Study design overview

PT-IN-MIND is a multisite, randomised feasibility trial investigating PT-IN-MIND for patients with chronic musculoskeletal pain and long-term opioid treatment. First, we will refine the I-EPT intervention protocol (study 1 aim). I-EPT is currently being studied in patients after spine surgery (NCT04770480),27 28 however, key stakeholder feedback from physical therapists and patients is needed to refine the protocol (ie, stakeholder suggestions to maximise the acceptability of the protocol to both patients and physical therapists) for patients with chronic musculoskeletal pain and long-term opioid treatment. Second, we will evaluate the I-EPT training programme with respect to intensity to inform future study planning (study 2 aim). Third, we will evaluate physical therapists’ fidelity to the I-EPT refined treatment protocol and assess key feasibility outcomes (study 3 aim). These study aims will be carried out sequentially. We will evaluate feasibility of procedures needed to conduct our future trial; therefore, the results of an early study aim may require modification of certain procedures during a later study aim. This flexibility will allow for thorough methodological evaluation to maximise the likelihood of successfully conducting our future trials. Any important modifications to the protocol will be submitted the National Institutes of Health (NIH)/ National Center for Complementary and Integrative Health (NCCIH), the University of Utah IRB and ClinicalTrials.gov as necessary.

Project aims

Study 1 aim: Refine and manualise the I-EPT treatment protocol for patients with chronic musculoskeletal pain and long-term opioid treatment.

Study 2 aim: Evaluate different intensities of a physical therapist training programme for the refined I-EPT treatment protocol.

Study 3 aim: Evaluate the feasibility of the I-EPT intervention across domains of the RE-AIM framework.

Settings and participants

This multisite feasibility study will be conducted at University of Utah Health in Salt Lake City, Utah and Brooks Rehabilitation in Jacksonville, Florida.

Study 1 aim: refine and manualise the I-EPT treatment protocol for patients with chronic musculoskeletal pain and long-term opioid treatment

The I-EPT treatment protocol is currently used by members of our study team for an ongoing trial (NCT04770480) examining patients after spine surgery.27 28 The protocol integrates principles of MORE, a treatment that integrates mindfulness training, cognitive reappraisal skills and positive emotion regulation into a therapeutic approach designed to reduce opioid overuse, opioid misuse and functional interference resulting from chronic pain.16 29–31 MORE is an evidence-based intervention that has been tested in multiple RCTs32; in the largest clinical trial of MORE conducted to date (N=250), MORE reduced opioid dose by more than 50% compared with a support group which demonstrated a 15% reduction in opioid dose, and 50% of patients reported clinically significant decreases in chronic pain severity.33 MORE is composed of three core components29 31 that the I-EPT protocol integrates across eight physical therapy sessions: (1) mindfulness to reduce pain and increase self-regulation over opioid use (integrated into physical therapy sessions 2 and 3); (2) reappraisal to regulate negative emotions and promote active coping instead of catastrophising and opioid self-medication (physical therapy session 5); and (3) savouring to promote a focus on positive daily experiences as a means of boosting motivation and restoring dysregulated reward neurocircuitry function associated with pain and opioid use after spine surgery (physical therapy session 7). The integration of MORE core components within the physical therapy episode of care is described in table 2 which includes minor modification to the protocol being used after spine surgery27 for adaptation within the civilian outpatient physical therapy setting. Physical therapists trained to provide I-EPT integrate MORE practice components (mindfulness, reappraisal and savouring exercises) into EPT activities, (eg, integrating mindfulness into a walking programme and using body scan meditation while stretching). Brief didactic components covering mindfulness, mindful savouring or mindful reappraisal are included in treatment sessions 2, 3, 5 and 7 are provided while patients are exercising or receiving other interventions (eg, manual therapy) depending on the preferences of patients and physical therapists. This approach will be used as a starting point with which to refine the I-EPT treatment for patients with chronic musculoskeletal pain and long-term opioid treatment who attend outpatient physical therapy.

Study 1: study design and methods

An iterative approach will be used to refine the current version of the I-EPT treatment protocol. We will conduct semistructured qualitative interviews with separate cohorts of two key stakeholder types who we will identify through purposeful sampling; 15 physical therapists (7 from Utah; 8 from Florida) who manage patients with chronic musculoskeletal pain and 15 patients (7 from Utah; 8 from Florida) with chronic musculoskeletal pain and long-term opioid treatment. Four weeks prior to the interviews, we will provide the physical therapists with the I-EPT treatment protocol manual (including the modifications noted above) developed by members of our study team for use with patients after spine surgery. A summary of the protocol in the form of an online voiceover virtual slide presentation will be provided to the patients 4 weeks prior to their interviews. This presentation will include a description of mindfulness and specific examples of mindfulness activities I-EPT. A coinvestigator or a trained research assistant (RA) will conduct the interviews after the physical therapists and patients review the protocol.

