Remedy to Diabetes Distress (R2D2): Development Protocol for a Scalable Screen-to-Treat Program for Families of School-Age Children

Abstract

Background:

School-age children with type 1 diabetes (T1D) need help from parents or other adult caregivers (caregivers) to effectively manage T1D, resulting in greater vulnerability to Diabetes Distress (DD) for both children and caregivers. Unfortunately, there are no scalable screen-to-treat programs for clinics to adopt to identify and treat DD in school-age families.

Methods and Analyses:

We aim to design a scalable, clinic-based screen-to-treat program for DD in families of school-age children and to test whether our new program to reduce caregiver and child DD also reduces child glycemic levels. Our Remedy to Diabetes Distress (R2D2) program will target caregivers and children with T1D who are between 8-12 years old. It will merge routine and automated surveillance of DD in the clinical setting with at home digital delivery of a theory-based behavioral and psychological treatment of DD. We will use the ORBIT Model for Behavioral Intervention development to guide four small and cost-effective formative studies to develop our R2D2 program and assess initial treatment effects. In tandem, we will implement clinic-based DD screening in school-age families and assess feasibility and acceptability of our screening platform as a Quality Improvement activity. The study started in September 2020 and is scheduled to conclude in 2025.

Conclusions:

The study will use a single Institutional Review Board (IRB) with Children’s Mercy-Kansas City operating as the IRB of record. We will disseminate study results through presentations at scientific conferences and through peer-reviewed journals read by the psychology and diabetes care communities.

Background

There are approximately 200,000 children in the United States (US) living with type 1 diabetes (T1D)(1). To optimally manage T1D requires daily attention to a rigorous treatment regimen as well as a high level of knowledge, skills, and resources (2). As such, clinical care guidelines recommend that school-age children receive help from their parents or other adult caregivers (caregivers) to complete daily T1D management (2). However, this puts children and caregivers at risk of experiencing feelings of Diabetes Distress (DD), a distinct and multi-symptom emotional condition that relates to living with and managing T1D (3). Persons who experience DD may report fear, grief, anger, and/or sadness (3, 4). DD can also manifest as burnout, making it harder for caregivers/children to optimally engage in T1D management and at risk of employing less adaptive coping strategies (e.g., guessing an insulin dose to avoid checking blood glucose) (3). Results from a large US study reported 40% of school-age children with T1D identified feeling at least some DD, while 61% of parents reported feeling some DD (5). The most recent update of the American Diabetes Association Standards of Care recommend that clinics regularly screen for DD in youth, starting at 8-years-old, and their primary caregivers (2), although few clinics do this. It is possible clinic-based DD screening could help to facilitate treatment referral and improve the health and wellbeing of families who are experiencing clinically significant DD.

Our multidisciplinary team has experience in developing a robust and automated in-clinic depression screening program for youth with T1D (6). Additionally, we have experience using video-based telehealth to deliver a tailored cognitive behavioral therapy (CBT) intervention to reduce DD in primary caregivers of school-age children (7). Here, we outline how we propose to use theory, prior evidence, and a systematic framework for intervention development (ORBIT Model; (8) to design, build, and test a scalable clinic-based screen-to-treat program for DD for school-age families, which we call Remedy to Diabetes Distress (R2D2).

Methods

Study Aims

Our study aims are: 1) define and iteratively refine a new screen-to-treat program (R2D2) for DD in school-age families to maximize feasibility and acceptability; 2) test whether R2D2 can successfully reduce caregiver and child DD and child glycated hemoglobin (HbA1c) levels in school-age families. We hypothesize that our R2D2 screening platform will be acceptable and scalable as determined by stakeholders’ (i.e., caregivers and clinic staff) acceptability ratings and screening rates (≥80% eligible families screened at least annually). We further hypothesize that our R2D2 treatment will be acceptable to families of school-age children and will show promise in reducing DD symptoms and child HbA1c levels.

