Coordinated Healthcare Interventions for Childhood Asthma Gaps in Outcomes (CHICAGO Plan)
Phase: NA
Conditions: Asthma
Sponsor: University of Illinois at Chicago

PCORI contract # AS 1307-05420 
 
CHICAGO Plan Protocol 
v4.0 12/1/2017 
Page 1 of 36 
 
 
 
Study protocol 
December 1, 2017 
 
 
 
UIC PAF #: 2014-01275 
UIC IRB protocol #: 2014-1214 
Clinicaltrials.gov registration #: NCT02319967 
 
Patient-Centered Outcomes Research Institute, contract # AS 1307-05420 
Project period: March 1, 2014 – May 31, 2017

PCORI contract # AS 1307-05420 
 
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12-01-2017 
 
 
 
 
 
 
 
 
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TABLE OF CONTENTS 
 
 
Page 
I. 
Executive summary 
II. 
Overview of pragmatic trial 
III. 
Primary and secondary aims 
IV. 
Study population 
V. 
Interventions and comparators 
VI. 
Randomization 
VII. 
Data collection 
A. Screening and enrollment (registration) into the study (in person)  
B. 1-month follow-up visit after ED discharge (telephone)   
C. 3-month follow-up visit after ED discharge (telephone)   
D. 6-month follow-up visit after ED discharge (in person) 
E. 12-month follow-up visit after ED discharge (telephone)   
VIII. 
Outcomes 
A. Primary outcomes 
B. Secondary outcomes  
IX. 
Analysis plan 
X. 
Barriers and facilitators of successfully implementing the intervention  
(secondary aim) 
XI. 
Timeline / milestones 
XII. 
Protection of human subjects  
A. Risks to human subjects 
B. Source of materials  
C. Potential risks  
D. Adequacy of protection against risks  
E. Potential benefits of the proposed research to the subjects and others 
F. Importance of the knowledge to be gained 
G. Data safety monitoring plan 
H. Clinicaltrials.gov requirements 
I. Inclusion of women and minorities 
XIII. 
References 
XIV. 
Appendices 
A. CAPE tool 
B. Outline of home visit procedures 
  
 
3 
4 
4 
5 
7 
9 
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11 
13 
 
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15 
 
 
 
 
 
 
 
 
 
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I. Executive summary 
1 
 
2 
Chicago is an epicenter for asthma health disparities in the United States, with African American 
3 
children 5-11 years old bearing a disproportionate share of the burden. Gaps in implementation at 
4 
provider and patient levels contribute to these asthma disparities, with studies suggesting that 
5 
minority children are less likely than white children to be prescribed and use guideline-
6 
recommended asthma care, respectively. Effective strategies to implement national asthma 
7 
guideline recommendations in this population are needed.  As part of a Patient-Centered Outcomes 
8 
Research Institute contract (AS 1307-05420; Coordinated Healthcare Interventions for Childhood 
9 
Asthma Gaps in Outcomes [CHICAGO] Plan), we used methods in user-centered design to inform 
10 
the development of interventions to implement asthma guidelines in the ED and at home.  We then 
11 
conducted a pragmatic trial to evaluate the effectiveness of ED and home-based interventions on 
12 
patient- and caregiver-centered endpoints.   
13 
 
 
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II. Overview of the pragmatic trial  
15 
 
16 
The CHICAGO Plan was a randomized 3-arm parallel group, multi-center pragmatic trial in six 
17 
Emergency Departments (EDs) affiliated with public or private hospitals who served a high 
18 
proportion of black or Latino children in Chicago to compare: 1) an ED-only intervention 2) an 
19 
ED-plus-home intervention; and 3) Enhanced usual care.  Eligibility criteria were intended to be 
20 
clinically applicable and recruitment took place in multiple EDs serving underserved communities 
21 
in Chicago (six Clinical Centers serving different populations of children 5-11 years presenting 
22 
with asthma).  Data collection employed validated approaches, but were also intended to minimize 
23 
participant burden 
24 
 
25 
III. Primary and secondary aims 
26 
 
27 
Primary aim 
28 
Conduct a 3-arm multi-center pragmatic trial comparing the effectiveness of the ED-only, ED-
29 
plus-home, and usual care strategies.   
30 
 
31 
Secondary aims 
32 
 Examine the potential for heterogeneity of treatment effects. 
33 
 Identify barriers and facilitators of successfully implementing the interventions to inform 
34 
subsequent research to accelerate the uptake of study findings.   
35 
 
 
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Figure 1:  Children ages 5 to 11 years who presented with uncontrolled asthma to the emergency 
39 
department (ED) were randomly allocated to one of three groups:  Enhanced usual care vs. ED-
40 
based intervention using the CHICAGO Action Plan after Emergency department discharge 
41 
(CAPE) decision support and communication tool for children and caregivers (ED-only), vs. the 
42 
same ED-only intervention plus community health worker-led home visits at 2-3 days, 2 weeks, 1 
43 
month, 3 months, and 6 months after ED discharge to help implement the CAPE and reduce 
44 
environmental triggers (ED-plus-home). Outcomes were assessed at baseline (in-person prior to 
45 
ED discharge), 1 month (via phone), 3 months (via phone), and 6 months (in-home or via phone; 
46 
time point for the primary outcome) after ED discharge.  
47 
 
48 
IV. Study population 
49 
 
50 
Eligibility criteria were designed to be clinically relevant and feasible to implement in an ED 
51 
setting.    Due to lower than expected randomizations during the first half of the recruitment period, 
52 
we modified the study eligibility criteria after review by an independent Data and Safety and 
53 
Monitoring Board, institutional IRBs (Site-specific IRB approval dates: Lurie – 9/14/2015; Rush – 
54 
9/8/2015; Sinai – 9/10/2015; Stroger – 8/18/2015; UC – 9/1/2015; UIC – 7/28/2015), and 
55 
discussions with the program officer from the Patient-Centered Outcomes Research Institute.  
56 
Original and revised eligibility criteria are below; to be eligible, patients needed to meet all 
57 
inclusion criteria and none of the exclusion criteria below. 
58 
 
59 
ORIGINAL ELIGIBILITY CRITERIA: 
60 
Original eligibility criteria approved by prime site IRB (UIC #2014-1214) on 12/19/2014.  
61 
0 month  
randomization  
3 months  
6 months 
Enhanced usual care
ED-only
Outcomes assessments  
ED-plus-home  
Legend 
CHW home visits 
Enrollment + 
baseline  
1 month  
ED-based decision 
support and 
communication tool  
Intervention  

