The Tailored Adherence Incentives for Childhood Asthma Medications (TAICAM) Trial
Phase: NA
Conditions: Medication Adherence, Asthma in Children
Sponsor: Children's Hospital of Philadelphia

 
 
Title:   
        
           The Tailored Adherence Incentives for Childhood Asthma  
 
 
           Medications (TAICAM) Trial 
Short Title:                
The TAICAM Trial 
Drug or Device  
 
N/A 
Name(s):  
FDA IND                     
N/A 
Regulatory Sponsor:  
National Insititutes of Health 
EiRB Number                       18-015434 
Protocol Last Updated:          3/31/2023 
NCT Number:                        NCT03907410 
 
 
 
 
 
Sponsor: 
National Heart Lung & Blood Institute 
31 Center Street  
Bethesda, MD, 20892 
USA 
Study Principal Investigator: Chén Kenyon, MD, MSHP 
Children’s Hospital of Philadelphia 
Roberts Center for Pediatric Research 
2716 South Street  
Philadelphia, PA, 19146 
Phone 267-426-6339 
email: kenyonc@email.chop.edu 
 
 

  
 
 
 
 
 
 
 
ii
TABLE OF CONTENTS 
Table of Contents ................................................................................................................... ii 
Abbreviations and Definitions of Terms ............................................................................. iv 
Abstract .................................................................................................................................. v 
Table 1: Schedule of Study Procedures .............................................................................. vi 
Figure 1: Study Diagram ..................................................................................................... vii 
1 
BACKGROUND INFORMATION AND RATIONALE ....................................................................... 1 
1.1 
INTRODUCTION ..................................................................................................................................... 1 
1.2 
NAME AND DESCRIPTION OF INVESTIGATIONAL PRODUCT OR INTERVENTION..................................... 1 
1.3 
SELECTION OF DRUGS AND DOSAGES ................................................................................................... 1 
1.4 
RELEVANT LITERATURE AND DATA ..................................................................................................... 1 
1.5 
COMPLIANCE STATEMENT .................................................................................................................... 2 
2 
STUDY OBJECTIVES .............................................................................................................................. 2 
2.1 
PRIMARY OBJECTIVE (OR AIM)............................................................................................................. 2 
2.2 
SECONDARY OBJECTIVES (OR AIM) ...................................................................................................... 2 
3 
INVESTIGATIONAL PLAN .................................................................................................................... 2 
3.1 
GENERAL SCHEMA OF STUDY DESIGN.................................................................................................. 2 
3.1.1 
Screening Phase .............................................................................................................................. 2 
3.1.2 
Run-in Phase (Month 1 – first 2 weeks) .......................................................................................... 3 
3.1.3 
Experiment Phase (Months 1-3) and Observation Phase (Months 4-6) ......................................... 3 
3.1.4 
Follow-up Phase .............................................................................................................................. 4 
3.2 
ALLOCATION TO TREATMENT GROUPS AND BLINDING ........................................................................ 4 
3.3 
STUDY DURATION, ENROLLMENT AND NUMBER OF SITES ................................................................... 4 
3.3.1 
Duration of Study Participation ...................................................................................................... 4 
3.3.2 
Total Number of Study Sites/Total Number of Subjects Projected .................................................. 4 
3.4 
STUDY POPULATION ............................................................................................................................. 5 
3.4.1 
Inclusion Criteria ............................................................................................................................ 5 
3.4.2 
Exclusion Criteria ........................................................................................................................... 5 
4 
STUDY PROCEDURES ............................................................................................................................ 5 
4.1 
TECHNOLOGY INTEGRATION ................................................................................................................ 5 
4.2 
SCREENING VISIT (VISIT 1)................................................................................................................... 6 
4.3 
STUDY RUN-IN PHASE (PHASE 1) ......................................................................................................... 6 
4.4 
STUDY EXPERIMENT PHASE (PHASE 2) ................................................................................................. 6 
4.5 
VISIT 2 (CLINIC OR HOME PREFERRED, TELEPHONE IF NOT POSSIBLE) – MONTH 2 ................................ 7 
4.6 
VISIT 3 (CLINIC OR HOME PREFERRED, TELEPHONE IF NOT POSSIBLE) – MONTH 4 ................................ 7 
4.7 
STUDY OBSERVATION PHASE (PHASE 3) .............................................................................................. 7 
4.8 
VISIT 4 (CLINIC OR HOME PREFERRED, TELEPHONE IF NOT POSSIBLE) – MONTH 7 ................................ 7 
4.9 
VISIT 5 (CLINIC OR TELEPHONE) – MONTH 12-13 .................................................................................. 7 
4.10 
SUBJECT COMPLETION/WITHDRAWAL ................................................................................................. 7 
4.10.1 
Early Termination Study Visit ..................................................................................................... 7 
5 
STUDY EVALUATIONS AND MEASUREMENTS.............................................................................. 8 
5.1 
SCREENING AND MONITORING EVALUATIONS AND MEASUREMENTS .................................................. 8 
5.1.1 
Medical Record Review ................................................................................................................... 8 
5.1.2 
Other Evaluations, Measures .......................................................................................................... 8 
5.2 
EFFICACY EVALUATIONS ...................................................................................................................... 8 
5.2.1 
Diagnostic Tests, Scales, Measures, etc. ......................................................................................... 9 
5.3 
SAFETY EVALUATION ........................................................................................................................... 9 
5.4 
PRIMARY ENDPOINT ............................................................................................................................. 9 
5.5 
SECONDARY ENDPOINTS ...................................................................................................................... 9 
5.6 
STATISTICAL METHODS ...................................................................................................................... 10 

 
 
 
 
 
 
 
 
iii
5.6.1 
Baseline Data ................................................................................................................................ 10 
5.6.2 
Efficacy Analysis ........................................................................................................................... 10 
5.7 
SAMPLE SIZE AND POWER .................................................................................................................. 11 
6 
STUDY MEDICATION (STUDY DEVICE OR OTHER STUDY INTERVENTION) .................... 14 
6.1 
DESCRIPTION ...................................................................................................................................... 14 
7 
SAFETY MANAGEMENT ..................................................................................................................... 14 
7.1 
CLINICAL ADVERSE EVENTS .............................................................................................................. 14 
7.2 
ADVERSE EVENT REPORTING ............................................................................................................. 14 
8 
STUDY ADMINISTRATION ................................................................................................................. 14 
8.1 
TREATMENT ASSIGNMENT METHODS ................................................................................................. 14 
8.1.1 
Randomization ............................................................................................................................... 14 
8.1.2 
Blinding ......................................................................................................................................... 15 
8.2 
DATA COLLECTION AND MANAGEMENT ............................................................................................ 15 
8.3 
CONFIDENTIALITY .............................................................................................................................. 20 
8.4 
REGULATORY AND ETHICAL CONSIDERATIONS.................................................................................. 20 
8.4.1 
Data and Safety Monitoring Plan.................................................................................................. 20 
8.4.2 
Risk Assessment ............................................................................................................................. 20 
8.4.3 
Potential Benefits of Trial Participation ....................................................................................... 20 
8.4.4 
Risk-Benefit Assessment ................................................................................................................ 20 
8.5 
RECRUITMENT STRATEGY .................................................................................................................. 21 
8.6 
INFORMED CONSENT/ASSENT AND HIPAA AUTHORIZATION ............................................................ 21 
8.6.1 
Partial Waiver/alteration of HIPAA Authorization ....................................................................... 21 
8.6.2 
Waiver of Consent ......................................................................................................................... 22 
8.7 
PAYMENT TO SUBJECTS/FAMILIES ...................................................................................................... 24 
9 
PUBLICATION ........................................................................................................................................ 24 
10 
REFERENCES ......................................................................................................................................... 25 
 

  
 
 
 
 
 
 
 
iv 
ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE 
 
Adverse event 
API 
 
Application Programming Interface 
App 
 
Mobile application 
BTE 
 
Bluetooth Low Energy 
cACT 
 
Child Asthma Control Test 
CHOP 
 
Children’s Hospital of Philadelphia 
CSV 
 
Comma Separated Values 
DHS 
 
Department of Human Services 
DMS 
 
Data Management System  
ED 
 
Emergency Department 
FDA 
 
Food and Drug Administration 
HAU 
 
Healthcare Analytics Unit 
ICS 
 
Inhaled Corticosteroids 
ID 
 
Identification 
PII 
 
Personal Identifiable Information 
PMACS 
 
Penn Medicine Academic Computing Services 
SAE 
 
Serious Adverse Event 
SQL  
 
Structured Query Language 
UPenn 
 
University of Pennsylvania 
WTH 
 
Way to Health 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

  
 
 
 
 
 
 
 
v
ABSTRACT 
Context:  (Background) 
Poor adherence to inhaled corticosteroid (ICS) medications for children with high risk asthma 
is a well-documented and poorly understood problem with a disproportionate prevalence and 
impact on urban minority children. Financial incentives have been shown as a compelling 
method to engage a high-risk asthma population in regular ICS use, but whether and how 
adherence can be maintained and lead to sustained high adherence trajectories is unknown.  
Objectives: (primary and important secondary objectives) 
1) Determine the marginal effects of financial ICS incentives on adherence (1° 
outcome) and healthcare system use and costs (2° outcomes) in a prospective cohort 
of child-caregiver dyads. 
2) Assess proposed mechanisms by which intervention strategy influenced adherence 
trajectory, including (1) participant self-efficacy, (2) medication responsibility, and 
(3) habit formation. 
3) Explore caregiver and child perceptions of acceptability of intervention components 
and how they influenced adherence trajectory.  
Study Design:  
Basic design: Randomized controlled trial 
Setting/Participants: 
To accomplish the above objectives, we propose to enroll 125 children and their parents in a 
six-month intervention with a six-month follow-up period. Children will be ages 5-12, and 
must have two or more visits to any combination of the outpatient, ED or hospital setting in 
the past year for asthma exacerbations at Children’s Hospital of Philadelphia.  
Study Interventions and Measures:  
The study intervention will include daily automated medication reminders (either via text 
message or push reminder), an app to track daily medication use, and nominal incentives to 
promote daily controller use.  Inhaled controller medication adherence and rescue medication 
use will be measured using electronic monitors affixed to the inhalers. Factors associated with 
differential adherence will be assessed using surveys administered during enrollment, the 
experiment interval (months 2 and 4), the observation interval (month 7), and study 
completion (months 12-13). Efficacy outcomes will include change in parent-reported asthma 
control and mean adherence to ICS between study arms during the experiment interval, as 
well as the observation interval. 
 

 
vi  
 
 
 
 
 
 
 
TABLE 1: SCHEDULE OF STUDY PROCEDURES  
Study Phase 
Screening and 
initial survey  
Run-in 
period 
Study survey 
Experiment 
period 
Study 
survey 
Observation 
period 
Study survey 
Study completion 
survey 
Visit Number 
1 (clinic 
/hospital/phone) 
 
2 (clinic/ 
phone) 
 
3 (clinic/ 
phone) 
 
4 
(clinic/home 
phone) 
5 (clinic/phone) 
Arms 
1,2,3 
1,2,3 
1,2,3 
1 
2 
3 
1,2,3 
1,2,3 
1,2,3 
1,2,3 
Study Month 
0 
0 
2 
1-3 
4 
4-6 
7 
12-13 
Informed Consent/Assent 
X 
 
 
 
 
 
 
 
 
 
Review Inclusion/Exclusion 
Criteria 
X 
 
 
 
 
 
 
 
 
 
Demographics/Medical 
History 
X 
 
 
 
 
 
 
 
 
 
Prior/Concomitant 
Medications 
X 
 
 
 
 
 
 
 
 
 
Dispense Electronic 
Monitors 
X 
 
 
 
 
 
 
 
 
 
Questionnaires  
X 
 
X 
 
 
 
X 
 
X 
X 
Child asthma control tool  
X 
 
X 
 
 
 
X 
 
X 
X 
Electronic monitoring  
 
X 
 
X 
X 
X 
 
X 
X 
X 
Daily medication reminders  
 
 
 
X 
X 
 
 
 
 
 
Adherence incentives  
 
 
 
X 
 
 
 
 
 
 
 
.

 
page vii 
  
 
 
 
FIGURE 1: STUDY DIAGRAM 
A flow diagram of the study is included below.  
 
