Improving Self-management of Type 2 Diabetes in Latinx Patients: Protocol for a Sequential Multiple Assignment Randomized Trial Involving Community Health Workers, Registered Nurses, and Family Members

Background The rate of Type 2 diabetes mellitus (T2DM) among Mexican American individuals is 16.3%, about twice that of non-Hispanic White individuals. While a number of education approaches have been developed and shown to improve diabetes self-management behaviors and glycemic control for Spanish-speaking Latinx patients with T2DM, there is little research to guide health practitioners regarding which interventions to apply and when so that resources are used efficiently, and treatment outcomes are maximized. Objective This study aimed to describe an adaptive intervention that integrates community mental health workers, diabetes nurse educators, family members, and patients as partners in care while promoting diabetes self-management for Mexican American individuals with T2DM. The project incorporates four evidence-based, culturally tailored treatments to determine what sequence of intervention strategies work most efficiently and for whom. Given the increasing prevalence of T2DM, achieving better control of diabetes and lowering the associated medical complications experienced disproportionally by Mexican American individuals is a public health priority. Methods Funded by the National Institute of Nursing Research (National Institutes of Health grant R01 NR015809), this project used a sequential multiple assignment randomized trial and included 330 Spanish-speaking Latinx patients with T2DM. In the first phase of the study, subjects were randomly assigned to an evidence-based diabetes self-management educational program called Tomando Control delivered in a group format for 6, biweekly 1.5-hour sessions, led either by a community health worker or a diabetes nurse educator. In the second phase of the study, those subjects who did not improve their diabetes self-management behaviors were rerandomized to receive either an augmented version of Tomando Control or a multifamily group treatment focused on problem-solving. The primary outcome measure was the “Summary of Diabetes Self-Care Activities.” Evaluations were made at baseline and at 3, 6, and 12 months. Results This study was funded in June 2016 for a period of 5 years. Institutional review board approval was obtained in November 2016. Between March 2017 and September 2020, a total of 330 patients were recruited from the outpatient primary care clinics of Olive View-UCLA Medical Center, with a brief hiatus between May 2020 and July 2020 due to COVID-19 restrictions. The study interventions were completed in December 2020. Data collection began in March 2017 and was completed in December 2021. Data analysis is expected to be completed in Spring 2023, and results will be published in Fall 2023. Conclusions The results of this trial should help practitioners in selecting the optimal approach for improving diabetes self-management in Spanish-speaking, Latinx patients with T2DM. Trial Registration ClinicalTrials.gov NCT03092063; https://clinicaltrials.gov/ct2/show/NCT03092063 International Registered Report Identifier (IRRID) DERR1-10.2196/44793

determine what sequence of intervention strategies work most efficiently and for whom.Given the ever increasing prevalence of Type 2 diabetes, achieving better control of diabetes and lowering the associated medical complications experienced disproportionally by Mexican Americans is a public health priority.

CRITIQUE 1
Significance: 1 Investigator(s): 1 Innovation: 1 Approach: 3 Environment: 1 Overall Impact: This study aims to advance the science of family centered self-management for Mexican-American patients with Type 2 diabetes by using a Sequential Multiple Assignment Randomized Trial design to evaluate culturally adapted practices for promoting diabetes selfmanagement.This is an outstanding proposed study, one that is highly likely to make a sustained and powerful impact.Major strengths include the significance of the problem, the responsiveness of the proposed study to the program announcement, the innovative study design and the well-reasoned selection of interventions to study.The investigators are well-qualified and present a thoughtful and convincing work plan for achieving the goals of the study.In this resubmission, the investigators were responsive to previous critiques.The sole weakness in the approach noted by this reviewer is the inclusion of a wide age range, which may result in attenuated intervention effects.Offsetting this concern, however, are the advantages in generalizability that come from such a broad inclusion range.

Strengths
Increasing prevalence of Type 2 diabetes in Mexican-Americans and large, disproportionate burden arising from suboptimal control of diabetes in this population heightens the significance.
Clear and convincing rationales for interventions selected for comparison.
Will provide test of Individual and Family Self-Management Theory.

Weaknesses
None noted.

Strengths
PI is Chief of Psychiatry at Olive View UCLA Medical Center (OVMC) and an established investigator with ample relevant experience and expertise with psychosocial intervention studies of Mexican-Americans, including studies of the Multifamily Group (MFG) approach.
Dr. Ruiz is an expert on the impact of culture in the treatment of chronic disease.She is particularly well-qualified for training and monitoring the promotoras and nurses providing the interventions.
Drs. Namby and Wali provide complementary expertise in statistics and internal medicine, respectively.
Investigative team includes highly experienced research coordinator.