Project Overview

This multisite study will take place at Nemours Children’s Health (NCH) and Children’s Mercy- Kansas City (CMKC). We started recruiting families for the first of four R2D2 projects in February 2021 and we anticipate completing the final project in 2025. We will use the ORBIT Model of Behavioral Intervention development to guide our study design and to enhance reproducibility (8). The ORBIT Model defines four specific phases of intervention development with the overall intent to encourage researchers to use small and cost-effective formative studies to develop an intervention and establish early efficacy before initiating a large clinical trial (8). We will conduct four projects that will fulfill the goals of ORBIT Phase 1: Define and Phase 2: Preliminary Testing. A future protocol may pursue a larger trial to fulfill ORBIT Phase 3 and 4 goals (8) (see Figure 1).

Figure 1.

Modified ORBIT Model for the R2D2 Study

R2D2 Screen to Treat Program

We plan to build a scalable system that will merge routine and automated DD surveillance in the clinical setting with at-home digital delivery of a theory-based behavioral and psychological DD treatment. R2D2 will target families of school-age children with T1D (8-12 years old; see Figure 2).

Figure 2.

Conceptual Model of the R2D2 Screen-to-Treat Program

R2D2 Screening.

We will create the R2D2 screening platform either by expanding the capabilities of an existing health system-wide patient-facing mobile application or by building upon an existing clinic-based screening platform that uses REDCap (9, 10). To determine which system to use, we will conduct structured interviews with key clinic staff (e.g., clinic-based mental health providers, physicians, nurses, medical assistants) to gauge their experiences in collecting person-reported outcome data as well as their impressions of current clinic adoption of any existing health system-wide mobile applications. We will work with technology consultants and local Quality Improvement teams (including caregivers) to design, build, and test the R2D2 screening platform. To minimize impact to clinic flow, we intend to design and build a smart system that will automatically 1) identify children and caregivers eligible for screening, 2) push out the screening tools to families at least semi-annually, 3) score the completed DD screeners, 4) document the results of the completed screeners in the child’s electronic health record (EHR), and 5) trigger an automated alert to clinic providers for positive DD screens. Of note, NCH and CMKC use different EHR systems (e.g., Epic and Cerner, respectively). Nonetheless, we will attempt to design parallel systems to promote standardization in how we administer the screeners, how we record the results, and how we collect data to evaluate uptake and completion of our screeners.

R2D2 Treatment.

Based on theory (11–14) and preliminary data (7), the R2D2 treatment will involve delivery of CBT, mindfulness, and Behavioral Activation strategies to help children and caregivers learn how to manage feelings of DD (15). R2D2 treatment will include mHealth content that caregivers and children will be able to access together from their home. Through a partnership with a professional video production company, we will create short, engaging videos to deliver the treatment content. We will supplement the videos with a daily mood screener that caregivers can complete, links to web-based tools to provide additional ways to practice R2D2 treatment strategies (i.e., web-based meditation or relaxation tools), and detailed information sheets. Families will also have access to assistance from clinic-based counselors while working through the R2D2 treatment. In our trial, clinic-based counselors will include social workers or psychologists who are already employed by our clinics. However, we will create R2D2 so that it can be effectively delivered by professionals from other disciplines (i.e., nursing) with minimal additional preparation. Also, to promote future scalability, we include a study to assess the acceptability and initial treatment effect of R2D2 based on various levels of counselor support (i.e., no support, limited support, weekly support) to determine the dose that best balances treatment effect with provider effort.