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Inclusion criteria (all of the following):   
62 
1. Child is 5-11 years of age (a population in whom a diagnosis of asthma is generally reliable, 
63 
and in whom exacerbations are common);  
64 
2. Child is presenting to the ED, urgent care center, or observation unit at a participating clinical 
65 
center (Anne and Robert H. Lurie Children’s Hospital of Chicago, Sinai Health System’s 
66 
Mount Sinai Hospital, John H. Stroger Jr. Hospital of Cook County Health & Hospitals 
67 
System, Rush University Medical Center, University of Chicago Medicine Comer Children’s 
68 
Hospital, and the University of Illinois Hospital & Health Sciences System);  
69 
3. Child is treated with at least 1 dose of an inhaled or nebulized short-acting bronchodilator 
70 
(quick-relief medication);  
71 
4. Child received systemic corticosteroids in the ED; 
72 
5. Child and caregiver approached at least 1 hour after receipt of the first dose of quick-relief 
73 
medication or systemic corticosteroids, whichever occurred last;  
74 
6. Diagnosis of asthma exacerbation by treating clinician;  
75 
7. Treating ED clinician indicates the child is likely to be discharged to home;  
76 
8. Caregiver reports that English or Spanish is the preferred language at home.  
77 
 
78 
Exclusion criteria (none of the following): 
79 
1. Caregiver declines to provide informed consent, or the child declines to provide assent;  
80 
2. Child is discharged to a location other than home (e.g., hospital or another healthcare facility);  
81 
3. Child or another member of the child’s primary household is a current or previous participant 
82 
in the CHICAGO Plan;  
83 
4. Child is enrolled in another study involving a health-related intervention;  
84 
5. A CHW is already visiting the home as part of another program;  
85 
6. Child is expected to move out of Chicago within the next 6 months. 
86 
 
87 
REVISED ELIGIBILITY CRITERIA: 
88 
Revised eligibility criteria approved by prime site IRB (UIC #2014-1214) on 7/28/2015. Revisions 
89 
occurred over a period of a few months across all of the other clinical centers (after local 
90 
institutional review).  
91 
 
92 
Inclusion criteria (all of the following):  
93 
1. Child is 5-11 years of age (a population in whom a diagnosis of asthma is generally reliable, 
94 
and in whom exacerbations are common); 
95 
2. Child is presenting to the ED, urgent care center, or observation unit at a participating clinical 
96 
center (Anne and Robert H. Lurie Children’s Hospital of Chicago,  Sinai Health System’s 
97 
Mount Sinai Hospital, John H. Stroger Jr. Hospital of Cook County Health & Hospitals 
98 
System, Rush University Medical Center, University of Chicago Medicine Comer Children’s 
99 
Hospital, and the University of Illinois Hospital & Health Sciences System); 
100 
3. Child is treated with at least 1 dose of an inhaled or nebulized short-acting bronchodilator 
101 
(quick-relief medication); 
102 
4. Child received systemic corticosteroids in the ED OR the caregiver reported at least 1 
103 
additional acute care visit for asthma in the previous 6 months (defined as an asthma-related 
104 
ED visit or urgent care visit, or course of systemic corticosteroids); 
105 
5. Child and caregiver approached at least 1 hour after receipt of the first dose of quick-relief 
106 
medication or systemic corticosteroids, whichever occurred first; 
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6. Diagnosis of asthma exacerbation by treating clinician; 
108 
7. Treating ED clinician indicates the child is likely to be discharged to home;  
109 
8. Caregiver reports that English or Spanish is the preferred language at home.  
110 
 
111 
Exclusion criteria (none of the following): 
112 
1. Caregiver declines to provide informed consent, or the child declines to provide assent; 
113 
2. Child is admitted to an intensive care unit or transferred to another healthcare facility; 
114 
3. Child or another member of the child’s primary household is a current or previous participant in 
115 
the CHICAGO Plan;  
116 
4. Child is enrolled in another study involving a health-related intervention; 
117 
5. A Community Health Worker (CHW) is already visiting the home as part of another program;  
118 
6. Child does not reside in Chicago.  
119 
 
120 
V.  Interventions and comparators 
121 
 
122 
All children who participated in the CHICAGO Plan received asthma care per their ED clinicians. 
123 
In addition, the CHICAGO Plan’s ED Coordinator provided all participants two metered dose 
124 
inhaler (MDI) spacers free-of-charge and used teach-to-goal methodology (repeated rounds of 
125 
education and evaluation until the child achieves mastery) to educate the child and the caregiver 
126 
about appropriate MDI inhaler technique. Patient education regarding the MDI device was selected 
127 
because it is commonly used for quick-relief medications and is also the device for many inhaled 
128 
controller medications. Children were then randomly assigned to either of two active comparators 
129 
or enhanced usual care. 
130 
 
131 
1. ED-only.  Based on feedback from our stakeholders, we developed the CHICAGO Action 
132 
Plan after Emergency department discharge tool (CAPE; APPENDIX A1); a culturally 
133 
tailored and literacy-appropriate communication tool for use on ED discharge.  Based on 
134 
the ED treating clinician’s discharge instructions, a CHICAGO Plan ED Coordinator 
135 
utilized the CAPE to support guideline recommended asthma care on ED discharge (a 
136 
course of systemic corticosteroids; daily inhaled corticosteroids or other controller; as 
137 
needed quick-relief inhaled medication; education about the medications and appropriate 
138 
inhaler technique; education about asthma trigger avoidance; and a post-discharge follow-
139 
up appointment) and to support appropriate asthma self-management in the home. The 
140 
CAPE tool uses simplified language, visual learning, and options for individualization to 
141 
facilitate communication about discharge instructions between clinicians and the child and 
142 
caregiver. 
143 
 
144 
2. ED-plus-home.  Participants randomly allocated to the ED-plus-home intervention received 
145 
the same ED-only intervention described above but were also offered up to five home visits 
146 
over 6 months conducted by a CHW visits to: 1) assist in the implementation of the ED 
147 
discharge instructions, 2) update the asthma treatment plan with input from the patient’s 
148 
ambulatory clinician utilizing the CAPE tool called the Asthma Home Plan (APPENDIX 
149 
A2), 3) develop a plan to manage asthma during school hours (e.g., access to quick-relief 
150 
medications, action plan in case of respiratory difficulty), and 4) develop a specific and 
151 
feasible plan to reduce environmental triggers at home (e.g., environmental tobacco smoke, 
152 
roach, mice).  Home visits were scheduled for 60 to 90 minutes, and occurred 
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approximately at 2-3 days, 2 weeks (14 days), 1 month (30 days), 3 month (90 days), and 6 
154 
months (180 days) after ED discharge.  
155 
  
