Toolkit for Optimal Recovery After Orthopedic Injury; A Multisite Feasibility Study to Prevent Persistent Pain and Disability
Phase: NA
Conditions: Acute Orthopedic Injury
Sponsor: Massachusetts General Hospital

 
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PARTNERS HUMAN RESEARCH COMMITTEE DETAILED PROTOCOL 
 
Principal Investigator:  
Ana-Maria Vranceanu, PhD 
 
Protocol Title:  
Toolkit for Optimal Recovery after Orthopedic Injury; A multi-site 
feasibility study to prevent persistent pain and disability 
 
 
Funding:  
National Center for Complementary and Integrative Health 
(NCCIH) 
 
 
Version Date: 12/26/23 
 
 
I. 
BACKGROUND AND SIGNIFICANCE 
Acute orthopedic musculoskeletal injuries are prevalent and costly.  
Acute musculoskeletal orthopedic injuries (e.g., fractures, dislocations, also known as 
traumatic musculoskeletal injuries) represent the leading cause of adult hospital admissions1. 
Approximately 20-50% of patients go on to develop persistent (e.g., chronic) pain and 
disability1,15 despite making adequate recovery of their bones and soft tissues. These patients 
tend continue to have multiple surgeries and medical appointments, resulting in increased health 
care costs and a significant public health burden2,3. 
Psychosocial factors in the acute phase after the orthopedic injury, predict chronic pain 
and disability.  
Catastrophic thinking about pain, pain anxiety, depression, and prolonged opioid use are 
established risk factors for disability and pain in patients with musculoskeletal injuries4–10, 
regardless of the severity10,15,16, location8,17 or type of injury6,18,19. Recognizing these 
psychosocial factors early in the recovery process creates a window of opportunity to identify 
and intervene with patients who are at risk for chronic pain and disability in the acute phase, 
when psychosocial treatments are most effective20,21. A recent systematic review conducted by 
our team showed that there are no evidence based psychosocial treatments targeting psychosocial 
factors in patients with acute orthopedic injuries22. This provides urgency for the development of 
feasible, accepted, evidence-based interventions to prevent chronic pain and disability in at risk 
patients with orthopedic musculoskeletal injuries early in the recovery process, along with 
medical care. 
The care of patients with orthopedic musculoskeletal injuries follows an outdated 
biomedical model.  
Current usual care for patients with acute traumatic musculoskeletal injuries consists 
primarily of surgical interventions and pain medications. However, medical care is undergoing a 
shift in priorities recognizing the multifactorial influences on successful recovery after injury, 
and the pivotal role of psychosocial factors within orthopedic care23, 24. Although surgeons are 
now aware of the importance of psychosocial factors in recovery after musculoskeletal injuries12, 
they are often uncomfortable referring patients for outpatient care12,25,26. Referrals are often done 
after multiple unsuccessful medical procedures, when patients have become invested in a 
medical cure, pain has already become chronic, and treatments are generally less efficacious25,26. 

 
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Further, engaging pain patients in traditional mental health treatments has been challenging due 
to stigma associated with mental health concerns among this population7,23. Referrals are also 
challenging due to lack of trained providers, particularly for patients in rural areas for whom 
travel to clinic for additional visits would be an additional burden. Travel to clinic is a burden 
even for patients who are geographically proximal to clinic but are often unable to drive and 
have to rely on family and friends for transportation. 
Mind body approaches delivered to patients with acute orthopedic injuries may help.  
Over the last decade, mind-body interventions have demonstrated utility for improving 
psychological and pain-related outcomes and have potential to help patients who seek care for 
musculoskeletal injuries in orthopedic surgical practices as an adjunct to medical care27–36. Brief 
mind body programs show promise among orthopedic patients37. In a fully powered randomized 
controlled single blinded study we have shown that a 60-seconds, personalized, live video 
mindfulness exercise is highly accepted, feasible and useful for patients with non-traumatic hand 
and upper extremity orthopedic conditions waiting for their medical appointment with a surgeon, 
and is associated with momentary decrease in pain and distress compared to an attention placebo 
control38. 
We developed the first mind-body program – The Toolkit for Optimal Recovery after 
orthopedic injury (TOR) – to prevent chronic pain and disability in at-risk patients with orthopedic 
injuries. We used the fear avoidance model as the theoretical framework to guide the development 
of TOR.51 The fear avoidance model provides a useful framework to understand the transition from 
acute to persistent or chronic symptoms in patients with acute orthopedic injuries. The model 
specifies that catastrophic thinking about pain (i.e., misattributions about pain), and anxiety about 
pain (i.e., hypervigilance to pain sensations) lead to avoidance of activity and escape behaviors, 
which in turn, lead to increased pain and disability. Using this model and feedback from surgeons 
and patients with acute orthopedic injuries, we iteratively developed a 4-session, individual, live 
video mind-body program, TOR, focused on optimizing recovery and preventing chronic pain and 
disability in patients with orthopedic injuries who endorse catastrophic thinking about pain and/or 
pain anxiety and are thus at risk for chronic pain and disability, based on our prior work.  
TOR directly targets catastrophic thinking about pain (i.e., misconceptions about pain and 
activity, hopelessness, helplessness and magnification of pain) and pain anxiety (i.e., cognitive, 
physiological and pain avoidance elements) through teaching relaxation response and mindfulness 
skills, correction of misconceptions (e.g., through education and adaptive thinking techniques), 
acceptance and value-based engagement in activities, and activity pacing. The goal is to “confront” 
rather than “avoid” the pain experienced and activities that may be associated with pain and thus 
prevent the transition toward chronic pain. Each TOR session is about 45 minutes, and all 4 are 
delivered within a period of 4-5 weeks (TOR and control arm will be yoked for the timing of 
interventions). Brief mind-body interventions have shown to be feasible to implement and 
acceptable to patients in busy orthopedic practices. The live video delivery format aims to bypass 
established barriers to biopsychosocial care for orthopedic patients (e.g., transportation, inflexible 
schedules)30. These format/dosage considerations are all in line with feedback we received from 
surgeons and patients with acute orthopedic injuries during the iterative treatment development 
process. It is unlikely that TOR intervention causes any risk of physical or psychological harm 
other than potential experience of psychological discomfort while discussing their experiences 
during intervention sessions. As indicated, our pilot feasibility RCT of TOR at MGH showed 
evidence for feasibility, acceptability, and satisfaction for TOR. 