 
ARM 1 
Experiment Period 
(Months 1-2) 
Incentives, reminders, 
feedback 
ARM 3 
Experiment Period 
(Months 1-2) 
Ongoing electronic 
monitoring 
ARM 2 
Experiment Period 
(Months 1-2) 
Reminders & feedback 
 
Visit 1: Enrollment (Month 0) 
 
• 
Informed Consent, Survey 
1, affix electronic sensor, 
download app 
Run-in Period (Month 0, @2 weeks) 
Randomization (Month 0, @4 weeks) 
Visit 2: Followup (Month 2) 
Followup survey, cACT 
ARM 1 
Experiment Period 
(Month 3) 
Incentives, reminders, 
feedback 
ARM 2 
Experiment Period 
(Month 3) 
Reminders & feedback 
 
ARM 3 
Experiment Period 
(Month 3) 
Ongoing electronic 
monitoring 
Visit 3: Followup (Month 4) 
Followup survey, cACT, semi-structured interview 
Observation Period (Months 4-6) 
Followup survey, cACT, semi-structured interview 
Visit 4: Followup (Month 7) 
Followup survey, cACT 
Visit 5: Study Completion (Months 12-13) 
Followup survey, cACT 
Ineligible or choose not 
to participate 
Run-in Non-responders 

 
  
 
 
 
1
1 
BACKGROUND INFORMATION AND RATIONALE 
1.1 Introduction 
Poor adherence to asthma controller medications is a well-documented yet poorly understood 
problem. Despite compelling evidence demonstrating improved disease control, fewer 
exacerbations, and hospitalizations with regular use of ICS, adherence with prescribed 
regimens for inhaled corticosteroids in childhood asthma is approximately 50% of prescribed 
doses.1 In urban minority populations, who suffer higher rates of morbidity and mortality from 
asthma, adherence estimates are even lower, ranging from 11 to 37%.2–5  
1.2 Name and Description of Investigational Product or Intervention 
The intervention will be a three-arm randomized control trial that assesses the effects of 
different strategies for withdrawing financial incentives for ICS use targeting a cohort of 
children with multiple asthma hospitalizations in the preceding year. The intervention 
leverages mobile health technology to provide a daily cue (reminder message) and reward 
(feedback message with performance-based incentives) designed to reinforce routine ICS use. 
1.3 Selection of Drugs and Dosages 
No new medications will be prescribed as part of this intervention. We will use an FDA-
registered Class 1 device that affixes to most common inhalers to assess the use of currently 
prescribed ICS and rescue medication during the study interval.  
1.4 Relevant Literature and Data 
Improving adherence, particularly in high-risk populations, is challenging. Previous 
interventions to improve medication adherence have demonstrated effects that are modest, at 
best6,7; thus, several emerging areas of study have catalyzed reinvestment in adherence 
interventions. First, technology-enhanced reminder systems have demonstrated robust ICS 
adherence improvements in other countries.8–10 Second, adult interventions infused with 
financial and social incentives from behavioral economics have enhanced behaviors as varied 
as medication adherence to smoking cessation.11,12 Few studies, however, have attempted to 
leverage mobile health technology and incentive design to improve medication adherence in 
children with high-risk asthma.  
Two critical challenges limit the effectiveness of existing adherence interventions: (1) lack of 
knowledge of what it takes to engage high risk children and their caregivers, and (2) lack of 
enduring behavior change beyond the active intervention phase. Recent studies have begun to 
identify intervention components that tend to be more effective in engaging minority 
demographic groups13 and lead to sustained behavior change or habit formation.14 We recently 
conducted a pilot study of daily adherence reminders and feedback enriched with nominal 
financial adherence incentives ($1/day for 30 days for perfect adherence) in families of 
children ages 5-11 with 3 asthma hospitalizations in the prior year. Study enrollment (69%) 
and mean ICS adherence (80%) during the intervention month were robust; however, 
adherence dropped to 33% after incentives, reminders, and feedback ceased. These findings 
reveal that financial incentives are a compelling method to engage this high-risk asthma 
population in regular ICS use, but whether and how adherence can be maintained and lead to 
sustained high adherence trajectories is unknown in pediatric populations.   

 
  
 
 
 
2
1.5 Compliance Statement 
This study will be conducted in full accordance all applicable Children’s Hospital of 
Philadelphia Research Policies and Procedures and all applicable Federal and state laws and 
regulations including 45 CFR 46. All episodes of noncompliance will be documented. 
The investigators will perform the study in accordance with this protocol, will obtain consent 
and assent, and will report unanticipated problems involving risks to subjects or others in 
accordance with Children’s Hospital of Philadelphia IRB Policies and Procedures and all 
federal requirements. Collection, recording, and reporting of data will be accurate and will 
ensure the privacy, health, and welfare of research subjects during and after the study.  
2 
STUDY OBJECTIVES 
The purpose of the study is to automate a technology intervention to determine ICS adherence 
trajectories in children who are at high risk for asthma hospitalizations, identify potential 
mechanisms for adherence, and assess the efficacy and acceptability of the intervention among 
children and caregivers. 
2.1 Primary Objective (or Aim) 
The primary objective of this study is to determine the marginal effects of financial ICS 
incentives on adherence (1° outcome) and healthcare system use and costs (2° outcomes) in a 
prospective cohort of child-caregiver dyads. 
2.2 Secondary Objectives (or Aim) 
The secondary objectives are to: 
• Automate intervention delivery by developing a closed loop for electronic 
monitoring of ICS inhaler use and adherence incentive feedback. 
• Assess proposed mechanisms by which intervention strategy influenced adherence 
trajectory, including (1) participant self-efficacy, (2) medication responsibility, and 
(3) habit formation. 
• Explore caregiver and child perceptions of acceptability of intervention components 
and how they influenced adherence trajectory.  
3 
INVESTIGATIONAL PLAN 
3.1 General Schema of Study Design 
This is a three arm, randomized control trial study to assess the marginal effects of different 
strategies of financial incentives for ICS use targeting a cohort of children with high risk 
asthma.  
3.1.1 Screening Phase 
Potential subjects will be screened through the daily census listings for the inpatient units on 
the Epic medical record at CHOP using the protocol inclusion and exclusion criteria. Epic 
alerts and patient lists identifying high risk children with asthma will assist research staff in 
screening potential subjects. 

 
  
 
 
 
3
Eligible children and their caregivers will be recruited during an asthma hospital admission, 
whenever possible, or in the month following hospital discharge, if the study team is unable 
to reach the family during the hospitalization. In the latter circumstance or if the child is 
eligible through asthma related outpatient visits, the study team will contact eligible 
participants by phone and if the caregiver expresses interest, the study team will approach the 
caregiver and child for informed consent/assent at a follow-up visit or via phone, if in-person 
recruitment is not feasible.   
Parental/guardian permission (informed consent) and, if applicable, child assent, will be 
written on a physical copy of the consent form, when consent/enrollment takes place in person, 
prior to any study related procedures being performed. In the circumstance of telephonic 
enrollment, electronic consent via the REDCap platform will be obtained prior to any study 
related procedures.  
If subjects consent to enrollment, the Study Run-in Phase will begin on the day of enrollment.  
3.1.2 Run-in Phase (Month 0) 
 
The study will be broken down into three 
discrete phases: (1) Run-in (2) Experiment, 
and (3) Observation (Figure 2). During the 
Run-in phase, every caregiver-child dyad 
will have access to the inhaler sensor app 
and will receive electronic ICS use 
monitoring. ICS use will be monitored 
using an electronic sensor that affixes to 
their ICS inhaler and will remain through the 
study Observation phase. Participants will be 
sent 4 text messages, each designed to elicit a response from the caregiver about the study 
technology or the study itself. (See Appendix 1 for content of the Run-in text messages) 
Participants for whom any inhaler use data is transmitted to the study platform within the first 
2 weeks of the Run-in Phase AND reply to one or more of the 4 text messages sent from the 
study platform (“Responders”) will be randomized into one of three arms at the end of the 
Run-in phase. (see section 4.10 for details on procedures for “Non-responders”) The second 
two weeks of the Run-in Phase is designed to provide baseline adherence data.  
3.1.3 Experiment Phase (Months 1-3) and Observation Phase (Months 4-6)  
The three experimental conditions will be: financial incentives, adherence reminders, and 
feedback (Arm 1); adherence reminders and feedback without incentives (Arm 2); or 
electronic monitoring alone (Arm 3).  The financial incentives in Arm 1 will consist of 3 
months of fixed-ratio incentives for each ICS actuation (i.e. 25 cents per puff for children on 
4 daily ICS doses and 50 cents per puff for children on 2 daily doses), with a maximum of $1 
per day. With regard to the reminders and feedback in Arms 1 and 2, study participants will 
receive automated daily text message or push notification reminders and automated weekly 
feedback summarizing their adherence performance through Way to Health, a mobile health, 
electronic monitoring platform (described below in section 4.1). At the end of the first month 
of the experiment phase, families will be contacted by study staff to complete a follow-up 
survey that will reassess disease control, medication supply, and intentions and behaviors with 
Figure 2: Study schema for proposed RCT 

 
  
 
 
 
4
regard to ICS use (study visit 2). After the experiment interval, families will be contacted 
again by study staff to complete a follow-up survey and a semi-structured interview (study 
visit 3). At this point, all reminders, feedback, and incentives will cease, but daily ICS use 
monitoring will continue with the electronic sensors for all study arms (Observation phase) to 
assess for enduring effects. There will be a fourth study visit in the 7th study month, when 
study surveys will be completed, and a fifth and final study visit at one year assessing asthma 
control and health care utilization outside of the CHOP system.  
For participants receiving adherence incentives in the experiment phase, accrued incentive 
value will be summed at the end of each 30-day interval (maximum $30) and added to a debit 
card that will be provided to the child upon enrollment. In the experiment phase, children 
randomized to Arms 2 and 3 who have any actuations recorded in the experiment phase will 
receive a $10 disbursement at the end of each month of the Experiment phase. Children in all 
3 study arms will receive a $10 disbursement for each month during the Observation phase 
for which any adherence data (for the prior month) is transmitted to the platform. This 
compensation will not be contingent upon the participant’s ICS adherence. Separate study 
visit compensation ($20) will be provided to the caregiver after enrollment and the 4th study 
visit, as well as after follow-up visits/calls at two, four, and 12-months. 
3.1.4 Follow-up Phase 
After completion of the Observation interval, participants will enter into a follow-up phase. 
Participants will complete a brief final study survey at during months 12-13 with study staff. 
The study team will also assess the number of ED visits, hospitalizations, and oral steroid 
courses for asthma at CHOP over this time period within the CHOP EMR. Electronic 
monitoring of daily ICS medications will continue during the follow-up phase to assess for 
ongoing feasibility and acceptability of electronic monitoring, if the data is available.  
3.2 Allocation to Treatment Groups and Blinding 
Following consent, confirmation of eligibility, and the study Run-in phase (2-weeks to 
confirm that the participants’ technology is functioning appropriately and 2-weeks to collect 
baseline data on the participants’ adherence), patients will be assigned to one of three arms 
for the Experiment phase of the study using a 2:1:2 randomization scheme.   
3.3 Study Duration, Enrollment and Number of Sites 
3.3.1 Duration of Study Participation 
The study duration will be up to 13 months, beginning with screening and enrollment on day 
1 and continuing through the study completion visit at the end of the follow-up period at 12-
13 months.  
3.3.2 Total Number of Study Sites/Total Number of Subjects Projected 
The study will be conducted at CHOP alone. 
We plan to enroll approximately 125 child-parent dyads. For our funder, enrollment will be 
reported as randomization into experiment phase. 