Weaknesses
None noted.

Strengths
Application of Sequential, Multiple Assignment Randomized Trial (SMART) design to familycentered self-management studies.
Relatively few diabetes self-management education (DSME) interventions have targeted Hispanic families along with patients.DSME intervention that targets family's collective behaviors.
Will extend study of multifamily group (MFG) approach to families of patients with type-2 diabetes.

Weaknesses
None noted.

Strengths
Study design permits assessing multiple attributes of interventions--including format (group vs. individual), type of educator and treatment target.
Plausible and theory-based rationale for identifying effect moderators under consideration (in Aim 4).

Sound measurement and randomization plans.
Attention to monitoring and maintaining intervention fidelity.
Well-developed statistical analysis plans.

Weaknesses
The inclusion of such a broad patient age range (18-65 years old) should be better justified by the investigators (a concern also raised by a previous reviewer), given the pros and cons of such a decision.A broad range can attenuate the apparent effect of the intervention, particularly if the effectiveness of family-centered self-management interventions varies with the developmental life stage of the patient.On the other hand, age is nominated as an effect moderator in Aims 3 and 4, so permitting a wide range of ages facilitates assessing age as an effect moderator.

Strengths
OVMC is well-suited to achieve recruitment goals and to otherwise support proposed research.
UCLA SIStat Data Core will provide data entry, management and analysis support.

Weaknesses
None noted.

Vertebrate Animals:
Not Applicable (No Vertebrate Animals)

Resubmission:
Mostly responsive to previous critiques.

Resource Sharing Plans:
Not Applicable (No Relevant Resources)

Recommend as Requested
No concerns were identified.

CRITIQUE 2
Significance: 3 Investigator(s): 1 Innovation: 2 Approach: 2 Environment: 1 Overall Impact: This is a resubmission of a proposal that aims to test four family-based treatments to improve self-management behaviors and self-efficacy among Mexican Americans with type 2 diabetes.Type 2 diabetes is an important public health concern, and Latinos are particularly impacted.This is a 1 R01 NR015809-01A1 6 NRCS KOPELOWICZ, A strong application.The application proposes an innovative SMART design that will allow for testing multiple interventions across time, and will use a stepped-up family engagement strategy to improve program attendance and outcomes.Another key strength is that the intervention will test family-based approaches, which have been shown to be particularly successful in Latino populations.The use of the Family Self-Management Theory appears appropriate.The intervention represents an important advancement in the field.

Strengths
Type 2 diabetes is a growing public health crisis and Latinos have higher incidence and morbidity than non-Latino whites.
Little is known about the success of family-based interventions for Latinos.
If successful, the study could lead to a greater understanding of the effectiveness of familybased interventions addressing type 2 diabetes.
Previous evaluations have tested family-based approaches for addressing mental illness in Mexican Americans and type 1 diabetes in adolescents, but key knowledge about whether the approach is effective in improving self-management practices among Latinos with uncontrolled diabetes is lacking.
The intervention addresses the key issue with success of any self-management program, that is, adherence with the program components.

Weaknesses
Given the comparison between a nurse-led and promotora-led program, it would appear that a 'missed opportunity' may be the inclusion of a cost-effectiveness assessment.Moreover, the nurse may have been integrated with the electronic health record and more access to the medical care team.While the promotora is considered lower cost, from a human resource perspective, a lack of understanding of the cost-effectiveness may hinder the advancement of this field.

Strengths
The investigator team appears strong, with expertise in nursing, and a history of leading promotora programs.Notably, a co-I for the project, Dr. Wali, is also the chief of medicine at Olive View-UCLA Medical Center, whose primary care clinics will serve as recruitment sites for the study.

Weaknesses
A minor weakness is that the expertise of the PI is mental health; the inclusion of an investigator with expertise in diabetes prevention and assessment may be useful.

Strengths
The study will use an innovative, SMART, design, which will allow for the testing of multiple interventions across time.

Strengths
The approach is well-founded in research.Latinos highly value family, thus testing family-based intervention is appropriate.
The use of the Family Self-Management Theory appears appropriate given the emphasis on family in the intervention.