R2D2 Screening Implementation

While designing and building R2D2, our team will also complete steps to support future clinic-based implementation. This includes the design of a clinic-based implementation toolbox. Guiding our toolbox design, we will use the Consolidated Framework for Implementation Research (CFIR) (16). The CFIR provides a taxonomy for organizing potential barriers or facilitators of clinic-based implementation according to clinic characteristics (e.g., available resources, leadership support), intervention characteristics (e.g., complexity, evidence strength), process (e.g., stakeholder engagement), and individual characteristics (e.g., families’ knowledge and attitudes) (16). First, we will conduct brief structured interviews with diabetes clinic staff (e.g., check-in staff, rooming personnel, direct care providers, and clinic-based educators and counselors) to identify barriers and facilitators to successfully implementing R2D2 screening. We anticipate conducting at least ten staff interviews but will continue interviewing staff until we achieve thematic saturation. We will use these interviews to help us in developing Job Aids and other implementation tools to support R2D2 screening implementation. Some implementation tools we anticipate creating include: a Job Aid to review steps for talking to families about a positive DD screen, a Job Aid to standardize how clinic staff respond to any caregiver and child questions about the screening, and local treatment resources. We also anticipate developing marketing materials to promote family buy-in for the R2D2 screening platform. Presently, the participating diabetes clinics do not provide any clinic-based mental health screening to children younger than 12-years-old. Thus, while implementing the R2D2 screening platform could be burdensome, it provides an opportunity to enhance current standard of care.

To roll out clinic-based DD screening for families of 8-12-year-olds, we will first seek Human Subjects Determination that our R2D2 screening qualifies as a Quality Improvement Activity. Then, we will initiate screening across NCH and CMKC diabetes clinic locations sequentially beginning with the largest clinics at each site and bringing additional clinics on board one at a time. All the clinics will use the R2D2 screening platform to identify caregivers and children eligible for screening, administer and score the screeners, document the screener results within the child’s EHR, and trigger an alert to providers for any positive screens. After clinics are up and running with screening for at least four weeks, we will ask clinic staff two questions that will use a 7-point rating scale to quantify their level of satisfaction (0=not satisfied, 6=highly satisfied) and willingness to continue using (0=not willing, 6=very willing) the R2D2 screening platform as part of routine care. We will use these answers to measure perceptions of Staff Acceptability based on a mean item response threshold of ≥5.0 (4= neutral). To assess feasibility, we will use a threshold of ≥80% of eligible families screened (e.g., # screened/total # eligible), which we will track by clinic each week for the duration of the study. As needed, we will meet with clinic providers to devise new implementation tools if Staff Acceptability is <5.0 or a clinic falls below an 80% screening rate for more than four consecutive weeks.

R2D2 Research Projects

The study will conduct four projects which meet the definition of Human Subjects research. These projects are: 1) Cut-Point Study: a brief longitudinal, observation study to examine proposed cut-points for clinically elevated DD; 2) Crowdsource Study: an online, qualitative study to collect feedback from caregivers for our R2D2 treatment; 3) R2D2 Pre-Trial: a brief randomized pilot of the R2D2 treatment to identify an optimal dose of counselor support plus access to our mHealth materials; 4) Proof-of-Concept Pilot: a randomized clinical trial to test whether treating DD leads to reductions in child HbA1c.

Participants and Recruitment

We will recruit four separate samples of children and a caregiver to participate. For the Cut-Point Study, we will recruit 125 child-caregiver dyads. For the Crowdsource Study, we will recruit 50 caregivers. For the R2D2 Pre-Trial, we will recruit 36 child-caregiver dyads. For our Proof-of-Concept Pilot, we will recruit 190 child-caregiver dyads. We intend to recruit children and caregivers from racial and ethnic backgrounds that mirror the clinic populations from which they are drawn and generally reflect the characteristics of children with T1D in the US (17). When appropriate, we will purposively recruit families from under-represented racial and ethnic backgrounds to promote diversity in our samples.

Inclusion and Exclusion

Eligible children must be between 8-12 years-old, have a physician-confirmed diagnosis of T1D, be on an intensive insulin regimen (e.g., insulin pump or multiple daily injections), and be English speaking. Eligible caregivers must be English speaking and have a child who meets child eligibility criteria. For the Crowdsource study, we will recruit caregivers only. For our R2D2 Pre-Trial and Proof-of-Concept Pilot, we will have the additional inclusion criterion that either the child, the caregiver or both need to report elevated DD. We will identify families who meet this additional inclusion criterion through our R2D2 screening platform. Exclusion criteria include use of a conventional insulin regimen, an allergy or extreme sensitivity to the adhesive and/or skin preparation used for continuous glucose monitoring (CGM), and a comorbid chronic condition (e.g., renal disease).

