Efficacy and Implementation Planning Across the Veterans Affairs Polytrauma System of Care: Protocol for the REACH Intervention for Caregivers of Veterans and Service Members With Traumatic Brain Injury

Background The responsibility of care for Veterans and Service Members (V/SMs) with traumatic brain injury (TBI) often defaults to informal family caregivers. Caregiving demands considerable knowledge, skill, and support to facilitate the health and well-being of V/SMs and themselves. Persistent and common TBI caregiver issues include strain, depression, and anxiety. While evidence-based, brief interventions have been developed and implemented for family caregivers in Veteran neurodegenerative populations, few interventions have been developed, adapted, or tested to support the unique needs of caregivers of V/SMs with TBI. Objective This study will adapt and test an evidence-based, personalized, 6-session telehealth caregiver intervention, “Resources for Enhancing All Caregivers’ Health” (REACH), to meet the unique needs of caregivers of V/SMs with TBI. If successful, a community-based participatory research team will develop an implementation plan to roll out REACH TBI across the national Veterans Affairs Polytrauma System of Care. Methods This mixed methods, crossover waitlist control clinical trial will use a Type 1 Hybrid Effectiveness-Implementation approach to adapt and then test the effects of REACH TBI on key TBI caregiver outcomes. Results This study was funded by the Department of Defense in September 2023. Participant enrollment and data collection will begin in 2024. Conclusions If effective, REACH TBI will be the first evidence-based intervention for caregivers of V/SMs with TBI that can be scaled to implement across the Veterans Affairs Polytrauma System of Care and fill a notable gap in clinical services. International Registered Report Identifier (IRRID) PRR1-10.2196/57692

program is supported.The project timeline and feasibility appear appropriate given it is based on similar funded studies.
The study is well described and relatively simple in its design.The strength of the study is its foundation on numerous, previous studies with other medical populations.The current study is based on these others and uses similar methods, measures, and interventions except with caregivers with TBI.The initial part of the study will identify appropriate interventions for caregivers with TBI, the second part of the study will evaluate the effectiveness of this adapted REACH intervention, and the third part will develop and begin to implement the intervention to an extremely broad range of service providers who serve this population.The previously cited studies clearly indicate that the intervention leads to statistically and clinically significant improvements in health, functioning, and stress for caregivers of military personnel.
Stakeholder input is sought at all levels and across many sites and individuals (service members, veterans, researchers, clinicians, administrators).Their chosen measures are widely used across health outcome studies (ie, military and nonmilitary) and have proven to be very useful in previous studies (ie, ability to demonstrate improvement).
Weaknesses: The study proposes a crossover design in which 55 participants who receive the intervention are compared to 55 wait-listed controls over 3 months.Then the intervention and control groups are reversed for the next 3 months.This theoretically will allow for a comparison of the intervention to no intervention, but this assumes that the first intervention group will not demonstrate/report any benefits from the intervention when they serve as the control group (as is the case with crossover studies of medications).If the intervention does lead to lasting effects as proposed, then there are unlikely to be differences between the intervention and outcomes groups (the only likely difference will be between the first intervention and control groups at 3 months follow-up).A true control group is not addressed to determine if the intervention is effective or not (ie, sample with no intervention for 6 months, compared to 110 participants who receive the intervention).
The application is a bit inaccurate by stating the intervention involves "telehealth" when in fact it appears to involve telephone-based treatment.Without visual input available with telehealth, review of some of the intervention material will likely be less effective.

Scientist Reviewer B
Strengths: This is an area that is in need of interventions and prevention programs.The literature on caregiver mental health and strain is well reviewed, and a solid rationale for the study is provided.The research team currently has a grant that is looking at an adaptation of the REACH intervention for those with TBI and Alzheimer's.Previous studies have also found versions of the REACH intervention helpful for dementia, spinal cord injury, MS, and PTSD with small to medium effects.The amount of data supporting this intervention is solid, although larger effect sizes would be ideal.Research level 3 is an appropriate research level requested for the intervention based on the presented data.The research team has shown the ability to run clinical trials of this size, and the current proposal is likely to be completed within the proposed period.The overall primary and secondary outcomes are appropriate.A huge strength of this study is the hybrid type 1 study methodology, which will allow for implementation barriers and outcomes to be studied as well.The qualitative and quantitative aspects of this study are complementary and useful to move the intervention to be ready for larger scale dissemination.This can help set up a longer-term plan (ie, the hybrid type 3 study mentioned as next steps).The initial REACH intervention used a community based participatory research (CBPR) approach, and the proposed study will continue with this.The integration and feedback of the stakeholder groups are important and integrated into the research process.Table 4 of the proposal does a nice job laying out potential problems and solutions to the major concerns.The research team has thought this through with multiple perspectives in mind.
Inclusion and exclusion criteria are appropriate and allow for a wide enough catchment of the target population.The instruments are common data elements (CDEs) and overall are well-established outcomes measures.
Weaknesses: The primary outcome of strain is not discussed enough from a data standpoint.It is a possibility that strain is a mechanism for some of the secondary outcomes (eg, mental health outcomes).However, this is not tested in the current study.Additional support for strain as a primary outcome is not developed to solidify the argument.The satisfaction and implementation interview will likely take more than 30 minutes and is not adapted to be shorter or to ensure the participants know the length may be extended.The sample will also consist of caregivers of veterans/service members who have a range of level of TBI including mild, moderate, and severe.Additional comparison groups are not integrated (eg, a support group or control that accounts for time and focus of intervention) as a third condition to understand if the REACH program is better than a more active control condition.

