 2.32 (7.42, 2.78) 6.19 (1.73, 14.12), 0.12 3.01 (2.33, 8.35) 3.51 (4.86, 11.89), 0.41
Timed Up and Go
WL 0.15 (1.23, 0.93) e 0.04 (1.19, 1.27) e
PT 0.56 (1.32, 0.21) 0.41 (1.68, 0.86), 0.53 0.68 (1.53, 0.18) 0.71 (2.16, 0.73), 0.33
IBET 0.82 (1.68, 0.03) 0.68 (2, 0.65), 0.32 1.56 (2.53, 0.59) 1.6 (3.12, 0.08), 0.04
Weekly minutes of aerobic activity
WL 0.22 (1.73, 1.29) e 1.68 (3.37, 0) e
PT 1.11 (0.04, 2.17) 1.33 (0.45, 3.1), 0.14 0.76 (0.43, 1.9) 2.45 (0.45, 4.44), 0.02
IBET 2.25 (1.04, 3.46) 2.47 (0.61, 4.33), 0.01 0.83 (0.52, 2.18) 2.52 (0.42, 4.61), 0.02
Weekly minutes of stretching
WL 0.47 (1.5, 0.57) e 1.37 (2.32, 0.43) e
PT 1.61 (0.89, 2.33) 2.08 (0.87, 3.3), 0.00 0.29 (0.38, 0.97) 1.67 (0.55, 2.78), 0.00
IBET 0.84 (0.02, 1.67) 1.31 (0.03, 2.59), 0.04 0.59 (0.18, 1.36) 1.96 (0.79, 3.13), 0.00
Weekly minutes of strengthening
WL 0.47 (0.67, 1.61) e 0.17 (1.4, 1.05) e
PT 2.02 (1.21, 2.82) 1.55 (0.22, 2.88), 0.02 1.12 (0.25, 2) 1.3 (0.15, 2.74), 0.08
IBET 1.08 (0.17, 1.99) 0.61 (0.79, 2.01), 0.39 1.19 (0.2, 2.17) 1.36 (0.16, 2.88), 0.08
Patient global assessment of change e right knee
WL 0.15 (0.38, 0.69) e 0.2 (0.74, 0.33) e
PT 1.43 (1.04, 1.81) 1.27 (0.64, 1.91), 0.00 0.63 (0.24, 1.03) 0.83 (0.2, 1.47), 0.01
IBET 0.60 (0.17, 1.03) 0.45 (0.21, 1.11), 0.18 0.75 (0.29, 1.20) 0.95 (0.28, 1.62), 0.00
Patient global assessment of change e left knee
WL 0.07 (0.52, 0.65) e 0.33 (0.92, 0.26) e
PT 1.03 (0.63, 1.42) 0.96 (0.28, 1.64), 0.00 0.34 (0.08, 0.77) 0.67 (0.03, 1.37), 0.06
IBET 0.56 (0.11, 1.01) 0.49 (0.22, 1.20), 0.17 0.82 (0.35, 1.29) 1.15 (0.43, 1.88), 0.00
394 K.D. Allen et al. / Osteoarthritis and Cartilage 26 (2018) 383e396

