Delaware Physical Exercise and Activity for Knee Osteoarthritis (PEAK)
Phase: NA
Conditions: Knee Osteoarthritis
Sponsor: University of Delaware

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Statistical Analysis Plan 
Delaware Physical Exercise and Activity for Knee osteoarthritis  
(Delaware PEAK) 
 
IRB Protocol Number: 1730922 
 
National Clinical Trial (NCT) Identified Number: NCT04980300 
Principal Investigator (PI): Daniel K. White 
 
Sponsor: University of Delaware 
 
Funded by: Rheumatology Research Foundation 
 
Date of SAP: 7/14/2023 
 
 
Version 
Date 
Summary of changes 
v0.01 
07/14/2023 
Original 
 
 
 
 
 
 
 
 
 
 
 
 

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1 SAP Signatures 
I give my approval for the attached SAP entitled “Delaware Physical Exercise and Activity for 
Knee osteoarthritis (Delaware PEAK)” dated 06/14/2023 
 
Statistician (Author) 
Name: Barry A. Bodt 
 
Signature: 
  
 
Date:  
 July 14, 2023                                                
Statistician Reviewer (As applicable) 
Name: 
 
Signature: 
                                                
 
Date:  
                                                 
Principal Investigator 
Name:  Daniel K. White 
 
 
 
Signature: 
 
Date:  
                 7/14/2023                                
 
 
 
 
 
 
 
 
 
 
 

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2 Table of Contents 
1 
SAP Signatures 
2 
2 
Table of Contents 
3 
3 
Abbreviations and Definitions 
5 
4 
Introduction 
5 
4.1 
Preface 
5 
4.2 
Scope of the analyses 
6 
5 
Study Objectives and Endpoints 
6 
5.1 
Study Objectives 
6 
5.2 
Endpoints 
6 
6 
Study Methods 
6 
6.1 
General Study Design and Plan 
6 
6.2 
Inclusion-Exclusion Criteria and General Study Population 
8 
6.3 
Randomization and Blinding 
8 
6.4 
Study Assessments 
9 
7 
Sample Size 
12 
8 
General Analysis Considerations 
12 
8.1 
Timing of Analyses 
12 
8.2 
Analysis Populations 
12 
8.2.1 
Full Analysis Sample (Intention to Treat) 
12 
8.2.2 
Per Protocol Sample, set 1 
12 
8.2.3 
Per Protocol Sample, set 2 
13 
8.2.4 
Secondary Data Analysis Sample 
13 
8.3 
Covariates and Subgroups 
13 
8.4 
Missing Data 
13 
9 
Summary of Study Data 
14 
9.1 
Subject Disposition 
14 
9.2 
Protocol Deviations 
16 
9.3 
Demographic and Baseline Variables 
17 
9.4 
Treatment Compliance 
17 
10 
Efficacy Analyses 
17 
10.1 
Primary Efficacy Analysis 
18 
10.2 
Secondary Efficacy Analyses 
18 
10.2.1 
Secondary Analyses of Primary Efficacy Endpoint 
18 
10.2.2 
Analyses of Secondary Endpoints 
18 
10.3 
Exploratory Efficacy Analyses 
18 
11 
Safety Analyses 
19 
11.1 
Adverse Events 
19 

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11.2 
Deaths, Serious Adverse Events and other Significant Adverse Events 
19 
12 
Reporting Conventions 
19 
13 
Quality Assurance of Statistical Programming (As Applicable) 
19 
14 
Summary of Changes to the Protocol and/or SAP 
20 
15 
References 
20 
16 
Listing of Tables, Listings and Figures 
21 
 
 
 
 

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3 Abbreviations and Definitions 
 
AE 
Adverse Event 
CRF 
Case Report Form 
SAP 
Statistical Analysis Plan 
PT 
Physical Therapy 
MVPA 
Moderate-to-Vigorous intensity Physical 
Activity 
SED 
Sedentary Behaviors 
LPA 
Light Intensity Physical Activity 
NICE 
National Institute for Health and Care 
Excellence 
IPAQ 
International Physical Activity Questionnaire 
 
4 Introduction 
4.1 Preface 
 
Knee Osteoarthritis (OA) is a serious disease.  In 2010, OA moved up from 15th to 11th in 
rankings for global burden of disease,1 and the most common weight-bearing joint affected 
by OA is the knee.2 More than 15 million Americans currently have symptomatic knee OA.3 
The estimated annual cost to treat knee OA is $27 billion,4 which is similar to the cost to treat 
stroke (~$34 billion5). The incidence of knee OA is expected to increase with the aging and 
obese US population.6 Walking difficulty is the primary functional limitation in people with 
knee OA that, in turn, makes OA the leading cause of disability among older adults.7 Not 
only is walking difficulty related to disability, but it is also associated with a 55% higher risk of 
premature death.8,9 Without a cure, treatment for knee OA focuses primarily on managing 
pain and reducing disability. 
 