After the semistructured interviews, members of the PT-IN-MIND team will review the qualitative results from the analytical process described below (study 1 aim: analysis plan—qualitative data). To ensure the accuracy of our interpretation of qualitative data at this stage, we will conduct a member-check34 by sharing qualitative results with physical therapists and patients that we interviewed. The results will be used to arrive at an adapted, refined and manualised version of the I-EPT treatment protocol to be used in aims 2 and 3 of this study.

Study 1: eligibility, recruitment and consent of participants

Study 1: qualitative interviews

Interview scripts (online supplemental appendix 2) will be piloted prior to use and will include open-ended questions that explore: the physical therapist and patient impressions of the I-EPT treatment protocol, the likelihood of physical therapist and patient acceptability and how the protocol could be improved for use in routine outpatient physical therapy practice. Qualitative results will inform potential modifications to the treatment protocol while maintaining the core components of MORE (mindfulness, reappraisal and savouring).31 Consent for audio recorded interviews lasting approximately 30 min will be requested. Participants will be provided US$50 for participation in the qualitative interviews.

Study 1: analysis plan: qualitative data

Rapid content analysis (RCA) using a team approach will be used to analyse qualitative interview data in preparation for training physical therapists in the refined I-EPT treatment protocol. RCA is a valid alternative to more time intensive analytic strategies,36 which is important as study 1 results are required prior to advancing to study 2. First, we will create targeted domains that represent each interview question and are guided by aim 1. These domains will then be organised in a case summary template. Next, we will test the case summary template for usability and relevance on a subset (two physical therapists and two patients) interview transcripts. Testing will involve identifying missing domains, checking for appropriate labelling and determining whether the domains will allow the PT-IN-MIND team to meet the goals of study aim 1. After establishing agreement among the analysis team on the case summary template’s usability, the transcripts will be divided among team members and summarised. Direct interview quotes will populate each case summary template’s domains, with paraphrasing used for long or complicated responses. Each case summary will be transferred into a single case summary matrix which the team will use to identify trends in responses across groups of respondents. Domains across respondents will be summarised and used to inform the refinement of the I-EPT treatment protocol manual.

Study 2 aim: evaluate different intensities of a physical therapist training programme for the refined I-EPT treatment protocol

Our future trial will randomise physical therapists to manage patients with chronic musculoskeletal pain and long-term opioid treatment using usual care (UC) or the refined I-EPT treatment protocol. The optimal programme used to train physical therapists in the provision of I-EPT is unknown. Therefore, the primary objective of study 2 aim is to evaluate which training approach (high-intensity training (HighIT) or low-IT (LowIT)) is a likely candidate to use for training physical therapists for a future clinical trial. LowIT is a manualised, LowIT approach; the physical therapists will be provided with a mindfulness-based training manual for self-study and no other training activities. HighIT is a hybrid, HighIT approach; the physical therapists will be provided with the same manual as in the LowIT approach and they will asynchronously view prerecorded mindfulness-related didactic lectures online then attend a live virtual mindfulness-based training session. The primary endpoint for the study 2 aim is physical therapist competency for providing mindfulness-based interventions I-EPT following training. We will also assess our recruitment and randomisation procedures for physical therapists.

Study 2: study design and methods

Physical therapists will be recruited and randomised 1:1:1 from University of Utah Health (n=21) and Brooks Rehabilitation (n=24) to no training, LowIT and HighIT training arms with block size of 3–6 stratified by healthcare system (figure 2, red box). Each training arm is described in greater detail below. Both and LowIT arms educate physical therapists in provision of the revised I-EPT treatment protocol developed in study 1. The training programmes for HighIT and LowIT can be modified for future use, and both are candidates for training a larger group of physical therapists for our future trial. The control arm will receive no training. Four to six weeks after HighIT and LowIT trainings the Modified MORE-FM26 will be used to assess individual physical therapist competency in the provision of the I-EPT treatment during mock patient encounters using trained actors as standardised patients. This extended time will allow trained physical therapists to implement I-EPT in clinical practice prior to competency assessment. Assessing competency will provide vital information to help us determine which training programme to use in our future trial. This randomised study design will also allow for assessment of several feasibility outcomes for patients managed by trained and untrained physical therapists (study 3 aim).