156 
3. Enhanced usual care.    Based on stakeholder feedback, we modified usual care so that 
157 
children in the “usual care” group also received teaching about appropriate MDI technique 
158 
using teach-to-goal methodology and two MDI spacers free-of-charge, as well as doorknob 
159 
hangers depicting facts about asthma unrelated to the study interventions. We therefore 
160 
refer to this group as “Enhanced usual care.”   To describe usual care at each site, the site 
161 
project manager conducted chart abstractions (masked to treatment assignment).  Site 
162 
project managers were to complete chart abstractions within 3 business days of enrolling 
163 
the participant in the study.   
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VI. Randomization 
166 
 
167 
Randomization occurred at the patient level, with permuted block sizes stratified by site and race 
168 
(black vs. non-black). Based on data from the Clinical Centers, we expected about 70% of enrolled 
169 
participants to be black, 23% to be white, and that the remainder would be mostly Asian.  Of the 
170 
planned enrollment of 640 children, we expected 15% to be Hispanic/Latino.  Stratification by race 
171 
for the purposes of randomization was “Black” (those who selected Black or African American, 
172 
includes multi-race if at least one race was Black or African American) vs. “non-Black” (American 
173 
Indian/Alaskan Native, Asian, Native Hawaiian or other Pacific Islander, white, and multi-race if 
174 
none are Black or African American).   
175 
 
176 
The CHICAGO Plan Research Electronic Data Capture (REDCap) system for study personnel 
177 
(available 24 hours x7 days/week) provided the random treatment assignment: ED-only, ED-plus-
178 
home, or Enhanced usual care.   
179 
 
180 
VII. Data collection 
181 
 
182 
A. Screening and enrollment (registration) into the study (in person; ~40 minutes). The ED 
183 
coordinator, a member of the research team, at each Clinical Center screened patients in the ED, 
184 
Urgent Care, or Observation Unit after treatment initiation for asthma exacerbation and before 
185 
discharge.  The ED coordinator obtained verbal assent from the ED clinician prior to approaching 
186 
the child/caregiver for informed consent.  Following informed consent, the ED coordinator 
187 
obtained Baseline data, registered the patient in a customized, secure, on-line CHICAGO Plan 
188 
REDCap portal developed by the DCC, then obtained the treatment assignment (ED-only, ED-
189 
plus-home, or Enhanced usual care).  The ED Coordinator offered to arrange the date/time of the 
190 
1-month follow-up visit (see below). 
191 
 
192 
B. 1-month follow-up contact after discharge (telephone; ~15 minutes).  Post-baseline data 
193 
collection was performed by the DCC Research Assistant, who was masked to treatment 
194 
assignment. The Research Assistant conducted a telephone interview to assess outcomes 
195 
approximately 1 month after discharge.  The interview was also designed to collect / update 
196 
contact information and to promote retention in the CHICAGO Plan. The DCC Research Assistant 
197 
arranged date/time of the 3-month follow-up visit (see below), or inquired about the best time to 
198 
call again. 
199 
 
200 
C. 3-month follow-up contact after ED discharge (telephone; ~15 minutes).  The DCC Research 
201 
Assistant, masked to treatment assignment, conducted a telephone interview to assess outcomes 
202 
approximately 3 months after ED discharge.  The interview was also designed to collect / update 
203 
contact information and to promote retention in the CHICAGO Plan. The DCC Research Assistant 
204 
arranged date/time of the 6-month follow-up visit (see below), or inquired about the best time to 
205 
call again.  
206 
 
207 
D. 6-month follow-up contact after discharge (in person or by telephone; ~40 minutes).  The DCC 
208 
Research Assistant, masked to treatment assignment, conducted a study visit in person or via 
209 
telephone (per participant preference) to assess outcomes approximately 6 months after discharge.  
210 
The in-person visit afforded the ability to conduct an assessment of home trigger avoidance; 
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review inhaler technique; and assess cACT (child) and PACQLQ, which are more easily collected 
212 
during in-person visits. 
213 
 
214 
E. 12-month follow-up contact after discharge (in person or by telephone; ~40 minutes).  We 
215 
proposed re-assessing outcomes at 12 months to examine the durability of effects observed at 6 
216 
months.   Despite significant efforts, retention in the study also proved to be challenging, and 
217 
therefore the 12-month follow-up visit was discontinued at the request of PCORI in September 
218 
2016.  
219 
 
220 
VIII. Outcomes 
221 
 
222 
The selection of primary outcomes was based on several criteria: 1) patient-centeredness, defined 
223 
as domains identified as important by children and their caregivers; as described in our previous 
224 
publications;  2) availability of validated measures in English and in Spanish that could be 
225 
administered in person and by phone; 3) plausibility that such measures could be responsive to an 
226 
effective intervention in the target population; and 4) limited burden (e.g., time) for study 
227 
participants.   On this basis, we selected two NIH Patient-Reported Outcomes Measurement 
228 
Information System (PROMIS) measures as primary outcomes (1 for the child and 1 for the 
229 
caregiver).  Several measures were selected for secondary outcomes to address recommendations of 
230 
national asthma guidelines, expressed preferences of caregivers and other stakeholders, and to 
231 
compare results of the CHICAGO Plan with previous studies.    
232 
 
233 
A.  Primary outcomes 
234 
1. The change in asthma impact at 6 months compared to the baseline assessed in the ED served as 
235 
the primary outcome in children. In children 5 to 7 years, we assessed asthma impact using the 
236 
PROMIS Parent Proxy Short Form v1.0 – Asthma Impact 8a.  In children 8 to 11 years, we used 
237 
the PROMIS Pediatric Short Form v1.0 – Asthma Impact 8a.  
238 
 
239 
2. The change in Satisfaction with Participation in Social Roles at 6 months compared to the 
240 
baseline assessed in the ED served as the primary outcome in the caregiver.  We used the PROMIS 
241 
Short Form v1.0 – Satisfaction with Participation in Social Roles 4a.  
242 
 
243 
B.  Secondary outcomes  
244 
For children:   
245 
1) The Childhood Asthma Control Test (cACT) at 6 months compared to the baseline assessed 
246 
in the ED  
247 
2) Acute care visits at 6 months (number of all-cause urgent care visits, ED visits, 
248 
hospitalizations, using electronic health records)   
249 
 
250 
For caregivers:  
251 
1) Pediatric Asthma Caregiver’s Quality of Life Questionnaire (PACQLQ) at 6 months 
252 
compared to the baseline assessed in the ED  
253 
2) NIH PROMIS measures for anxiety, depression, fatigue, sleep disturbance at 6 months 
254 
compared to the baseline assessed in the ED  
255 
 