 
  
 
 
 
5
3.4 Study Population 
3.4.1 Inclusion Criteria 
1) Males or females age 5 to 12 years and their parent or legal guardian.   
2) Caregiver has an app enabled cellular phone (i.e., smartphone) 
3) Prescribed inhaled corticosteroid or corticosteroid/long acting beta agonist combination 
for daily use 
4) At least 2 asthma exacerbations in the preceding year (Any combination of 
hospitalizations, ED visits, or outpatient visits where oral steroid courses were 
administered for asthma)  
5) Parental/guardian permission (informed consent) and if appropriate, child assent. 
3.4.2 Exclusion Criteria 
1) Subjects prescribed a controller medication to which the electronic device cannot affix: 
AirDuo (and generic AirDuo), QVAR Redihaler, Asmanex Twisthaler  
2) Subjects in which the mobile app is not compatible with their smartphone model 
3) Subjects with major developmental delays or disabilities 
4) Subjects with comorbid chronic diagnoses that influence their asthma management such 
as cystic fibrosis, bronchopulmonary dysplasia, or cyanotic heart disease 
5) Families with active Department of Human Services (DHS) involvement 
6) Non-English speaking families  
7) Parents/guardians or subjects whose medical team recommends against approaching for 
enrollment in a research study. 
Subjects that do not meet all of the enrollment criteria will not be enrolled. Any violations of 
these criteria must be reported in accordance with IRB Policies and Procedures.  
4 
STUDY PROCEDURES 
4.1 Technology Integration 
To automate the computation of daily ICS adherence incentives and feedback for our study, 
we will first create a closed data loop connecting ICS puff actuation data from the electronic 
inhaler sensor and mobile health app with the Way to Health (WTH) platform. WTH is an 
NIH-sponsored, web-based platform that automates many of the research functions necessary 
for conducting randomized controlled trials of behavioral incentives. It has been used in 
numerous prior research studies.15–17 We will obtain the application programming interface 
(API) of the electronic inhaler actuation sensor (developed by Propeller Health, a sensor 
company with whom we have worked previously). We will work with WTH staff to program 
the computation of ICS adherence incentives and language of weekly adherence feedback 
messages to study participants. This integrated infrastructure will facilitate transmission of 
daily adherence data from the inhaler sensor platform to Way to Health via the sensor API. 

 
  
 
 
 
6
Way to Health will use the adherence data to automatically tabulate financial incentives and 
send weekly adherence feedback messages to participants. We will collaborate with the 
engineering teams at WTH and Propeller to develop this integrated infrastructure. The WTH 
team has previously integrated 11 devices similar to this sensor for prior research studies.  
4.2 Screening Visit (Visit 1) 
• Note: For some participants Visit 1 may be completed in the hospital or at a follow-
up visit in the month following hospitalization. This will be done 1) to accommodate 
participants’ preferences and scheduling, and 2) to ensure that electronic monitors 
are provided when the child’s asthma control inhaler is available for the device to be 
attached. For participants enrolled after physical distancing measures set in place for 
COVID-19, Visit 1 may be completed over the phone. This will be done 1) to ensure 
the safety of participants and study personnel, and 2) in accordance with hospital 
policy preventing study personnel from approaching patients in the hospital. In this 
circumstance, electronic monitoring devices will mailed to participants following 
telephonic enrollment.  
• Informed Consent 
• Epic Medical Record Review 
• Study visit 1 survey question blocks (see section 4.11.2)  
• Dispense and explain use of electronic monitoring devices  
• Download and set up inhaler sensor app  
4.3 Study Run-in Phase (Phase 1) 
The study run-in phase will begin once families complete the screening visit. A study team 
member will instruct the family to use the inhaler as directed by their physicians and to care 
for the child’s asthma as directed by the child’s physicians.  
Data collected during the study visits will be stored on the secure WTH web-based platform. 
Adherence monitoring data will be stored on the secure Propeller Health web-based 
platform and downloaded to WTH in real-time through the integrated API (see Section 7.2: 
Data Collection and Management for full descriptions of the WTH and sensor platforms, as 
well as the data management plan details). 
4.4 Study Experiment Phase (Phase 2) 
The child-caregiver dyads will be randomized into one of three arms for months 1-3: (1) 
receiving daily reminders, weekly feedback, and incentives, (2) receiving reminders and 
weekly feedback without incentives, or (3) receiving no reminders, feedback, or incentives. 
Participants will not know which group they are randomized to until they begin this phase of 
the study. Study participants will be contacted by telephone call or text message to inform 
them to which study arm they were randomized. At this time, study staff will help participants 
randomized to Arm 1 select an adherence reward goal of $30 value.  

 
  
 
 
 
7
4.5 Visit 2 (clinic or home preferred, telephone if not possible) – month 2 
• Study visit 2 survey question blocks (see section 4.11.2)  
• Equipment and medication refill check  
4.6 Visit 3 (clinic or home preferred, telephone if not possible) – month 4 
• Study visit 3 survey question blocks (see section 4.11.2)  
• Semi-structured interview on intervention experiences and preferences 
• Equipment and medication refill check  
4.7 Study Observation Phase (Phase 3) 
During months 4-6, all three arms will be in the observation phase, in which none of the 
participants receive reminders, feedback, or adherence-contingent incentives.  
4.8 Visit 4 (clinic or home preferred, telephone if not possible) – month 7 
• Study visit 4 survey question blocks (see section 4.11.2)  
4.9 Visit 5 (clinic or telephone) – month 12-13 
• Study visit 5 survey question blocks (see section 4.11.2) 
4.10 Subject Completion/Withdrawal 
Because the study intervention is dependent on functioning cellphone-sensor-platform data 
connection, subjects for whom the research staff cannot establish a functional adherence 
data feed and two-way text message communication with-in two weeks of enrollment will 
not be randomized by study staff. Specifically, these “non-responders”, for whom no 
electronic adherence data is transmitted and do not reply to any of the 4 text messages sent 
during the first two weeks of the Run-in Phase, will not undergo randomization and enter 
into the Experiment or Observation Phases. This criteria for randomization will be explicitly 
stated in the study informed consent form. Participants will be informed that their data from 
the Electronic Health Record can still be accessed and used as part of this research and data 
collection until the study ends. In order to take back this permission, participants must 
inform the study team of their wish to withdraw from the study. 
Additionally, subjects may withdraw from the study at any time. They may also be 
discontinued from the study at the discretion of the Principal Investigator for inappropriate or 
threatening behavior with study staff.  
4.10.1 Early Termination Study Visit 
Subjects who withdraw from the study will have all procedures enumerated for Visit 1, 2, 3 
or 4 as the early termination visit.  Participants who withdraw from the study prior to 
completion will have the option to have their earlier responses redacted from the database. If 

 
  
 
 
 
8
participants choose this option, any data collected in study visits 1-4 will be excluded from 
subsequent analysis.  
4.11 Screening and Monitoring Evaluations and Measurements 
4.11.1 Medical Record Review 
Variables to be abstracted from the medical chart: 
• Child sex 
• Date of birth 
• Weight and height  
• Date of qualifying hospital admission and discharge  
• Asthma severity  
• Last spirometry result and date of assessment (if reported) 
• Name and dose of current asthma medications (both controllers and rescue) 
• Number of prescriptions and refills in the prior year for each asthma medication   
• Number and date of ED visits, hospitalizations, and oral steroid courses for asthma in 
the preceding year 
• Number and date of ED visits, hospitalizations, and oral steroid courses for asthma 
during the 13-month study period 
4.11.2 Other Evaluations, Measures 
The following instruments (or question blocks from the following instruments) will be used 
to assess key constructs at each study visit:   
• Child and parent self-efficacy, measured using the Child and Parent Asthma 
Management Self Efficacy scale18,  
• Parent/child responsibility for asthma care measured using the Asthma 
Responsibility Questionnaire19, 
• ICS habit strength, measured using the Habit Strength Index adapted for asthma 
controller use20.  
4.12 Efficacy Evaluations 
We will collect a number of efficacy outcomes including parent reported asthma control and 
use of prescribed medicine over the study interval.  

 
  
 
 
 
9
4.12.1 Diagnostic Tests, Scales, Measures, etc. 
• Child Asthma Control Tool (cACT) 
• Daily Medication adherence – calculated as the mean daily proportion of prescribed 
doses taken by study month. Days that reflect >1 will be truncated to 1. 
4.13 Safety Evaluation 
Subject safety will be monitored by adverse events. 
4.14 Primary Endpoint 
The primary outcome will be adherence to ICS regimen both during the Experiment interval 
(months 1-3). Adherence over these study intervals will be characterized as a daily observed-
to-prescribed ICS adherence proportion averaged by study month. To operationalize this, a 
daily medication use log composed of 180 sequential ICS use observations will be generated, 
representing the count of ICS doses taken each day of study enrollment. These daily counts 
will be converted into proportions by dividing by the daily prescribed dose and imposing an 
upper limit of 1 in order to prevent doses taken above the prescribed limit – either during the 
use of flare plans or attempted “gaming” of the incentives by the participants – from 
influencing interval adherence estimates. Observed actuations will be quantified using 
electronic sensors.  
4.15 Secondary Endpoints 
Secondary endpoints will include the following: 
• Adherence to ICS regimen in Observation interval (months 4-6) 
• Adherence trajectory, as determined by group-based modeling of adherence patterns. 
• Change in cACT score from first study visit to the second, third, fourth, and fifth study 
visits.  
• Number of asthma-related emergency room visits, hospitalizations, and oral steroid 
courses between study conditions. 
• Healthcare costs associated with emergency room visits, hospitalizations, and oral 
steroid courses between study conditions. 
• Continued use of sensors in 7-13 month follow-up period (feasibility outcome)  
Health system use outcomes will be assessed primarily using CHOP electronic health record 
data and, secondarily, via caregiver report to account for utilization that may have occurred 
outside of CHOP. ED visits, hospitalizations, and oral steroids courses will be characterized 
as asthma-specific using existing, validated asthma registry definitions that include asthma 
visit diagnoses, medication orders, and asthma pathway order set activation. Costs will be 
estimated using average insurance payments for asthma ED visits, hospitalizations, and oral 
steroid courses in addition to the costs of the intervention components (i.e. sensors, incentive 
value, and research staff support).  
 