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Figure 2

Study design and flow for aim 2 (red box) and aim 3 (blue box). I-EPT, Mindfulness Integrated Evidence-Based Physical Therapy.

Study 2: eligibility, recruitment and consent of participants

Recruitment of physical therapists will occur by research staff and investigators providing an overview of the project at routinely scheduled University of Utah Health and Brooks Rehabilitation staff meetings. Eligibility and consent of physical therapists will follow similar methods as described for the study 1 aim with the following exclusion criteria to ensure that physical therapists randomised to the training and no training arms will be naive to mindfulness interventions. These criteria will also help ensure that those in the no-training arm are naive to the I-EPT protocol. For study 2 aim, physical therapists must not have (1) attended any experiential (ie, practice sessions with real or simulated patients) mindfulness training to be used for patient care; (2) attended any training on using mindfulness in patient care lasting more than 3 hours; (3) self-reported using mindfulness interventions such as savouring and cognitive reappraisal (core components of MORE) as a primary intervention strategy for the majority of their caseload for patients with chronic musculoskeletal conditions. Online supplemental appendix 3 contains the IRB-approved informed consent document for study 2.

Study 2: randomisation and blinding

A computer-generated randomisation schedule will be developed prior to enrolment by a separate unblinded biostatistician and implemented using the randomisation function in REDCap.35 The study PI at both clinical sites and leading biostatistician will remain blinded until the study database is locked. Study coordinators, RAs and investigators involved in the training and competency assessment will be unblinded.

Study 2: intervention arms

We will include three separate intervention arms for this study (figure 2, red box).

Study 2: competency assessment

Team members will oversee the competency assessments. Approximately 6 weeks after participating in LowIT or HighIT training approaches, physical therapists will apply their skills in teaching mindfulness-based treatments, during mock patient encounters using trained actors as standardised patients. These physical therapists will have had approximately 6 weeks to practice integrating the core components of MORE into the management of their patients prior to the competency assessment. Physical therapist competency will be assessed during these mock patient encounters using a Modified version of the MORE-FM V.2.0.26 Each item is scored 0–6 with scores summed and averaged. A mean score of >3 (ie, at least ‘adequate’ skill on each item) on a 0–6 point scale on the items MORE-FM indicates that the physical therapist provided I-EPT with acceptable competency. MORE-FM scored will be manually entered into REDCAp by study staff. Physical therapists will be provided US$50 for their participation in training programme and competency assessment.

Study 2: analysis plan

Descriptive statistics will be computed to summarise physical therapist characteristics within each group (LowIT, HighIT and No Training) and by healthcare system (Utah or Florida). Measures of central tendency and dispersion will be computed for continuous data, and frequency distributions will be checked for categorical data. Transformations of variables will be sought for variables with skewed distribution. Any observed differences in MORE-FM scores between LowIT and HighIT arms and between Utah and Florida physical therapists will be discussed among study investigators to inform which training programme to use in a future study.

Study 3 aim: evaluate the feasibility of the I-EPT intervention across domains of the RE-AIM framework

The primary objective of study 3 Aim is to evaluate our ability to deliver I-EPT, enrol and retain patients and longitudinally collect patient-reported outcomes. The coprimary endpoints for study 3 aim are the 12-week Pain, Enjoyment of Life and General (PEG) scale38 and the Timeline Followback (TLFB)39 collection rates. We will also (1) evaluate our ability to enrol patients for management by physical therapists randomised to the training and no training groups; (2) assess our longitudinal data collection procedures; (3) measure physical therapist I-EPT treatment fidelity; (4) evaluate for differences in feasibility outcomes between patients managed by physical therapists who received HighIT or LowIT training approaches to inform future study planning and (5) interview key stakeholders to learn about their lived experiences in providing or receiving the refined I-EPT treatment.

Study 3: study design and methods

The RE-AIM framework (table 1) will guide the mixed-methods feasibility evaluation for this study. First, we will enrol patients with chronic musculoskeletal pain and long-term opioid treatment who meet our eligibility criteria (box 1), and pilot test the refined I-EPT treatment protocol (figure 2, blue box). We will collect and evaluate key quantitative feasibility outcomes for patients managed by physical therapists randomised to the training and no training arms described in study 2 aim. Next, we will conduct semistructured interviews with key multilevel stakeholders (ie, patients, physical therapists, support staff, clinic managers and health system leadership) who had experience with the I-EPT treatment protocol to learn from their experiences (ie, was I-EPT difficult to integrate into clinical practice; was the treatment acceptable to patients and physical therapists) and gain further insight into our quantitative feasibility results.