 
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II. SPECIFIC AIMS 
 
Aim 1 (Year 1): Develop a semi-structured qualitative interview script that will be used 
to conduct separate focus groups with surgeons and with supportive medical staff (e.g., 
nurses, medical assistants) at the 3 original sites. 
 
Deliverables: 1) Develop a study protocol including milestones, and strategies to maximize 
success of Aim 2; 2) develop education materials to facilitate referrals and study procedures 
for surgeons and staff; and 3) finalize the Toolkit for Optimal Recovery after Orthopedic 
(TOR), as needed; 4) anticipate and develop alternative plans for potential study challenges, 
at each site.  
 
Aim 2 (Years 2, 3, & 4): Conduct a 4-site feasibility RCT (180 participants total, 60 at 
the parent site, 50 completers; 40 per child site; 33-34 completers per site) to compare 
the TOR versus a minimally enhanced usual care control (MEUC). The trial will be 
informed by our preliminary data and activities of Aim 1. This trial will be used to 1) 
determine whether the study methodology and TOR meet a priori set benchmarks 
necessary for the success of a subsequent efficacy trial and 2) determine whether the 
study methodology and TOR meet a priori set benchmarks for the 27 secondary 
outcomes related to the success of the subsequent efficacy trial. After the conclusion of 
the intervention, we will also solicit feedback from orthopedic trauma providers about 
their perceptions of the feasibility, acceptability, and appropriateness of the TOR study 
in their clinic. 
 
 
Deliverables: 1) refined protocol of patient recruitment, study protocol, and fidelity 
materials, 2) study procedures that are individualized to each site and feasible, appropriate, 
and accepted by patients and staff, and have the potential to decrease pain and increase 
physical function/decrease disability; 3) ability to meet feasibility, acceptability, 
appropriateness and fidelity benchmarks at each of the 4 sites in preparation for the 
UG3/UH3. 
 
The PI has experience adapting and conducting mind body interventions via 
videoconferencing, and has received IRB approval on 2 ongoing studies assessing efficacy of 
mind body interventions via videoconferencing that are currently progressing. 
 
III. SUBJECT SELECTION 
 
All adult, English-speaking, 18 or older patients presenting to the each of the 3 Level 1 Trauma 
Centers sites with a traumatic musculoskeletal injury will be invited to enroll.  The study will be 
described in detail and a member of the IRB-approved study staff trained in obtaining consent 
will obtain informed consent.  Patients will be given a copy of the consent form and be informed 
that their participation is voluntary and that they can withdraw at any time. Subjects will be 
identified by referrals through surgeons and other orthopedic medical providers. We will aim at 

 
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recruiting N = 60 participants at the parent site and N = 40 participants per child site (total N = 
180).  
 
Aim 1: Inclusion/Exclusion Criteria 
 
Eligible participants must meet the following inclusion criteria: 
1) Male and female medical staff (surgeon, fellow, resident, nurse, medical assistant, front 
desk, phone, research staff) in the Level 1 Trauma Center of one of the 3 sites.  
2) Willingness to participate 
 
One or more of the following exclusion criteria will render a participant ineligible: 
1) Chief of orthopedic trauma  
 