Treatment guidelines for knee OA champion the use of supervised exercise.  The 
recently released 2019 ACR/Arthritis Foundation guidelines for the treatment of OA strongly 
support the use of supervised exercise.10 These recommendations are consistent with those 
of the Osteoarthritis Research Society International (OARSI), which promote exercise, self-
management, and education.11 Both guidelines (ACR and OARSI) come from the robust and 
pervasive research findings that exercise reduces pain and improves physical function in 
adults with knee OA.8  
 
Few adults with knee OA try supervised exercise to manage their OA. For example, 
less than 10% of adults with knee OA exercise regularly,12,13 and only one-in-ten patients are 
seen for supervised exercise 5 years before a knee replacement.14 Health claims data show 
a similar trend, with a doubling in the prescription of opioids and a 50% reduction in referrals 
for Physical Therapy (PT) in the past decade.15 Hence, few adults with knee OA are utilizing 
physical activity and/or supervised exercise to address their symptoms of knee OA. 
 
The objective of this study is to examine the efficacy of Delaware PEAK to increase physical 
activity in adults with knee OA compared to a control group receiving web-based resources 
about knee OA and exercise. The rationale for our study is that there is a need to examine 
whether Delaware PEAK can directly target the mismatch between OA recommendations 
and practice patterns. Our central hypothesis is that Delaware PEAK will increase physical 
activity and will increase the belief that exercise is helpful and not harmful, compared with a 

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control group receiving web-based OA treatment resources. Successful completion of this 
proposal will provide the evidence necessary to scale up this low-cost intervention, with the 
goal of increasing the number of adults who use exercise to manage their knee OA and thus 
reducing the burden of disease.   
 
4.2 Scope of the analyses 
 
These analyses will assess the efficacy of a physical therapist-delivered exercise 
intervention (Delaware PEAK) versus a control group receiving web-based resources about 
knee OA and exercise regarding change in Moderate-to-Vigorous intensity Physical Activity 
(MVPA) over 12 weeks in adults with knee OA. We call the intervention group an Expanded 
Intervention and the control group a Brief Intervention. 
5 Study Objectives and Endpoints 
5.1 Study Objectives 
 
The purpose of this study is to examine the efficacy of Delaware PEAK to increase physical 
activity in adults with knee OA compared to a control group receiving web-based resources 
about knee OA and exercise. 
5.2 Endpoints 
The primary endpoint of our study is to examine the efficacy of a physical therapist-delivered 
exercise intervention (Delaware PEAK) to increase MVPA over 12 weeks compared to a 
control group receiving web-based resources about knee OA and exercise.  
 
The secondary analyses endpoint of our study is to examine the efficacy of a physical 
therapist-delivered exercise intervention (Delaware PEAK) to increase health beliefs, light 
physical activity (LPA), and steps per day, over 24 weeks compared to a control group 
receiving web-based resources about knee OA and exercise. We also will assess change in 
MVPA over 24 weeks, the number of Adverse events over 12 weeks, and treatment 
adherence. 
6 Study Methods 
6.1 General Study Design and Plan 
(ICH E3;9) 
 
We will conduct a pragmatic randomized controlled trial with a 2-group, superiority, parallel-
design. The intervention group will receive a physical therapist-delivered exercise 
intervention (Delaware PEAK), i.e., the Expanded Intervention, while the control group will 
receive web-based resources about knee OA and exercise, i.e., the Brief Intervention. The 
study was assessor-blinded, i.e., all members of the research team who were involved with 
the assessment of the primary and secondary outcomes were blinded. Participants will not 
be blinded to group assignment but will not be informed about study hypotheses until study 
completion. The physical therapist will not be blinded to group assignment. 
 
 

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Figure 1: Study flow-chart 
 
 
 
 

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6.2 Inclusion-Exclusion Criteria and General Study Population 
(ICH E3;9.3. ICH E9;2.2.1) 
 
In order to be eligible to participate in this study, an individual must meet all of the following 
criteria: 
1. Provision of an electronically signed and dated informed consent form 
2. >45 years of age, 
3. Resides in the contiguous United States  
4. Available for the duration of the intervention portion of the study (12 weeks) and 
willing to wear physical activity monitors  
5. Looking to move more, i.e., be more active. 
6. Knee OA diagnosis by the NICE criteria 
7. Comfortable participating in a program delivered in English  
8. Is able to safely participate in moderate-intensity exercise as determined by a pre-
exercise screen questionnaire,29  
9. Has either a smartphone or a laptop/desktop computer with an internet connection. 
10. Has a working email address. 
 
An individual who meets any of the following criteria will be excluded from participation in 
this study: 
1. Regularly exercise for more than 60 minutes/week. 
2. Has a scheduled knee or hip joint replacement  
3. Has had physical therapy for knee OA in the past 6 months 
4. Participated in a strength training program for the lower extremities in the past 6 
months 
6.3 Randomization and Blinding  
(ICH E3; 9.4.3, 9.4.6. ICH E9; 2.3.1, 2.3.2) 
 
Participant-level randomization will be performed to assign each participant to either the 
Intervention group (referred to as Expanded Intervention) or the Control group (referred to as 
Brief Intervention) using block randomization schedule with block sizes of 4. Randomization 
was performed using REDCap’s built-in randomization function and will occur after 
participants sign the informed consent and complete baseline data collection. Participants 
will be randomized into one of two groups: (1) the Expanded Intervention group, who will 
receive the Delaware PEAK program with a physical therapist, or (2) the Brief Intervention 
group, who will receive pre-recorded, web-based resources. 
 