256 
 
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Indicators of guideline-consistent asthma care provided on ED discharge:  
258 
1) Systemic corticosteroids prescribed for use at home (yes/no) 
259 
2) Inhaled corticosteroids or another controller medication prescribed for use at home (yes/no) 
260 
3) Quick-relief medications prescribed for use at home (yes/no) 
261 
4) Follow-up appointment scheduled (yes/no) 
262 
Child’s/caregiver’s self-management practices after ED discharge: 
263 
1) Filled prescriptions for systemic corticosteroids within 7 days of ED discharge (yes/no) 
264 
2) Filled prescription for inhaled corticosteroids or other asthma controller within 7 days of 
265 
ED discharge (yes/no) 
266 
3)   Attendance at outpatient appointment with patient-identified asthma provider within 4 
267 
weeks of ED discharge (yes/no) 
268 
 
269 
IX. Analysis plan 
270 
 
271 
All primary and secondary outcomes were analyzed according to the intention-to-treat principle. 
272 
All randomized subjects were included in the primary analysis, unless subjects were terminated 
273 
due to ineligibility.  Baseline sociodemographic and clinical characteristics in the intervention and 
274 
control groups were compared using the frequency and percentages for categorical variables and 
275 
median with inter-quartile or mean with standard error for continuous variables.  For bivariate 
276 
analyses, the pairwise comparisons between three intervention arms for the change in primary and 
277 
some secondary outcomes from baseline to 3 or 6 months were tested by Wilcoxon rank sum test.  
278 
The W statistic, p-value and mean rank were reported together with horizontal mirror bar plots. For 
279 
primary outcomes, a statistical significance occurred when p-value was less than 0.0167 after 
280 
Bonferroni correction for three pairwise comparisons (0.05/3). In addition, chi-square tests were 
281 
also conducted for other secondary outcomes. 
282 
 
283 
To address missing data in the analyses, we checked the missing completely at random (MCAR) 
284 
assumption and then employed a multiple imputation strategy. Using a logistic regression method 
285 
described in Hedeker & Gibbons (2006), we found that the current outcome missingness was not 
286 
statistically associated with previous observed outcomes across time. Additional characteristics 
287 
comparisons between participants with and without missing primary outcomes across time was 
288 
also done using Chi-square tests for categorical variables and Mann-Whitney U test for continuous 
289 
variables. No statistical difference was observed between the two groups (i.e. with and without 
290 
missing primary outcomes). We therefore used a fully conditional specification (FCS) approach to 
291 
impute the missing values with variables of interest in the primary analysis models for 30 
292 
imputations.  The raw and imputed data had similar distributions (mean, standard deviation, 
293 
minimum and maximum values). 
294 
 
295 
Since the two primary outcomes were not normally distributed and our data satisfied the MCAR 
296 
assumption, we used generalized estimating equations (GEE) to examine the effect of intervention 
297 
group on outcomes at 3 and at 6 months compared to that of the enhanced usual care group using 
298 
ordinal logistic regression models; the continuous dependent variables were categorized into 
299 
quartiles. The main predictors of the unadjusted GEE models were time (0, 1, 3, and 6 months), 
300 
intervention group, and their interactions. In an adjusted model, we added pre-specified covariates 
301 
including, race (Black vs. non-Black), ethnicity (Latino vs. non-Latino), gender (boy vs. girl), 
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health insurance (Public aid vs. Other), site enrolled (sites 1 to 6), number of all-cause acute care 
303 
use in the 12 months prior to enrollment (at least one vs. none). To access the intervention effect 
304 
between groups across time, we reported our results as odds ratios (ORs for higher quartiles) of 
305 
interactions between study group and time and their 98% confident intervals [CIs; corresponding 
306 
to a 2-sided alpha=0.0167) to account for Bonferroni adjustments for the three pairwise 
307 
comparisons.  
308 
 
309 
In secondary analyses, we explored heterogeneity of treatment effects by adding a three-way 
310 
interaction between intervention, time, and a subgroup factor in the model described previously. 
311 
Pre-specified subgroup factors included race (Black vs. non-black), ethnicity (Latino vs. non-
312 
Latino), gender (boy vs. girl), and number of all-cause acute care use in the 12 months prior to 
313 
enrollment (at least one vs. none). 
314 
 
315 
Power / sample size calculation. The power analyses did not incorporate adjustment for the 
316 
presence of two primary outcomes. Such an adjustment is not commonly made in biomedical 
317 
trials, as multivariate (viz. MANOVA) analyses are not commonly conducted. The power analysis 
318 
for single outcomes employed the Rochon (1991) method based on Hotelling's T-squared, which 
319 
was adapted to a 3-group comparison by adjusting the alpha level using a Bonferroni-style 
320 
technique.  This approach tends toward a conservative (larger) sample size.   We proposed to 
321 
enroll and randomize 640 participants over 18 months (~200-215 for each of the 3 treatment 
322 
groups).   Assuming evaluable data in 80% of enrolled participants (n=512) at 6 months (the time-
323 
point for the analyses of the primary outcomes), sample size calculations suggest ample power.  
324 
Our approach was based on the methods of Rochon, with a Bonferroni adjustment for 3 pair-wise 
325 
comparisons (2-sided α =0.05/3 =0.0167; enhanced usual care and two active intervention groups), 
326 
power 80%, 4 measurements per individual (0, 1, 3, and 6 months), within individual correlation 
327 
0.80, correction for within ED clustering (design effect of 2), and a coefficient of determination 
328 
(R2) for control of individual-level demographics = 0.15.  Based on these considerations, a sample 
329 
size of 426 (well within the expected sample size of 512) was estimated to be sufficient for a 
330 
minimum detectable difference of 0.35 standard deviations (SDs) (midway between Cohen’s 
331 
“small” (0.2 SDs) and “medium” (0.5 SDs) effect sizes) for each of the two primary continuous 
332 
outcomes compared pairwise across the three treatment groups. The minimum detectable 
333 
difference of 0.35 SDs corresponds to sufficient power to detect a T-score difference of 3.5, which 
334 
is approximately mid-way between estimates of the minimum important difference (MID) for 
335 
PROMIS T-scores (2 to 5).  
336 
 
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X.  Barriers and facilitators of successfully implementing the intervention (Secondary aim) 
339 
 