Aim 2: Inclusion/Exclusion Criteria 
 
Eligible patients must meet the following inclusion criteria: 
1) Outpatient adults in the Level 1 Trauma Center at the 4 sites 
2) Age 18 or older 
3) Able to meaningfully participate (English fluency and literacy, stable living situation as 
determined by the medical staff at each site). 
4) A score of 8/10 or more on the Short Portable Mental Status Questionnaire ONLY IF a 
participant is 65 or older, or if a participant’s cognitive abilities are unclear to research 
staff 
5) Sustained one or more acute orthopedic injuries (e.g., fracture, dislocation, rupture) 
approximately 1-2 months earlier (acute phase). 
6) PCS ≥20 or PASS-20 ≥40 
7) Willingness to comply with the study protocol, including randomization, questionnaire 
completion, and potential home practice and weekly sessions. 
8) No psychotropics for at least 2 weeks prior to initiation of treatment or stable for >6 
weeks and willing to maintain a stable dose  
9) Cleared by orthopedic surgeon for activities using the injured limb within the next 4 
weeks 
One or more of the following exclusion criteria will render a patient ineligible: 
1) Serious comorbidity expected to worsen in the next 6 months (e.g., malignancy) 
2) Current untreated or unstable severe mental health conditions like bipolar disorder, 
schizophrenia, or active substance use 
3) Current suicidal ideation 
4) Other unmanaged serious non-orthopedic injuries that occurred alongside the orthopedic 
injury (i.e., TBI, ruptured internal organs, etc.) 
5) Currently in litigation or under Workman’s Comp 
6) Surgery complications (e.g., uncontrolled infection, need for repeat surgery) 
7) Self-reported pregnancy 
8) Practice of meditation, or other mind body techniques that elicit the RR, for at least 45 
total min a week each week over the last 3 months 
 

 
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After the conclusion of the RCT, we will also solicit feedback from orthopedic trauma providers 
(up to 80 participants total) about their perceptions of the feasibility, acceptability, and 
appropriateness of the TOR study in their clinic. 
 
Eligible participants must meet the following inclusion criteria: 
1) Male and female medical staff (surgeon, fellow, resident, nurse, medical assistant, front 
desk, phone, research staff) in the Level 1 Trauma Center of one of the 4 sites.  
2) Willingness to participate 
 
Recruitment 
 
Aim 1: Participants will be surgeons and medical staff at each of the 4 sites. We will conduct 
separate focus groups with surgeons and with the rest of the medical staff. Trauma chiefs (Co-Is 
on this grant) will not be included in the focus groups to avoid bias. The site PI and surgeon 
champion at each site, with support from the trauma chiefs will give presentations during the 
staff meetings to discuss the aim of the study, present preliminary data, discuss potential benefits 
to patients, and encourage participation. The RA at each site will next assist with recruitment, 
consent, and scheduling focus groups.  
Aim 2: Participants will be recruited from each of the 4 Level 1 Trauma Center sites: MGH, 
Kentucky, Dell and Vanderbilt following a recruitment protocol developed and individualized 
for each site, consistent with prior recommendations13,14, and informed by aim 1. Potential 
participants will be identified through screening of the medical record by the RA (injury in the 
prior 1-2 months, consistent with our preliminary data). The RA will next notify the medical 
staff (medical assistant) who will alert the surgeons. The surgeon will do a “warm hand-off” and 
introduce the RA and the study to the participants at the end of the medical visit. The RA will 
assess for eligibility (per criteria above). All participants will sign a consent form in REDCap 
prior to study procedures. All forms of recruitment will be submitted for IBR approval prior to 
use. Participants who meet eligibility criteria will complete baseline questionnaires on an iPad or 
on paper in clinic. The RA will be available to answer any questions.  
 
Eligible cases may also be identified by daily screening of Epic admission reports. 
 
After the conclusion of the intervention, we will also solicit feedback from orthopedic trauma 
providers about their perceptions of the feasibility, acceptability, and appropriateness of the TOR 
study in their clinic. Participants will be surgeons and medical staff at each of the 4 sites. Site PIs 
and surgeon champions will distribute survey links via email to providers at their site. After 
reviewing a consent fact sheet, participants will be asked to complete a brief demographic 
questionnaire as well as a brief survey regarding their perceptions on the implementation of the 
TOR study in their clinic (11 items). 
 
 
IV. SUBJECT ENROLLMENT 
 
Aim 1: Surgeons and medical staff at the original 3 sites will be asked to participate in focus 
groups. It is anticipated that focus groups will comprise the following participants: 4 surgeon 
attendings, 1 fellow, 2 residents, 2 medical assistants, 1 nurse, 2 front desk staff, and 4 

 
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administrative assistants (MGH); 5 surgeons attendings, 27 fellows, 8 medical assistants, 2 
nurses, 4 front desk staff (Kentucky); 4 attendings, 8 fellows, 2 nurses, 4 medical assistant, 6 
front desk staff, and 10 other stuff (e.g., schedulers, orthopedic technicians) (Dell). We have the 
full support from the orthopedic leadership at each site for these activities. 
 