 
  
 
 
 
10
4.16 Statistical Methods 
4.16.1 Baseline Data  
Baseline and demographic characteristics will be summarized by standard descriptive 
summaries (e.g. means and standard deviations for continuous variables such as age and 
percentages for categorical variables such as gender). 
4.16.2 Efficacy Analysis 
We will assess the effectiveness of randomization by comparing the study arm balance on key 
demographic, clinical, and past health care utilization variables using analysis of variance 
(ANOVA) and t-tests or the nonparametric equivalent for continuous variables and chi-square 
tests or Fisher exact tests for categorical variables. 
Primary analysis: Our primary outcome will be monthly ICS adherence in months 0-3 
(Experiment Phase). Secondary outcomes will include monthly ICS adherence in months 4-6 
(Observation Phase), asthma control at the end of the Experiment and Observation period. 
Secondary outcomes will also include monthly ICS adherence in months 7-13 (follow up 
period) to assess feasibility and acceptability of longer durations of electronic monitoring. We 
will consider arcsine transformation on the ICS adherence outcomes as necessary. This 
technique is commonly used for proportion data. We will use generalized estimating equations 
(GEE) to adjust for within-subject correlations due to repeated measures for the study’s 
primary and secondary monthly adherence outcomes. Models will include main effects for 
arm and time (month) and arm-by-month interaction terms to allow for differing ICS 
adherence over time between arms. The dependent variable of monthly ICS adherence will be 
defined as mean daily observed-to-prescribed ICS actuation proportion for each study month. 
Mean daily adherence proportion will be capped at 1, such that participants taking more than 
their prescribed daily dose cannot receive “extra credit” for doses taken on those days. All 
statistical tests will be 2-sided. A P-value <0.05 will be considered statistically significant.  
Secondary analysis: We will construct adherence trajectories for the combined Experiment + 
Observation interval for each study participant using group based trajectory modeling 
(GBTM). This modeling approach accounts for changing behavior over time and allows for 
identification of several distinctive developmental progressions without imposing the 
requirement that they vary normally about the population mean.21,22 Thus, participants with 
similar daily adherence trajectories are grouped about 
similar longitudinal trends and the model output is 
probabilistic assignment of each individual to one of 
several (up to six) adherence groups. Based on group-
based modeling research on medication adherence from 
other conditions, anticipated ICS trajectory groupings 
will likely include: (1) severe early non-adherence, (2) 
severe delayed non-adherence, (3) moderate or episodic 
non-adherence, and (4) sustained adherence.23,24 (See 
Figure 3 for a preliminary 3-group ICS adherence 
trajectory model from our prior work.) Adherence 
group/category will then become the dependent variable 
for subsequent analysis in which a multinomial or 
ordered logistic regression will be applied with treatment 
arm as the exposure, adjusting for the covariates 
Figure 3: 30-day post-discharge ICS adherence trajectories. 
(From Kenyon, et al. J Asthma. 2018.) 

 
  
 
 
 
11
described above. For each adherence trajectory group, relative risk ratios for arms 1 and 2 
compared to arm 3 will be calculated. We will test for overall effect of treatment arm on 
adherence trajectory in addition to important permutations (i.e. Arm 1 compared to Arm 3 
within sustained adherence trajectory) using chi-square tests and generate marginal estimates 
of the probability of trajectory group membership, given treatment arm assignment (e.g. the 
probability of being in the sustained trajectory group if randomized to Arm 1 vs Arm 2 vs 
Arm 3). Findings presented alongside the primary analysis of observed-to-prescribed interval 
adherence percentage.    
 
4.17 Sample Size and Power 
Our analysis of pilot data demonstrates a 48% difference in ICS adherence when comparing 
a time interval with financial incentives (the same schema proposed in this study) to a time 
period without incentives. To ensure a power of 80% at a significance level of 0.05 to detect 
a more conservative 30% difference in average adherence between arms 1 and 3 in the 
Experiment phase (corresponding to 65% and 35%, respectively), 40 patients are required in 
each of these two arms. To ensure scientific rigor given the vulnerable nature of the 
population, we estimate ~20% loss to follow-up. Therefore, we will aim to enroll 50 
participants in study arms 1 and 3 and 25 participants in arm 2, or 125 participants total, to 
achieve sufficient power to detect a difference between arms 1 and 3. The study is not to be 
powered to detect differences in arms 1 to 2 or 2 to 3 (hence the 2:1:2 randomization schema) 
or for health outcomes or cost offset; rather, it is intended to obtain preliminary estimates of 
marginal effects of the intervention components and effect sizes on utilization outcomes by 
comparing arm 1 to 2 and 2 to 3 to power a future multicenter study. Baseline data reveals 
that ~50% of children with at least 2 prior hospitalizations have a repeat ED visit or inpatient 
stay 6 months after the 2nd hospital discharge. 
4.18 Additional analyses 
Hypothesis 1.2 Longer time intervals to next asthma-related ED or inpatient visit, and reduced 
healthcare use and costs, will be observed in Arm 1 compared to Arms 2 and 3 (and in Arm 2 
compared to Arm 3). 
Time to next asthma-related ED or inpatient visit from enrollment will be first modeled using 
the Kaplan-Meier plots. Study arms will be compared using log-rank tests and unadjusted Cox 
proportion hazards models. Adjusted hazard models will include the additional covariates 
described above and the Anderson-Gill method will be used to account for recurrent events. 
Total medical costs will be estimated for the 12 months following study enrollment, 
accounting for each asthma-related ED visit and hospitalization, as well as the expenses 
incurred with study participant incentives, sensors, and use of the WTH automated platform. 
We predict that intervention will reduce medical costs, thereby contributing to a cost offset. 
We will estimate potential savings in medical costs by calculating the difference in average 
total medical costs minus study-related expenses between study arms.  

 
  
 
 
 
12
Aim 2. Assess proposed mechanisms by which intervention strategy influenced 
adherence trajectory. 
Aim overview: The broad goal 
of this aim is to assess which 
participant 
and 
study 
characteristics are associated 
with 
different 
longitudinal 
adherence 
trajectories. 
Characteristics to be examined 
include baseline factors (demographic, clinical, and prior health utilization factors), 
intervention strategy (study arm), and potentially modifiable behavioral characteristics. Of 
specific interest is how intervention strategy in the Experiment phase (study arm) influences 
child asthma self-efficacy, shared medication responsibility, and medication habit over time 
and how these characteristics vary with longitudinal ICS adherence trajectories. [Figure 4] 
Hypothesis 2: Increases in (1) participant self-efficacy, (2) shared medication responsibility, 
and (3) habit score will partially mediate the relationship between study arm and sustained 
adherence trajectory. 
ICS adherence trajectories will be characterized using group-based trajectory modeling 
(GBTM). GBTM is an analytic technique used to identify and characterize differential 
patterns of changing behavior over time in a population of interest. In GBTM, an individual 
is assumed to belong to only one group, of which each group has its own trajectory. I will 
specify several models with different number of groups (e.g. 2 to 5) using quadratic 
trajectories (or possibly higher order polynomials) and compare these models to identify the 
one that best fits our ICS use data based on both the Bayesian information criterion and group 
percentages that are sufficiently large (e.g. >5% of the entire sample) to ensure study power 
as well as model stability. The group-based trajectory modeling will be performed using 
PROC TRAJ macro implemented in SAS (SAS 9.3).  
Once adherence trajectory groups have been determined, I will first use bivariate multinomial 
or ordered logistic regression models to estimate odds ratios (ORs) for the three predictors of 
interest, as well as baseline demographic, clinical, and health utilization characteristics, on 
trajectory group membership. When applying the ordered logistic regression, I will check the 
proportional odds assumption using the Brant test. All variables that are not marginally 
predictive of any trajectory group in bivariate analyses (P-value>0.2) will not be included in 
the multivariable analysis. I will then construct a final multivariable multinomial regression 
model of trajectory of all marginally predictive covariates, first including (1) baseline 
demographic and clinical characteristics, then (2) study arm, and lastly, (3) the three 
hypothesized potential mechanisms.7 Mediation analysis will be conducted with variables 
associated with both study arm and trajectory membership. Covariance matrices will be 
generated and regression estimates standardized to obtain an overall mediated effect of each 
potential mechanism variable (e.g. child self-efficacy) on each study arm. The percentage of 
the total effect of study arm that is mediated by child self-efficacy, for instance, will be 
calculated using standardized beta estimates.8 If self-efficacy, shared responsibility, and habit 
index are not associated with study arm or adherence trajectory, I will then assess the 
additional behavioral constructs described in the “Covariates” section (medication beliefs, 
Sustained 
adherence 
trajectory 
self efﬁcacy,        
shared responsibility, 
medication habit
Mechanisms (Aim 2)
Study arm
Figure 4: Potential mechanisms for study arm effect on adherence trajectory    

 
  
 
 
 
13
descriptive and injunctive norms, and current asthma symptom burden) as potential alternative 
mediators.  
Aim 3. Explore caregiver and child perceptions of acceptability of intervention 
components and how they influenced adherence trajectory. 
Aim overview: The final aim will use data from the semi-structured interviews conducted at 
the 6-month visit in a randomly selected subset of study participants to gain in-depth insight 
into the family and child experience of the intervention components with particular attention 
to perceived influence, or lack of influence, of the ICS adherence incentives on adherence 
behavior. In addition, we will explore other factors children and caregivers perceived as 
influencing their daily ICS adherence. Interview prompts will include the perceived impact of 
the intervention components (financial incentives, adherence reminders, adherence feedback, 
study app, electronic monitoring), component design factors (duration of incentive exposure, 
duration and frequency of reminders and feedback, child and caregiver engagement strategies, 
and potential alternative incentive strategies), and non-intervention factors (medication 
access, perceived medication efficacy, and family and social circumstances). Using the 
trajectory groupings derived from the prior aims, we will then assess whether themes differ 
between families of children with different daily use trajectories. 
Semi-structured interviews will be audio-recorded. Audio files will be transcribed verbatim. 
Field notes and interview transcripts will be uploaded to NVivo 12 software. Co-mentor Dr. 
Victoria Miller will help train a research assistant to assist in the coding of data. We will use 
inductive theory-building9 and the constant comparative method10 to identify data patterns. 
We will first read through all documents using open coding to record salient themes that 
emerge that will be further refined during axial coding in a second stage. At this stage, we will 
begin to generate explanations for emerging patterns in the data. After generating a draft code 
list, we will review interview transcripts and our field notes to determine which codes fit the 
concepts suggested by the data. As we discover themes and patterns, we will consistently 
search for negative cases within the data to refine our analysis.11 Coding discrepancies will be 
logged and discussed by myself, co-mentor Dr. Miller, and the research assistant to examine 
reasons for the discrepancy, to inform theory and interpretation of the data, and refine analytic 
procedures.  
We will then use trajectory group membership from the prior aims to categorize participants 
into sustained ICS versus non-sustained trajectory and explore the ways in which perceived 
intervention effects and experiences differ between these groups. If the distribution allows, 
we will attempt further categorization of the non-sustained group into specific trajectory 
grouping (i.e. severe early non-adherence, intermittent adherence, etc). 
 

