AdheRence to Inhaled Corticosteroids in Asthma
Phase: NA
Conditions: Medication Adherence, Asthma
Sponsor: Duke University

 
 
 
 
 
AdheRence to Inhaled Corticosteroids in Asthma 
Research Summary 
NCT03769519 
 
Document Date: December 14, 2020 
 

Purpose of the Study 
This study aims to develop a clinical intervention to improve the health outcomes of adult African 
Americans (AAs) with asthma. Toward that end, we intend to refine a novel patient-centered inhaled 
corticosteroid (ICS) adherence intervention called ARICA (AdheRence to Inhaled Corticosteroids in 
Asthma), using qualitative methods and usability testing. 
Background & Significance 
Asthma in adult AAs is a significant health problem.(Jimenez-Gonzalez, Santini et al. 2008) Many 
national organizations, including the National Heart, Lung, and Blood Institute’s (NHLBI) Center for 
Translational Research and Implementation Science (CTRIS) are working to identify gaps and research 
opportunities to address inequities in a variety of health conditions, including asthma. ICS adherence in 
adult AAs is one potentially important target for interventions. ICS adherence rates are 22%-64% in the 
general population and worse in adult AAs (adjusted OR 0.35, 95% CI, 0.13-0.95). ICS adherence is 
associated with reduced asthma exacerbations, reduced asthma-related acute care utilization, and 
reduced health care cost.(Bender, Milgrom et al. 2003, Haynes, Ackloo et al. 2008, National Asthma and 
Prevention Program . Third Expert Panel on the Management of 2010, Williams, Peterson et al. 2011, 
Ivanova, Bergman et al. 2012, Moullec, Gour-Provencal et al. 2012, Viswanathan, Golin et al. 2012, 
Denford, Taylor et al. 2014) Though we do not have specific ICS adherence rates in North Carolina or the 
Duke Health System, there is no evidence to suggest that rates are different than nationally reported 
estimates. 
Adherence interventions in adult AAs have not been effective. I conducted a systematic review that 
found ICS adherence interventions in adult AAs(Martin, Catrambone et al. 2009, Apter, Wang et al. 
2011, Apter, Wan et al. 2013, Kolmodin MacDonell, Naar et al. 2016) to be ineffective in improving ICS 
adherence, health care utilization, FEV1, asthma control, or asthma quality of life (manuscript under 
review). Interventions did not target multiple barriers to adherence and were not consistently informed 
by behavior change theory or stakeholder engagement—recommended strategies for developing 
behavior change interventions in minorities.(Martin, Catrambone et al. 2009, Apter, Wang et al. 2011, 
Press, Pappalardo et al. 2012, Apter, Wan et al. 2013, Kolmodin MacDonell, Naar et al. 2016) 
Theory-informed, multi-component approaches may be critical for successful behavior change.(Michie, 
van Stralen et al. 2011, French, Green et al. 2012) I conducted a scoping literature review and engaged 
local community stakeholders to identify the most common patient-reported barriers to asthma 
medication adherence in adult AAs (drafting). I then mapped the barriers to the Theoretical Domains 
Framework (TDF), a behavior change theory with 14 domains covering a wide range of potential barriers 
that is thought to be able to identify a higher number of potential intervention strategies than a single 
behavior theory. (Michie, van Stralen et al. 2011, Cane, O’Connor et al. 2012) The most common types 
of patient barriers, when classified by TDF domains, were: knowledge (e.g., do not know when to use 
ICS), belief about consequences (e.g., belief ICS is not needed for asthma control), environmental 
context and resources (e.g., costs), skills (e.g., cannot technically use inhaler), emotion (e.g., fear of side 
effects or dependence), and memory, attention, and decision processes (e.g., too busy). Using the 
Behavior Change Wheel, a systematic and evidence-based approach to developing an intervention, I 
identified intervention strategies and created a preliminary logic model for a novel intervention 
package, called ARICA (Figure 1). (Michie, van Stralen et al. 2011, Cane, O’Connor et al. 2012) Using 
online questionnaires, patients will identify the extent of their nonadherence and their barriers to 