For Aim 1, we will obtain verbal consent from the medical professionals who agree to participate 
in the focus group sessions. Prior to verbal consent, study staff will inform participants that the 
focus group discussions will be audio recorded, as these recordings will be utilized to inform 
implementation of our mind-body intervention. All participants will be ensured that participation 
is strictly voluntary and confidential, and that it does not affect their care at any of the Partners 
Healthcare institutions. In addition, we will inform the participants about the confidentiality 
measures that the research group will take during the process. Only members of the research 
team will have access to the data, and the recorded transcriptions will be de-identified as to not 
contain identifiable or confidential information. The verbal consent process will include pertinent 
information on study design, risks and benefits, and voluntary nature of the research and 
confidentiality. Due to the nature of this study and the minimum risk, we would like to waive the 
written documentation of informed consent. However, study staff will document verbal consent 
by retaining a list of names of the participants who verbally consented and participated in the 
focus group. The consent process will be executed in a manner consistent with the IRB approved 
protocol, and the most recent version of the IRB-approved protocol will be used. Participants 
will be encouraged to review the study fact sheet, in its entirety, before verbally consenting. 
Study staff will answer any questions that participants may have. Participants will be given a 
copy of the fact sheet. 
 
Aim 2: Participants will be recruited from each of the 4 Level 1 Trauma Center sites: MGH, 
Kentucky, Dell and Vanderbilt following a recruitment protocol developed and individualized 
for each site, consistent with prior recommendations13,14, and informed by aim 1. Participants 
will be patients with acute orthopedic musculoskeletal injuries who are at risk for chronic pain 
and disability (PCS ≥ 20 and PASS-20 ≥ 40) and meet inclusionary/exclusionary criteria. 
Informed by guidelines for feasibility testing69 and Proctor’s framework13. Potential participants 
will be identified through screening of the medical record by the RA (injury/surgery in the prior 
1-2 months, consistent with our preliminary data). Study staff will ask all participants to provide 
verbal consent to participate in screening procedures prior to screening. This will happen in 
clinic when the participant arrives or over the phone prior to the clinic visit. The verbal consent 
will be documented. The RA will further assess for eligibility and conduct initial screening 
(using the PASS and PCS) and will notify the orthopedic surgeon that the patient is a potential 
study participant (verbally or via a note with the study logo attached to the door). Surgeons will 
also receive information regarding race and ethnicity of each participant in order to prioritize 
study referrals. The orthopedic surgeon will perform the medical visit and subsequently 
introduce the study to the potential participant using a predetermined script and 
materials/procedures. For the patients who express interest or want to learn more, the surgeon 
will conduct a “warm hand off” referral to the research assistant. The research assistant will 
finish the screening process using the screening checklist. If there are challenges in recruitment 
due to time required for study procedures, participants will be screened by study staff via phone 
prior to coming in for their 1–2-month follow-up visit so that they can be notified in advance if 
they are eligible to budget time for the research visit. 

 
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If a participant meets all study criteria, the RA will meet with the participant in a private 
location following their clinic visit to describe the study in detail including the consent form. All 
patients will have the opportunity to ask questions and will be given time to consider whether or 
not to participate. Participants will be informed of the potential risks and benefits of 
participation, and information regarding who they can contact for further questions. They will 
also be informed that participation is voluntary, that they can refuse to answer any questions, and 
they can withdraw from the study at any time. They will be informed that refusal to participate in 
the study will in no way impact their medical care. All participants will sign a consent form 
electronically in REDCap prior to study procedures. Participants will sign on an iPad in the 
clinic, or participants will be given the option to sign the consent form at home prior to 
completing study procedures remotely. Consent will include provision of consent to receive once 
daily text reminders to complete home practice (if randomized to TOR) as well as once daily 
reminders to record skills practiced (if randomized to TOR). All forms of recruitment will be 
submitted for IRB approval prior to use. Participants who meet eligibility criteria and consent 
will complete baseline questionnaires on an iPad or on paper in a private location in the clinic. 
The RA will be available to answer any questions. A trained research assistant will assist with 
the grip test (for upper extremity injuries) or walk test (for lower extremity injuries). Next, they 
will be randomized to TOR or Minimally Enhanced Usual Care (MEUC) and will receive a 
patient manual (TOR) or booklet (MEUC). Participants in both TOR and MEUC will also be 
provided with access to a website that contains the information from the treatment manual (for 
TOR) or printed booklet (for MEUC) and be assisted in accessing this website from their 
preferred device and bookmarking the website (e.g., downloading as an app), as desired. For 
those randomized to TOR the RA will install the Zoom secure live video platform on the 
participants’ smart phones. For those who prefer to use a laptop, desktop or iPad, the RA will 
email a link and schedule a call to assist with the set up. The RA will also download the study 
website with pre-recorded TOR skills onto the participants’ phones in an app form to aid with 
skills consolidation/practice. If enrolled participants do not have reliable access to a smartphone 
or other device or internet, the RA will provide the participant with a smartphone and set up a 
short-term data plan to enable participation in the study. Finally, the RA will schedule the first 
individual virtual visit with the clinician.  
 