Participants will not be blinded to group allocation; however, they will not be informed about 
the study hypotheses until the study is completed, at which time they will be provided a lay 
summary of findings. The treating physical therapist will not be blinded to group assignment, 
as they are delivering the Expanded Intervention. Research team members responsible for 
outcome data management will be blinded to group assignment. As all outcomes are 
collected either through a physical activity monitor or online questionnaires, this study is thus 
considered assessor-blinded for our primary outcome, physical activity. Statistical analyses 
will be performed in a blinded manner. 
 
 

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6.4 Study Assessments  
(ICH E3; 9.5.1. ICH E9; 2.2.2) 
 
Table 1: Timeline of Assessments 
 
 
Table 2: Analysis Time Windows 
Visit (target day) 
Lower bound (days) 
Upper bound (days) 
Enrollment (0) 
n/a 
n/a 
Baseline (14) 
-7 days 
+7 days 
12-week Follow-up (112) 
-7 days 
+28 days 
24-week Follow-up (206) 
-7 days 
+28 days 
 
 
STUDY PERIOD 
 
Enrollment/BL 
Randomization 
Intervention 
Follow-Up 
Timepoint 
-t1 
0w 
1w 
2w 
4w 
7w 
10w 
12w 
24w 
Enrollment: 
 
 
 
 
 
 
 
 
 
Screening Form 
X 
 
 
 
 
 
 
 
 
Verbal Eligibility Form 
X 
 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
General Information (Demographics) 
X 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
Intervention: 
 
 
 
 
 
 
 
 
 
Expanded Intervention 
 
 
X 
X 
X 
X 
X 
 
 
Brief Intervention 
 
 
X 
X 
X 
X 
X 
 
 
Assessment: 
 
 
 
 
 
 
 
 
 
Primary outcome 
 
 
 
 
 
 
 
 
 
Physical activity (MVPA via Actigraph) 
X 
 
 
 
 
 
 
X 
X 
Secondary outcomes 
 
 
 
 
 
 
 
 
 
Treatment Beliefs of Physical Therapy 
X 
 
 
 
 
 
 
X 
X 
Treatment Beliefs of Physical Exercise 
X 
 
 
 
 
 
 
X 
X 
Physical activity (steps/day, LPA via Actigraph) 
X 
 
 
 
 
 
 
X 
X 
Other measures 
 
 
 
 
 
 
 
 
 
Charlson Comorbidity Index 
X 
 
 
 
 
 
 
 
 
Knee Pain (Visual Analogue Scale) 
X 
 
 
 
 
 
 
X 
X 
Knee Injury and OA Outcome Score 
X 
 
 
 
 
 
 
X 
X 
Treatment Expectations Question 
X 
X 
 
 
 
 
 
 
 
Adverse Events (check, recording) 
 
X 
X 
X 
X 
X 
X 
X 
X 
Exercise Adherence Rating Scale (EARS)* 
 
 
 
 
 
 
 
X 
X 
*Collected in the those randomized to the expanded intervention group 

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Data collected outside of the time windows listed above will be classified as the intended 
visit the data was to reflect and noted as being outside the time window. Such data will be 
included in the primary analyses, however we will also perform a secondary analyses 
excluding data collected outside the time window. While the spacing of follow-up 
assessments makes it unlikely that multiple data collections will occur during the same 
window, the first valid set of assessments will be used for the corresponding timepoint. 
 
Descriptions of each outcome, timepoint of collection, and score range are described below. 
A table is also provided that summarizes this information. 
 
MVPA: Objectively-measured physical activity will be collected using the Actigraph GT3x at 
the baseline, 12-week, and 24-week timepoints. The primary outcome is change in MVPA, in 
minutes/week, from baseline to 12 weeks. We also will assess change in MVPA from 
baseline to 24 weeks. Minutes/week of MVPA can range from 0 minutes/week to 10,080 
minutes/week (7 days x 24 hours x 60 minutes). 
 
LPA, Daily Walking: Data collected using the ActiGraph GT3x activity monitor will also be 
used to assess change in minutes/week of LPA and average steps/day between baseline 
and both follow-up timepoints. Minutes/week of LPA can range from 0 minutes/week to 
10,080 minutes/week (7 days x 24 hours x 60 minutes). Steps/day can be any value greater 
than or equal to 0. 
 
Health Beliefs: Health beliefs will be measured with the Treatment Beliefs of OA: Physical 
Therapy (TOA-PT) and Treatment Beliefs of OA: Physical Exercise (TOA-PE) 
questionnaires, collected at the baseline, 12-week, and 24-week timepoints. The TOA 
provides separate scores for positive and negative treatment beliefs. The primary outcome is 
change in TOA-PT and TOA-PE scores from baseline to 12 weeks. We also will assess 
change in TOA-PT and TOA-PE scores from baseline to 24 weeks. The TOA-PT negative 
beliefs scores range from 4 to 16, TOA-PT positive scores range from 7 to 28, TOA-PE 
negative beliefs scores range from 4 to 16, TOA-PE positive scores range from 7 to 28. For 
all scales, a higher score indicates a greater amount of positive or negative treatment 
beliefs. 
 
