Asthma and Technology in Emerging African American Adults (The ATHENA Project): Protocol for a Trial Using the Multiphase Optimization Strategy Framework

Background Asthma causes substantial morbidity and mortality in the United States, particularly among African American emerging adults (AAEAs; aged 18-30 years), but very few asthma programs have targeted this population. Interventions that provide education and address underlying motivation for managing asthma may be the most effective. However, intensive face-to-face interventions are often difficult to implement in this population. Objective The purpose of this study is to develop an effective mobile asthma management intervention to improve control among AAEAs. Methods We will assess the ability of multiple technologic components to assist and improve traditional asthma education. The first component is the Motivational Enhancement System for asthma management. It is a mobile 4-session intervention using supported self-regulation and motivational interviewing. Personalized content is based on each participant’s activity level, daily experiences, and goals. The second component is supportive accountability. It is administered by asthma nurses using targeted mobile support (Skype/voice calls) to provide education, promote self-efficacy, and overcome barriers through a motivational interviewing–based framework. The third component is SMS text messaging. It provides reminders for asthma education, medication adherence, and physical activity. The fourth component is physical activity tracking. It uses wearable technology to help meet user-defined physical activity goals. Using a multiphase optimization strategy (MOST) framework, we will test intervention components and combinations of components to identify the most effective mobile intervention. The MOST framework is an innovative, and cost- and time-effective framework that uses engineering principles to produce effective behavioral interventions. We will conduct a component selection experiment using a factorial research design to build an intervention that has been optimized for maximum efficacy, using a clinically significant improvement in asthma. Participants (N=180) will be randomized to 1 of 6 intervention arms. Participants will be recruited from multiple sites of the American Lung Association-Airway Clinical Research Centers network and ambulatory care clinics at the Detroit Medical Center. Data collections will occur at baseline, and 3, 6, and 12 months. Results At study completion, we will have an empirically supported optimized mobile asthma management intervention to improve asthma control for AAEAs. We hypothesize that postintervention (3, 6, and 12 months), participants with uncontrolled asthma will show a clinically significant improvement in asthma control. We also hypothesize that improvements in asthma management behaviors (including physical activity), quality of life, symptoms, adherence, and exacerbation (secondary outcomes) will be observed. Conclusions AAEAs are disproportionately impacted by asthma, but have been underrepresented in research. Mobile asthma management interventions may help improve asthma control and allow people to live healthier lives. During this project, we will use an innovative strategy to develop an optimized mobile asthma management intervention using the most effective combination of nurse-delivered asthma education, a smartphone app, and text messaging. International Registered Report Identifier (IRRID) PRR1-10.2196/37946

This application proposes to develop a mobile asthma management intervention to improve control in African American emerging adults (AAEA) and using a multiphase optimization strategy (MOST) framework will conduct a randomized six-arm incomplete factorial design experiment to identify which components or combinations of components effectively optimize asthma control. During the discussion, the panel agreed the significance of addressing health disparities in asthma management among AAEA through technology-based interventions informed by applied behavioral theories of change is high, with potential to advance asthma control in underserved populations. This strong multidisciplinary investigative team was responsive to prior review and the application is improved, notably by providing justification for the design, including preliminary data on feasibility and acceptability, and expanding the data analytic plan. Reviewers noted that using the MOST framework to evaluate intervention components and integrating two theoretical models are innovative approaches. Additional strengths include strong preliminary data, a methodology tailored to participants' goals and providing smartphones when needed. The panel also identified addressable weaknesses including that a comprehensive baseline assessment of asthma characteristics is not planned and the lack of discussion of sex disparities in asthma management, engagement in mobile health interventions and barriers to physical activity. Overall, the reviewers agreed the application's strengths outweighed its weaknesses and will have a high impact on advancing asthma management in African American emerging adults.