For the provider feedback surveys, surgeons and medical staff at each of the 4 sites will 
be asked to participate. Up to 80 providers are expected to participate. Medical professionals 
who choose to participate will provide implied consent based on their review of a study fact 
sheet in REDCap. All potential participants will be provided with a study fact sheet as the first 
page of a REDCap survey. The study fact sheet provides detailed information on the 
methodology and purpose of the study and the potential benefits/ risks associated with 
participating. All participants will be ensured that participation is strictly voluntary and 
confidential. In addition, the study fact sheet will inform the participants about the 
confidentiality measures that the research group will take during the process. Only members of 
the research team will have access to the data, and data will be de-identified as to not contain 
identifiable or confidential information. The study fact sheet will include pertinent information 
on study design, risks and benefits, and voluntary nature of the research and confidentiality. 
Participants will be encouraged to review the study fact sheet in its entirety before continuing to 
complete the brief REDCap survey. The study fact sheet will also contain the names and 
numbers of members of study staff that participants can contact if they have additional questions 

 
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or concerns. Due to the nature of this study and the minimum risk, we would like to waive the 
written documentation of informed consent. The consent process will be executed in a manner 
consistent with the IRB approved protocol, and the most recent version of the IRB-approved 
protocol will be used.  
 
 
 
V. STUDY PROCEDURES 
 
Aim 1: Participants will be surgeons and medical staff at the original 3 sites. Participants will 
provide verbal informed consent prior to participation. Participants will be informed their 
participation in voluntary and they are not obligated to answer any questions. Next, we will 
conduct separate focus groups with surgeons and with the rest of the medical staff. Trauma 
chiefs (Co-Is on this grant) will not be included in the focus groups to avoid bias. The site PI and 
surgeon champion at each site, with support from the trauma chiefs will give presentations 
during the staff meetings to discuss the aim of the study, present preliminary data, discuss 
potential benefits to patients, and encourage participation. The RA at each site will next assist 
with recruitment, consent, and scheduling focus groups. For MGH surgeons, ideal focus groups 
are at 6:30 am or 7:00 am. Each site will prioritize recruitment, and the number of focus groups 
will depend on ability to schedule participants at each site. Exit interviews will be administered 
immediately after. 
 
Aim 2: We will conduct a 4-site feasibility RCT and recruit 180 participants total (60 at the 
parent site, 50 completers; 40 per child site, 33-34 completers).  
 
Baseline and follow-up assessments will include measurements of grip strength (for upper 
extremity injuries) or a walking test (for lower extremity injuries), which measures the time 
required to travel 10 meters, self-report measures assessing the primary (pain intensity and 
disability), and secondary (depression, PTSD, pain catastrophizing and pain anxiety) variables, 
and demographic information. Patients will complete the following reliable and valid battery of 
questionnaires, which will take approximately 20 minutes to complete: 
o 
Demographics: Age, gender, race/ethnicity, education, employment, income, 
marital status, current psychotropic/pain medication intake, comorbid medical 
conditions, history of depression or other mental health conditions. 
o 
Clinical variables: Injury type, date, location, prior pain (all by self report). 
o 
Pain: Numerical Rating Scale, requires the patient to rate their pain on a defined 
scale (11-point scale from 0 (no pain) to 10 (worst pain)). 
o 
Pain: Use of analgesics; Concomitant treatment: Daily self-report log.  
o 
Physical function self-report: PROMIS Physical Function assesses one's ability 
to carry out activities that require physical actions, ranging from self-care to 
social and work. 
o 
Physical function self-report: Short Musculoskeletal Function Assessment 
assesses patient’s function as well as how bothered they are by their injury. 
o 
Emotional function: The Center for Epidemiologic Study of Depression measures 
self-reported symptoms of depression. 

 
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o 
Emotional function: The PTSD Checklist civilian version measures symptoms of 
PTS. 
o 
Coping: Pain Catastrophizing Scale assesses hopelessness, helplessness and 
rumination about pain. 
o 
Coping: Pain Anxiety Scale, short form assesses avoidance, fearful thinking, 
cognitive and somatic symptoms of anxiety. 
o 
Coping: Measures of Current Status (MOCS) assesses ability to engage in a series 
of healthy coping skills (e.g., relaxation, social support, adaptive thinking). 
o 
Credibility and Expectancy Scale 
o 
Mindfulness: 15-item Five-Facet Mindfulness Questionnaire (FFMQ-15) 
o 
Experiential Avoidance: Acceptance and Action Questionnaire (AAQ-2) 
Subjects will complete these questionnaires in the clinic or if there is not enough time, a 
researcher will send the questionnaires via a secure REDCap link for participants to complete at 
their home. At the 4 week follow up (after the intervention), they will also complete the Client 
Satisfaction Questionnaire49 to assess satisfaction with intervention. Patients will complete these 
measures on line via REDCap either in the clinic or from home. The walk test will be performed 
near a wall and a researcher will accompany the subject for the duration of the test. The subject 
will be informed that they should use the wall or researcher for balance, if needed, and this will 
be recorded. The grip strength test is routinely performed by researchers as part of other research 
projects in the department. The protocol for training and safety to ensure the reliability of results 
will be followed for this study. The grip strength test and walk test will be optional and subjects 
can refuse participation. Subjects may experience minimal pain during these exercises. The 
researchers will check the subject’s medical record for any potential restrictions in activity and 
discuss with the treating physician any concerns about safety.  We expect that most of the 
healing would have already occurred because we will be enrolling subjects about 0-3 months 
post injury date. Subjects in wheelchairs will not participate in the walk test.  
 