Charlson Comorbidity Index (CCI): The Charlson Comorbidity Index (CCI) is a 17-item 
questionnaire that creates a weighted score based on a range of common, comorbid 
conditions. This questionnaire will be collected at the baseline timepoint and scores range 
from 0 to 29, with a higher CCI score indicating greater levels of comorbidity. 
 
Visual Analog Scale (VAS) Pain: Change in knee pain will be measured using a single-item 
Visual Analog Scale (VAS) question in which the participant will indicate their pain in each 
knee. Scores range from 0-100 where 0 is no pain and 100 is the worst pain imaginable. 
 
Knee Injury and Osteoarthritis Outcome Score (KOOS): The Knee Injury and 
Osteoarthritis Outcome Score (KOOS) is a 42-item questionnaire that assesses five 
domains, including pain, symptoms (other than pain), function in activities of daily living, 
function in sport and recreation, and quality of life. The KOOS has subscale scores for Pain, 
Symptoms, ADL Function, Sport & Recreation Function, and Quality of Life. Scores are 
transformed to a 0-100 scale with 0 indicating extreme knee problems and 100 indicating no 
knee problems. 
 
Treatment Expectations Question: The participant will complete a Treatment Expectations 
Question, which asks the participant how effective they expect the intervention to be for their 
knee. This question will be collected at the baseline timepoint: right before and right after 

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randomization. Answers will be expressed as frequencies and percentages for each of the 
following categories: No effect at all, Minimal improvement, Moderate improvement, Large 
improvement, and Complete recovery, as well as reported as an increase, decrease, or no 
change in treatment expectations. 
 
Exercise Adherence: For the Expanded Intervention, adherence to strengthening exercises 
and physical activity will be measured using the Exercise Adherence Rating Scale (EARS). 
The EARS includes 6 items whose total score ranges from 0 to 24, where a higher score 
indicates greater adherence. The EARS also includes 10 items on what helps or hinders 
exercise adherence. These scores range from 0 to 40, where a higher score indicates better 
outcome.  
 
Brief Intervention Utilization: For the Brief Intervention, intervention utilization will be 
measured via a self-report questionnaire administered on REDCap. The participant will be 
asked to confirm that they viewed the informational videos, accessed the associated 
weblink, and note how many times they visited the site for each webpage section. 
Percentage of Brief Intervention participants that utilize the website will be reported. 
Utilization of the Brief Intervention will be measured at the 12-week follow-up timepoint.  
 
Adverse Events (AE): Information on potential adverse events (AE) will be collected by the 
treating physical therapist at the beginning of each session in the Expanded Intervention, by 
a Research Assistant during follow-up reminder phone calls in the Brief Intervention, or by 
spontaneous report on the part of the participant (e.g., reaching out to the study team by 
phone or email). AEs will be reported as frequencies and percentages. 
 
General Information Form: The participant will complete a General Information Form that 
collects height, weight, date of birth, gender, race, ethnicity, veteran status, highest level of 
education attained, employment status, and approximate household income. This form will 
be collected at the baseline timepoint. Continuous variables will be expressed as means and 
standard deviations while categorical variables will be expressed as frequencies and 
percentages. 
 
Table 3: Outcome Timepoints and Scoring 
 
Outcome 
Timepoints collected 
Scoring 
MVPA 
Baseline, 12-week, 24-week 
0 to 10,080 minutes/week 
TOA (PT and PE) 
Baseline, 12-week, 24-week 
4 to 16 for negative 
7 to 28 for positive 
EARS 
12-week, 24-week 
0 to 24 
Telehealth Acceptability 
12-week (Expanded only) 
14 to 70 
Participant Satisfaction 
12-week 
0 to 6 
LPA 
Baseline, 12-week, 24-week 
0 to 10,080 minutes/week 
Daily Walking 
Baseline, 12-week, 24-week 
At least 0 steps/day 
VAS Pain 
Baseline, 12-week, 24-week 
0 to 100 

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KOOS 
Baseline, 12-week, 24-week 
0 to 100 for each subscale 
General Information Form 
Baseline 
n/a 
Treatment Expectations 
Baseline (x2) 
n/a 
CCI 
Baseline 
0 to 29 
Adverse Events 
Throughout 
n/a 
7 Sample Size  
(ICH E3; 9.7.2. ICH E9; 3.5) 
 