DESCRIPTION (provided by applicant):
Asthma causes substantial morbidity and mortality in the U.S., particularly among African American emerging adults (AAEA; ages 18-30), but very few asthma programs have targeted this population. Interventions that provide education and address underlying motivation for managing asthma may be most effective. However, intensive, face-to-face interventions are often difficult to implement, especially among emerging adults. The purpose of this proposal is to develop an effective mobile asthma management intervention to improve control in AAEA. We will assess the ability of multiple technologic components to assist and improve traditional asthma education: 1) MES. The Motivational Enhancement System (MES) for Asthma Management is a mobile 4-session intervention utilizing supported self-regulation and Motivational Interviewing (MI). Personalized content is based on each participant's activity level, daily experiences, and goals. 2) SA. Supportive accountability (SA) is administered by asthma nurses utilizing targeted mobile support (Skype/voice calls) to provide education, promote self-efficacy, and overcome barriers through an MIbased framework. 3) SMS. Text messaging (SMS) provides reminders for asthma education, medication adherence, and physical activity. 4) PAT. Physical activity tracking (PAT) uses wearable technology to help meet user-defined physical activity goals. Using a multiphase optimization strategy (MOST) framework, we will test these 4 intervention components and combination of components to identify the most effective mobile intervention. MOST is an innovative, cost-and time-effective framework that utilizes engineering principles to produce effective behavioral interventions. We will conduct a component selection experiment using a factorial research design to build an intervention that has been optimized for maximum efficacy. We will use a clinically significant improvement in asthma control as the criterion for determining which components should be kept in the optimized intervention. Participants (N=180) will be randomized to 1 of 6 intervention arms consisting of various combinations of the intervention components. This experimental design is equivalent to conducting multiple pilot randomized clinical trials to evaluate the efficacy of each component, yet uses only a fraction of the sample size and resources. At the completion of the study, we will have an empiricallysupported, optimized mobile asthma management intervention to improve asthma control for AAEA. Participants will be recruited from multiple sites of the American Lung Association Airway Clinical Research Center network and ambulatory care clinics at the Detroit Medical Center. Data collections will occur at baseline, 3, 6, and 12 months. We hypothesize that post-intervention (3, 6, and 12 months), participants with uncontrolled asthma will show clinically-significant improvement in asthma control. We hypothesize that improvements in asthma management behaviors (including physical activity), quality of life, symptoms, adherence, and exacerbations (secondary outcomes) will also be observed.

PUBLIC HEALTH RELEVANCE:
African American emerging adults (ages 18-30) are disproportionately impacted by asthma, but have been under-represented in research. Mobile asthma management interventions may help improve asthma control and allow people to live healthier lives. During this project, we will use an innovative strategy to develop an optimized mobile asthma management intervention using the most effective combination of nurse-delivered asthma education, a smart phone app, and text messaging.

CRITIQUE 1
Significance: 2 Investigator(s): 2 Innovation: 4 Approach: 3 Environment: 2 Overall Impact: In this R01 resubmission, the investigators propose a randomized trial with MOST design to evaluate the effects of different mHealth interventions to improve asthma control among African American emerging adults with uncontrolled asthma. The application has multiple important strengths. First, it is highly significant because of its focus on an underserved population of young adults that accounts for a substantial proportion of asthma morbidity. Second, the scientific premise of the application is built upon extensive work by the co-PIs that have applied behavioral theories of change to develop effective technology-based interventions to improve asthma outcome sin underserved populations. Overall, the investigative team and intellectual environment are strong and provide all elements necessary for the successful completion of the proposed studies. Although the application is essentially the continuation of ongoing work by the investigators and it is not particularly novel, the proposed clinical trial represents the first study that would to test different components individually and in combination in a sufficient number of participants and with a follow-up period of up to one year. Overall, the study is scientifically rigorous, possible pitfalls are addressed, and multiple outcomes evaluated within a rigorous study design. Among the weaknesses are the lack of consideration for possible effects of other asthma-related factors (including current treatment, health care access, obesity, allergy to specific allergens), the lack of a comprehensive baseline assessment of asthma clinical characteristics, and the inclusion of possibly heavy smokers that may introduce an independent source of obstructive lung disease (other than asthma). Overall, strengths outweigh weaknesses and this application is likely to have a significant impact in the field of asthma managements among AAEAs.