Human Subject Recruitment
Average Score: 9.0

Scientist Reviewer A
Strengths: The study has indicated that a sufficient number of participants will be recruited for the evaluation (n = 110), which the power analyses indicate will be appropriate to draw meaningful conclusions.In addition, the number of participants from which they can recruit is substantial and based on existing resources (eg, PSCs).
Weaknesses: The percentage of individuals from minority and underserved communities appears to be low (0/75 Native American, 1/75 Asian, 1/75 Pacific Islander).Information is provided about the racial/ethnic makeup of samples from previous REACH studies, but if they have such a large sample from which to draw they could increase the number of participants from underserved populations.Previous studies have recruited primarily women (70/75).
The study involves a crossover design, with 55 participants receiving the intervention initially followed by the 55 initial controls.This complicates the ability to determine the effects of the intervention to a true control group (ie, one that does not receive the intervention at any time).Identification of another control group that can be compared to the intervention group at 6 months post study is not developed that would allow for better generalization of the findings.

Scientist Reviewer B
Strengths: The study proposal will look at caregivers for primarily veterans who have a TBI.This population is one that the research team has area of expertise and access to within the VA system.Although some participants may be active duty, the majority will likely be veterans.The screening process and recruitment are strengths of this proposal.The team also has significant experience recruiting caregivers.Potential problems identified in terms of retaining and recruiting are addressed within the proposal in a meaningful way, including being flexible with scheduling.The proposal identifies that the majority of caregivers are women and so the majority of the sample will likely be women based on their previous work.The distribution of proposed enrollment is appropriate for recruiting more women than men given the previous data.
Weaknesses: The research does not include a plan to recruit unrepresented groups, which is an area of concern in this literature.The previous research by this group shows a somewhat diverse sample, with ~ 26% identifying as Black or African American, Asian, Native Hawaiian or other Pacific Islander, more than one race, or unknown/not reported.Additional information on how to recruit from these groups is not developed.

Scientist Reviewer A
Strengths: The intervention is strong as it is based on one that has been developed for service members and veterans with other medical conditions and shown to be effective for all.It is also very feasible and realistic as it is based on 6 one-hour interventions that are focused on problems identified by the caregiver and with manualized treatment interventions.
Weaknesses: The abstract and various parts of the application indicate that the intervention involves telehealth (implying video capabilities) when in fact it appears to involve only telephone-based interventions.Telehealth is increasingly used, particularly over telephone-based applications only, and has advantages in that visual information can be more easily shared and discussed, which may be important for any visual materials, notebooks, and manuals that may be shared.

Scientist Reviewer B
Strengths: The REACH intervention was developed by federal employees and is openly available for this trial.Supporting caregivers is an important area of work with significant data suggesting that the intervention is needed.Caregivers of veterans with other important issues (eg, dementia, PTSD) have a caregiver intervention, and this adaptation helps hit an important population.The previous clinical findings across caregiver programs that the current proposal would adapt are supportive of impacting the target outcomes and clinical need.The research components of this intervention are clearly defined in the consent form and processes laid out.
Weaknesses: It is not totally known what the correct dosing is of the intervention.This could be important to explore as the research team also identifies the time needed for the intervention and scheduling the intervention could be a barrier for some caregivers.Understanding what the potent dosage is could improve access to the intervention.The effect sizes for the interventions are small to medium on the primary outcomes.The 6 sessions may not be necessary for each caregiver.The intervention is still fairly resources intensive, which makes it unclear if this is sustainable longer term.

Impact and Relevance to Military Health
Average Score: 9.2

Scientist Reviewer A
Strengths: The study is directly related to improving the health and functioning of service members and veterans with TBI and their family members and is based on relevant research that indicates the need for increasing support for these populations given the increasing number who have experienced TBIs over the past decades and their impact on them and their families.The relevance is also demonstrated through a focus on use of telehealth/telephones to increase accessibility to service members in underserved areas (eg, rural US).
Weaknesses: No weaknesses were noted.(Page 6 of 13) Procurement Sensitive Document Do not copy or distribute without CDMRP written permission.

Scientist Reviewer B
Strengths: The results of this study could have a positive impact on caregivers, a population that is important to support.The trial focuses on strain and mental health outcomes, looking to see if the intervention has a positive impact on these outcomes as well as starting to understand the potential barriers to implementation of this intervention at a larger scale and across systems.The knowledge gained from this study could help understand how to best adapt REACH, determine if it works, and identify what might cause barriers to implementation-all of which are important to the psychological health for those impacted by TBI.If results turn out as planned, this project could have a long-term impact on caregivers, and this is a new intervention for caregivers that would be tailored using community based participatory research strategies.The research team has identified many issues that could come up and will also collect data on additional barriers to the intervention.Overall, the proposal is in an area of need.
Weaknesses: The program has been tested in several other areas and been shown to be effective.The current proposal does not focus enough on implementation of this across the VA system.The long-term impact of the intervention has not been studied with additional longitudinal data that would provide more insight into the long-term impact of the REACH intervention.

Consumer Reviewer
Strengths: This application intends to decrease the negative effects on caregivers for veterans and service members suffering from TBI by utilizing 6 telehealth sessions known as Resources for Enhancing All Caregiver's Health (REACH).The success of this research would be moderately to greatly effective in providing caregivers the skills and resources to cope with negative effects of caring for a veteran or service member.This application has the potential outcome to help the VA PSC further understand the needs and stressors of the caregiver as well as information to better provide applicable needed resources for the caregiver.This application has the potential to greatly impact the caregiver by documenting ongoing emotional and psychological markers given a particular caregiver's individual resiliency.The success of this research may help decrease caregiver dependency on pharma by providing alternate proven mental health support and resources to the caregiver.This research helps fill a void in the documentation and assistance needed to help the caregiver of a veteran or service member with TBI.Over time, it's inevitable that a veteran or service member's condition will worsen and the demands on caregivers will increase.This anticipated increase in care directly correlates with added stress and negative impacts subjected on the caregiver.
Weaknesses: This application may not fully address the caregiver's availability of time given other potential dependents such as children, daily responsibilities, or other constant stress of decreased governmental funding/removal of the caregiver program.This research only looks at a given period of time in a caregiver's assistance to a veteran or service member suffering from TBI.Although the REACH program may provide some skills and resources to address the effects on a caregiver today, it may not be as impactful as a veteran or service member's condition worsens over time.This research does not distinguish the severity of veteran or service member TBI patients participating in the study.This research may have skewed data points included in the outcome from possible distrust of the VA caregiver system and the potential for dismissal or decrease in benefits from showing improvements.

Discussion Notes
There was some discussion about study participants not being completely straightforward in answering questions due to a fear of dismissal or loss of benefits based on their answers, which could also apply to

Scientist Reviewer A
Strengths: A strength of the planned analyses is their simplicity, i.e., demonstration of improvement in outcome measures compared to control group.The identified statisticians have worked on existing REACH studies and appear to have strong academic backgrounds, credentials, and track records.
Weaknesses: The proposal acknowledges weaknesses in not having a pure control group in that the initial intervention group is expected to demonstrate carryover effects, but the proposal then only indicates that "traditional carryover design statistical analysis (will not be) used."The specifics for how to address this weakness are not adequately expressed.

Scientist Reviewer B
Strengths: The statistical analyses will include a linear mixed-effects model, which is appropriate for the design.The intent to treat analysis is a strength given it is more conservative.Maximum likelihood estimation will be used for missing data, which is also appropriate.The exploratory moderation analysis by injury level is also an important one, although additional information on expected number of individuals within different levels of injury is not integrated.The qualitative data analysis will use an established software and a commonly used qualitative data analysis technique.
Weaknesses: Not enough details about the statistical plan (eg, linear mixed-effect model) are presented to evaluate the appropriateness.The power analysis uses a medium to large effect size, and the previous data suggest small to medium effect on the main outcome.It is unclear why this effect size was chosen given the presentation of the other data.Additional details (if comparisons will be made of other subgroups) are not developed.

Biostatistician Reviewer
Strengths: The design is a classic wait-list crossover design after randomization; one group will receive the 3-month intervention, while the other will wait 3 months and then start the intervention.Power is based on a difference between means and does embed this analysis in the repeated design.The analysis plan is appropriate for the design.Use of mixed models is appropriate to deal with attrition, repeatedmeasures analysis, and missing values, which are all discussed.The modeling process is discussed, including assessing interaction/moderation.Control for baseline and inclusion of covariates are discussed.
Weaknesses: Minor weaknesses are the following: Attrition is assumed equal in the 2 arms.There is no clear statement of the impact unequal attrition will have on generalizability and analysis.Missing values are assumed to be missing at random (MAR) or missing completely at random (MCAR), if the process leading to missingness is included in the model.While likely true, there is not a definitive statement for checking the assumption and a plan if the MAR assumption does not hold.Use of baseline Y is appropriate.However, which baseline to be employed for the wait-list group isn't specified.Likely, the baseline at 3 months is appropriate.Embedded in the analysis structure is a test of treatment x period interaction.If significant, while proper control for baseline may ameliorate some of the problem, there is a counterfactual issue.
Analysis of secondary variables is listed.A really small weakness is that if the primary hypothesis is not rejected, it is unclear how the results of these secondary analyses will be couched.And, if the primary does reject the null hypothesis, it is unclear whether there will be the same step-down procedures for testing of the interaction.It is not clear how the results will be assessed in the presence of a period x intervention interaction.No definitive statement for inclusion of time-varying covariates is presented.Incorporation of time-varying mediation (process) variables is not developed.