The sample size is n = 100 randomized participants. In order to be randomized, participants 
must complete baseline assessments. 
8 General Analysis Considerations 
8.1 Timing of Analyses 
Final analyses will be performed when data collection is completed. In particular, the final 
analyses will be performed when all enrolled study subjects have completed the 24-week 
follow up timepoint or dropped out prior to the 24-week timepoint. The final analysis will be 
performed on data transferred to a file from REDCap, having been documented as meeting 
the cleaning and approval requirements after the finalization and approval of this SAP 
document. Data cleaning will involve checking REDCap surveys for errors/discrepancies, 
ensuring all responses are correctly scored REDCap, and then performing a quality check to 
ensure answers were scored accurately. For the ActiGraph, we will ensure data was 
recorded at 60Hz, that data fell within the expected wear time range, and that included 
participants met our wear time criteria of at least 4 days and at least 10 hours on those days. 
As well, we will cross-reference the date the monitor was worn from the Actigraph is 
between the dates the monitor was send the received from REDCap. We will also check that 
the file names and dates of the Actigraph files correspond to names and dates from 
REDCap.  
8.2 Analysis Populations 
(ICH E3; 9.7.1, 11.4.2.5. ICH E9; 5.2) 
 
8.2.1 Full Analysis Sample (Intention to Treat) 
● All subjects who were randomized 
● The ActiGraph monitor was worn for > 4 days of 10 hours at the baseline and 12-
week follow-up timepoints  
● This sample will be the primary efficacy sample 
8.2.2 Per Protocol Sample, set 1 
● All subjects who adhere to the major criteria in the protocol 
o Subjects who did not drop out  

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▪ 
Completed their respective intervention, (60% of Intervention)  
▪ 
Did not drop out over the 12 weeks of follow up after the intervention 
o The ActiGraph monitor was worn > 4 days at each time point (baseline and 
12-week follow-up timepoints). 
8.2.3 Per Protocol Sample, set 2 
● All subjects who adhere to the major criteria in the protocol 
o Subjects who did not drop out  
▪ 
Completed their respective intervention (60% of Intervention) 
▪ 
Did not drop out over the 24 weeks of follow up after the intervention 
o The ActiGraph monitor was worn > 4 days at each time point (baseline, 12-
week, 24-week follow-up timepoints). 
8.2.4 Secondary Data Analysis Sample 
o We will repeat the Intention to Treat and Per Protocol analyses excluding 
participants who worn their activity monitors outside of our established visit 
windows. 
 
 
The exact process for assigning the statuses (Full Analysis Sample and Per Protocol 
Sample) will be defined and documented prior to breaking the blind along with any 
predefined reasons for eliminating a subject from a particular population. 
 
8.3 Covariates and Subgroups 
(ICH E3; 9.7.1, 11.4.2.1. ICH E9; 5.7) 
 
Baseline demographics will be assessed for group assignment differences after 
randomization. Covariates will be determined based on the presence of group differences. 
 
8.4 Missing Data 
(ICH E3; 9.7.1, 11.4.2.2. ICH E9;5.3. EMA Guideline on Missing Data in Confirmatory 
Clinical Trials) 
 
Missing data will be given careful attention in the analysis. In this RCT we have two 
treatment arms and three fixed times for assessment. It is anticipated that drop-outs from the 
study will be at random because study participants were considered treatment-seeking. 
However, it is possible that participants may not attend all follow-ups. Drastically fewer 
participants in the final analysis would affect study sensitivity and excessive missed follow-
ups would potentially bias model parameter estimates. Under the assumption of limited data 
that is missing completely at random (MCAR) or missing at random (MAR), the mixed-effect 
model using restricted maximum likelihood estimation is a full information approach and 
leads to unbiased model parameter estimates. Selection between models with two common 
covariance structures, Toeplitz and independent errors will be accomplished using the 
Akaike Information Criterion (AIC). 
 
In the event that assumptions are not met regarding missing value frequency, MAR, or 
MCAR and missing values are occurring with higher frequency or are truly missing not at 
random (MNAR), the analysis may be biased. To test the missingness assumptions, missing 
data will first be summarized by group, time, each design cell, and each of the three 

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covariates, age, sex and body mass index in an effort to graphically or tabularly detect 
patterns in the variation of missingness. More formally, missing/non-missing will be taken as 
a dichotomous outcome in a logistic regression for continuous covariates and will be 
compared with between and within factors and sex using chi-square tests. Significant logistic 
regression coefficients or significant chi-square tests indicate a pattern of missingness 
variation that will be identified and reported and whose impact on the analysis will be 
explained if possible. Model residuals will be evaluated for normality using the Shapiro-Wilk 
test, homogeneity of variance using Levine’s test, and transformations, if necessary, will be 
chosen from among the Box-Cox transformations. 
 