340 
Health system interventions are often multi-component, and when they successfully improve care or 
341 
outcomes, it is helpful to know whether all components of the intervention were necessary for 
342 
success.  Also, when care outcomes are not improved, it is unclear if barriers to implementation 
343 
(fidelity) or lack of efficacy contributed to a lack of effect. We therefore  a mixed -methods 
344 
approach to  1) assess the fidelity of implementing the ED-only and ED-plus-home interventions; 
345 
and 2) conduct interviews to debrief with study staff and a convenience sample of caregivers.    
346 
 
347 
(1) Intervention fidelity: We assessed our key performance indicators (see APPENDIX B) as 
348 
completed or not completed to measure the extent to which each patient received each component 
349 
of the CHICAGO Plan intervention, based on their allocation to the three treatment groups.   
350 
 
351 
(2) Focus groups:  We completed debrief interviews with caregivers to better understand if they 
352 
were satisfied with the content, comprehension, and relevance of the intervention material.  We 
353 
also asked about the satisfaction with the interventions provided by the ED coordinator and CHWs, 
354 
and any other comments the patient or caregiver would like to offer about how to improve the 
355 
CHICAGO Plan. We informed the participants that their responses would be used to help 
356 
determine how to improve studies in the future (UIC IRB # 2017-0888). 
357 
 
358 
(3) Interviews of ED Coordinators, DCC Research Assistants, and CHWs:  We asked study staff 
359 
provide feedback about barriers and facilitators to completing study procedures (e.g., space or time 
360 
constraints when providing ED-based instruction; availability of participants at scheduled home 
361 
visit times).  We informed study staff that their responses would be used to help determine how to 
362 
improve studies in the future (UIC IRB # 2017-0888). 
363 
 
364 
 
 
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XI. Timeline / milestones 
366 
 
367 
We originally proposed a 15 month recruitment period, which was extended to be 18 months 
368 
because of slow enrollment after approval by the Patient-Centered Outcomes Research institute. 
369 
The planned date for end of the follow-up was also modified to allow the last enrolled participant 
370 
to complete the 6-month follow-up assessment (primary endpoint).   
371 
  
372 
Key dates 
373 
 
Original date 
Final date  
(approved by study funder and 
DSMB)  
Start of enrollment 
March 1, 2015  
March 1, 2015 (no change)  
End of enrollment period 
May 31, 2016  
August 31, 2016  
End of study visits/data collection 
November 30, 2016  
March 31, 2017  
 
374 
 
375 
 
 
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XII. Protection of human subjects  
377 
 
378 
A. Risks to human subjects 
379 
 
380 
Human subjects involvement and characteristics 
381 
The trial aimed to include approximately 640 children ages 5-11 years and their caregivers.  The 
382 
eligibility criteria are discussed in an earlier section of this protocol.  Children and caregivers were 
383 
randomly allocated to 1) ED-only; 2) ED-plus-home; or 3) Enhanced usual care.  All participants 
384 
were asked to complete study procedures for at least 6 months, regardless of the group they are 
385 
assigned to; a study coordinator (masked to the treatment assignment) conducted assessment visits 
386 
at baseline, 1, 3, and 6 months post index ED visit.  
387 
 
388 
B. Sources of materials 
389 
 
390 
Sources of materials included: Questionnaires administered by the ED coordinator (baseline data), 
391 
and those administered by the DCC research assistant (follow-up data); Pharmacy dispensation 
392 
data and electronic health records (EHR); Direct observation (e.g., home inspection / completion 
393 
of environmental assessment checklist; review of inhaler technique using checklist). 
394 
 
395 
C. Potential risk 
396 
 
397 
Participants and caregivers were subject only to minimal risks through this research; we were 
398 
testing two different approaches to promoting guideline recommended care (ED-only; ED-plus-
399 
home) compared to usual Enhanced usual care.  Potential risks included inconvenience or 
400 
embarrassment involved in completing questionnaires or demonstrating self-management skills, or 
401 
permitting the CHW (or research assistant) to conduct home visits for interventions (or for 
402 
assessments), or in allowing the DCC to obtain pharmacy dispensation records (used for measuring 
403 
adherence).  The caregiver was not required to answer any questions (or conduct any part of the 
404 
study) that he/she was reluctant to discuss/conduct. There was also a risk of loss of confidentiality.  
405 
The CHW was instructed to avoid providing patients/caregivers with any type of medical advice, 
406 
but had direct access to health care providers to address any patient/caregiver clinical questions or 
407 
concerns. If the CHW was contacted about clinical questions, the CHW was instructed to connect 
408 
the participant/caregiver with a health care provider familiar with the participant’s medical 
409 
condition immediately. On enrollment, caregivers were instructed to call their health care provider 
410 
or seek emergency services in case of worsening symptoms, as opposed to directing questions to 
411 
the CHW. All participants were informed in advance that they may withdraw from the study at any 
412 
time without negatively affecting their medical care or any other benefits they might receive.  
413 
 
414 
D. Adequacy of protection against risks 
415 
 
416 
Recruitment and informed consent/assent 
417 
We sought informed assent in all children that were capable of providing assent (age ≥7 years old) 
418 
and permission of their caregiver in the ED. In children < 7 years old, consent was obtained from 
419 
the caregiver in the ED. As this study was no greater than minimal risk, the permission of only one 
420 
parent or guardian was sufficient for research to be conducted under the Additional Protections for 
421 
Children Involved as Subjects in Research (45 CFR Part 46.404). Assent from the child and 
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permission or consent from the parent/guardian was be obtained by the ED coordinator at each 
423 
participating clinical site. All staff were trained in informed consent/assent procedures and were 
424 
available to read the consent/assent forms to individual with low literacy levels. The consent/assent 
425 
forms were available in English and Spanish.  
426 
 
427 
All caregiver/family information, including contact information, questionnaires, pharmacy 
428 
dispensation and clinical information was available only available to  designated members of the 
429 
research team.  Case report forms were locked in cabinets and electronic data was stored on 
430 
password-protected files.  Only authorized study staff had access to study data.  Study reports 
431 
presented to external collaborators did not contain any identifiable information and findings were 
432 
presented in aggregate (or by treatment group).   
433 
 