 
  
 
 
 
14
5 
STUDY MEDICATION (STUDY DEVICE OR OTHER STUDY INTERVENTION) 
5.1 Description 
There is no study medication or device that is being evaluated in this study. Rather, the 
reminder, feedback, and incentive intervention described above will be the subject of 
investigation. In order to capture ICS medication use, we will use an electronic sensor device 
(described below) that attaches to the exterior of the ICS inhaler and transmits pressure-
activated device actuation data via Bluetooth to a mobile phone app. The Propeller sensors 
(Propeller, Madison, Wisconsin) are FDA 510k cleared, portable device attaches onto a 
patient’s asthma medication (see exclusion criteria in section 3.4.2 for a list of medications 
that are not compatible with the Propeller sensor). These devices record the time and date of 
each inhaler actuation and transmit this information via Bluetooth to either a smartphone or 
hub. Data is then sent via the cellular network to the secure Propeller server. The data will 
then be transmitted onto the secure, password-protected Way to Health platform through the 
integrated API.    
 
6 
SAFETY MANAGEMENT 
6.1 Clinical Adverse Events 
Clinical adverse events (AEs) will be monitored throughout the study. However, since this is 
a minimal risk study, we do not expect clinical adverse events to be related to study 
procedures. 
6.2 Adverse Event Reporting 
Since the study procedures are not greater than minimal risk, SAEs are not expected. If any 
unanticipated problems related to the research involving risks to subjects or others happen 
during the course of this study (including SAEs) they will be reported to the IRB in accordance 
with CHOP IRB SOP 408: Unanticipated Problems Involving Risks to Subjects. SAE and AE 
reporting are summarized in the DSMP in Appendix 2. 
7 
STUDY ADMINISTRATION 
7.1 Treatment Assignment Methods 
7.1.1 Randomization 
At the time of enrollment, patients will be assigned to one of three arms using a 2:1:2 block 
randomization scheme with a block size of 50.  Randomization will be accomplished 
automatically by the Way to Health web-based platform. During the Run-in interval of the 
study, every caregiver-child dyad will receive electronic ICS use monitoring. Participants for 
whom we received any adherence monitoring data and at least one text message reply by the 
end of week 2 will be randomized into one of three experimental conditions at the end of the 
Run-in period. 
Participants will be randomized using block randomization, so arms 1 and 3 will have 
approximately equal sample sizes and arm 2 will have approximately half the number of 

 
  
 
 
 
15
participants(as the study is powered to detect a difference between arms 1 and 3). A total n of 
125 will be randomized, with a recruitment goal of about 50 in arms 1 and 3 and 25 in arm 2. 
7.1.2 Blinding 
Only the PI (Dr. Kenyon) and the statistics team will remain blinded to the assignment of 
study arm. Neither the subjects nor the study team will be blinded to the study conditions, 
given that the intervention groups will be receiving incentives and/or reminders (whereas the 
control group will not) and the study team will provide monthly incentive payments and help 
facilitate tech support based on the study arm. 
7.2 Data Collection and Management 
Each study subject will be assigned a study ID at the time of enrollment, which will serve as 
the means of protecting personal health information during data transfers and storage. These 
master study IDs will be kept in a separate CHOP network folder from the datasets and will 
be retained for at least 6 years according to CHOP policy A-3-9.   
Epic medical record and study questionnaire data will be entered directly into the Way to 
Health platform (in the case of patient identifiable information) or on a paper form during the 
study visits. Coded electronic adherence data will be transferred electronically from the 
Propeller Health Platform to the Way to Health Platform via the API of the Propeller sensor.  
An additional data transfer will be used to extract a coded analytic data set to the secure CHOP 
research server for analysis. All databases created will be password-protected and only study 
team members will have access. All data sets downloaded through the Propeller Health or 
Way to Health platforms will be password-protected and stored on the CHOP secured network 
drive, only accessible to study team members. For a summary of data entry and transfer, refer 
to Figure 4 below. 
 
Way to Health Platform: 
Propeller Platform 

 
  
 
 
 
16
Research material will be obtained from participant surveys entered directly into the Way to 
Health portal, and from the data transmitted from Propeller Health’s device trackers to the 
WTH platform via the integrated API. Research material that is obtained will be used for 
research purposes only. The same procedure used for the analysis of automated data sources 
to ensure protection of patient information will be used for the survey data, in that patient 
identifiers will be used only for linkage purposes or to contact patients. The study 
identification number, and not other identifying information, will be used on all data collection 
instruments. All study staff will be reminded to appreciate the confidential nature of the data 
collected and contained in these databases. The Penn Medicine Academic Computing Services 
(PMACS) will be the hub for the hardware and database infrastructure that will support the 
project and is where the Way to Health web portal is based. The PMACS is a joint effort of 
the University of Pennsylvania's Abramson Cancer Center, the Cardiovascular Institute, the 
Department of Pathology, and the Leonard Davis Institute. The PMACS provides a secure 
computing environment for a large volume of highly sensitive data, including clinical, genetic, 
socioeconomic, and financial information. Among the IT projects currently managed by 
PMACS are: (1) the capture and organization of complex, longitudinal clinical data via web 
and clinical applications portals from cancer patients enrolled in clinical trials; (2) the 
integration of genetic array databases and clinical data obtained from patients with 
cardiovascular disease; (3) computational biology and cytometry database management and 
analyses; (4) economic and health policy research using Medicare claims from over 40 million 
Medicare beneficiaries. PMACS requires all users of data or applications on PMACS servers 
to complete a PMACS-hosted cybersecurity awareness course annually, which stresses federal 
data security policies under data use agreements with the university. The curriculum includes 
Health Insurance Portability and Accountability Act (HIPAA) training and covers secure data 
transfer, passwords, computer security habits and knowledge of what constitutes misuse or 
inappropriate use of the server. We will implement multiple, redundant protective measures 
to guarantee the privacy and security of the participant data. All investigators and research 
staff with direct access to the identifiable data will be required to undergo annual responsible 
conduct of research, cybersecurity, and HIPAA certification in accordance with University of 
Pennsylvania regulations. All data for this project will be stored on the secure/firewalled 
servers of the PMACS Data Center, in data files that will be protected by multiple password 
layers. These data servers are maintained in a guarded facility behind several locked doors, 
with very limited physical access rights. They are also cyber-protected by extensive firewalls 
and multiple layers of communication encryption. Electronic access rights are carefully 
controlled by University of Pennsylvania system managers. We will use highly secure 
methods of data encryption for all transactions involving participants’ financial information 
using a level of security comparable to what is used in commercial financial transactions. We 
believe this multi-layer system of data security, identical to the system protecting the 
University of Pennsylvania Health Systems medical records, greatly minimizes the risk of loss 
of privacy. In addition, risk of loss of confidentiality will be minimized by immediately 
destroying paper copies of surveys after entering data into the WTH platform. Each subject 
will be assigned a unique identifier without identifying information, and data will be entered 
into an electronic database using only the unique identifier. Only trained study staff will have 
access to the code that links the unique identifier to the subject’s identity. Electronic data will 
be stored on secure, password-protected firewalled servers at the University of Pennsylvania 
and Children’s Hospital of Philadelphia. 
WTH uses a role-based access control (RBAC) approach to assure that participant 
confidentially and study integrity is preserved. Principle investigators and statisticians are 

 
  
 
 
 
17
restricted using RBAC, with a role that provides them access to coded data sets only. Other 
staff such as project managers and research coordinators require access to identifiable data in 
order to conduct normal study operations such as follow up study visits, monitoring 
enrollment statuses, and updating contact information. These roles can toggle between 
identified and coded views as needed. Prior to receiving access to the platform, the study’s 
project manager must confirm that the staff person has been added to the IRB and has 
completed their CITI Protection of Human Subjects Research Training – ORA. Research staff 
users must read and sign the WTH Data Security Agreement upon initial login to the platform. 
They cannot access PHI or any other data on the platform until that agreement has been 
reviewed and signed. 
The WTH Team supports all research studies run on the platform. Default views within the 
platform for all WTH staff display coded participant data. As a part of support and 
troubleshooting, the WTH Team is trained to use only these coded views. In rare cases where 
the issue involves viewing identifiable participant data, the WTH team may need to view this 
data to assist the study team. 
The WTH Team are employees of the University of Pennsylvania and Penn Medicine. All 
WTH team members have completed HIPAA Security training and CITI Protection of Human 
Subjects Research Training - ORA.   
Access to the backend database is restricted and only available to a select group of developers. 
The database is accessible only via a secure VPN (Virtual Private Network) and cannot be 
accessed from the public internet at all, i.e. authorized users can only access the databases 
from within Penn’s network and over a secure VPN channel.  
To maximize security, WTH assumes that all data in the system is electronic protected health 
information (ePHI). All data at-rest is stored on encrypted disks using encryption keys 
managed by WTH. Encrypted disks use AES encryption with a minimum of 256-bit keys, or 
keys and ciphers of equivalent or higher cryptographic strength. User passwords are never 
stored in clear text; they are “salted” and “hashed” to eliminate data leakage. All data 
transmission is encrypted end to end using encryption keys managed by WTH. Transmission 
encryption keys use a minimum of 2048-bit RSA keys, or keys and ciphers of equivalent or 
higher cryptographic strength (e.g., 256-bit AES session keys in the case of IPsec encryption). 
Data downloads are generally prohibited by policy. Where appropriate, most datasets are 
blinded of all personally identifiable information when exported for analysis. A limited 
number of exports including identifiers exist to assist research staff with recruitment tracking 
and study management efforts. These datasets are only accessible to certain user roles. These 
user roles are required to sign and adhere to a WTH Security Agreement as described above 
To monitor ongoing usage of the system and identify unauthorized usage of the system, all 
access to the application and the database are logged automatically. These logs are reviewed 
as described in the WTH policies.  
WTH has automated procedures to create and maintain retrievable exact copies of ePHI 
utilizing our Backup Service. These backup procedures are run on a daily basis and stored in 
a different location. Backups are encrypted. Backups are retained for a rolling 14 day period. 
Recovery from backups is also tested on a quarterly basis.  