 
 
9  Summary of Study Data 
All continuous variables will be summarized using the following descriptive statistics: n 
(non-missing sample size), mean, and standard deviation. The frequency and 
percentages (based on the non-missing sample size) of observed levels will be reported 
for all categorical measures. In general, all data will be listed, sorted by treatment and 
subject, and when appropriate by visit number within subject. All summary tables will be 
structured with a column for each treatment in the order (Brief Intervention, Expanded 
Intervention) and will be annotated with the total population size relevant to that 
table/treatment, including any missing observations. 
9.1 Subject Disposition 
 
We establish how many subjects reached the various stages of the trial (Enrollment, 
Allocation, Follow-up, and Analysis) using the following list: 
 
Enrollment: 
- 
Regularly exercise > 60 min/wk 
- 
Scheduled knee replacement 
- 
Received physical therapy or prescribed an exercise program in past 6 months 
- 
Did not receive medical clearance after failing the Adult Pre-Exercise Screening System 
questionnaire 
- 
< 45 years of age 
- 
No activity related knee pain 
- 
Morning stiffness > 30 min 
- 
Reside outside of the contiguous United States 
- 
Not comfortable with a program delivered in English 
- 
Not seeking to be more physically active 
- 
Did not have a smartphone/ computer with internet access 
- 
Did not complete the baseline data collection 
Allocation: 
- 
Did not receive allocated intervention 
Follow-up: 
- 
Lost to Follow-up 
- 
Discontinued the intervention 
 
 
 
 
 
 

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Figure 2: CONSORT Diagram Template 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table 4: Anticipated Recruitment Schedule 
 
 
9.2 Protocol Deviations 
 
Potential protocol deviations include: follow-up assessments collected outside of preset time 
window, participants delaying assessment due to unforeseen circumstances, or the activity 
monitors not being sent/being lost in the mail. All would be considered missing data and 
would be handled in the manner described in the Missing Data section of this document. 
 
 
 
 
 
 
 
 
 
 

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9.3 Demographic and Baseline Variables 
 
Table 5: Demographic and Baseline Characteristics 
 
Characteristic [mean ± SD or n (%)] 
All 
n= 
Expanded 
Intervention 
n= 
Brief 
Intervention 
n= 
Age (years) 
 
 
 
Gender (female) 
 
 
 
BMI (kg/m2) 
 
 
 
Race (Non-White) 
 
 
 
Comorbidity (CCI) 
 
 
 
Education (at least a college degree) 
 
 
 
Employment 
 
 
 
Income 
 
 
 
History of knee injury/surgery 
 
 
 
Duration of OA diagnosis 
 
 
 
MVPA at baseline (minutes/day) 
 
 
 
Steps/day at baseline 
 
 
 
9.4 Treatment Compliance 
 
Table 6: Treatment Compliance Measures 
 
Characteristic [mean ± SD or n (%)] 
All 
n= 
Expanded 
Intervention 
n= 
Brief 
Intervention 
n= 
Average number of Intervention sessions 
completed 
 
 
 
Percentage of participants completing 60% 
of Intervention sessions 
 
 
 
10 Efficacy Analyses 
 
The primary and secondary outcomes will be summarized stratified by treatment group at 
each study timepoint (baseline, 12-week, 24-week). Our primary analysis will use an 
intention-to-treat (ITT) analysis that includes all participants who wore the monitor for ≥4 
days for 10 hours/day at baseline. The statistical model underlying the analysis a mixed-
effects model to examine the main and interaction effects of group (Expanded Intervention 

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vs. Brief Intervention) and time (BL, 12-week) on MVPA (minutes/day). The null hypothesis 
is that there is no difference in change in MVPA in the Expanded Intervention group 
compared to the Brief Intervention group. The alternative hypothesis is that there is a 
difference between groups. The nature of the hypothesis is confirmatory as this study has 
been powered to detect a difference should one exist. The mixed-effect model will be used 
to calculate the mean and 95% Confidence Interval time in MVPA at each study time point. 
We will also calculate the difference in means and 95% Confidence Intervals between the 
Expanded Intervention and Brief Intervention group at each study time point. We will also 
calculate 2-sided p-values to determine statistical significance of differences between groups 
by time in MVPA. Data will be summarized by intervention group. Means, Standard 
Deviations, Minimums and Maximums will be used to summarize continuous variables. 
Categorical variables will be summarized as frequencies and percentages. 
 
Mixed-effect modeling will be used to estimate MVPA over time. The mixed-effect model 
using restricted maximum likelihood estimation is a full information approach and leads to 
unbiased model parameter estimates in the presence of MCAR or MAR missingness. 
Selection between models with two common covariance structures, Toeplitz and 
independent errors, will be accomplished using the Akaike Information Criterion (AIC). 
10.1 Primary Efficacy Analysis 
 
The primary endpoint of our study is to examine the efficacy of a physical therapist-delivered 
exercise intervention (Delaware PEAK, referred to as the Expanded Intervention) to increase 
MVPA over 12 weeks compared to a control group receiving web-based resources about 
knee OA and exercise (referred to as the Brief Intervention). 
 