adherence. Then I will select an evidence-based intervention strategy to remediate each identified 
barrier.(Michie, van Stralen et al. 2011, Cane, O’Connor et al. 2012) Each category of barriers (TDF 
domains) is connected to an intervention activity (Figure 1 legend). For example, patients who cannot 
afford medications will be enrolled in a copayment assistance program and those who do not believe 
adherence is needed for control will receive objective feedback on asthma control using spirometry. In 
addition to the interchangeable activities, everyone will receive texts/emails dispelling asthma myths to 
help reinforce adherence after the core intervention activities. Their providers will receive alerts about 
nonadherent patients identifying their barriers to adherence as well as recommended provider 
intervention strategies (e.g., referrals)  and discussion points to be used at the next encounter. All 
adherence information and recommendations will be added to the chart so it will be readily available 
during encounters. 
ARICA is a personalized, patient-centered adherence intervention designed to remediate barriers to 
adherence by focusing on 3 areas of interest for REACH Equity: (a) improving the quality of the clinical 
encounter by facilitating patient-provider communication about the extent of adherence and barriers to 
adherence; (b) promoting interpersonal relationship building by providers helping patients understand 
their barriers and acknowledge the difficulty of adherence; and, (c) targeting the whole person by 
customizing intervention components according to each patient’s unique barriers. 
The proposed research is novel in at least 4 ways. (1) Unlike most adherence studies,(Martin, 
Catrambone et al. 2009, Apter, Wang et al. 2011, Apter, Wan et al. 2013, Kolmodin MacDonell, Naar et 
al. 2016) we are targeting African Americans. This is important because AAs have disproportionately 
high asthma morbidity and mortality.(Adams, Kirzinger et al. , Agency for Healthcare Research Quality , 
Centers for Disease Control , Goeman, Aroni et al. 2004) (2) Our intervention’s theory-based approach 
may yield a more potent intervention than those identified and studied in the past. There is increasing 
evidence that theory-informed, multi-component approaches are critical for successful behavior 
change.(Michie, van Stralen et al. 2011, French, Green et al. 2012) A meta-analysis of 147 medication 
adherence studies that used behavior theory to inform intervention development reported a statistically 
significant improvement in medication adherence outcomes.(Conn, Enriquez et al. 2016) To our 
knowledge, the proposed research is the first to use the TDF, behavior theory, and the Behavior Change 
Wheel (intervention development framework) to design an ICS adherence intervention in adult AAs with 
asthma. (3) We will engage key stakeholders to ensure our interventions are relevant and can be easily 
translated into routine clinical practice. Stakeholder engagement is critical to the success of asthma 
interventions in minorities.(Press, Pappalardo et al. 2012) (4) We will target multiple barriers for ICS 
adherence and poor asthma outcomes among adult AAs. Prior ICS adherence interventions in adult AAs 
have targeted one barrier to ICS adherence. The proposed research targets multiple barriers to ICS 
adherence that have been identified at the national level in my scoping review and confirmed locally by 
community stakeholders. 
Design & Procedures 
Study the feasibility and acceptability of ARICA in Duke Health.  
Study Design: I will (1) implement ARICA in Duke Health and (2) evaluate the feasibility and acceptability 
of the implementation of ARICA in a randomized controlled study employing mixed methods (i.e., 
quantitative and qualitative assessments). 