Appendix Table 4
Differences in mean changes between IBET and PT and 95% CIs

Outcome Difference in baseline to 4-month vs Difference in baseline to

PT (95% CI), P-value 12-month vs PT (95% CI), P-value

WOMAC total
ITT 0.67 (2.23, 3.56), 0.65 1.04 (4.13, 2.05), 0.51
Multiple Imputation* 0.85 (2.06, 3.75), 0.57 0.96 (4.06, 2.14), 0.54
Per Protocol 1.3 (1.9, 4.5), 0.43 1.13 (4.49, 2.23), 0.51
WOMAC function
ITT 1.04 (1.07, 3.15), 0.33 0.11 (2.34, 2.13), 0.93
Multiple Imputation 1.00 (1.09, 3.08), 0.35 0.36 (2.55, 1.84), 0.75
Per Protocol 1.41 (0.92, 3.73), 0.23 0.17 (2.58, 2.23), 0.89
WOMAC pain
ITT 0.47 (1.20, 0.26), 0.20 0.45 (1.18, 0.27), 0.22
Multiple Imputation 0.41 (1.16, 0.33), 0.28 0.40 (1.13, 0.32), 0.27
Per Protocol 0.4 (1.2, 0.4), 0.33 0.47 (1.27, 0.32), 0.24
PASE total
ITT 13.77 (29.73, 2.19), 0.09 0.09 (14.41, 14.23), 0.99
Multiple Imputation 13.74 (29.76, 2.27), 0.09 1.52 (13.12, 16.16), 0.84
Per Protocol 11.24 (28.97, 6.49), 0.21 0.39 (15.74, 14.96), 0.96
PASE leisure
ITT 4.61 (9.49, 0.28), 0.06 1.01 (7.20, 5.18), 0.75
Multiple Imputation 5.00 (9.98, 0.03), 0.05 1.12 (7.06, 4.82), 0.71
Per Protocol 4.57 (10.02, 0.87), 0.09 0.39 (7.12, 6.34), 0.91
PASE household
ITT 8.09 (17.13, 0.94), 0.08 6.02 (14.27, 2.24), 0.15
Multiple Imputation 6.77 (15.76, 2.21), 0.14 6.14 (14.69, 2.42), 0.16
Per Protocol 7.97 (17.77, 1.82), 0.11 6.5 (15.46, 2.46), 0.15
PASE work
ITT 2.98 (13.45, 7.49), 0.58 7.87 (1.79, 17.53), 0.11
Multiple Imputation 2.77 (13.58, 8.04), 0.62 8.63 (0.73, 17.99), 0.07
Per Protocol 1.38 (13.1, 10.34), 0.82 7.11 (3.12, 17.34), 0.17
Unilateral stand time
ITT 0.61 (0.16, 1.38), 0.12 0.00 (0.78, 0.77), 1.00
Multiple Imputation 0.61 (0.20, 1.43), 0.14 0.04 (0.72, 0.80), 0.92
Per Protocol 0.79 (0.01, 1.58), 0.05 0.09 (0.74, 0.92), 0.83
30 s chair stand
ITT 0.63 (0.40, 1.66), 0.23 0.74 (0.17, 1.64), 0.11
Multiple Imputation 0.73 (0.30, 1.75), 0.16 0.73 (0.17, 1.64), 0.11
Per Protocol 0.82 (0.3, 1.95), 0.15 0.83 (0.16, 1.82), 0.10
2 m march test
ITT 2.86 (8.94, 3.21), 0.35 0.01 (6.40, 6.42), 1.00
Multiple Imputation 2.52 (8.47, 3.43), 0.41 0.29 (6.34, 6.92), 0.93
Per Protocol 1.99 (8.5, 4.52), 0.55 1.28 (5.53, 8.1), 0.71
Timed Up and Go
ITT 0.24 (1.23, 0.74), 0.63 0.72 (1.85, 0.41), 0.21
Multiple Imputation 0.34 (1.40, 0.73), 0.53 0.53 (1.69, 0.62), 0.36
Per Protocol 0.27 (1.35, 0.82), 0.63 0.89 (2.13, 0.36), 0.16
Weekly minutes of aerobic activity**
ITT 0.79 (0.62, 2.2), 0.27 0.07 (1.69, 1.54), 0.93
Multiple Imputation 0.9 (0.57, 2.37), 0.23 0.02 (1.67, 1.63), 0.98
Per Protocol 1.15 (0.38, 2.67), 0.14 0.07 (1.66, 1.8), 0.93
Weekly minutes of stretching**
ITT 0.48 (1.46, 0.5), 0.33 0.45 (0.44, 1.34), 0.32
Multiple Imputation 0.37 (1.37, 0.63), 0.46 0.44 (0.49, 1.37), 0.35
Per Protocol 0.77 (1.82, 0.28), 0.15 0.3 (0.67, 1.27), 0.55
Weekly minutes of strengthening**
ITT 0.51 (1.6, 0.58), 0.36 0.14 (1.03, 1.31), 0.81
Multiple Imputation 0.38 (1.47, 0.72), 0.50 0.15 (1.05, 1.34), 0.81
Per Protocol 0.94 (2.09, 0.21), 0.11 0.07 (1.19, 1.32), 0.92
Patient global assessment of change e right knee
ITT 0.93 (1.44, 0.42), 0.00 0.05 (0.58, 0.48), 0.85
Multiple Imputation 0.92 (1.45, 0.4), 0.00 0.07 (0.6, 0.46), 0.80
Per Protocol 0.83 (1.38, 0.28), 0.00 0.12 (0.46, 0.69), 0.69
Patient global assessment of change e left knee
ITT 0.47 (0.99, 0.05), 0.07 0.39 (0.18, 0.97), 0.17
Multiple Imputation 0.45 (0.99, 0.09), 0.10 0.43 (0.13, 0.98), 0.13
Per Protocol 0.47 (1.04, 0.1), 0.10 0.48 (0.13, 1.08), 0.12
*
Multiple Imputation was performed on missing values under the ITT paradigm.
**
A square root transformation was applied due to superior diagnostics in statistical models.
 K.D. Allen et al. / Osteoarthritis and Cartilage 26 (2018) 383e396
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