Recruitment

We will recruit families through two pediatric diabetes clinic networks in the Southeast (NCH) and Midwestern (CMKC) regions of the US. Research and clinic staff will use the EHR, a clinic-based registry, or provider referral (in the case of families who screen positive for elevated DD) to identify eligible families. We will approach eligible families in person or via phone, email, and text message.

Project-Specific Procedures and Methods

Cut-Point Study.

In a prospective, longitudinal, observational study, we will collect data to identify clinical thresholds of elevated DD in families of school-age children. We will obtain informed consent and caregivers’ permission for their child to participate. We will also seek child assent. We will use REDCap (9, 10) to electronically administer study surveys to children and caregivers. Children will also complete a validated, home HbA1c kit (18). Participating child-caregiver dyads will do these tasks during two study visits that are six-months apart. Table 1 provides a list of the caregiver and child surveys that we intend to use in R2D2 as well as other outcomes of interest to the study. We will compensate child-caregiver dyads $20 US dollars for completing the study procedures at each visit ($40 total).

Table 1.

R2D2 Outcome measures

Outcome	Measure	Planned Project/Use
Child Diabetes Distress	Problem Areas in Diabetes-Child (PAID-C): 11-item survey of diabetes distress validated for children 8-12 years-old. Higher scores reflect more distress (Cronbach’s α=0.91)(5).	CI, CP, PT, POC
Caregiver Diabetes Distress	Parent Problem Areas in Diabetes-Child (P-PAID-C): 16-item survey of diabetes distress validated for parents of children. Higher scores reflect more distress (Cronbach’s α=0.92)(5).	CI, CP, PT, POC
Child Resilience	Diabetes Strengths and Resilience (DSTAR): 12-item survey of resilience validated for children 8-12 years-old. Higher scores reflect more resilience (Cronbach’s α=0.89) (19).	CP, PT, POC
Caregiver Resilience	Brief Resilience Scale (BRS): 6-item survey of resilience validated for adults. Higher scores reflect more resilience (Cronbach’s α=0.80)(20).	CP, PT, POC
Child Cognitive-Emotional Regulation	Cognitive-Emotional Regulation Questionnaire-Kids (CERQk): 18-item survey validated for children 7-12 years-old. Measures regulation skills across nine domains: self-blame, other-blame, rumination, catastrophizing, positive refocusing, planning, positive reappraisal, perspective taking, acceptance. Higher scores reflect greater use of each domain (Cronbach’s α’s=0.62-0.79) (21).	PT, POC
Caregiver Cognitive-Emotional Regulation	Cognitive-Emotional Regulation Questionnaire-Short (CERQs): 18-item survey validated for adults. Measures regulation skills across nine domains: self-blame, other-blame, rumination, catastrophizing, positive refocusing, planning, positive reappraisal, perspective taking, acceptance. Higher scores reflect greater use of each domain (Cronbach’s α’s=0.68-0.81) (22).	PT, POC
R2D2 Treatment Satisfaction-Child	8-item survey to assess child perceptions of acceptability/satisfaction with the R2D2 treatment.	PT, POC
R2D2 Treatment Satisfaction-Caregiver	14-item survey to assess parent perceptions of acceptability/satisfaction with the R2D2 treatment	PT, POC
Demographics	Caregiver-report survey to assess child and family demographics (e.g., age, race, ethnicity, sex, income)	CP, CS, PT, POC
T1D History	Caregiver-report survey to assess child insulin regimen, use of CGM, history of T1D-related acute complications (e.g., hypoglycemia, diabetes ketoacidosis)	CP, CS, PT, POC
Treatment Engagement	Diabetes Self-Management Questionnaire (DSMQ): 9-item, caregiver-report survey to assess perceptions of treatment engagement. Higher scores suggest higher levels of engagement (23).	CP, PT, POC
Child HbA1c	We will use a valid mail-in kit and central laboratory that will process samples using automated high performance liquid chromatography (reference range: 4.0-6.0%, Tosoh 2.2, Tosoh Corporation, San Francisco, CA). This procedure is reliable to DCCT standards.(24)	CP, PT, POC
Child Time in Range	We will collect CGM data from children to calculate time in range based on Bergenstal et al.(25) or glucose values falling between 70-180mg/dL.	CP, PT, POC