434 
Incomplete disclosure 
435 
As participants in this trial were aware of which treatment group they are assigned to, there was a 
436 
risk for Hawthorne effect (change in behavior as a result of monitoring alone) and information bias 
437 
as it relates to answering questions for the patient-reported outcomes (the primary outcomes and 
438 
several secondary outcomes). Although there may have been changes in behavior (e.g., improved 
439 
adherence to corticosteroids), our studies and those of others have shown that monitoring does not 
440 
itself result in sustained adherence. To minimize this risk, however, there was incomplete 
441 
disclosure of the interventions in the CHICAGO study during informed consent. The study was 
442 
described as testing different communication strategies combining written and verbal instructions 
443 
to all participants.  Using doorknob hangers, as was successfully performed in a recent study, we 
444 
aimed to mask the participants.  Regardless of the arm the participant is randomized in, children 
445 
and caregiver/families will receive a doorknob hanger in the form of a plasticized document, 
446 
depicting one or more facts about asthma unrelated to the study interventions (e.g., 
447 
recommendations for influenza vaccinations).  To minimize the risk of bias, the DCC research 
448 
assistant who collected outcome data was be masked to the treatment group.  
449 
 
450 
Incomplete disclosure is generally necessary in studies of bias or social desirability (such as 
451 
monitoring of adherence) and is considered acceptable by medical ethicists, the American 
452 
Psychological Association, and IRBs when certain strict criteria are met. In designing this study, as 
453 
with previous studies conducted by Dr. Krishnan, we had been guided by the American 
454 
Psychological Association (APA) Ethics Code for conducting research.  Specifically, we believed 
455 
that incomplete disclosure was minimal risk to participants and was unavoidable since we were 
456 
proposing to monitor behavior while minimizing the risk of Hawthorne effect.  Moreover, we 
457 
followed the recommendations of the APA and Bersoff et al. that call for a full debriefing of 
458 
participants at the conclusion of the study. 
459 
 
460 
E. Potential benefits of the proposed research to the subjects and others 
461 
 
462 
It is difficult to know if the participants benefited from the research.  All study 
463 
participants/caregivers received instruction about appropriate MDI use with the teach-to-back 
464 
methodology; they also received two MDI spacers for their use.  Other than these specific benefits, 
465 
we did not indicate any benefits from participating.   
466 
 
 
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F. Importance of the knowledge to be gained 
468 
 
469 
African American and Latino children suffer disproportionate asthma outcomes compared to non-
470 
Latino whites, as evidenced by emergency department (ED) visits for uncontrolled asthma. This 
471 
study aimed to evaluate the effectiveness of using multi-level interventions to increase self-
472 
management skills and patient-centered outcomes in a minority pediatric ED population with 
473 
uncontrolled asthma. If this intervention proves successful, it could make a significant impact in 
474 
adherence to the asthma guidelines and equalize asthma care and health care utilization, among 
475 
African American and Latino children with asthma. Risks to participants and their caregivers 
476 
involved in the research were minimal.  
477 
 
478 
G.  Data safety monitoring plan 
479 
 
480 
The study was reviewed by the IRB at each participating institution and approval was sought 
481 
before study activities begin.  We also submitted IRB continuing reviews annually and adverse 
482 
event reports as specified by each IRB.  This study used a Data and Safety Monitoring Board 
483 
(DSMB) which included 5 individuals  who were not affiliated with any of the participating 
484 
institutions (1 chair with extensive expertise multi-center clinical trials, 2 pediatricians, 1 
485 
statistician, and 1 caregiver). The DSMB convened once in Year 1 (review/approve final study 
486 
protocol) and twice per year in Year 2 and Year 3.  The DSMB made affirmative decisions at each 
487 
meeting whether to continue or terminate the study.  Early termination was always an option for 
488 
the DSMB, particularly if there were serious concerns about patient safety or there is evidence of 
489 
futility or sufficient evidence of efficacy; decisions regarding early termination were made by the 
490 
DSMB during convened meetings. No interim analyses of outcomes for efficacy or futility were 
491 
planned before the study or requested by the DSMB throughout the study.  In general, the DSMB 
492 
was provided data grouped by treatment (i.e., masked to treatment assignment).  If the DSMB had 
493 
requested, for the purpose of competent deliberation, to see the treatment assignments (by group or 
494 
individual), these would have been provided by the DCC biostatistician.  Insofar as possible, the 
495 
investigators remained masked to the treatment assignments of individual patients unless it was 
496 
judged that it was in the best interests of an individual patient.   
497 
 
498 
H. ClinicalTrials.gov requirements 
499 
 
500 
This trial was registered in ClinicalTrials.gov prior to start of enrollment of participants. The 
501 
results of the trial will be reported within the required timeframe. The registration will be updated 
502 
and results be made available according to the requirements. 
503 
 