 
  
 
 
 
18
Security is a paramount concern at WTH. We perform regular (at least monthly) vulnerability 
scans of our systems to identify and patch any known vulnerabilities in our systems. We also 
run Intrusion Detection Systems (IDS) to identify unauthorized system access. 
1) Questionnaire Data: 
This study will use Way to Health’s online survey tool to collect answers to survey questions 
from participants. Survey answers will be entered by the study team member and are stored 
on the Way to Health platform. Study staff members review the survey content to ensure that 
no questions in any of the surveys ask for patient identifiers. If there are problems connecting 
to the internet for questions to be completed on a laptop computer, a paper form of the WTH 
surveys will be used. All paper surveys will be recorded in WTH at the earliest possible 
convenience by study staff. Paper forms will be inserted into a locked box for materials to be 
shredded once information is entered and confirmed into WTH.  
2) Electronic Adherence Data (Propeller Health sensor and platform): 
Following activation of the electronic monitoring device, time-stamped data is transferred 
from the electronic monitoring device via Bluetooth to a smartphone or cellular modem, which 
then sends it via the cellular network to the Propeller platform. The cellular upload identifies 
the patient only by a unique identifier. The cellular transmission has no patient-identifying 
information and no IP addresses are collected during this information transfer. The coded daily 
adherence data will then be available to the study team on the secure, password-protected 
Propeller provider platform. 
Data collected in Propeller are stored within a US HIPAA compliant system, meaning that 
personal health information is protected during capture, during transmission to the server, 
and when on the server. Propeller has been certified to offer industry leading policies and 
controls for data protection under the HITRUST framework. For more information, anyone 
(including patients and providers) can visit https://www.propellerhealth.com/privacy-policy/ 
Propeller HIPAA Adherence statement: 
Data collected in Propeller are stored within a US HIPAA compliant system, meaning that 
personal health information is protected during capture, during transmission to the server, and 
when on the server. Propeller has been certified to offer industry leading policies and controls 
for data protection under the HITRUST framework. For more information, anyone (including 
patients and providers) can visit https://www.propellerhealth.com/privacy-policy/ 
 
3) Epic Medical Record Data: 
Study staff will extract asthma-related primary care, ED, and hospital data points (see Section 
4.11.1 for specific data points to be extracted) from Epic into Way to Health via individual 
chart review. Individual patient data will be labeled with the patient’s study ID upon 
population of Way to Health for subsequent storage and data analysis. 
4) Semi-structured interviews:  

 
  
 
 
 
19
Semi-structured interviews will be recorded via two-way microphones. Recordings will be 
uploaded to a secure site for transcription (by ADA transcription service; agreement in place 
for this study).  Then transcripts will be downloaded to our secure CHOP network drive and 
uploaded into NVivo, a qualitative software program that meets CHOP’s IT standards for 
security, for coding and analysis.  
Data Transfer Description 
1.)  Propeller platform to Way to Health platform: coded study adherence data will be 
transferred from Propeller Health to the Way to Health platform through the integrated API.  
This file will contain no PHI, only the subjects’ study ID. Way to Health will use the adherence 
data to automatically tabulate financial incentives and send weekly adherence feedback 
messages to participants. 
2.)  Way to Health to CHOP Server: Coded data from the study visits, including initial survey, 
follow-up surveys, and electronic adherence data will be converted to a CSV file and uploaded 
onto the CHOP server to a dedicated research folder on the study PI’s virtual desktop. No PHI 
will be involved in this transfer, only the subject’s study ID.   
The Health Analytics Unit (HAU) will assist the study staff in converting these coded data 
from the CSV file to an analytic file for subsequent cleaning and analysis. All transferred and 
created files will be stored in a password-protected folder available only to study staff on 
CHOP’s secured shared network drive. The study key will be stored in a separate password 
protected folder assigned to this study. All identifiers will be deleted following publication of 
the study results. 
Study Recruitment Tracking File: 
Recruitment and enrollment tracking will be stored in a REDCap database, only available to 
study team members. This database will include patient identifying information necessary for 
registration, enrollment, and follow-up (see 9.6, waiver of HIPAA authorization).  Following 
enrollment, this database will be used to maintain a log of enrolled patients.  For families who 
are not enrolled, patient identifying information will be destroyed.  A non-identifiable list of 
patients that were not enrolled will be retained for the purpose of calculating response rate. 
Consent Forms: 
Consent will be obtained using a physical copy of the form if enrollment is conducted in 
person. REDCap electronic consent will be obtained if initial enrollment is conducted via 
telephone. Families will receive an electronic copy of the consent form that they will digitally 
sign. If consent is not obtained electronically, paper consent forms will be stored in a locked 
filing cabinet and retained per CHOP policy A-3-9.  
Anonymization: 
Data will be extracted from the secure WTH platform for the purpose of data analysis.  Any 
datasets and computer files that leave the WTH firewall will be stripped of all identifiers and 
individuals will be referred to by their study ID. The study ID will also be used on all analytical 
files. 

 
  
 
 
 
20
7.3 Confidentiality 
All data and records generated during this study will be kept confidential in accordance with 
Institutional policies and HIPAA on subject privacy and the Investigator and other site 
personnel will not use such data and records for any purpose other than conducting the study.  
Survey and interview responses will be stored on the WTH platform.  The site is HIPAA 
compliant.  Please see Section 9.2 for measures taken to assure confidentiality. 
Data regarding adherence to metered-dose inhaler use will be stored on the website of 
Propeller Health and transferred to the WTH platform through the integrated API.  The 
Propeller Health site is HIPAA compliant. Please see Section 7.2 for measures taken to assure 
confidentiality.  
No identifiable data will be used for future study without first obtaining IRB approval.  
7.4 Regulatory and Ethical Considerations 
7.4.1 Data and Safety Monitoring Plan 
Please see Appendix 2 for the DSMP for this study. A local DSMB has been appointed for 
this study with guidance from the Clinical Trials Office at the NHLBI. The PI has developed 
a number of additional strategies to ensure the accuracy, security, and validity of the various 
data sources. First, identifiable information will be converted to study ID for storage and 
analysis. Data extracted from the Epic medical record by the research assistant and the study 
questionnaire responses will be entered into and stored in the WTH platform at Penn by study 
ID. Coded adherence data from the Propeller platform will be downloaded to the WTH 
platform in data downloads through the API.  
Second, the data sources that will contain identifiable information, namely the Propeller and 
WTH platforms, will be held to the highest of security standards. Please see section 7.2 for 
the security features of the Propeller and WTH platforms.  
Please see section 7.2 for further details of the measures in place to protect data confidentiality, 
especially with respect to data transfers.  
7.4.2 Risk Assessment 
Risks are minimal.  There is no risk or discomfort to the study intervention.  The study 
intervention merely adds electronic monitoring and text message notifications to already 
prescribed medications. The main risk is breach of confidentiality.  Please refer to the above 
Sections 7.2, 7.3, and 7.4.1 for a list of strategies in place to avoid a breach of confidentiality. 
7.4.3 Potential Benefits of Trial Participation 
Improving adherence may lead to better control of asthma and therefore decrease school 
absences, parental work absences, and the number of visits to the ED or admissions to the 
hospitals.   
7.4.4 Risk-Benefit Assessment 
The risks of this study are minimal.  The main risk of the study is breach of confidentiality.  
Methods of avoiding a potential breach of confidentiality are described above in Sections 7.2, 
7.3, and 7.4.1.  The potential to improve asthma adherence may improve asthma control and 

 
  
 
 
 
21
decrease ED visits or hospital admissions for asthma.  The potential benefits of study 
participation outweigh the risks. 
7.5 Recruitment Strategy 
7.5.1 Recruitment Strategy 
Prospective subjects will be identified in the Epic medical record at CHOP. Patients with at 
least 2 asthma exacerbations (hospitalizations, ED visits, or outpatient visits where an oral 
steroid course was given for asthma) in the last year will be recruited from general pediatrics 
services. Epic alerts and patient lists will assist research staff in identifying eligible patients. 
Potential participants will be approached in-person by a trained study team member during 
the course of their hospital stay, at a hospital follow-up appointment, or by telephone.  No 
more than 125 subjects will be enrolled. 
7.5.2 Study Information Sheet 
The study information sheet will be used as a recruitment tool to give participants information 
about our study. It includes a brief overview of our study and our contact information for 
potentially interested subjects to contact us.  
7.6 Informed Consent/Assent and HIPAA Authorization 
Subjects will be approached in person while in the hospital, at a hospital follow-up 
appointment, or by telephone and given information about the study by a trained study team 
member.  Potential participants will not need to decide on participation right away; they may 
decide whether or not to participate up until the time of discharge from the hospital or end of 
their follow-up appointment.   
Electronic consent via the REDCap platform or written consent on a physical copy of the form 
will be obtained following agreement to participate in the study.  
To reduce low literacy barriers, the study team member will go through the consent form with 
the family and answer any questions pertaining to the material.  Participants will be given 10-
15 minutes to review the consent form on their own.  This process will be done in a HIPAA 
compliant manner.   
Assent will be obtained for children aged seven or older, as per the CHOP IRB regulations 
via the REDCap electronic consent platform or on a physical copy of the consent form. The 
study will be explained in an age-appropriate manner.  This process will be done in a HIPAA 
compliant manner. 
7.6.1 Partial Waiver/alteration of HIPAA Authorization 
We request a partial waiver of HIPAA authorization under 45 CFR 164.512(i.)(2)(ii).   
Study staff propose to assess patient eligibility by screening the daily census of patients 
admitted to a General Pediatrics service at CHOP for patients 5-12 who have an 
admission diagnosis of asthma and for whom the asthma pathway order is activated 
using the Epic medical record.   

 
  
 
 
 
22
(A) The use or disclosure of protected health information involves no more than a 
minimal risk to the privacy of individuals, based on the following elements:   
1.) Plan to protect the identifiers from improper use and disclosure: 
Only authorized study staff will access the Epic medical record for screening 
purposes.  Information from the screening will be stored in a REDCap database 
only used by study staff.   
2.) Plan to destroy the identifiers at the earliest opportunity consistent with 
conduct of the research: 
For those who do not consent to study inclusion, protected health information will 
be deleted upon the family’s decline or if the family is not enrolled in the study for 
other reasons (unable to approach parent for consent due to lack of parental 
availability).  For those who do consent to be enrolled in the study, HIPAA 
authorization for the collection of PHI will be obtained at the time of enrollment. 
3.) Protected health information will not be reused or disclosed: 
Protected health information will not be reused or disclosed to any other person or 
entity, except as required by law, for authorized oversight of the research project, 
or for other research for which the use or disclosure of protected health information 
would be permitted.   
(B) The research could not practicably be conducted without a partial waiver of 
HIPAA authorization.   
There are over 2500 admissions for asthma on yearly basis at CHOP with hospital 
lengths of stay generally less than 24-48 hours, and each of these cases could be 
potentially eligible for recruitment.  Given the limited time each patient is in the 
hospital and the number of potential patients, it would not be feasible to consent each 
of these 2500 for screening of their electronic medical records for eligibility.   
(C) The research could not practicably be conducted without access to and use of the 
protected health information.   
Access to protected health information is necessary in order to assess eligibility for the 
study.  For example, protected health information would be used to identify current 
inpatients, screen for eligible ages based on our inclusion criteria, subject’s date of 
admission, primary care doctor, and whether the subject has been prescribed the 
specific daily controller medications which are compatible with the electronic 
monitoring devices. 
7.6.2 Waiver of Consent 
We request a Waiver of Consent under 45 CFR 46.116(d). 
Study staff propose to assess patient eligibility by screening the daily census of patients 
admitted to a General Pediatrics service at CHOP for patients 5-12 who have at least 2 
admissions for asthma OR 1 admission AND at least 1 ED visit in the last 365 days using the 
Epic medical record and Epic alerts and patient lists.   