We will use a Quan->QUAL sequential collection and analysis of quantitative feasibility measures and qualitative data (our semistructured interviews). Quantitative feasibility data will be collected and analysed first. Qualitative data will then be collected to explore the quantitative results. ‘Expansion’ (ie, using a qualitative data set to answer questions raised by a quantitative data set) is an additional function of this mixed method design.40 Through this process, we will achieve triangulation in data findings (ie, confirmation of results obtained via qualitative and quantitative methods).41 42 Descriptions of quantitative and qualitative procedures are described in greater detail below.

Study 3: eligibility, recruitment and consent of participants

Patients with chronic musculoskeletal pain and long-term opioid treatment meeting our eligibility criteria (box 1) and scheduled with a participating physical therapist are eligible to participate in the pilot testing component of this study. Randomised physical therapists will identify potentially eligible patients during the initial physical therapy consultation and interested patients will be referred to a study coordinator for obtaining informed consent. Online supplemental appendix 4 contains the IRB-approved informed consent document for the patients participating in Study 3.

Study 3: baseline and follow-up assessments of patients

Patient self-reported measures will be collected via REDCap.35 At each assessment, participants will input data directly into REDCap. If a participant is unable to directly input data using a computer, paper forms will be available with data uploaded later by a blinded RA. At each assessment, participants will also be interviewed to collect information about their opioid use (see below for information on the TLFB). Baseline data will be collected after enrolment (T0) and, depending on the outcome measure, the majority of follow-up data will be collected 6 weeks (T1) and 12 weeks (T2). Enrolled participants will be supported with US$25 per T0–T2 assessments for a potential total of US$75.

Study 3: patient self-report measures

Patient self-report measures will assess the impact of the I-EPT treatment (table 3). This study will have two coprimary outcomes to assess the feasibility of collecting chronic musculoskeletal pain and long-term opioid treatment measures; the percentage of scores collected at 12 weeks for the PEG and for the TLFB. The PEG is a validated measure derived from the Brief Pain Inventory that includes three items, each assessed on a 0–10 scale.38 The items ask about Pain intensity in the past week, interference with Enjoyment of life, and interference with General activity. The total score is the average of the items (range 0–10; higher scores indicate worse pain impact). The TLFB is a valid measure used to track substance use for periods up to 90 days or greater.39 A trained RA will administer the TLFB over the phone.43 Data obtained during the TLFB interview will be used to calculate the patient’s total morphine milligram equivalents (MMEs) used between assessment periods. We will use conversion reference tables from the US Centers for Disease Control and Prevention to calculate MMEs for opioid prescription.44

This study will also collect several secondary outcomes used to assess the feasibility of collecting chronic pain, mindfulness integration and treatment acceptability measures.

Study 3: pilot testing I-EPT treatment

Physical therapists who received I-EPT training will be encouraged to manage the patients based on the refined treatment protocol developed in aim 1. Physical therapists who did not receive I-EPT training will manage their patients according to their usual clinical practice.

Study 3: fidelity assessment

Fidelity to the refined I-EPT treatment protocol will be measured by audio recording of patient encounters across an episode of care for each visit for one patient managed by each physical therapist randomised to the LowIT and HighIT training arms described in study 2 aim. The number of recorded visits will be based on the recommended number of visits in the refined I-EPT treatment protocol, which, we anticipate, could be up to eight visits. Trained RAs will listen to each recorded visit and assess treatment fidelity using the Modified MORE-FM described above.26 This fidelity assessment, combined with the immediate assessment of I-EPT treatment competency described in study 2 aim, provides us information with which to determine which I-EPT training approach (HighIT or LowIT) to consider for training physical therapists in our future trial. Research staff performing these fidelity assessments will be blinded to whether the physical therapist received the LowIT or the HighIT training approach.

Study 3: RE-AIM feasibility measures

To assess our ability to recruit and retain patients, achieve treatment fidelity and collect patient outcome data across physical therapists located in Utah and Florida, we will track important feasibility measures with corresponding a priori benchmarks (table 1). Failure to achieve any of the benchmarks will prompt the PT-IN-MIND team to develop solutions that will be used for future study planning.