The statistical model underlying this analysis is a mixed-effects model to examine the main 
and interaction effects of group (Expanded Intervention vs. Brief Intervention) and time 
(baseline, 12-week) on MVPA (minutes/day). 
10.2 Secondary Efficacy Analyses 
10.2.1 Secondary Analyses of Primary Efficacy Endpoint 
The per protocol samples, instead of the ITT sample will be used for the analysis of the 
primary efficacy endpoint. 
10.2.2 Analyses of Secondary Endpoints 
The secondary analyses endpoints are to examine the efficacy of a physical therapist-
delivered exercise intervention (Delaware PEAK, referred to as the Expanded Intervention) 
to increase treatment beliefs, increase LPA, and increase steps/day over 12 weeks 
compared to a control group receiving web-based resources about knee OA and exercise 
(referred to as the Brief Intervention). Additionally, we will examine the efficacy of the 
intervention to increase MVPA over 24 weeks. 
10.3  Exploratory Efficacy Analyses 
Further, we will explore the efficacy of a physical therapist-delivered exercise intervention 
(Delaware PEAK, referred to as the Expanded Intervention) to decrease VAS pain and 
increase KOOS subscale scores over 12 weeks compared to a control group receiving web-
based resources about knee OA and exercise (referred to as the Brief Intervention). We also 
will explore the change in exercise adherence from the 12-week to 24-week follow-up 
timepoints in the Expanded Intervention group only. Lastly, we will examine changes in 
treatment expectations between group from before to after randomization.  

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11 Safety Analyses 
 
● All-Cause Mortality: A table of all anticipated and unanticipated deaths due to any 
cause, with frequencies and percentages of such events in each Intervention group 
will be reported. 
 
● Serious Adverse Events: A table of all anticipated and unanticipated serious adverse 
events, grouped by organ system, with frequencies and percentages of such events 
in each Intervention group will be reported. 
 
● Other (Not Including Serious) Adverse Events: A table of anticipated and 
unanticipated events (not included in the serious adverse event table) that exceed a 
frequency threshold of 5% within either Intervention group, grouped by organ system, 
with frequencies and percentages of such events in each Intervention group will be 
reported. 
 
11.1 Adverse Events 
 
We will report on the frequencies and percentages of adverse events that are possibly or 
definitely related to the study. 
 
11.2 Deaths, Serious Adverse Events and other Significant Adverse 
Events 
 
We will report on the frequencies and percentages of deaths, serious adverse events, and 
other significant adverse events that are possibly or definitely related to the study. 
12 Reporting Conventions 
P-values ≥0.01 will be reported to 3 decimal places; p-values less than 0.001 will be 
reported as “<0.001”. The mean, standard deviation, and any other statistics other than 
quantiles, will be reported to one decimal place greater than the original data. Quantiles, 
such as median, or minimum and maximum will be reported to one decimal place.   
13 Quality Assurance of Statistical Programming (As Applicable) 
 
At the time of this writing, data will be stored on REDCap, a password-protected 2-factor 
authentication, data management platform hosted by the Center for Human Research 
Coordination at the University of Delaware. 
 
At the time of this writing, data analysis will be performed using JMP, Version 17.0.0. SAS 
Institute Inc., Cary, NC, USA.  
 

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For quality assurance, all summary score calculations will be performed by REDCap 
software and checked by a research assistant for accuracy.  
14 Summary of Changes to the Protocol and/or SAP 
 
Rationale for Adjustments of Statistical Analysis Plan from Protocol (March 12, 2023) 
The changes from the protocol-specified definitions of aims, outcomes and statistical analytic 
approaches are outlined below. These changes reflect an error in data collection during the 
trial. Questionnaires are collected via automated survey in REDCap, and the automated 
survey did not include the SEE for the 12-week and 24-week follow-up timepoints. 
Therefore, SEE was only collected at the baseline timepoint and cannot be assessed for 
change after the intervention. 
15 References 
1. Lawford BJ, Delany C, Bennell KL, Hinman RS. "I was really skeptical...But it worked 
really well": a qualitative study of patient perceptions of telephone-delivered exercise 
therapy by physiotherapists for people with knee osteoarthritis. Osteoarthritis 
Cartilage. 2018;26(6):741-750. 
2. Lawford BJ, Delany C, Bennell KL, Hinman RS. "I Was Really Pleasantly Surprised": 
Firsthand Experience and Shifts in Physical Therapist Perceptions of Telephone-
Delivered Exercise Therapy for Knee Osteoarthritis-A Qualitative Study. Arthritis 
Care Res (Hoboken). 2019;71(4):545-557. 
3. Hurley MV, Walsh N, Bhavnani V, Britten N, Stevenson F. Health beliefs before and 
after participation on an exercised-based rehabilitation programme for chronic knee 
pain: doing is believing. BMC Musculoskelet Disord. 2010;11:31. 
4. Sanchez-Heran A, Agudo-Carmona D, Ferrer-Pena R, et al. Postural Stability in 
Osteoarthritis of the Knee and Hip: Analysis of Association With Pain Catastrophizing 
and Fear-Avoidance Beliefs. Pm r. 2016;8(7):618-628. 
5. Lawford BJ, Bennell KL, Hinman RS. Consumer Perceptions of and Willingness to 
Use Remotely Delivered Service Models For Exercise Management of Knee and Hip 
Osteoarthritis: A Cross-Sectional Survey. Arthritis Care Res (Hoboken). 
2017;69(5):667-676. 
6. US Department of Health and Human Services. 2008 physical activity guidelines for 
Americans. 2008:1-10. www.health.gov/paguidelines/. 
7. Dominick G, Zeni J, White D. The association of psychosocial factors with physical 
activity and function after total knee replacement: An exploratory study. Arch Phys 
Med Rehab. 2015:In Press. 
8. Fransen M, McConnell S, Harmer AR, Van der Esch M, Simic M, Bennell KL. 
Exercise for osteoarthritis of the knee. Cochrane Database Syst Rev. 
2015;1:Cd004376. 
9. Christiansen MB, Thoma LM, Master H, et al. The feasibility and preliminary 
outcomes of a physical therapist-administered physical activity intervention after total 
knee replacement. Arthritis Care Res. 2019;25(10):23882. 
10. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of 
Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of 
the Hand, Hip, and Knee. Arthritis Care Res (Hoboken). 2020;72(2):149-162. 