 
  
 
 
 
23
The research meets the criteria for a Waiver of Consent based on the following elements: 
(A) The research involves no more than minimal risks to the subjects, based on the 
following 3 elements: 
1.) Plan to protect the identifiers from improper use and disclosure: 
Only authorized study staff will access the Epic medical record for screening purposes.  
Information from the screening will be stored in a REDCap database only used by study 
staff.2.) Plan to destroy the identifiers at the earliest opportunity consistent with conduct of 
the research: 
For those who do not consent to study inclusion, protected health information will be 
destroyed upon the family’s decline or if the family is not enrolled in the study for other 
reasons (unable to approach parent for consent due to lack of parental availability).  For those 
who do consent to be enrolled in the study, HIPAA authorization for the collection of PHI 
will be obtained at the time of enrollment via informed consent. 
3.) Protected health information will not be reused or disclosed: 
Protected health information will not be reused or disclosed to any other person or entity, 
except as required by law, for authorized oversight of the research project, or for other research 
for which the use or disclosure of protected health information would be permitted.   
(B) The waiver will not adversely affect the rights and welfare of the subjects: 
When potential participants are determined to be eligible for enrollment, a study team member 
will explain the study and ask if they would like to participate.  Consent will be obtained in a 
HIPAA compliant manner, as described in the study procedures (see above Section 9.6).  
Participants will retain the right to choose whether they want to participate and provide 
consent.  Patients who are deemed ineligible based on screening of the Epic medical record 
will not be approached for enrollment. The only information that will be retained for those 
screened ineligible will be the reason why they were deemed ineligible.   
(C) The research could not practicably be carried out without the waiver: 
There are over 2500 admissions for asthma on yearly basis at CHOP with hospital lengths of 
stay generally less than 24-48 hours, and each of these cases could be potentially eligible for 
recruitment.  Given the limited time each patient is in the hospital and the number of potential 
patients, it would not be feasible to consent each of these 2500 for screening of their electronic 
medical records.   
(D) Whenever appropriate, the subjects will be provided with additional pertinent 
information about participation. 
Following screening using the Epic medical record, potentially eligible subjects will have the 
opportunity to review the study consent form and ask questions of the study team member.  
The Principal Investigator may also be contacted by phone if more information is needed.  The 
consent form includes contact information, and the participants may request additional 
information at any time.  Patients who are deemed ineligible based on screening of the Epic 

 
  
 
 
 
24
medical record will not be approached for enrollment and only the reason for study 
ineligibility will be retained. 
7.7 Payment to Subjects/Families 
7.7.1 Compensation  
Non-responders who do not undergo randomization will receive a $10 disbursement for their 
participation and not be paid further. At the completion of Visit 1, caregiver study participants 
will receive an automatic debit card credited with $20. For participants who are enrolled by 
telephone, they will be mailed their automatic debit card following enrollment. At the end of 
Study Visits 2, 3, 4, and 5, caregiver participants will be credited $20 for each study visit, for 
a total of $100. Additionally, children in Arm 1 will receive a performance-based reward 
payment during each month of the Experiment phase with a maximum value of $30/month. 
Children randomized to Arms 2 and 3 who have any actuations recorded each month of the 
Experiment phase will receive a $10 disbursement at the end of each month (for a total of $30) 
and children in all study arms will receive a $10 disbursement at the end of each month with 
recorded actuations during the Observation phase (for an additional $30), none of which will 
be contingent upon ICS adherence. 
8 
PUBLICATION 
Data will be analyzed by the investigators, with the help of a study statistician, and submitted 
for presentation at national meetings and publication in academic journals.  
 
 

 
  
 
 
 
25
9 
REFERENCES 
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Drotar D, Bonner MS. Influences on Adherence to Pediatric Asthma Treatment: A 
Review of Correlates and Predictors: Journal of Developmental & Behavioral Pediatrics. 
2009;30(6):574-582. doi:10.1097/DBP.0b013e3181c3c3bb 
2.  
Farber HJ, Johnson C, Beckerman RC. Young inner-city children visiting the 
emergency room (ER) for asthma: risk factors and chronic care behaviors. J Asthma. 
1998;35(7):547-552. 
3.  
Rand CS, Butz AM, Kolodner K, Huss K, Eggleston P, Malveaux F. Emergency 
department visits by urban African American children with asthma. Journal of Allergy and 
Clinical Immunology. 2000;105(1):83-90. doi:10.1016/S0091-6749(00)90182-9 
4.  
Bartlett SJ, Lukk P, Butz A, Lampros-Klein F, Rand CS. Enhancing medication 
adherence among inner-city children with asthma: results from pilot studies. J Asthma. 
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5.  
McNally KA, Rohan J, Schluchter M, et al. Adherence to Combined Montelukast 
and Fluticasone Treatment in Economically Disadvantaged African American Youth with 
Asthma. Journal of Asthma. 2009;46(9):921-927. doi:10.3109/02770900903229651 
6.  
Kahana S, Drotar D, Frazier T. Meta-Analysis of Psychological Interventions to 
Promote Adherence to Treatment in Pediatric Chronic Health Conditions. Journal of 
Pediatric Psychology. 2007;33(6):590-611. doi:10.1093/jpepsy/jsm128 
7.  
Pai ALH, McGrady M. Systematic Review and Meta-Analysis of Psychological 
Interventions to Promote Treatment Adherence in Children, Adolescents, and Young Adults 
With Chronic Illness. J Pediatr Psychol. 2014;39(8):918-931. doi:10.1093/jpepsy/jsu038 
8.  
Tran N, Coffman JM, Sumino K, Cabana MD. Patient reminder systems and asthma 
medication adherence: a systematic review. Journal of Asthma. 2014;51(5):536-543. 
doi:10.3109/02770903.2014.888572 
9.  
Foster JM, Usherwood T, Smith L, et al. Inhaler reminders improve adherence with 
controller treatment in primary care patients with asthma. Journal of Allergy and Clinical 
Immunology. 2014;134(6):1260-1268.e3. doi:10.1016/j.jaci.2014.05.041 
10.  
Chan AHY, Stewart AW, Harrison J, Camargo CA, Black PN, Mitchell EA. The 
effect of an electronic monitoring device with audiovisual reminder function on adherence 
to inhaled corticosteroids and school attendance in children with asthma: a randomised 
controlled trial. Lancet Respir Med. 2015;3(3):210-219. doi:10.1016/S2213-2600(15)00008-
9 
11.  
Volpp KG, Troxel AB, Pauly MV, et al. A randomized, controlled trial of financial 
incentives for smoking cessation. N Engl J Med. 2009;360(7):699-709. 
doi:10.1056/NEJMsa0806819 
12.  
Kimmel SE, Troxel AB, Loewenstein G, et al. Randomized trial of lottery-based 
incentives to improve warfarin adherence. Am Heart J. 2012;164(2):268-274. 
doi:10.1016/j.ahj.2012.05.005 

 
  
 
 
 
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13.  
Haff N, Patel MS, Lim R, et al. The role of behavioral economic incentive design 
and demographic characteristics in financial incentive-based approaches to changing health 
behaviors: a meta-analysis. Am J Health Promot. 2015;29(5):314-323. 
doi:10.4278/ajhp.140714-LIT-333 
14.  
Loewenstein G, Price J, Volpp K. Habit formation in children: Evidence from 
incentives for healthy eating. J Health Econ. 2016;45:47-54. 
doi:10.1016/j.jhealeco.2015.11.004 
15.  
Halpern SD, French B, Small DS, et al. Randomized Trial of Four Financial-
Incentive Programs for Smoking Cessation. New England Journal of Medicine. 
2015;372(22):2108-2117. doi:10.1056/NEJMoa1414293 
16.  
Asch DA, Troxel AB, Stewart WF, et al. Effect of Financial Incentives to 
Physicians, Patients, or Both on Lipid Levels: A Randomized Clinical Trial. JAMA. 
2015;314(18):1926. doi:10.1001/jama.2015.14850 
17.  
Patel MS, Asch DA, Rosin R, et al. Individual Versus Team-Based Financial 
Incentives to Increase Physical Activity: A Randomized, Controlled Trial. Journal of 
General Internal Medicine. March 2016. doi:10.1007/s11606-016-3627-0 
18.  
Bursch B, Schwankovsky L, Gilbert J, Zeiger R. Construction and Validation of 
Four Childhood Asthma Self-Management Scales: Parent Barriers, Child and Parent Self-
Efficacy, and Parent Belief in Treatment Efficacy. J Asthma. 1999;36(1):115-128. 
doi:10.3109/02770909909065155 
19.  
McQuaid EL, Penza-Clyve SM, Nassau JH, et al. The Asthma Responsibility 
Questionnaire: Patterns of Family Responsibility for Asthma Management. Children’s 
Health Care. 2001;30(3):183-199. doi:10.1207/S15326888CHC3003_2 
20.  
Bolman C, Arwert TG, Völlink T. Adherence to prophylactic asthma medication: 
Habit strength and cognitions. Heart & Lung: The Journal of Acute and Critical Care. 
2011;40(1):63-75. doi:10.1016/j.hrtlng.2010.02.003 
21.  
Nagin DS. Group-based trajectory modeling: an overview. Ann Nutr Metab. 
2014;65(2-3):205-210. doi:10.1159/000360229 
22.  
Nagin DS, Odgers CL. Group-based trajectory modeling in clinical research. Annu 
Rev Clin Psychol. 2010;6:109-138. doi:10.1146/annurev.clinpsy.121208.131413 
23.  
Modi AC, Rausch JR, Glauser TA. Patterns of nonadherence to antiepileptic drug 
therapy in children with newly diagnosed epilepsy. JAMA. 2011;305(16):1669-1676. 
doi:10.1001/jama.2011.506 
24.  
Franklin JM, Krumme AA, Shrank WH, Matlin OS, Brennan TA, Choudhry NK. 
Predicting adherence trajectory using initial patterns of medication filling. Am J Manag 
Care. 2015;21(9):e537-e544. 
 

 
  
 
 
 
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Appendix 1 
Run-in phase text messages and automated responses:  
Text 1: PARTICIPANT_FIRSTNAME, welcome to the run-in period! We will be sending you a few 
texts over the next 2 weeks. Please respond to these messages if they ask for a response, otherwise you 
may be removed from the study. Text 1 to confirm you received this text. 
 
Automated response: Great, thank you!  
Text 2: Are you having problems with the Propeller sensors or app? Text 1 for YES or 2 for NO. 
If 1, automated response: Thank you for your response. A study team member will be contacting you 
shortly. 
If 2, automated response: Great, thank you!  
Text 3: Is the app getting puff information from the sensors? Text 1 for YES or 2 for NO. 
If 1, automated response: Thank you for your response. A study team member will be contacting you 
shortly.  
If 2, automated response: Great, thank you!  
Text 4: Are you receiving our texts? Text 1 for YES. If you haven't responded to any of our messages, 
you will be removed from the study. And we want you to stay! 
If 1, automated response: Great, thank you!  
 
Experiment phase text message reminders:  
1. Hi! This is your friendly daily controller inhaler reminder. Quick fact: children who take 
controller medication daily have fewer future asthma attacks.  
 