504 
I.  Inclusion of women and minorities 
505 
 
506 
The proportion of girls included in the study intended to mirror the prevalence of this condition in 
507 
the community and the patient population of the medical centers in which the study took place. 
508 
The study took place at different medical centers that serve a large number of racial or ethnic 
509 
minorities. The investigators anticipated that approximately 70% of participants would be African 
510 
American, 15% Latino, 8% Caucasian and 7% other (Asian, Native American, Pacific Islander) 
511 
reflecting the racial and ethnic background of our patient populations.  Minorities were enrolled as 
512 
they presented to enrollment sites, and Spanish-speaking participants were included. 
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XIII.  References 
514 
1. 
U.S. Department of Health and Human Services (HHS). Expert panel report 3: Guidelines for 
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the diagnosis and management of asthma. Bethesda, MD: HHS, National Heart, Lung and 
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Blood Institute, National Institutes of Health. Publication No. 07–4051. 2007. 
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http://www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-guidelines (accessed 
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November 30, 2017). 
519 
2. 
Centers for Disease Control and Prevention: AsthmaStats. 
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http://www.cdc.gov/asthma/asthma_stats/ accessed November 30, 2017). 
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Moorman JE, Akinbami LJ, Bailey CM, et al. National Surveillance of Asthma: United States, 
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2001–2010. National Center for Health Statistics. Vital Health Stat 3(35). 2012. 
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Akinbami LJ, Moorman JE, Simon AE, Schoendorf KC. Trends in racial disparities for 
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asthma outcomes among children 0 to 17 years, 2001-2010. J Allergy Clin Immunol.2014 
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Illinois Department of Public Health.  Asthma burden update, 2013.  
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http://www.iedasp.org/iedasp/AsthmaBurdenBrief_201305_final.pdf accessed November 30, 
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Cabana MD, Lara M, Shannon J. Racial and ethnic disparities in the quality of asthma care. 
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Crocker D, Brown C, Moolenaar R, Moorman J, Bailey C, Mannino D, Holguin F. Racial and 
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8.   National Heart, Lung, and Blood Institute.  National Asthma Education and Prevention 
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MU, Weiselberg L, Catrambone CD, Evans A, Kee R, Miller J, Kimmel L, Grammer LC. The 
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17. Krieger J, Takaro TK, Song L, Beaudet N, Edwards K. A randomized controlled trial of 
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18.  Crocker DD, Kinyota S, Dumitru GG, Ligon CB, Herman EJ, Ferdinands JM, Hopkins DP, 
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22.  Erwin K, Martin MA, Flippin T, Norell S, Shadlyn A, Yang J, Falco P, Rivera J, Ignoffo S, 
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24.  Erwin K, Norell S, Martin MA, Paik M, Press VG, Thompson TA, Krishnan JA.   Applying 
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design methods to care delivery science: Improving the care of minority children with 
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uncontrolled asthma and their caregivers who present to six Emergency Departments in 
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Chicago through a stakeholder-optimized discharge tool. Journal of Information Design 2017 
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25.   Krishnan JA, Martin MA, Lohff C, Mosnaim GS, Margellos-Anast H, DeLisa JA, McMahon 
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K, Erwin K, Zun LS, Berbaum ML, McDermott M, Bracken NE, Kumar R, Margaret Paik S, 
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54.  Patient-Reported Outcomes Measurement Information System. Dynamic Tools to Measure 
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56.   Hasegawa K, Sullivan AF, Tsugawa Y, Turner SJ, Massaro S, Clark S, Tsai CL, Camargo CA 
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Jr; MARC-36 Investigators. Comparison of US emergency department acute asthma care 
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quality: 1997-2001 and 2011-2012. J Allergy Clin Immunol. 2015 Jan;135(1):73-80. 
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57.  Hedeker D, Gibbons RD.   Longitudinal data analysis.  Hoboken, NJ: John Wiley & Sons, 
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Inc., 2006. 
707 
58.   Li P, Stuart EA, Allison DB. Multiple Imputation: A Flexible Tool for Handling Missing 
708 
Data. JAMA. 2015;314(18):1966-1967. 
709 
59.   Li Y, De A.  Multiple imputation by fully conditional specification for dealing with missing 
710 
data in a large epidemiologic study.  Int J Stat Med Res 2015; 4(3): 287-295. 
711 
60.  Anise A, Hasnain-Wynia R. Patient-centered outcomes research to improve asthma outcomes.  
712 
J Allergy Clin Immunol. 2016 Dec;138(6):1503-1510. 
713 
61.  Illinois Department of Public Health. Illinois Asthma State 
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Planhttp://www.dph.illinois.gov/sites/default/files/publications/publicationsohpmillinois-
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asthma-state-plan.pdf (accessed November 30, 2017) 
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XIV. Appendices 
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A. CAPE tool 
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B. Key performance indicators 
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APPENDIX A1.  CAPE -Asthma Discharge Plan (Version June 19, 2015) 
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APPENDIX A2. CAPE -Asthma Home Plan (Version May 22, 2015)  
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APPENDIX B: Key performance indicators 
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For each, we will monitor the % completion on a monthly basis at our Steering Committee meetings 
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and provide these key performance metrics to the DSMB prior to the scheduled meetings. 
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A. Emergency Department (ED)-level intervention performance metrics 
756 
 
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(1) 
Randomize n children/caregivers per month per site X 15 months (hereafter referred to as 
758 
participants).  The per-site n values are based on historical data from each site:   
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A. John H. Stroger Jr. Hospital of Cook County:  1.7 children/caregivers per month  
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B. Lurie Children’s Hospital of Chicago: 17.5 children/caregivers per month 
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C. Rush University Medical Center:  3.9 children/caregivers per month  
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D. Sinai Health System: 4.0 children/caregivers per month 
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E. University of Chicago: 12.7 children/caregivers per month 
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F. University of Illinois Hospital & Health Sciences System/University of Illinois at 
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Chicago: 2.6 children/caregivers per month 
766 
(2) 
% of participants who meet study eligibility criteria 
767 
(3) 
% of participants who have appropriate documentation of informed consent (written 
768 
informed consent and assent)  Age that assent is needed varies by site, listed below (site: age 
769 
for assent):  
770 
 
 
A. John H. Stroger Jr. Hospital of Cook County:  7 years old  
771 
 
 
B. Lurie Children’s Hospital of Chicago: 12 years old  
772 
 
 
C. Rush University Medical Center:  8 years old  
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D. Sinai Health System: 8 years old  
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E. University of Chicago: 8 years old  
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F. University of Illinois Hospital & Health Sciences System/University of Illinois at 
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Chicago:  7 years old  
777 
(4) 
% of participants who receive the intervention as per randomized treatment assignment:  (a) 
778 
for the Usual Care group, the ED coordinator provides MDI instruction and Doorknob 
779 
hanger;  (b) for CAPE group, ED coordinator provides MDI instructions, Doorknob hanger, 
780 
and completes the CAPE with the participants prior to ED discharge; (c) for ED-plus-home 
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group, ED coordinator provides MDI instructions, Doorknob hanger, completes the CAPE 
782 
with the participants prior to ED discharge, and arranges appointment for the first home visit 
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by the community health worker.   
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Additional ED-level performance indicators for participants assigned to CAPE groups (ED-only or 
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ED-plus-home):  
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788 
(5) 
% of participants who were prescribed a systemic corticosteroid for use after ED discharge 
789 
(as measured by documentation of a new prescription, an active prescription, or other 
790 
instructions to use systemic corticosteroids after discharge.)  
791 
(6) 
% of participants who)  were prescribed inhaled corticosteroids (or another controller) for use 
792 
after ED discharge (as measured by documentation of a new prescription, an active 
793 
prescription, or other instructions to use inhaled corticosteroids or another controller after 
794 
discharge) 
795 
(7) 
% of participants who received a post-ED follow-up appointment with the child’s provider 
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within 28  days of ED discharge (date/time/name),  
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(8) 
% of participants who were prescribed a rescue /quick-relief medication for use after ED 
798 
discharge (as measured by documentation of a new prescription, an active prescription, or 
799 
other instructions to use a rescue/quick-relief medication after discharge) 
800 
(9) 
% of participants who received instruction using teach-to-goal methodology to (a) increase 
801 
comprehension about (5) to (8), (b) green/yellow/red zones of the asthma action plan, and (c) 
802 
need to avoid known environmental triggers;  
803 
 
804 
The site project manager will conduct ED chart reviews within 3-4 business days of discharge for all 
805 
study participants to assess (5) to (9).  These data will be used to assess performance and to also 
806 
evaluate the extent to which there is contamination across treatment groups. Training or re-training 
807 
will be performed and documented on a case-by-case basis.  
808 
 