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11. McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI Guidelines for the Non-
Surgical Management of Knee Osteoarthritis. Osteoarthritis Cartilage. 2014(0). 
12. White DK, Tudor-Locke C, Felson DT, et al. Do radiographic disease and pain 
account for why people with or at high risk of knee osteoarthritis do not meet physical 
activity guidelines? Arthritis Rheum. 2013;65(1):139-147. 
13. Dunlop DD, Song J, Semanik PA, et al. Objective physical activity measurement in 
the osteoarthritis initiative: Are guidelines being met? Arthritis Rheum. 
2011;63(11):3372-3382. 
14. Dhawan A, Mather RC, 3rd, Karas V, et al. An epidemiologic analysis of clinical 
practice guidelines for non-arthroplasty treatment of osteoarthritis of the knee. 
Arthroscopy : the journal of arthroscopic & related surgery : official publication of the 
Arthroscopy Association of North America and the International Arthroscopy 
Association. 2014;30(1):65-71. 
15. Khoja SS, Almeida GJ, Freburger JK. Recommendation Rates for Physical Therapy, 
Lifestyle Counseling and Pain Medications for Managing Knee Osteoarthritis in 
Ambulatory Care Settings. Cross-sectional Analysis of the National Ambulatory Care 
Survey (2007-2015). Arthritis Care Res (Hoboken). 2019:10.1002/acr.24064.
16  Listing of Tables, Listings and Figures 
This section is to give precise details for each table, listing or figure to be produced. 
 
Mock Table 1: MVPA at each study time point using the ITT sample 
 
 
Baseline 
12-week 
24-week 
Brief Intervention 
 
 
 
Expanded Intervention 
 
 
 
Brief-Expanded 
 
 
 
 
Mock Table 2: TOA-PT at each study time point using the ITT sample 
 
 
Baseline 
12-week 
24-week 
Brief Intervention 
 
 
 
Expanded Intervention 
 
 
 
Brief-Expanded 
 
 
 
 
Mock Table 3: TOA-PE at each study time point using the ITT sample 
 
 
Baseline 
12-week 
24-week 
Brief Intervention 
 
 
 
Expanded Intervention 
 
 
 
Brief-Expanded 
 
 
 
 
Mock Table 4: Steps/day at each study time point using the ITT sample 
 
 
Baseline 
12-week 
24-week 
Brief Intervention 
 
 
 
Expanded Intervention 
 
 
 
Brief-Expanded 
 
 
 
 

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Mock Table 5: VAS Pain at each study time point using the ITT sample 
 
 
Baseline 
12-week 
24-week 
Brief Intervention 
 
 
 
Expanded Intervention 
 
 
 
Brief-Expanded 
 
 
 
 
Mock Table 6: KOOS at each study time point using the ITT sample 
 
 
Baseline 
12-week 
24-week 
Brief Intervention 
 
 
 
Expanded Intervention 
 
 
 
Brief-Expanded 
 
 
 
 
Mock Table 7: MVPA at each study time point using the per-protocol sample 
 
 
Baseline 
12-week 
24-week 
Brief Intervention 
 
 
 
Expanded Intervention 
 
 
 
Brief-Expanded 
 
 
 
 
Mock Table 8: TOA-PT at each study time point using the per-protocol sample 
 
 
Baseline 
12-week 
24-week 
Brief Intervention 
 
 
 
Expanded Intervention 
 
 
 
Brief-Expanded 
 
 
 
 
Mock Table 9: TOA-PE at each study time point using the per-protocol sample 
 
 
Baseline 
12-week 
24-week 
Brief Intervention 
 
 
 
Expanded Intervention 
 
 
 
Brief-Expanded 
 
 
 
 
Mock Table 10: Steps/day at each study time point using the per-protocol sample 
 
 
Baseline 
12-week 
24-week 
Brief Intervention 
 
 
 
Expanded Intervention 
 
 
 
Brief-Expanded 
 
 
 
 
Mock Table 11: VAS Pain at each study time point using the per-protocol sample 
 
 
Baseline 
12-week 
24-week 
Brief Intervention 
 
 
 
Expanded Intervention 
 
 
 
Brief-Expanded 
 
 
 
 

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Mock Table 12: KOOS at each study time point using the per-protocol sample 
 
 
Baseline 
12-week 
24-week 
Brief Intervention 
 
 
 
Expanded Intervention 
 
 
 
Brief-Expanded