Study 3: analysis plan (quantitative feasibility measures)

Analyses will be conducted separately for training and no training arms and also stratified by HighIT and LowIT training approach subgroups. We will check for potential outliers and aberrant measurements (eg, those extremes beyond third IQR). Following data quality checks, descriptive statistics will be used to characterise patients. Proportions will be used to report each feasibility measure with corresponding 95% CIs. We will also calculate the change in each secondary outcome from baseline to each follow-up time point.

We will conduct planned interim analyses. After the first 20 patients are managed by the trained physical therapists, an unblinded research team member will access the data to identify patients who were non-adherent and contact them to enquire about their reasons for non-adherence.

Study 3: patient enrolment target

We plan to enrol two patients scheduled for management by each physical therapist randomised in study 2 aim, yielding a total of 90 patients for enrolment. The pragmatic sample size for this aim is based on recommendations for determining the sample size for feasibility studies.58 Further support for this pragmatic sample size includes (1) testing the feasibility of recruiting and retaining patients for management by physical therapists randomised in study 2 aim and (2) enrolling and retaining patients under the challenges of delivering a complex intervention in outpatient physical therapy during routine clinical practice.

Study 3: eligibility and recruitment of key stakeholders for qualitative interviews

Purposeful sampling will be used to identify key stakeholders (patients, physical therapists, support staff, clinic managers and health system leadership) with experience providing or receiving the I-EPT treatment protocol. We expect to recruit 2 separate cohorts of 28 participants from Utah and 28 from Florida. Each cohort will contain approximately 8 physical therapists (4 each from the HighIT and LowIT training approaches), 13 patients and 7 between support staff and clinic managers. Eligible physical therapists must have been randomised to the LowIT or HighIT training arms. Eligible patients must have been managed by physical therapists randomised to the LowIT or HighIT training arms and meet the eligibility criteria (box 1). Recruitment of patients will occur as described for aim 1. During routinely scheduled staff meetings, we will invite support staff and clinic managers to participate in qualitative interviews. In order to participate in the interviews, all stakeholders must be aged 18 years or older. Online supplemental appendix 5 contains the IRB-approved informed consent document for the stakeholders participating in the study 3 interviews.

Study 3: qualitative interviews

Consent for audio recorded interviews lasting approximately 60 min will be requested. We will conduct qualitative semistructured interviews with enrolled patients, physical therapists, clinic managers, support staff and members of health system executive teams (ie, outpatient division leadership) from both Utah and Florida. Qualitative interview data will be used to (1) confirm findings from the quantitative feasibility data (eg, validation or convergence of findings); (2) gain insight into the process through which patients are enrolled and retained that may not be easily determined from the quantitative data alone (eg, complementarity of findings) and (3) assist in the planning and execution of our future fully powered clinical trial. Additionally, during the interviews, we will ask organisational contextual questions on barriers and facilitators to providing I-EPT to inform future study planning. Participants who are interviewed will each receive US$50. Interviews will be professionally transcribed.

Study 3: analysis plan (qualitative data)

We anticipate achieving thematic saturation with our data that combine individual interviews from patients and physical therapists as saturation can be achieved with as few as 10 interviews.59 These interviews will be complemented by the interviews with clinic managers and support staff. Codebook construction will follow the qualitative editing method as outlined by Crabtree and Miller which is designed for research conducted within the health sciences.60 The construction of the codebook will begin after one-third of that data have been collected per cohort and transcribed to ensure a thorough understanding of potential themes. Audit trails will be employed to document the creation of codes for the codebook. The codebook will be modified, as needed, to incorporate new themes gained through the iterative analytical approach of coding with new codes applied to all relevant transcripts. Using the codebook, study staff will use a grounded theory approach61 to code the interviews. As part of the coding process, the analysts will meet and process any differences in the assessment of codes for each case until agreement is achieved. The codes determined through this agreement process will then be recorded in a master file, which will become the basis for the final analysis.

Patient and public involvement

No patient involved.

Independent monitoring committee

An Independent monitoring Committee (IMC) composed of one PhD biostatistician, one internal medicine physician and two PhD physical therapists will oversee the conduct of studies 2 and 3. The IMC is guided by the studies’ data safety monitoring plan. Physical therapist participants will be instructed to report any adverse events among their patient participants to the study staff who will relay the information on the adverse event to the PI. The PI will report any adverse events to the IMC and follow-up as necessary with the participant who experienced the adverse event.