809 
B. Home visit-level intervention performance metrics (for participants randomized to ED-plus-
810 
home) 
811 
 
812 
Performance metrics for completion of home visits by community health worker (CHW) . We will 
813 
consider 3 levels of completion: within window, after window has ended, and not completed for the 
814 
following metrics: 
815 
(10) 
% of participants who receive Home Visit #1 within 3 business days of discharge (window 
816 
ends 3 business days after discharge) 
817 
(11) 
% of participants who receive Home Visit #2 within 17 calendar days of discharge (window 
818 
is 14 days +/- 3 calendar days) 
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(12) 
% of participants who receive Home Visit #3 within 37 calendar days of discharge (window 
820 
is 30 days +/- 7 calendar days) 
821 
(13) 
% of participants who receive Home Visit #4 within 97 calendar days of discharge (window 
822 
is 90 days +/- 7 calendar days) 
823 
(14) 
% of participants who receive Home Visit #5 within 187 calendar days of discharge (window 
824 
is 180 days +/- 7 calendar days) 
825 
 
826 
Performance metrics for completion of all elements of each home visit: 
827 
(15) 
% of participants who receive each of the following elements by the CHW during Home 
828 
Visit #1: introduction and explanation of the CHICAGO  Plan; review asthma action plan 
829 
developed in ED (CAPE); review of asthma basics; review of symptom recognition and 
830 
understanding of controlled (green zone) vs. uncontrolled asthma (yellow/red zones): teach-
831 
to-goal instruction about use of MDIs; assistance to develop a behavior change plan (related 
832 
to preceding elements) 
833 
(16) 
% of participants who receive each of the following elements by the CHW during Home 
834 
Visit #2:  review asthma action plan updated since ED discharge in collaboration with 
835 
patient’s provider (CAPE); review of asthma basics; review of symptom recognition and 
836 
understanding of controlled (green zone) vs. uncontrolled asthma (yellow/red zones): teach-
837 
to-goal instruction about use of MDIs; identification of and help with strategies to reduce the 
838 
3 major triggers; assess progress towards behavior change plan developed during home visit 
839 
#1 and assistance to develop updated plan (related to preceding elements); educate about 504 
840 
plan and how to submit paperwork (school nursing and administrative support)  
841 
(17) 
% of participants who receive each of the following elements by the CHW during Home 
842 
Visit #3:  review asthma action plan updated since ED discharge in collaboration with 
843 
patient’s provider (CAPE);  teach-to-goal instruction about use of MDIs; identification of and 
844 
help with strategies to reduce the 3 major triggers; assess progress towards behavior change 
845 
plan developed during home visit #2 and assistance to develop updated plan (related to 
846 
preceding elements); educate about 504 plan and how to submit paperwork (school nursing 
847 
and administrative support)  
848 
(18) 
% of participants who receive each of the following elements by the CHW during Home 
849 
Visit #4:  review asthma action plan updated since ED discharge in collaboration with 
850 
patient’s provider (CAPE);  teach-to-goal instruction about use of MDIs; identification of and 
851 
help with strategies to reduce the 3 major triggers; assess progress towards behavior change 
852 
plan developed during home visit #3 and assistance to develop updated plan (related to 
853 
preceding elements); educate about 504 plan and how to submit paperwork (school nursing 
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and administrative support)  
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(19) 
% of participants who receive each of the following elements by the CHW during Home 
856 
Visit #5:  review asthma action plan updated since ED discharge in collaboration with 
857 
patient’s provider (CAPE);  teach-to-goal instruction about use of MDIs; identification of and 
858 
help with strategies to reduce the 3 major triggers; assess progress towards behavior change 
859 
plan developed during home visit #4 and assistance to develop updated plan (related to 
860 
preceding elements); educate about 504 plan and how to submit paperwork (school nursing 
861 
and administrative support). 
862 
 
863 
The Data Coordinating Center collected these data in the REDcap database, which was used by the 
864 
CHW to document attempted and completed home visits.  The Supervising CHWs (from the Sinai 
865 
CHW Coordinator Center) accompanied CHWs during home visits in a sample of home visits to 
866 
review in-person site-specific CHW performance. Training or re-training was performed and 
867 
documented on a case-by-case basis. 
868 
 
869 
C. DCC data collection performance metrics (for all participants) 
870 
Performance metrics for data collection. We considered 3 levels of completion: within window, after 
871 
window has ended, and not completed for the following metrics:  
872 
 
873 
(20) 
% of participants with in-person BASELINE data collection prior to ED discharge 
874 
(21) 
% of participants with 1-month FOLLOW-UP data within 52 calendar days of discharge 
875 
(window is 38 days + 14 calendar days) 
876 
(22) 
% of participants with 3-month FOLLOW-UP data within 112 calendar days of discharge 
877 
(window is 98 days + 14 calendar days) 
878 
(23) 
% of participants with 6-month  FOLLOW-UP data within 202 calendar days of discharge 
879 
(window is 188 days + 14 calendar days) 
880 
(24) 
% of participants with 12-month FOLLOW-UP data within 367 calendar days of discharge 
881 
(window is 360 days +/- 7 calendar days); this data collection time-point is only for those 
882 
participants enrolled within first 7.5 months of enrollment period (50% of enrollment period) 
883 
to ensure there is adequate observation time for data collection at 12 months. 
884 
During the conduct of the study, we reviewed missing data and time to complete data collection; 
885 
these data were used to provide feedback and additional training to study staff as needed.  
886 
The Data Coordinating Center collected these data in the REDcap database, which will be used by 
887 
the DCC research assistants to document attempted and completed outcome assessments. Training or 
888 
re-training was performed and documented on a case-by-case basis. 
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The study design employed the “large simple trial” or “pragmatic trial” format, rather than an 
890 
efficacy design.  The target performance varied by metric.  For elements linked to human subjects 
891 
protection (e.g., obtaining written informed consent from the caregiver; assent from the child >7yrs), 
892 
the definition for major protocol deviation is <100%.  For elements linked to implementing the 
893 
interventions or data collection linked to specific time points, the definition for major protocol 
894 
deviation is <50%.   The goal is 100% performance on all metrics; we will ask site PIs to develop a 
895 
written corrective action plan if site-level performance for implementing the protocol is <80% 
896 
(<100% if there are deviations linked to human subjects protection).  We reported major protocol 
897 
deviations to the DSMB within 14 days after the event has been discovered by the contact PI.  
898 
Depending on the site-specific reporting requirements, we may also report major deviations to the 
899 
site’s Institutional Review Board (IRB); for example, we will report all instances where informed 
900 
consent was not obtained, but, depending on the institution may not need to report completion rates 
901 
of study visits prior to the annual continuing review date for that institution’s IRB. 
902 
 
903 
 
904