Next, following guidelines for psychosocial clinical trials43, we plan for a 1:1 RCT comparing 2 
arms: 1) TOR (delivered via Zoom) + MEUC and 2) MEUC. Patients will be randomized based 
on scores on Pain Catastrophizing (PCS) and Pain Anxiety (PASS). PCS and PASS were chosen 
for the randomization based on our prior work with this population, which showed that PCS was 
the strongest predictor of pain intensity and PASS of long term disability2. This method of 
randomization (median split on PASS and PCS) was successful in our previous face to face 
RCT1. We will stratify participants by site, using the randomization module in REDCap, which 
will be prepared using permuted blocks by the study statistician. Out of the 180 participants 
enrolled, 90 will be randomized to TOR and 90 to MEUC. Within the 60 participants at the 
parent site, 30 will be randomized to TOR and 30 to MEUC. Within each of the 40 participants 
at the child sites, 20 will be randomized to TOR and 20 to MEUC. We will report on our primary 
and secondary outcomes specifically for each site (separate by study site strata). There will be 3 
assessment points for the intervention: 1) baseline (0-3 months post trauma and before the 
intervention), 2) first follow-up post intervention (4 weeks post baseline), 3) second follow-up 
post intervention (3 months post baseline). 
 
TOR has been developed tested and found efficacious in improving disability, pain, mood and 
coping in patients with orthopedic trauma, and we are ready to test it via videoconferencing to 
improve access to care. TOR has 4 sessions, 45 minutes each. TOR is focused on 1) discussing 

 
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the rationale for treatment and conducting motivational interviewing, 2) cognitive restructuring 
of patients’ negative thoughts/misconceptions, 3) teaching patients to elicit the relaxation 
response through breathing retraining, progressive muscle relaxation and guided imagery, 4) 
helping patient decrease avoidance and return to activities including the injured limb, 5) 
increasing resiliency and preventing relapse. In both groups, patients will receive usual medical 
care (e.g., pain medications, physical therapy, and meetings with surgeons, medical staff) as 
currently delivered by orthopedic surgeons. In addition, participants in the control group, will 
receive a booklet containing brief summarized information that reflects the active intervention 
topics including the trajectory of pain and recovery after orthopedic illness, the role of relaxation 
strategies to manage pain and the importance of returning to engagement in activities of daily 
living. Participants in the MEUC will also be provided with access to a website that contains the 
educational information from the printed booklet in electronic format and be assisted in 
accessing this website from their preferred device and bookmarking the website, as desired. 
Participants in MEUC who do not own a smart phone will not be provided with one as they can 
also access the educational information in printed form access to a website that contains the 
educational information from the printed booklet in electronic format. The randomization 
process will increase likelihood of comparability of the two groups on the main study variable 
pain catastrophizing. Clinical staff at MGH will deliver TOR to participants at all sites. 
 
Participants randomized to TOR will undergo set-up for the live video intervention prior to 
leaving the clinic. This includes: 1) installing Zoom and teaching participants how to use it; 2) 
scheduling their 4 weekly intervention sessions with the clinician; 3) setting up EZ texting to 
receive reminders; and 4) installing the TOR web platform (with session content and guided 
exercises) as an app on their phones. Participants who do not own a smart phone will be given 
one, and the RA will set their phone up at the first visit.  We will also provide study participants 
with a data plan for the duration of the study, or brainstorm ways to access free internet (e.g., 
library, friends’ houses), if needed. Our study team has used these strategies in prior studies. The 
RA will also schedule the participant’s first session of TOR and ensure the participant writes 
down the date and time of the first session. 
 
In order to ensure that participants in the TOR program are familiar with Zoom, the psychologist 
will schedule a brief session to go over how the software works and prepare the participants for 
the intervention. 
 
Participants randomized to TOR will also receive daily text reminders through Twilio to practice 
program skills as well as record their skills practice if they consent to receive text reminders.  
 
For the provider feedback surveys, surgeons and medical staff at each of the 4 sites will 
be asked to participate. Up to 80 providers are expected to participate. Participants will provide 
implied informed consent prior to participation. After reviewing a consent fact sheet, participants 
will be asked to complete a brief demographic questionnaire as well as a brief survey regarding 
their perceptions on the implementation of the TOR study in their clinic (11 items). Site PIs and 
surgeon champions will distribute surveys to providers at their site. We have the full support 
from the orthopedic leadership at each site for these activities.  
 