Strengths
• The scientific premise of this application is strong and based on previous work that this investigative team (and the two co-PIs in particular) have completed in using technology to BMHO MACDONELL, K improve asthma management in African Americans. The proposed MOST trial is the continuation of this work • The focus on African Americans (as an underserved population) and on emerging adults (as a phase of life particularly susceptible to negative outcomes in asthmatics) reinforces the significance of the proposed study • The significance of some elements of the design (e.g., completion of all trial phases remotely, systematic use of cell phones and other electronic devices in asthma management) is also enhanced in the context of the COVID pandemic

Weaknesses
• None noted

Strengths
• Dr MacDonell is an associate professor with extensive experience in the use of technology to improve asthma management in African Americans. She is the PI of an ongoing RCT to test a multi-component technology-based intervention in AAs with asthma, which has provided critical preliminary data and scientific rationale in support of the current application individually and in combination in a highly cost-effective fashion • Procedures for refinement and beta-testing are well-integrated in the design • Overall, the study is scientifically rigorous, possible pitfalls are addressed, and multiple outcomes evaluated within a rigorous study design

Weaknesses
• The possible effects of baseline asthma characteristics (including current treatment, health care access, obesity, allergy to specific allergens) are not considered.
• The lack of a comprehensive baseline assessment of asthma characteristics (including clinical elements, such as lung function and FeNO) may also limit the conclusions that will be reached from this trial • Including smokers with up to 20 pack-years may introduce an independent source of obstructive lung disease (other than asthma) • investigators have been largely responsive to previous critiques. Most notably, the duration of follow-up has been extended to one year, the payment model has been revised, preliminary data from the ongoing RCT have been integrated in the design, and the description of the MOST study design and statistical approach has been expanded and improved.

Resource Sharing Plans:
Acceptable Budget and Period of Support:

CRITIQUE 2
Significance: 3 Investigator(s): 2 Innovation: 3 Approach: 3 Environment: 2 Overall Impact: This application seeks to refine and test an intervention to improve asthma control among young African Americans with asthma. The resubmission is responsive to prior critiques, revising the participant compensation model, follow-up period, statistical analysis plan, and clarifying innovative aspects. The need for refinement of the intervention is not a major weakness and fits well within the study timeline. Strengths include a focus on improving health outcomes among African Americans, the rigorous randomized MOST trial design, and the strong study team. Weaknesses include limited justification for using smart watches and overlooking sex as a potentially important factor given the potential sex differences in barriers to increasing physical activity and engaging with digital health interventions. Overall, strengths outweigh these weaknesses, and the project is expected to have high impact.

Significance:
Strengths BMHO MACDONELL, K • Improving outcomes among individuals with asthma, a chronic and debilitating disease, will have significant public health impact.
• This application is based on rigorous prior research of the intervention components, which enhances the significance of this project.

Weaknesses
• Sex is overlooked as a potentially important variable in this mostly female population.

Strengths
• The investigative team is strong and well suited to this project.
• The study team has the requisite expertise and training to successfully carry out the project.

Strengths
• Integrating two theoretical approaches and multiple efficacious interventions will shift research and practice paradigms towards these approaches.
• Targeting young African Americans with asthma is innovative.
• The multiphase optimization strategy (MOST) design is innovative and efficient.

Strengths
• Use of a MOST design enhances the likelihood of the project's success in accomplishing the proposed aims.
• The statistical analysis plan and sample size justification are thorough and appropriate to the project.

Weaknesses
• Use of a smartwatch to track physical activity over less expensive options (i.e., fitness trackers) is not well justified and limits the potential uptake of this approach.

Strengths
• The study environment is excellent and well suited to the project.

Strengths
• The study timeline is acceptable.

Protections for Human Subjects:
Acceptable Risks and/or Adequate Protections • Acceptable risks and adequate protections are described.
Data and Safety Monitoring Plan (Applicable for Clinical Trials Only):

Acceptable
• The data and safety monitoring plan is acceptable.

Inclusion Plans:
• Sex/Gender: Distribution justified scientifically • Race/Ethnicity: Distribution justified scientifically • Inclusion/Exclusion Based on Age: Distribution justified scientifically • Inclusion plans are acceptable.

Vertebrate Animals:
Not Applicable (No Vertebrate Animals)

Resubmission:
• The resubmission is responsive to prior critiques. The participant compensation model has been revised, the follow-up period has been extended, the statistical analysis plan has been revised, and innovative aspects of the project have been clarified. The need for refinement of the intervention is not a major weakness and fits well within the study timeline.

