A Mobile and Web-Based Self-Directed Complementary and Integrative Health Program for Veterans and Their Partners (Mission Reconnect): Protocol for a Mixed-Methods Randomized Controlled Trial

Background Complementary and integrative health (CIH) is a viable solution to PTSD and chronic pain. Many veterans believe CIH can be performed only by licensed professionals in a health care setting. Health information technology can bring effective CIH to veterans and their partners. Objective This paper describes the rationale, design, and methods of the Mission Reconnect protocol to deliver mobile and Web-based complementary and integrative health programs to veterans and their partners (eg, spouse, significant other, caregiver, or family member). Methods This three-site, 4-year mixed-methods randomized controlled trial uses a wait-list control to determine the effects of mobile and Web-based CIH programs for veterans and their partners, or dyads. The study will use two arms (ie, treatment intervention arm and wait-list control arm) in a clinical sample of veterans with comorbid pain and posttraumatic stress disorder, and their partners. The study will evaluate the effectiveness and perceived value of the Mission Reconnect program in relation to physical and psychological symptoms, global health, and social outcomes. Results Funding for the study began in November 2018, and we are currently in the process of recruitment screening and data randomization for the study. Primary data collection will begin in May 2019 and continue through May 2021. Projected participants per site will be 76 partners/dyads, for a total of 456 study participants. Anticipated study results will be published in November 2022. Conclusions This work highlights innovative delivery of CIH to veterans and their partners for treatment of posttraumatic stress disorder and chronic pain. Trial Registration ClinicalTrials.gov NCT03593772; https://clinicaltrials.gov/ct2/show/NCT03593772 (Archived by WebCite at http://www.webcitation.org/77Q2giwtw) International Registered Report Identifier (IRRID) PRR1-10.2196/13666

1 I01 RX002775-01A1 3 RRD4 HAUN, J and PTSD, and their partners. We propose a four-year mixed-methods randomized controlled trial of MR with two arms (treatment & wait-list control) in a clinical sample of Veterans with comorbid pain and PTSD, and their partners (e.g., spouse). The specific aims are to: (Aim 1) Determine MR effectiveness for physical (pain, sleep), PTSD (intrusion, arousal, avoidance, numbing), and psychological (depression, stress, anxiety) symptoms, and global health (quality of life); (Aim 2) Determine MR effectiveness for social (relationship satisfaction, compassion for self/others) outcomes among Veterans and their partners; and (Aim 3) Describe Veteran and partner perceived value of MR in a subsample of participants. The sample will consist of Veteran and partner dyads (N = 228) at the Ann Arbor, Puget Sound, and Tampa VA facilities. Aim 1 & 2 data collection will include self-report assessment of 4-data points over a 4-month period to evaluate physical, psychological, and social outcomes. Eight weekly reports will also be collected for the first two months of MR use to assess MR utilization, and pain and stress levels. Aim 3 data collection will include telephone interviews from a randomly selected sub-sample of MR treatment group dyads (n = 42) to examine MR user experiences and their suggestions making MR useful for Veterans and their partners.

PUBLIC HEALTH RELEVANCE:
This project is responsive to RR&D's current special areas of interest for non-pharmacological activitybased interventions for chronic pain impacting pain reduction, function and quality of life. This project aligns with the VA mandate for complementary and integrative health (CIH) care for Veterans and their families. CIH complements traditional care for Veterans managing chronic conditions, such as chronic pain and PTSD. Mission Reconnect (MR) is a user-driven, dyadic, CIH self-care management program delivered remotely that teaches techniques the Veteran/partner dyad can use to reduce pain, anxiety and stress, promote well-being and improve relationship quality. The research goal is to evaluate MR as an approach to manage chronic pain and PTSD symptoms, for potential subsequent implementation. This study will possibly provide a model for establishing remote access and sustainable implementation of CIH within VA.

CRITIQUE 1
Significance and Innovation: The proposal is for a two-arm RCT comparing Mission Reconnect to a waitlist/ treatment as usual control in VA patients with confirmed pain and PTSD diagnoses. Mission Reconnect is a CIH program delivered via the web and mobile app that focuses on massage and mindfulness and includes Veteran's partners. Mission Reconnect has been previously developed and tested with NIH SBIR funding on a non-clinical community sample of Veterans. The current proposal extends this research by testing Mission Reconnect in a VA clinical sample. The proposal is strongly grounded within the biopsychosocial model. This project is significant because comorbid pain and PTSD is a common problem in VA patients and current interventions are often inadequate. The proposal is novel in several ways. First, it delivers the intervention via a website and mobile app allowing veterans who do not desire or are unable to engage in traditional in-person intervention to engage in care. Second, it involves the Veteran's partner which can increase engagement in care and help address common sources of relationship stress. Third, it is studying a highly accessible application of massage, which has received little past research attention. Overall, the background provides a good and clearly written rationale for this study. The revised proposal has been strengthened by providing additional background on types of partner-assisted interventions. Background now also includes a detailed review of the evidence for message and mindfulness. These additions indicate that the current proposal is building off existing evidence while investigating novel research questions.
Importance and Impact: This proposal addresses an important problem: co-morbid chronic pain and PTSD in VA patients. Should the intervention prove effective, it would provide a highly accessible intervention and a novel addition to tradition treatment.
RRD4 HAUN, J Contribution to VHA: Should the aims of the project be achieved it could make an important contribution to VA health care services. The revised proposal now plans to directly address pain functioning and quality of life. This helps to further align the proposal with the mission of RR&D.
Methods (Data Analysis): Overall, the proposal describes a well-designed two-arm RCT that includes 228 dyads in quantitative aims and a subsample of 42 dyads in the experimental group who will participate in qualitative interviews. The design has many strengths including the use of VA administrative data to identify their participant pool and a proactive method for participant recruitment.
The measurement battery appears to assess all relevant domains and was designed to minimize participant burden. The plan for qualitative data collection, coding, and analysis is well developed and described. The primary analyses (GLMM), power calculations, and plan for missing data are all strong, as is the dissemination plan. The revised application clarified that the goal of this research is not to engage Veterans who are not currently engaged in care. This alleviated my concerns about the study targeting the wrong patient population. The revised application also addressed a previously noted concern that it would be difficult to detect the effect of Mission Reconnect in the midst of so many other treatments. Strategies to address this include carefully tracking concurrent treatment, stratifying randomization by treatment status and conducting subgroup analyses of the effect of MR in the presence and absence of evidence-based treatments. My only remaining concern is that the 2-items used to assess concurrent Pain and PTSD treatments are unlikely to be adequate. Patients may not be able to self-report whether the treatments they are receiving are evidenced-based treatment as defined by VA/ DOD Clinical Practices Guidelines. A medical chart review will be needed for this. I see that a CRPS chart review is conducted prior to randomization. A review for concurrent treatment could be added here. The revised application also more carefully defined chronic musculoskeletal pain.

Adequacy of Data:
The proposed method is likely to be successful in collecting the proposed data. The proposal described a number of relevant preliminary studies that lend support to the investigative team's ability to conduct this study. Strengths of the preliminary data include consultation with a Veteran engagement board, and data from the NIH RCT on the clinical significance of declines in PTSD and pain among Veterans who received Mission Reconnect.

Project Organization and Management:
A detailed project organization plan is included that describes how data collection will be coordinated across the three sites.

Investigator Qualifications:
The investigative team, including the Principal Investigator (PI), is well qualified to conduct this research and all needed areas of expertise are covered by the Co-I's and consultants.

Facilities and Resources:
Letters of support demonstrate good facility support and documented agreements with consultants. A new letter of support from the Office of Connected Care was added in the revised application. This letter states, "Connected Care does not typically engage with non-VA apps at the stage of evaluating effectiveness but if Mission Reconnect is determined to have positive outcomes for Veterans and their partners, OCC will engage in collaborative discussions with Dr. Haun's team to evaluate potential to support the Mission Reconnect commercial app for use in VHA healthcare facilities, for clinical use and for direct patient care." This alleviates concerns that there is no pathway for this app enter eventually become part of regular VA services. The scientific environment at all three sites is very good.

Human Subjects:
No concerns were noted regarding risk to participants, potential benefits, knowledge to be gained, or data safety and monitoring.

Inclusion of Women, Minorities and Children:
The proposal aims to recruit 25% female Veterans and expects that minorities will be well-represented. No children will be included. 1 I01 RX002775-01A1 6 RRD4 HAUN, J Adequacy of Data: As before, Data Management and Access Plan is reasonable. Preliminary studies section is strong, including the prior study on Mission Reconnect and the pilot study conducted specifically for proposal submission on Veteran use of CIH and readiness for Mission Reconnect.

Project Organization and Management:
As noted before, the study timeline provided seems reasonable. Sufficient time is allocated for data preparation, management, and analysis, which is often overlooked/underestimated. There is a detailed plan for project organization and management, which is necessary and helpful in this case given the number of sites and individuals involved. The number of sites and individuals involved does add a level of complexity with a number of opportunities for miscommunication, etc.
Investigator Qualifications: See my prior review comments in this area. The revised proposal is very responsive. Dr. Shirley Glynn is a great addition to the team. This reviewer had noted that additional expertise in family studies may be warranted. A table has been added to highlight the complementary and integrated nature of the team. The revised proposal also addresses that the PI has not previously led a large clinical trial.

Facilities and Resources:
As noted before, facilitates and resources are sufficient. The fact that the Veteran Engagement Panel reviewed the proposal is a strength. The revised proposal now includes details on feedback received and changes/decisions made as a result.

Human Subjects:
No concerns related to proposed use of human participants and protections from research risk relation to their participation. Risk to participants; adequacy of protection against risks; potential benefits of the proposed research to the participants and others; importance of the knowledge to be gained; and data and safety monitoring were all addressed.

Vertebrate Animals: Not Applicable
Biohazard and Radioisotopes: Not Applicable.

Inclusion of Women, Minorities and Children:
The revised proposal explains how women and minorities recruitment will mirror site distribution based on sex and race. The proposal now addresses how this distribution will be achieved and strategies/plans for any difficulties in reaching these numbers.
Budget (unscored): No concerns. Detail has been added to the budget justification for Mission Reconnect, LLC expenses. Documentation has been provided that Qualtrics is approved for this particular project, etc.
Data Management and Access Plan (for data sharing, unscored): No concerns. DMAP has been revised to address qualitative data. What does a de-identified qualitative data set contain/look like?
Overall Strengths:  A strong case is made for the importance of the problem that the proposed research is seeking to address (i.e., comorbid chronic pain and PTSD) and the impact of solving this problem.  Potential to contribute to VHA and complement existing services/programs (operational support provided). Clear alignment with mission of RR&D.  Preliminary studies and pilot data. Also, use of biopsychosocial model and conceptual framework to guide the proposed study.  Very responsive resubmission.
Overall Weaknesses: Rationale for RCT/efficacy trial still not sufficient/satisfactory. More could also be done to ensure/inform pathway to incorporate Mission Reconnect into regular clinical care in the future (e.g., implementation-related aim).