 

 
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VI. BIOSTATISTIC ANALYSIS 
 
Aim 1: 
 
We will use qualitative interviews and exit interviews to identify further understand the patient 
flow and clinic structure at each site, assess surgeon and staff perceptions and barriers and 
facilitators for study implementation and referrals, provide description of the TOR skills and 
perception of the utility of the TOR components (including suggestions for potential 
modifications), understand surgeon and medical staff beliefs and attitudes toward biopsychosocial 
care at each site, and learn barriers and facilitators for making patient referrals. The qualitative 
focus group data and individual exit interview data will be transcribed and analyzed, using NVivo 
10 qualitative software, and we will conduct thematic content analysis using guidelines provided 
by Miles and Huberman67. The 2 coders (study clinicians) will meet on an ongoing basis with Dr. 
Vranceanu and Elwy to discuss the structural thematic framework, categories, and coding plan, 
guided by the Proctor Framework, but allowing for the emergence of additional codes68. To ensure 
coding reliability, coding discrepancies will be resolved through discussion and comparison of raw 
data. Coding will continue until a high reliability (Kappa= >0.80) is established. Once these data 
analyses are completed, the multidisciplinary team will provide the expert review of data, to 
discuss the interpretation of our findings in the context of current research on chronic 
heterogeneous pain. We will also work on identifying whether site specific themes emerged that 
would require tailoring the training materials as well as staff training and methodology for aim 2 
to each site.   
 
Aim 2: 
 
The main purpose of this multi-site feasibility RCT is to assess feasibility, acceptability, 
appropriateness and fidelity of TOR and study procedures at each of the 4 sites, to meet 
benchmarks before an efficacy trial. We will calculate, for each site, number of patients identified 
via medical record, number referred by surgeon, number screened, number consented, number 
enrolled and randomized. The results will be reported using descriptive statistics (numbers, 
proportions, and mean scores).  
 
Given the feasibility RCT design, the trial is not fully powered for efficacy. Consistent with the 
feasibility design of this trial, we will report means and SDs of all measures at all time points, 
including distribution of scores and internal consistency. To determine the measures’ sensitivity 
to detect change, we will report within group change in all quantitative outcomes. We will also 
conduct exploratory between group analyses to inform the future fully powered RCT. 
 
VII. RISKS AND DISCOMFORTS 
 
Aim 2: 
 
The greatest discomfort associated with participation is the time required to complete the 
questionnaires and grip strength and walk test measurements. Subjects might experience minimal 
pain when completing these tests. Study physicians will be readily available should a subject 
experience discomfort while completing the measurements. The grip strength and walk test are 

 
12 
 
optional and subjects can refuse participation. Questionnaires and measurements will require 
approximately 25 minutes at the time of enrollment and about 25 minutes at the 3-month follow-
up.    
 
Patients are not obligated to answer any question.  The patient’s participation will not affect their 
medical care. Patients can withdraw from the study at any time.  Patients who are disturbed by 
any of the questions will be offered psychological counseling, referral to a psychiatrist, or 
immediate transfer to the emergency room for psychiatric evaluation, depending upon the 
severity of the reaction.  
 
Study physicians will be readily accessible for consultation should a study patient experience 
increasing discomfort while completing the questionnaire or during the intervention time period. 
In the extremely unlikely event that a patient has a severe adverse emotional disturbance while 
completing the questionnaire, we will contact the Acute Psychiatric Service and immediately 
take the patient to the Emergency Department for treatment.  Subjects removed to the 
Emergency Department for additional care will not be asked to complete the questionnaires and 
will be dropped from the study. 
 
VIII. POTENTIAL BENEFITS 
 
Aim 1: No direct benefit is anticipated.  
 
Aim 2: No direct benefit is anticipated. Participants may improve their ability to cope with pain 
and improve their mood, pain, and disability.  Information gained through this study may lead to 
a better understanding the importance of delivery method of mind body interventions.  
 
IX. MONITORING AND QUALITY ASSURANCE 
 
Electronic information will be stored in REDCap (Research Electronic Data Capture), a free, 
secure, and HIPAA-compliant web-based application hosted by the Partners HealthCare 
Research Computing Enterprise Research Infrastructure & Services (ERIS) group (based at the 
PHS Needham corporate datacenter). Data will be stored on password protected computers that 
will be stored in secure locations at all times. Paper data files (with coded subject identification) 
will be stored in a locked filing cabinet. Only research staff will have access to these data 
locations.  
 
A unique anonymous identifier will be assigned to each subject; subsequently, all data collected 
will be associated exclusively with this identifier. This includes all questionnaires administered 
over the course of the study, as well as home practice logs. 
 
Data from this study will be stored for three years after the publication of all study results, at 
which time all paper data files will be shredded, and computer files will be deleted.  
 
The following study staff will be blinded: 1) overall PI; 2) site PIs; 3) surgeon champions; 4) 
study statistician; 5) RA involved with any post and follow up self-report and objective 
assessments; 6) statistician who is performing blinded analyses.  

 
13 
 
To achieve RA blindness, treatment assignment will done by randomization RA, who will not be 
directly involved in evaluation or data collection. Survey data collection will be conducted by 
another RA who will be blinded to participant treatment assignment. Participant self-report 
surveys will be implemented using secured online survey software, which will significantly limit 
the potential of the RA to introduce bias.   The overall PI, site PIs and surgeon champions will 
not be involved in the group assignment or collection of data. Also analyses will be conducted 
when data are unlocked. The study statistician and statistician who perform blinding analysis will 
not have access to randomization algorithm key.  
 