Procedures: Consented subjects will receive a modified (adapted for patients with asthma who have 
been shown to face similar barrier to adherence) version of the validated Voils adherence questionnaire, 
which assesses 7-day self-reported medication adherence and barriers to adherence.(Voils, Maciejewski 
et al. 2012) If nonadherent, participants will select all their barriers to adherence, which will inform the 
development of a personalized adherence intervention targeting the patient’s unique needs. The 
specific intervention components for each patient will depend on the barriers identified. Patients will 
retake the Voils adherence questionnaire every month for up to 3 months. All patients will receive 
weekly text and email alerts dispelling asthma medication myths to help reinforce adherence for the 
study period (4 months).  
The asthma self-management course (group or individual depending on scheduling) will be held in a 
clinic conference room. For example, the conference room in the Duke Asthma Allergy and Airway 
Center, Duke Outpatient Clinic and Croasdaile Primary Care Clinic. 
Data Collection:  Data will be collected through RedCap surveys. Patients will have the option of 
completing the surveys online, via phone interview, or in person as part of a guided interview with the 
CRC (preferred). In the ARICA exit interview, questions were added about COVID-19 and how it affected 
the participant’s asthma and stress. 
Outcome Measures: The primary outcome is feasibility and acceptability, which will be assessed using 
qualitative methods (i.e., semi-structured interviews) at up to 3 months with the goal of characterizing 
and profiling how intervention components, as well as the unique case context of their use, may have 
impacted participants’ experiences. This will allow us to explore how the intervention may target or miss 
each patient’s needs and explore variability across providers and practices. We will use the barriers 
identified to facilitate discussion about how the intervention strategy impacted their ability to 
communicate about and get help with barriers to adhering and asthma management. In addition, we 
will contact patients and providers to ask them how easy the intervention was to use, whether there 
were barriers to use, how the intervention could be improved, and the extent to which the intervention 
hinders or facilitates clinical care. We will also seek to contact participants who drop out of the study to 
elicit their feedback, which may be distinctly different than that of participants who complete the study. 
Secondary Outcomes: We will collect secondary outcomes at baseline and up to 3 months. Baseline 
medication possession ratio (MPR) and asthma exacerbations will be calculated from the 6 and 12 
months prior to consent, respectively. Asthma exacerbation will be defined as any use of systemic 
steroids or an increase in daily systemic steroids for 3 or more days to treat respiratory symptoms or any 
asthma-related acute care utilization over the study period. The ACT, AQLQ, and the asthma KASE 
questionnaire are valid and reliable self-administered measures, validated in AA populations. We will 
also assess interpersonal communcation between patients and providers using the Interpersonal 
Process of Care Survey. During the baseline assessment, I will also collect demographics using a 
standardized questionnaire. Additional outcomes are listed in the Questionnaire Packet. 
Analysis: Primary Outcome: I will perform stakeholder (e.g., patient, provider, staff) to inform 
intervention modification. Interviews will be transcribed, coded independently by two members of the 
team, and analyzed to identify emergent themes. I will present preliminary findings to stakeholders to 
review the results and aid in the interpretation/significance of findings. Secondary Outcomes: I will 
assess the magnitude of change and confidence intervals for all quantitative outcomes. The proposed 

study will not be powered to detect an effect size because the primary outcome is feasibility and 
acceptability. 
Selection of Subjects 
Patients 
 
Inclusion Criteria for Aim 1: 
- At least 18 years of age 
- Self-identifying African American 
- Self-reported current asthma  
- Prescribed an inhaled corticosteroid (alone or combination) for ≥ 1 month 
- Presented at ANY Primary Care clinic visit within the past 3 years  
Inclusion Criteria for Aim 2: 
- At least 18 years of age 
- Self-identifying African American 
- Self-reported current asthma  
- Prescribed an inhaled corticosteroid (alone or combination) 
- Presented at a Duke Primary Care clinic visit within the past 3 years 
Exclusion for Aims 1 and 2: 
- Unable or unwilling to provide informed consent 
Patients will be identified through MaestroCare, DEDUCE queries, clinic visits, direct referrals, and 
community recruitment  
Providers 
  
Inclusion Criteria for Aims 1: 
- Must be a pulmonary or primary care provider (MD, DO, NP, or PA) having practiced for ≥ 1 year 
- Must clinically manage adult African Americans with asthma 
Exclusion Criteria for Aims 1 
- Unable or unwilling to provide informed consent 
  
Pulmonary providers will be recruited from Duke's three pulmonary practices: Duke Raleigh; Duke 
Asthma, Allergy, and Airway Center; and the Duke South 2F/2G Pulmonary Clinic. Primary care providers 
will be recruited from Duke, UNC and private practices in North Carolina 
  