Note. CI, clinic implementation (Quality Improvement Activity); CP, Cut-Point Study; CS, Crowdsource Study; PT, R2D2 Pre-Trial; POC, Proof-of-Concept Study.

Crowdsource Study.

We will use Crowdsourcing methodology (19, 20) to obtain caregiver feedback to help refine our new R2D2 mHealth treatment. Prior to enrolling caregivers, we will seek an Exempt Determination from the requirements of the Common Rule (45 CFR 46), which if granted, will enable us to waive documentation of signed informed consent. We will launch our crowdsource study by asking caregivers open-ended questions about their perceptions of and experience with DD. We will also ask caregivers to offer examples of strategies they use to prevent DD from getting in the way of their everyday life. Next, using caregivers’ qualitative responses, R2D2 team members who have experience developing intervention content will partner with a professional video production company to develop storyboards and accompanying narrative scripts for new treatment videos. Then, we will share these storyboards and narrative scripts with caregivers to iteratively refine them until caregivers approve the final versions. We intend to complete our crowdsource study using a closed social network community. We will compensate caregivers up to $88.

R2D2 Pre-Trial.

We will conduct a small comparative effectiveness trial to identify how much clinic-based counselor support may be needed to supplement our mHealth treatment materials and achieve an acceptable and potent intervention. We will recruit eligible child-caregiver dyads from a pool of families referred to R2D2 by their diabetes team because of a positive clinic-based screening result. We will seek informed consent and caregiver permission. We will also seek child assent. At enrollment child-caregiver dyads will complete online surveys (Table 1). Then, all child-caregiver dyads will gain access to the R2D2 mHealth treatment for eight weeks and we will randomize child-caregiver dyads 1:1:1 according to how much additional support they will receive from a clinic-based counselor. Specifically, families randomized to the Self-guided condition will independently work through the R2D2 treatment with no counselor assistance. Families randomized to the Enhanced Self-guided condition will complete three 30-minute video-based telehealth visits with a clinic-based counselor. During these visits, families can review treatment content and ask for assistance. Families randomized to the Video-based telehealth condition will complete eight weekly visits with a clinic-based counselor. During visits, families will watch a R2D2 treatment video, expand on the video through discussion with their counselor, and complete an at-home exercise. These visits will last about 45-50 minutes each. After eight weeks of treatment, we will remove family access to the R2D2 treatment, and we will ask child-caregiver dyads to complete a second round of online surveys. We will compensate child-caregiver dyads $40 for completing online surveys and a home HbA1c kit at enrollment and after treatment ($80 total).

Proof-of-Concept Study.

Our Proof-of-Concept Study will test our hypothesis that reducing caregiver and child DD will help families to reduce child HbA1c. This will be a two-arm randomized control study. We will recruit eligible child-caregiver dyads from a pool of families referred to R2D2 by their diabetes team because of DD. We will seek informed consent and permission from caregivers. We will also seek child assent. Following consent and assent procedures, we will ask child-caregiver dyads to complete online study-related surveys, we will measure children’s HbA1c using our validated home kit, and we will either place a CGM on children to collect 10 days of glucose data or obtain 10 days of glucose data from children’s personal CGM account (Table 1). Next, we will randomize child-caregiver dyads in a 1:1 ratio to either receive the R2D2 treatment or Standard Care. When randomizing child-caregiver dyads, we do not intend to stratify groups according to child sex or personal CGM use (yes or no) but will track these variables for later sensitivity analyses. We will not exclude children using a low glucose suspend insulin pump or hybrid closed-loop system from participating but may include this as a covariate in our analyses. Child-caregiver dyads randomized to R2D2 treatment will receive access to the R2D2 treatment for eight weeks, with the level of clinic-based counselor support that is determined to be optimal in the Pre-Trial. Child-caregiver dyads randomized to Standard Care will receive print or electronic educational materials about DD and how to access local mental health resources. At the end of eight weeks, access to the R2D2 treatment will end and all child-caregiver dyads will complete a second round of online surveys, an HbA1c home kit, and 10 days of CGM. Additionally, child-caregiver dyads receiving R2D2 will complete an online Treatment Satisfaction survey. We will follow up with a third round of assessments, which will include online surveys, a home HbA1c kit, and 10 days of CGM approximately one-year after study enrollment. We will compensate child-caregiver dyads $50 for completing online surveys, a home HbA1c kit, and 10 days of CGM at enrollment, after treatment, and at 12-months post-enrollment ($150 total).

Results

Cut-Point Study.

We will compute descriptive statistics for our sample and outcome measures. Then we will apply the author-recommended clinical cut-points to child and caregiver DD scores and examine their performance in our sample based on theoretically related factors (e.g., child and caregiver resilience, treatment engagement, child HbA1c). We will also use these data to calculate Minimal Clinically Important Differences (MCIDs) for our DD surveys based on the SEM small effect formula [1*(SD* √1-α)] (21).

Crowdsource Study.

We will use descriptive statistics to analyze any quantitative data (e.g., ratings) that caregivers may provide while reviewing our R2D2 treatment storyboards and narrative scripts. For caregivers’ open-ended responses, we will use Framework Matrix Analysis (FMA)(22, 23) because this approach will allow us to apply a priori themes to maximize the efficiency of our analyses. Some of the a priori themes that we will code for include content relevance, enjoyment and interest, presentation (e.g., music, animation), and ease of understanding. Once we complete an initial pass using FMA, we will re-code caregivers’ responses using a Grounded Theory approach (24) to identify relevant de novo themes.

R2D2 Pre-Trial.

We will run descriptive statistics and examine the statistical distributions of each variable within each treatment group (e.g., Self-guided mHealth, Enhanced Self-guided mHealth, or Video-based telehealth). Then, we will calculate the within-group standardized effect sizes (in SD units) and within-group changes (based on MCID) for our DD surveys based on data collected from child-caregiver dyads at enrollment and post-treatment. To determine the R2D2 delivery approach that has the greatest initial effect in reducing DD, we will visually compare effect sizes as well as the percent of child-caregiver dyads who achieve ≥1 MCID reduction in DD for each delivery approach. To denote initial treatment effect, we will either apply a threshold of at least a medium effect size reduction in DD or the highest percent of child-caregiver dyads reporting a reduction ≥1 MCID in distress. If more than one delivery approach demonstrates an initial treatment effect based on this criterion, we will visually compare groups using caregiver and child treatment satisfaction scores and select the delivery approach with the highest satisfaction score.

Proof-of-Concept Study.

We will use Linear Mixed-effects Models (LMM) to analyze each outcome according to Group (R2D2, SC), Visit (1, 2, and 3), and Group-by-Visit Interaction. We will code R2D2 and Visit 1 as the reference category for Group and Visit, respectively, i.e., $Y_{ij}=\left({\beta }_0+u_i\right)+{\beta }_1\left(\mathrm{S}\mathrm{C}\right)+{\beta }_2\left(V_2\right)+{\beta }_3\left(V_3\right)+{\beta }_4\left(\mathrm{S}\mathrm{C}\times V_2\right)+{\beta }_5\left(\mathrm{S}\mathrm{C}\times V_3\right)+{\epsilon }_{ij}$ where $Y_{ij}$ is an outcome measure of Subject $i$ at Visit $j,\mathrm{ }i=1,..., N;j=\mathrm{1,2},3,\mathrm{ }{u}_i$ and ${\epsilon }_{ij}$ are between-subject random effects and within-subject random errors, so that the fixed-effect coefficient (i) ${\beta }_1$ corresponds to the pre-post changes in the R2D2 arm (suggesting a within-group effect) and (ii) ${\beta }_4$ corresponds to the pre-post changes between arms (suggesting a between group effect for R2D2 versus standard care). We will set our significance level at 0.05/2 = 0.025 (Bonferroni correction) for each of the two clinical outcomes but control false discovery rate (FDR) at 5% level for all secondary outcomes using Benjamini-Hochberg’s procedure. In addition to fixed-effect estimates, 95% confidence intervals (CI), and p-values, we will also estimate Cohen’s d from pre-post changes for each arm, and f² from LMM using Selya et al. (25), to inform potential future larger trials.

Ethics and Dissemination

The study will use a single IRB with CMKC operating as the Institutional Review Board (IRB) of record and NCH operating under a reliance agreement. All research team members will be certified in Good Clinical Practice and up to date in responsible conduct of research training. Prior to the start of each research project, we will obtain appropriate IRB approval. For additional monitoring of our R2D2 Pre-Trial and Proof-of-Concept Study, we will recruit an external Data Safety and Monitoring Board who will review our recruitment and retention, protocol adherence, and documentation of adverse events semi-annually. We will share DSMB reports and meeting minutes with the IRB and study sponsor at least annually. We have registered R2D2 in ClinicalTrials.gov (NCT#05268250).

We will disseminate study results to the scientific community at conferences and through peer-reviewed manuscripts. Beyond facilitating screening and treatment for DD, we anticipate our R2D2 screen-to-treat program could help with the design and implementation of similar programs for adolescent depressive symptoms or anxiety or even programs targeting children and caregivers in other medical populations. Finally, because our R2D2 screen-to-treat program specifically targets DD in caregivers and school-age children and will leverage patient-facing mobile applications for its implementation, we believe it aligns with 2021 Strategic Plan goals of the National Institutes of Health to Address Risk and the Burden of Disease and to Develop and Optimize New Treatments for children and adults (26).

Strengths and Limitations

Our R2D2 Study is ambitious in its plan to design and implement a new screen-to-treat program for DD in school-age families via four foundational research projects. To our knowledge, this will be the first screen-to-treat program for DD specifically targeting families of school-age children. Our protocol design is scientifically rigorous and guided by an established framework for intervention development and testing. That said, our design has some limitations. Our Pre-Trial is not powered to conduct a true comparative effectiveness trial of the three proposed R2D2 treatment delivery approaches but should be adequate to help us identify the delivery approach to test in our Proof-of-Concept Study. Likewise, our Proof-of-Concept Study may not be fully powered to explore factors that mediate or moderate parent or child DD, though it may still provide helpful data to inform future adaptations or refinements to R2D2. Families who screen positive for DD may seek treatment for DD outside of the R2D2 program, which could affect the results of our Proof-of-Concept Study, though we will try to track and control for this in our analyses. Our R2D2 screen-to-treat program may not directly target all the factors that could exacerbate feelings of DD in families. For example, families who experience systemic racism, poverty, or other social determinants of health may experience high levels of DD, but R2D2 will not directly address these factors in the current protocol. A future protocol could test the added impact of a social work consult as part of R2D2 treatment. At the conclusion of this study, if we have evidence to support the feasibility, acceptability, and initial treatment effects of R2D2, we will be able to deliver a scalable screen-to-treat program that is ready for testing in a larger efficacy trial and subsequent implementation trial.