The following study staff will not be blinded: 1) randomization RA (RA who will randomize 
participants after consent and baseline and give participants study materials consistent with their 
respective treatment arm, and problem solves in real time and potential tech issues for those in 
TOR); 2) study therapists/clinicians; 3) the statistician who will develop the randomization 
scheme. The unblinded staff will have no access to data and no involvement in data monitoring 
and analyses.  
 
Data Management and Quality Control Procedures 
 
To maximize accuracy and security, all survey data will be collected and stored on REDCap. 
Research staff will ensure that proper consent has been obtained before sending the REDCap 
survey to each participant.  
 
REDCap (Research Electronic Data Capture) is a free, secure, HIPAA compliant web-based 
application hosted by the Partners HealthCare Research Computing Enterprise Research 
Infrastructure & Services (ERIS) group. Vanderbilt University, with collaboration from a 
consortium of academic and non-profit institutional partners, has developed this software toolset 
and workflow methodology for electronic collection and management of research and clinical 
study data. Data collection projects rely on a study-specific data dictionary defined by members 
of the research team with planning assistance from Harvard Catalyst, The Harvard Clinical and 
Translational Science Center EDC Support Staff. This iterative development and testing process 
results in a well-planned data collection strategy for individual studies. Using REDCap, the 
research team can also design web-based surveys and engage potential respondents using a 
variety of notification methods. REDCap provides flexible features that can be used for a variety 
of research projects and provides an intuitive interface to enter data with real time validation 
(automated data type and range checks). The system offers easy data manipulation with audit 
trails, reports for monitoring and querying participant records, and an automated export 
mechanism to common statistical packages (SPSS, SAS, Stata, R/S-Plus).  
 
Since consistency of application of the study protocol is critical to acquiring high quality data, all 
research personnel have undergone or will undergo a competency-based training program prior 
to enrolling subjects. 
 
Data and Safety Monitoring Plan 
 
Study data will be maintained in a locked filing cabinet and on password protected computers.  
Questionnaires and self-reported responses will not become part of the patient’s medical record 

 
14 
 
and will not contain medical record numbers or names.  Hardcopies of study related data and 
forms will be stored in a lockable file cabinet.  Patient information will remain confidential by 
keeping identifying information (name, medical record number, and subject number) in a 
separate locked file cabinet.  Only the investigators and study staff specified on the consent form 
will have access to this information 
 
Among the 4 recruitment sites (MGH, Dell, Kentucky, Vanderbilt), PHI will be shared related to 
enrolled study participants. MGH will send and receive PHI to/from Dell, Kentucky and 
Vanderbilt using encrypted email as well as shared storage in the Partners-approved platform 
Dropbox. PHI will not be shared with any study collaborators outside of MGH, Dell, Kentucky 
and Vanderbilt. Once data collection is completed, all data will be de-identified. Our collaborator 
at Brown University will receive only de-identified data.  
 
The study research assistant will be trained in procedures to protect study participant 
confidentiality. All data will be kept confidential, stored on password protected drives accessed 
through encrypted devices, accessible only to trained study staff. Participants’ data will be 
identified by ID number only, and a link between names and ID numbers will be stored 
separately and securely. Session recordings will be immediately downloaded from the recording 
device to the secure computer and subsequently deleted from the recording device. Recordings 
will be labeled with the patient ID and stored on a password protected computer; the recording 
will be subsequently and immediately deleted from the recording device. Just like a regular 
doctor’s appointment, the live-video visit will be kept private and confidential. The research 
team will report to the data safety and monitoring committee with details of any participant 
confidentiality breach and corresponding plans for corrective action. Data for all participants will 
be kept strictly confidential, except as mandated by law or as necessary for monitoring by IRB, 
or NCCIH. In the unlikely event of serious concerns of suicidality and to ensure patient safety, 
we will suspend confidentiality and alert the site PIs so that appropriate clinical interventions can 
be assured.  
 
All study staff have been trained in responsible research conduct through a CITI course. The 
RAs will be trained on the importance of maintaining confidentiality through the assignment of 
ID numbers. All data will be kept confidential, on password protected drives accessed through 
encrypted devices only, accessible only to trained study staff. Participant data will be identified 
by ID number only, and a link between names and ID numbers will be saved separately. Session 
recordings will be immediately downloaded from the recording device to the secure computer 
and subsequently deleted from the recording device. Recordings will be labeled with the patient 
ID and password protected. 
 
Adverse Event Monitoring: Throughout the study subjects will be monitored for the occurrence 
of events defined as any undesirable experience or unanticipated risk. Lack of effect of treatment 
is not considered an event. All adverse events will be reported on an adverse event form. The 
Principle Investigator has the responsibility of reporting serious adverse events (death, life 
threatening illness or injury, serious injury, or permanent disability) to PHRC within 24-72 hours 
of notification. 
 
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