Community Stakeholders 
  
Inclusion:  
- Must work with Durham County, NC residents 
- Must work with or advocate for African American communities (e.g. leadership/staff of nonprofit 
organizations, religious leaders, health insurance payers, government agency employees, etc.) 
Exclusion:  
- Belong to organizations focused exclusively on non-African American communities 
- Unable or unwilling to provide informed consent 
  

Potential participants will be recruited from the REACH Equity Community Advisory Board and 
organizations involved in the asthma stakeholder meeting reported in the background data collection 
(e.g. Durham Housing Authority, Lincoln Community Health Center, Project Access, Clean Air, AME Zion, 
etc.). 
 
Subject Recruitment and Compensation 
Describe recruitment procedures, including who will introduce the study to potential subjects. Describe 
how you will ensure that subject selection is equitable and all relevant demographic groups have access 
to study participation (per 45 CFR 46.111(a) (3)). Include information about approximately how many 
DUHS subjects will be recruited. If subjects are to be compensated, provide specific prorated amounts to 
be provided for expenses such as travel and/or lost wages, and/or for inducement to participate. 
Patients 
  
Patients will be recruited through direct referral, patient lists, Duke Asthma Allergy Airway research 
database, direct referral from community stakeholders and events, DEDUCE/EPIC query, MyChart 
Research Team query, or in the event that an eligible participant calls the recruitment team to express 
interest. We will use Duke's new cold-call policy. 
  
Using the results from MyChart Research Team's query, we will send a mychart message to all eligible 
participants from Dr. Riley describing the study and offering these patients an opportunity to participate 
in the study or to opt-out from participation. If the study team has not heard from a potential 
participant after 3 days, then a member of the study team will contact that individual using a phone 
script to confirm eligibility, answer questions, and schedule study activities if the individual expresses 
interest. The study team will not attempt to contact subjects who have opted out of research in 
MyChart. 
  
Providers 
Potential participants will be contacted by email and personal (verbal) invitation by the PI. 
  
Community Stakeholders 
Potential participants will be contacted by email and personal (verbal) invitation by the PI. 
  
Data Analysis & Statistical Considerations 
 
Primary Outcome: I will perform patient interviews to inform intervention refinement. Interviews will be 
transcribed, coded independently by two members of the team, and analyzed to identify emergent 
themes. I will present preliminary findings to stakeholders to review the results and aid in the 
interpretation/significance of findings. Secondary Outcomes: I will assess magnitude of change and 
confidence interval for quantitative outcomes, and patient's medication adherence rates based on 
pharmacy refill rate, Asthma Quality of Life AQLQ, and Asthma Control Test, (ACT).  The proposed study 
will not be powered to detect an effect size because the primary outcome is feasibility and acceptability. 
 

An outside vendor, (ETR Services) is being contracted to provide data analysis of the study audio 
recordings, the recordings will be transmitted for analysis via a secure Duke BOX folder.  No data will be 
sent until a work agreement with ETR Services is in place. 
 
Data & Safety Monitoring 
 
Dr. Riley will supervise this study at all times and will be in close and frequent contact with the Clinical 
Research Coordinator and Maestro Care Research group.  Investigators will adhere to established 
federal and institutional patient safety and protection guidelines.  To assure data accuracy, Dr. Riley and 
the CRC will review the iterative qualitative results on a biweekly basis.  Protocol compliance will be 
reviewed during weekly meetings between the clinical research coordinator and Dr. Riley (more 
frequent if required).  
  
We will closely safeguard participant privacy regarding protected health and personal information.  
Subject descriptive characteristics will be collected and stored in a REDCap database. Study ID numbers, 
generated at the time of enrollment, are linked to a separate Duke DHTS-maintained database that 
contains patient names and descriptors (e.g., patient, stakeholder, provider) that will be stored on the 
secured pulmonary drive on Duke's server. 
  
As described previously, this project will utilize a REDCap database system customized for our data 
needs.  For data validation, a series of project-defined data checks and conditional constraints can be 
required to ensure the highest quality data collection.