2. Hello! A friendly reminder to make sure your child took their daily controller inhaler. Even 
for older children, parents are an important part of improving asthma control.  
 
3. Hi! Did your child take their daily controller inhaler today? Quick fact: when taken 
regularly, daily controllers reduce the number of emergency room visits. 
 
4. Hello there! Has your child taken all of their daily controller puffs today? Remember to 
always use a spacer with those puffs.  
 
5. Hi! A quick reminder to make sure that your child took their daily asthma inhaler. Quick tip: 
have your child take their daily controller inhaler with another daily activity (tooth-
brushing).  
 
6. Hi! This is a friendly daily controller inhaler reminder for you. When taken regularly, daily 
inhalers reduce the number of missed school days. 

 
  
 
 
 
28
 
7. Hello! This is your friendly daily controller inhaler reminder. Quick tip: when your child is 
away from home remember to send medications and a spacer with them.  
 
 
8. Hi! Remind your child to take their asthma medicine. Each puff you take (as prescribed) gets 
you closer to your goal! 
 
 
9. Hi! Did you remind your child to take their controller inhaler today? 
 
 
10. Hi there! Make sure to remind your child to take their medicine today! 
 
 
 
 
 
 
 
 

 
  
 
 
 
29
Appendix 2: Data Safety and Monitoring Plan  
 
Study Oversight:  
 
This study will utilize an institutionally-appointed Data Safety and Monitoring Board (DSMB), 
which will hold DSMB yearly meetings via teleconference. The DSMB will be responsible for 
monitoring any data and/or safety issues and also providing recommendations as needed for the 
following:  
• 
Participant safety 
• 
Initial approval of the protocol and consent forms and subsequent amendments for human 
subject safety and research ethics 
• 
Data and statistical analysis plan 
• 
Efficacy of the study intervention 
• 
Benefit/risk ratio of procedures and participant burden 
• 
Selection, recruitment, and retention of participants 
• 
Adherence to protocol requirements 
• 
Completeness, quality, and analysis of measurements  
• 
Notification of and referral for abnormal findings  
 
Study Monitoring:  
 
The data to be presented to the DSMB for review will be proposed at the first DSMB meeting and then 
provided in aggregate at subsequent meetings. At a minimum, recruitment and retention data, baseline 
characteristics, changes to the protocol and consent or planned analysis, and the following outcome 
data will be included: asthma medication adherence and asthma-related healthcare utilization. In 
addition, data quality (timeliness and completeness of data collection, resolution of discrepancies), 
safety data (adverse events (AEs), serious adverse events (SAEs), and unanticipated problems), and 
study conduct (protocol deviations) will also be included.  
 
Ongoing monitoring of recruitment will be tracked using a master screening log stored on the study’s 
Way to Health database at the University of Pennsylvania. Way to Health is an NIH-sponsored, web-
based platform that automates many of the research functions necessary for conducting randomized 
controlled trials of behavioral incentives. 
 
Monitoring of data collection will be performed by the research project manager and research 
assistant:  
• 
Monthly review of adherence data from Way to Health  
• 
Monthly review of EHR data on asthma-related ED visits and hospitalizations 
 

 
  
 
 
 
30
Missing data will be managed by running twice monthly data query reports in the Way to Health 
database. Data discrepancies will be resolved by the study research assistant and other study staff with 
corrections and/or comments entered into the Way to Health database within one week of receiving 
data query.  
 
Protocol deviations will be identified by PI and research project manager and reported to the CHOP 
IRB through the electronic IRB reporting system in accordance with CHOP IRB policy. These events 
will be presented to the DSMB and reported to the research team at regularly scheduled study meetings. 
 
Safety Monitoring:  
 
An adverse event (AE) includes any event meeting the following definition:  
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign 
(for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally 
associated with the subject’s participation in the research, whether or not considered related to the 
subject’s participation in the research (modified from the definition of adverse events in the 1996 
International Conference on Harmonization E-6 Guidelines for Good Clinical Practice).  
 
A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that:  
• 
Results in death  
• 
Is life-threatening  
• 
Results in a persistent or significant disability/incapacity  
• 
Results in in-patient hospitalization or prolongation of existing hospitalization  
• 
Results in a congenital anomaly/birth defect. 
• 
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered a SAE when, based upon medical judgment, they may 
jeopardize the patient or participant and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition.  
 
Safety data collection:  
Information regarding unanticipated problems and adverse events (AE) and serious adverse events 
(SAE) will be collected at each study visit through follow-up questionnaires. Once the adverse event 
has been identified, determined to be unexpected, and at least potentially related to the research study, 
appropriate CHOP IRB electronic forms will be completed and submitted to the IRB.  
 
Safety data reporting:  
Events identified will be recorded and reported to the CHOP IRB. These events will be presented to 
the DSMB and reported to the research team at regularly scheduled study meetings. Led by the PI, the 
research team will review each event and make appropriate safety decisions.  

 
  
 
 
 
31
 
SAEs will be communicated by the research personnel immediately to the PI. For SAEs that are 
determined to be unexpected and at least potentially related to the research study, the study PI will 
notify the IRB committee assigned to this project at Children’s Hospital of Philadelphia, as well as the 
study DSMB, within 48 hours of first knowledge of the SAE. The IRB and DSMB’s assessments of 
such an event will then be forwarded to the NHLBI within 15 calendar days, as outlined in the 
“Reportable Events” table below. Because most enrolled patients will have moderate or severe asthma 
requiring hospitalization in the past, hospitalizations are expected to occur. All AEs (including SAEs) 
will be followed to their conclusion or stability, with necessary management recorded. Additional 
details for reporting unanticipated problems, AEs, and SAEs are detailed at the following CHOP Office 
of Regulatory Affairs website: https://irb.research.chop.edu/reportable-events and in accordance with 
CHOP IRB SOP 408: Unanticipated Problems Involving Risks to Subjects. The flowchart depicted 
below will be used to make assessments regarding the way the incident will be characterized for 
reporting. 
 
 
 
 
AEs and unanticipated problems will be summarized in narrative or other format and submitted to the 
IRB at the time of continuing review. This information will also be reported to NHLBI during the 
annual progress report. See below for a table which documents the reportable events and when they 
will be reported to the CHOP IRB, NHLBI, and by whom. 

 
  
 
 
 
32
 
Reportable Event  
When Reported 
to CHOP IRB 
When Reported to 
NHLBI   
Reported by 
Whom 
IRB suspension or study 
termination 
 
3 calendar days from 
initial receipt of 
information  
CHOP/PI  
Study related death or life-
threatening event 
Within 48 
hours of 
discovery 
7 calendar days from 
initial receipt of 
information 
PI 
Unexpected SAE related to 
study 
Within 48 
hours of 
discovery 
15 calendar days from 
initial receipt of 
information 
PI  
Unanticipated problems that 
are not SAEs 
7 calendar days 
15 calendar days from 
PI becoming aware of 
the problem 
PI 
Serious or continuing non-
compliance  
 
10 calendar days 
CHOP 
AE/SAEs determined not to 
be related to the study 
Annual 
continuing 
review  
Annual progress report  
PI  
Minor Protocol deviations 
(Determined not to be 
unanticipated problems) 
Annual 
continuing 
review 
Annual progress report  
PI  
Reproduced from https://www.nhlbi.nih.gov/research/funding/human-subjects/adverse-event  
 
Subjects who experience an SAE will be allowed to continue participation in the study. SAE 
management will be provided by the clinical teams that care for the participants with input from the 
PI on how medication adherence may have influenced the ED visit or hospitalization.  
 
Risks and Benefits:  
 
Potential risks of trial participation: While the child’s usual asthma care may not be minimal risk, risks 
directly related to study intervention are minimal. There is no risk of discomfort due to the study 
intervention. The study intervention merely adds electronic monitoring, text message notifications, 
and nominal financial incentives to already prescribed medications. The main risk is breach of 
confidentiality. Please refer to the section below on data security and participant confidentiality for the 
strategies in place to avoid this risk. Upon enrollment, the study team will emphasize to study 

 
  
 
 
 
33
participants that the trial’s activities are not clinical care and that study participants should follow the 
clinical recommendations and care of their clinical providers. This point is included on the study 
informed consent form and will be emphasized verbally to all study participants. 
 
Potential benefits of trial participation: Participants in this study may experience improvements in their 
adherence to their daily controller medications. Improved adherence may lead to better control of 
asthma and therefore decrease school absences, parental work absences, and the number of visits to 
the ED or admissions to hospitals.   
 
Risk-benefit assessment: The risks of this study are minimal. The main risk of the study is breach of 
confidentiality. The potential to improve asthma adherence may improve asthma control and decrease 
ED visits or hospital admissions for asthma.  Therefore, potential benefits of study participation 
outweigh the potential risks. 
 
Data acquisition, security, and participant confidentiality: 
 
Data will be obtained from participant surveys, the electronic medical record, and the electronic 
medication adherence sensors placed on the participants’ primary asthma controller and rescue 
medication. For a summary of data entry and transfer, refer to figure below. 
 
 
 
Each study subject will be assigned a study ID at the time of enrollment, which will serve as the means 
of protecting personal health information during data storage. The master list with study IDs will be 
kept in a separate CHOP network folder from the datasets and will be eliminated after all publication 
of findings are completed rendering the datasets deidentified.   

 
  
 
 
 
34
 
Epic medical record and study questionnaire data will be entered directly into the Way to Health 
platform (in the case of patient identifiable information) or on a paper form during the study visits. 
Electronic adherence data will be transferred electronically from the respiratory sensor platform to the 
Way to Health Platform via the respiratory sensor platform API (Application Programming Interface).  
An additional data transfer will be used to extract the analytic data set to the secure CHOP research 
server for analysis. All databases created will be password-protected and only study team members 
will have access. All data sets downloaded through the respiratory sensor or Way to Health platforms 
will be password-protected and stored on the CHOP secured network drive, only accessible to study 
team members. Please see study protocol section 7.2 for a full description of data security and patient 
confidentiality measures in place to protect data transfers and storage on the respiratory sensor and 
Way to Health platforms, CHOP secured network drives, and the transfers between the platforms and 
drives.  
 
Interim analyses and stopping rules:  
 
Given the minimal risk nature of this study, there are no planned interim analyses or criteria for 
prematurely stopping the study.   
 
Reporting:  
 
Any change to protocol or amendment to protocol will be approved by CHOP IRB prior to putting in 
place.  
 
Reports, every year, regarding participant accrual, study progress, AEs and SAEs, and data quality 
will be developed by the research team. Report by unidentified arms will be made available to the 
study statistician and the DSMB as specified by the trial protocol, Good Clinical Practices, and 
applicable regulations. Copies of these reports will be made available to the DSMB and NHLBI by the 
project biostatistician. Reports to the DSMB and the NHLBI will also include any protocol changes or 
study conduct issues including protocol deviations. 
 
Conflicts of interest:  
 
The Principal Investigator and co-Investigators have no conflicts of interest. Each year, research team 
members will be asked to state whether they have developed any new conflicts of interest since the 
last formal annual report. The research team will report to the DSMB any new potential conflicts of 
interest prior to each scheduled meeting. 
 
 

 
  
 
 
 
35