Weaknesses
One minor concern is a 10% attrition used in estimates for power calculations.Attrition could be higher given the intensity of the intervention program.Moreover, there could very well be differential attrition by groupit is unclear whether and how the team plans to assess or monitor this.
A second minor point is that the recruitment goal of 330 may be too small to conduct meaningful analysis of moderators of the intervention.

Strengths
UCLA is the primary applicant and has substantial research resources.
Olive View-UCLA treats about 10,000 individuals with type 2 diabetes each year, and about 60% of their patients are Mexican American.The chief of medicine is a co-I on the study.It appears to be in ideal environment for recruiting eligible patients.
The participation of the two promotoras will be facilitated by the Latino Behavioral Health Institute, which has a long and successful history of training and mentoring promotoras who serve in community settings throughout the Mexican American neighborhood of Los Angeles County.The promotoras will already be trained in Tomando Control de Su Salud.Weaknesses

Vertebrate Animals:
Not Applicable (No Vertebrate Animals)

Resubmission:
No concerns were identified.

Resource Sharing Plans:
Not Applicable (No Relevant Resources)

Recommend as Requested
No concerns were identified.

CRITIQUE 3
Significance: 1 Investigator(s): 1 Innovation: 1 Approach: 2 Environment: 1 Overall Impact: This is an exciting proposed study to work with Latinos, primarily of Mexican origin, who have Type 2 diabetes and expands the intervention to non-adherent participants to include their families as motivators.Drs.Kopelowicz and Ruiz have strong established track records in working with this proposed population.It is anticipated that this RCT design will significantly inform familial interventions for this population, making it applicable beyond diabetes, which is salient in reducing health disparities burdens.

Strengths
The PI presents clear rationale for the need for a family-focused diabetes self-management intervention.
Testing a familial model to address diabetes management adherence holds promise as a disease preventative intervention with the family as well, which is significant in this population that bears a disproportionate burden.
No score driving weaknesses.

Strengths
This is a strong team that has worked with the Latino population in other studies.They have made meaningful scientific contributions in the various areas, diabetes, family, methods etc., thus proving confidence that they will be able to conduct the research and disseminate it in a timely manner.

Weaknesses
No score driving weaknesses.

Strengths
This is a highly innovative application in that it is using multiple evidenced-based interventions coupled with a sequential multiple assignment randomization, that should strengthen the interpretation of rich data related to a best practice familial intervention.

Weaknesses
No score driving weaknesses.

Strengths
This is an exciting application.It is anticipated that this RCT design will significantly inform familial interventions for this population, making it applicable beyond diabetes, which is salient in reducing health disparities burdens.

Weaknesses
None noted.

Strengths
This is an outstanding research environment to conduct this study that includes a letter of support from the Latino Behavioral Health Institute.

Weaknesses
No score driving weaknesses.NIH has modified its policy regarding the receipt of resubmissions (amended applications).See Guide Notice NOT-OD-14-074 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-1R01 NR015809-01A1 11 NRCS KOPELOWICZ, A 14-074.html.The impact/priority score is calculated after discussion of an application by averaging the overall scores (1-9) given by all voting reviewers on the committee and multiplying by 10.The criterion scores are submitted prior to the meeting by the individual reviewers assigned to an application, and are not discussed specifically at the review meeting or calculated into the overall impact score.Some applications also receive a percentile ranking.For details on the review process, see http://grants.nih.gov/grants/peer_review_process.htm#scoring.

Protections for Human
Acceptable Risks and/or Adequate Protections No concerns were identified.Data and Safety Monitoring Plan (Applicable for Clinical Trials Only): Acceptable o No concerns were identified.Inclusion of Women, Minorities and Children: Sex/Gender: Distribution justified scientifically Race/Ethnicity: Distribution justified scientifically Inclusion/Exclusion of Children under 21: Including ages < 21 justified scientifically No concerns were identified.
It is unclear how geographically dispersed the clinics and patients areand what challenges this might pose to recruitment and retention.Protections for Human Subjects: Acceptable Risks and/or Adequate Protections No concerns were identified.Data and Safety Monitoring Plan (Applicable for Clinical Trials Only): Acceptable o No concerns were identified.Inclusion of Women, Minorities and Children: Sex/Gender: Distribution justified scientifically Race/Ethnicity: Distribution justified scientifically 1 of Children under 21: Including ages < 21 justified scientifically No concerns were identified.
Subjects: Acceptable Risks and/or Adequate Protections No concerns were identified.Data and Safety Monitoring Plan (Applicable for Clinical Trials Only): Acceptable o No concerns were identified.