Resource Sharing Plans:
Acceptable Budget and Period of Support: Recommend as Requested BMHO MACDONELL, K

CRITIQUE 3
Significance: 3 Investigator(s): 2 Innovation: 3 Approach: 4 Environment: 2 Overall Impact: The application is a resubmission of a previous R01 application. The proposed project addresses the significant health disparities issue with respect to asthma management among African American emerging adults (AAEA). The proposed project applies an innovative multiphase optimal strategy (MOST) framework to identify which components or combinations of components are most efficacious and efficient in improving asthma control and associated secondary outcomes (quality of life, asthma exacerbations, physical activity). The environment and investigative team are strong with demonstrated expertise in asthma behavioral interventions and mHealth and technological approaches within the target population. Weaknesses of the application include its limited generalizability due to the narrow focus on AAEA with asthma while ignoring other groups which face significant asthma disparities, lack of consideration of demographic characteristics or health comorbidities which may influence both intervention engagement and asthma management. The study team was responsive to previous critiques and made considerable changes to strengthen the application. Among the most important changes were the justification for the incomplete factorial design within the MOST framework, greater clarity regarding refinement of intervention components, inclusion of preliminary data on study components' feasibility and acceptability, and monetary considerations around cell phone access for participants through the intervention duration.

Strengths
• The application is significant in its focus on reducing asthma disparities among African American emerging adults (AAEA).
• Interventions to improve asthma self-management among AAEA are greatly needed, as this is a population that is under-researched in this field.
• Asthma disparities among AA compared to non-Hispanic whites persist, with AA having a higher lifetime prevalence of asthma and nearly a 3-fold higher mortality rate.

Weaknesses
• Generalizability of the intervention is limited by the narrow focus on AAEA ages 18-39. Other groups, including Latino (in particular Puerto Rican) EA also experience significant asthma disparities, however these are not acknowledged.

Strengths
• MPI team of Drs. MacDonnell and Baptist bring complimentary expertise in the fields of health psychology and medicine respectively.
• The PIs individually and collectively have a history of scholarship and funding in the areas of asthma management. BMHO

MACDONELL, K
• The study team is well suited to carry out the proposed study with additional expertise in biostatistics, mHealth, behavioral interventions (including MOST and SMART designs), nursing, and social work.

Weaknesses
• None

Strengths
• Key area of innovation is the use of the MOST design which is under-utilized among interventions to reduce asthma disparities.

Weaknesses
• Neither motivational interviewing-based interventions nor mHealth based approaches to asthma management are particularly innovative.

Strengths
• The MOST framework is an efficient design to assess which component(s) are most efficacious in improving asthma outcomes within this population. While the study proposes to use an incomplete factorial design, the reasons for this are well justified.
• Intervention components are theoretically grounded (MI and SRT) and tailored to participants' needs, goals, and preferences.
• The primary outcomes are clinically meaningful and the increase in length of follow-up to 1 year provides opportunity to observe sustained changes in behavioral management.
• Preliminary data regarding feasibility and acceptability of intervention components, retention of participants is included.
• Letters of support from additional American Lung Association -Airway Clinical Research Centers network sites are included.

Weaknesses
• Randomization by sex is mentioned, given that mPIs anticipate 65-70% of participants to be female, but there is no prior mention of additional tailoring of intervention components by sex. This is a concern given the existing literature regarding sex disparities in asthma management, engagement with mHealth and technological interventions, and barriers to physical activity.
• There is no mention of demographic or psychosocial factors (e.g. mental health comorbidities) which may impact both engagement with the intervention and also asthma control.
• No dissemination plan is included which seems like a missed opportunity given the engagement of various stakeholders in both the recruitment and refinement phases of the proposed study. • Hispanic and Latino participants are included in the enrollment numbers, but no within the study.

Environment
Participants include African American emerging adults ages 18 years to 29 years.

Not Applicable (No Vertebrate Animals)
Biohazards:

Not Applicable (No Biohazards)
Resubmission: • Overall, study team was responsive to previous critiques and made considerable changes to strengthen the application. Among the most important changes were the justification for the incomplete factorial design within the MOST framework, greater clarity regarding refinement of intervention components, inclusion of preliminary data on study components' feasibility and acceptability, and monetary considerations around cell phone access for participants through the intervention duration.
Resource Sharing Plans: