ED-Initiated School-based Asthma Medication Supervision
Phase: PHASE4
Conditions: Asthma, Asthma in Children
Sponsor: University of Arizona

ED-Initiated School-Based Asthma Medication
Supervision
(ED-SAMS)
PECARN Protocol Number 038
Pediatric Emergency Care Applied Research Network
National Heart, Lung, and Blood Institute (NHLBI)
Protocol Version 1.04
Version Date: March, 18, 2020
Printing Date: March 25, 2020

Copyright c⃝2016-2018. University of Utah School of Medicine on behalf of the
Principal Investigators, Lynn B. Gerald, PhD, MSPH and Kurt Denninghoﬀ, MD and the
Pediatric Emergency Care Applied Research Network (PECARN). All rights reserved.
This protocol is PECARN Protocol Number 038, and has been authored by Lynn B.
Gerald, PhD, MSPH and Kurt Denninghoﬀ, MD, University of Arizona, for implementa-
tion with the PECARN investigators. This study is supported by the National Heart,
Lung, and Blood Institute (NHLBI) awarded to the University of Arizona (PIs: Lynn B.
Gerald, PhD, MSPH and Kurt Denninghoﬀ, MD)
The PECARN Research Node Centers are the University of Michigan at Ann Ar-
bor, Cincinnati Children’s Hospital Medical Center, Columbia University, University of
California at Davis Medical Center, Children’s Hospital of Pittsburgh, and Children’s
National Medical Center and are supported by Cooperative Agreements U03-MC00003,
U03-MC22684, U03-MC00007, U03-MC00001, U03MC22685, and U03-MC00006 from the
Emergency Medical Services for Children (EMSC) Program, Maternal and Child Health
Bureau, Health Resources and Services Administration.
This document was prepared by the PECARN Data Coordinating Center (DCC)
located at the University of Utah School of Medicine, Salt Lake City, Utah. The document
was written and typeset using LATEX2ε. The DCC at the University of Utah is supported
by Cooperative Agreement U03-MC00008 from the Emergency Medical Services for
Children (EMSC) Program, Maternal and Child Health Bureau, Health Resources and
Services Administration.

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PROTOCOL TITLE:
ED-Initiated School-Based Asthma Medication Supervision
Short Title: ED-SAMS
PECARN Protocol Number: 038
Lead Investigators and Authors:
Lynn B. Gerald, PhD, MSPH and Kurt Denninghoﬀ, MD
University of Arizona
Protocol Version: 1.04
Version Date: March, 18, 2020
I conﬁrm that I have read this protocol, I understand it, and I will conduct the study
according to the protocol. I will also work consistently with the ethical principles that have
their origin in the Declaration of Helsinki and will adhere to the Ethical and Regulatory
Considerations as stated. I conﬁrm that if I or any of my staﬀare members of the Insti-
tutional Review Board, we will abstain from voting on this protocol, its future renewals,
and its future amendments.
Principal Investigator Name:
Principal Investigator Signature:
Date:
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Contents
1
Study Summary
9
1.1
Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9
1.2
Speciﬁc Aims . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9
1.3
Primary Endpoints . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9
1.4
Secondary Endpoint
. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
10
1.5
Subject Eligibility, Accrual and Study Duration . . . . . . . . . . . . . .
10
2
Introduction
11
2.1
Study Rationale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
11
3
Background
12
3.1
Signiﬁcance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
12
4
Study Design
13
4.1
Study Design Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . .
13
4.2
Participant Screening and Enrollment . . . . . . . . . . . . . . . . . . . .
14
4.3
Baseline Data Collection . . . . . . . . . . . . . . . . . . . . . . . . . . .
14
4.4
Follow-up Data Collection . . . . . . . . . . . . . . . . . . . . . . . . . .
14
4.5
PECARN Registry Data Review . . . . . . . . . . . . . . . . . . . . . . .
15
5
Study Procedures
16
5.1
Randomization and Enrollment . . . . . . . . . . . . . . . . . . . . . . .
16
5.2
Withdrawal From Study . . . . . . . . . . . . . . . . . . . . . . . . . . .
18
6
Data Analysis
18
6.1
Speciﬁc Aim Analyses
. . . . . . . . . . . . . . . . . . . . . . . . . . . .
19
6.2
Sample Size Calculations and Statistical Power . . . . . . . . . . . . . . .
21
6.3
Populations for Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . .
22
7
Data Management
22
7.1
Clinical Site Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
22
7.2
Electronic Data Capture System . . . . . . . . . . . . . . . . . . . . . . .
22
7.3
Study Monitoring
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
23
7.3.1
Pharmacy Monitoring
. . . . . . . . . . . . . . . . . . . . . . . .
23
7.4
Data Coordinating Center . . . . . . . . . . . . . . . . . . . . . . . . . .
23
7.4.1
Data Center Description . . . . . . . . . . . . . . . . . . . . . . .
23
7.4.2
Security and Conﬁdentiality . . . . . . . . . . . . . . . . . . . . .
25
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7.5
Record Access . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
26
8
Protection of Human Subjects
26
8.1
Institutional Review Board Approval . . . . . . . . . . . . . . . . . . . .
26
8.2
Informed Consent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
27
8.3
Potential Risks
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
27
8.3.1
Known Potential Beneﬁts
. . . . . . . . . . . . . . . . . . . . . .
28
8.3.2
Assessment of Potential Risks and Beneﬁts . . . . . . . . . . . . .
28
8.4
Adverse Events, Serious Adverse Events and Unanticipated Problems . .
29
8.4.1
Adverse Events . . . . . . . . . . . . . . . . . . . . . . . . . . . .
29
8.4.2
Time Period for Adverse Events . . . . . . . . . . . . . . . . . . .
31
8.4.3
Data Collection Procedures for Adverse Events
. . . . . . . . . .
32
8.4.4
Unanticipated Problems . . . . . . . . . . . . . . . . . . . . . . .
32
8.4.5
Monitoring Serious Adverse Events . . . . . . . . . . . . . . . . .
32
8.4.6
Follow-up of Serious, Unexpected and Related Adverse Events . .
33
9
Data and Safety Monitoring Plan
34
9.1
Data Safety Monitoring Board
. . . . . . . . . . . . . . . . . . . . . . .
34
9.2
Planned Interim Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . .
34
9.3
Study Discontinuation and Closure . . . . . . . . . . . . . . . . . . . . .
34
10 Study Training
35
10.1 Study Training
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
35
11 Regulatory Issues
35
11.1 Food and Drug Administration
. . . . . . . . . . . . . . . . . . . . . . .
35
11.2 Health Insurance Portability and Accountability Act
. . . . . . . . . . .
36
11.3 Inclusion of Women and Minorities . . . . . . . . . . . . . . . . . . . . .
36
11.4 ClinicalTrials.gov Requirements . . . . . . . . . . . . . . . . . . . . . . .
36
11.5 Retention of Records . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
36
12 References
37
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Nomenclature
AE: Adverse Event
CEA: Cost Eﬀectiveness Analysis
DCC: Data Coordinating Center
DSMB: Data Safety Monitoring Board
ED: Emergency Department
ED-SAMS: ED-Initiated School-Based Asthma Medication Supervision
FDA: Food and Drug Administration
HEDA: Hospital Emergency Department Aﬃliates
HIPAA: Health Insurance Portability and Accountability Act
IRB: Institutional Review Board
ICS: Inhaled Corticosteroid
MARs: Medication Administration Record
MedDRA: Medical Dictionary for Regulatory Activities
NAEPP: National Asthma Education and Prevention Program
NHLBI: National Heart Lung and Blood Institute
PECARN: Pediatric Emergency Care Applied Research Network
PI: Principal Investigator
RA/RC: Research Assistant/Research Coordinator
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Abstract
Asthma is a common chronic condition that causes substantial morbidity among
children and much of it is attributable to medication non-adherence.1, 2 The National
Asthma Education and Prevention Program (NAEPP) and the American Academy
of Asthma, Allergy, and Immunology have urged others to develop more eﬀective
adherence programs.3, 4 Schools are a logical setting to deploy such interventions
because they are where children congregate, spend much of their day, and are
frequently monitored.5 Because many schools serve a high proportion of minority
and low-income students, engaging them presents a unique opportunity to reach
populations who experience the greatest burden of preventable morbidity.
Supervising inhaled corticosteroid (ICS) use in the school setting can increase
medication adherence and reduce episodes of poor asthma control.6 Under certain
conditions, it can also be cost-eﬀective.7 However, recruiting children from school
settings tends to enroll children with mild asthma and infrequent health care use.8
Therefore, initiating supervised treatment in these children tends to burden school
personnel with unnecessary work and diminishes the program’s cost-eﬀectiveness.
To address this ineﬃciency, we propose to recruit children who are discharged from
the Hospital Emergency Departments (EDs) following successful treatment of an
asthma attack. Such children have much higher risk of a future asthma attack than
their peers.9
The Pediatric Emergency Care Applied Research Network (PECARN) com-
prises10 hospital-aﬃliated EDs that serve 1 million acutely ill and injured children
annually. Their primary research mission is to reduce childhood morbidity and
mortality by establishing creative partnerships between emergency medical service
providers and their surrounding communities. The networks size and geographic
diversity make it uniquely situated to develop, implement, and evaluate the feasibil-
ity and eﬀectiveness of ED-Initiated School-Based Asthma Medication Supervision
(ED-SAMS).
Approximately one-third of children treated for an asthma attack within PECARN
experience a second ED-managed attack within 6 months. While the NAEPP guide-
lines recommend that long-term ICS treatment should be initiated at ED discharge,11
<20% of children actually receive a prescription for controller therapy.12, 13 Obser-
vational data indicate that patients who use ICS following discharge are almost half
as likely as non-users to experience a repeat ED visit.14 Many have also argued
that ED-initiated treatment could be cost-eﬀective.14–16 However, simply providing
patients with a prescription does not ensure that they will actually use it once
discharged.10, 17–23 To ensure better medication adherence, we propose to dispense
ICS at discharge and supervise its use in the school setting.6, 7
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1
Study Summary
We intend to demonstrate that Pediatric Emergency Care Applied Research Network
(PECARN) Emergency Departments (EDs) can dispense inhaled corticosteroid (ICS)
and arrange its use in the school setting following successful management of an asthma
attack. Furthermore, we intend to demonstrate this intervention is well-accepted by
families, clinicians, and schools. Successful completion of this preliminary trial will inform
the development of a larger multicenter trial to determine ED-Initiated School-Based
Asthma Medication Supervision (ED-SAMS) eﬀectiveness and cost-eﬀectiveness among
elementary-age children with mild-to-moderate asthma treated in PECARN EDs.
1.1
Hypothesis
The hypothesis of this preliminary study is that ED-SAMS will be feasible to conduct,
and it will be acceptable to the providers, schools and families.
1.2
Speciﬁc Aims
This project has the following Speciﬁc Aims:
Speciﬁc Aim 1. Determine the feasibility and acceptability of dispensing inhaled cor-
ticosteroids in the emergency department and supervising its use in the school
setting.
Speciﬁc Aim 2. Estimate a range of plausible intervention eﬀect sizes to support the
development of a larger multi-center clinical trial.
Speciﬁc Aim 3. Conduct a preliminary cost-eﬀectiveness analysis (CEA).
1.3
Primary Endpoints
The primary endpoints of this study are to:
1. Evaluate our ability to recruit 90 participants within a 6-month period,
2. Evaluate our ability to initiate supervised ICS use in the school setting within 5
business days,
3. Evaluate our ability to retain participants for the 90-day intervention period,
4. Evaluate our ability to eﬀectively collect asthma severity data during the study
period, and
5. Evaluate caregiver, school, and ED provider satisfaction with the ED-SAMS program.
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1.4
Secondary Endpoint
The secondary endpoint of this study is to estimate a conﬁdence interval of the interven-
tion’s eﬀect size and conduct a preliminary CEA.
1.5
Subject Eligibility, Accrual and Study Duration
Eligible participants will be identiﬁed by on-site study staﬀ.
Inclusion criteria are:
1. Children 6-12 years of age; AND
2. Treated for an asthma exacerbation as determined clinically by the principal ED
provider based on symptoms such as shortness-of-breath, cough, and wheezing;
AND
3. Symptoms must improve following ≥1 dose of albuterol and ≥1 dose of systemic
corticosteroids such that he/she can be safely discharged home; AND
4. Must have physician-diagnosed asthma as reported by parents or documented in
the electronic medical record.
Exclusion criteria are:
1. Attends a non-participating school; OR
2. Attends a participating school less than 5x/week; OR
3. Enrolled in another research study; OR
4. Patients who are hospitalized; OR
5. The patient or their consenting parent/guardian does not speak English or Spanish;
OR
6. ICU admissions for asthma in the past year; OR
7. History of ≥2 hospitalizations for asthma in past year; OR
8. History of ≥2 controller medications for asthma in the past 30 days; OR
9. Study medication represents a step-down in asthma therapy in the judgement of
the ED physician; OR
10. Parent does not have a cell phone; OR
11. Parent cannot send and receive text messages.
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2
Introduction
2.1
Study Rationale
Asthma is a common chronic condition that causes substantial morbidity among children;
much of it is attributable to medication non-adherence.1, 2 The National Asthma Educa-
tion and Prevention Program (NAEPP) and the American Academy of Asthma, Allergy,
and Immunology have urged others to develop more eﬀective adherence programs.3, 4
Schools are a logical setting to deploy such interventions because they are where children
congregate, spend much of their day, and are frequently monitored.5 Because many
schools serve a high proportion of minority and low-income students, engaging them
presents a unique opportunity to reach populations who experience the greatest burden
of preventable morbidity.
Supervising ICS use in the school setting can increase medication adherence and
reduce episodes of poor asthma control.6 Under certain conditions, it can also be cost-
eﬀective.7 However, recruiting children from school settings tends to enroll children with
mild asthma and infrequent health care use. Therefore, initiating supervised treatment in
these children tends to burden school personnel with unnecessary work and diminishes the
program’s cost-eﬀectiveness.8 To address this ineﬃciency, we propose to recruit children
who are discharged from the ED following successful treatment of an asthma attack. Such
children have much higher risk of a future asthma attack than their peers.9 PECARN
comprises10 hospital-aﬃliated EDs that serve 1 million acutely ill and injured children an-
nually. Their primary research mission is to reduce childhood morbidity and mortality by
establishing creative partnerships between emergency medical service providers and their
surrounding communities. The network’s size and geographic diversity make it uniquely
situated to develop, implement, and evaluate the feasibility and eﬀectiveness of ED-SAMS.
Approximately one-third of children treated for an asthma attack within PECARN
experience a second ED-managed attack within 6 months. While the NAEPP guidelines
recommend that long-term ICS treatment should be initiated at ED discharge,11 <20%
of children actually receive a prescription for controller therapy.12, 13 Observational data
indicate that patients who use ICS following discharge are almost half as likely as non-users
to experience a repeat ED visit.14 Many have also argued that ED-initiated treatment
could be cost-eﬀective.14–16
However, simply providing patients with a prescription
does not ensure that they will actually use it once discharged.10, 17–23 To ensure better
medication adherence, we propose to dispense ICS at discharge and supervise its use in
the school setting.6, 7
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3
Background
3.1
Signiﬁcance
Approximately 8% of children in the United States have asthma. Each year, these chil-
dren experience 4 million asthma attacks that result in 725,000 ED visits and 100,000
hospitalizations. Unsurprisingly, the direct medical expenditures of children with asthma
are 75-90% higher than those of children without asthma. In 2016, this amount totaled 40
billion dollars. Substantial indirect costs are incurred when parents miss work to care for
their children who miss school. These additional costs raise the total economic burden of
asthma to $80 billion annually. Frequent asthma-related school absences impair academic
achievement and social functioning. This burden falls disproportionately on minority,
low-income, and urban populations. For example, black children have 60% more ED visits
and 75% more hospitalizations than white children even though they have similar asthma
attack rates.
Adherence to ICS is notoriously poor.20, 22, 23 While 86% of privately insured patients
who receive an ICS prescription will ﬁll it within 30 days, only 64% will subsequently
reﬁll it again within 180 days. Even worse, only 3% will ﬁll enough medication to cover
≥75% of prescribed days with average medication possession being approximately 20%.
Black and Hispanic patients are 20% less likely to ﬁll their initial prescription and are
40% less likely to reﬁll enough medication to cover ≥75% of prescribed days. Adherence
is similarly poor among the publicly insured. Among Medicaid-insured children, ICS is
only reﬁlled enough to cover 20% of prescribed days; fewer than 15% will ﬁll enough to
cover ≥50% of days.
At any given time, 40% of children with asthma are not well-controlled and much
of this is attributable to nonadherence. Simulation and modeling studies suggest that
maximizing ICS adherence among those prescribed ICS could reduce health care utiliza-
tion by 25-45%. Even greater reductions are hypothesized if ICS prescribing could be
expanded to all patients at risk of serious asthma-related exacerbations. However, a recent
Cochrane review concluded that current methods of improving adherence for chronic
health problems are mostly complex and not very eﬀective. New adherence strategies will
be needed if society is to achieve the gains suggested possible by simulations.
Medication non-adherence among patients with chronic disease is a multi-dimensional
challenge. The cost and convenience of obtaining medication (health system factors) and
the motivation needed to adhere with a daily health habit (patient-related factors) are
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common barriers to adherence that are addressed by this study. Medication acquisition
costs deter patients from ﬁlling and reﬁlling prescription medications. Even small $1-3
co-payments can appreciably reduce adherence. However, imposing additional time costs
by requiring more frequent reﬁlls has an even greater impact. Time costs can add $50-100
per prescription. Therefore, the $155 out-of-pocket spending estimate for children’s
asthma medication likely understates the true economic burden. Dispensing ICS in the
ED is therefore expected to improve adherence by reducing the substantial time and
travel costs associated with medication acquisition.
ICS treatment also burdens patients by requiring them to adopt a daily health habit.
For children, this burden primarily falls on parents. Parents weigh the perceived beneﬁts
of treatment against their perceptions of treatment risk and burden. Given that asthma
symptoms ﬂuctuate in response to treatment and season, many purposefully reduce
medication administration when their child’s symptoms wane (volitional non-adherence).
In the absence of treatment, the underlying inﬂammation is allowed to worsen and
exacerbation risk increases. This reactive pattern of medication use is substantiated by
the fact that 37% of all prescriptions for ICS are ﬁlled on the same day as prescriptions
for oral corticosteroid, suggesting after the exacerbation, not before it.18 Even more
disturbing, less than 50% of children who ﬁlled a prescription for oral corticosteroid
were ever noted to have ﬁlled an ICS prescription, meaning most lacked any access to
controller medication.18 Our proposal addresses the problem of primary non-adherence
by dispensing medication in the ED and addresses non-adherence by arranging supervised
use in the school setting.
4
Study Design
4.1
Study Design Overview
We propose to evaluate the feasibility and acceptability of ED-SAMS among elementary-
age children with mild-to-moderate asthma who are discharged from the ED following
an asthma attack. Children will be randomized to ED-dispensing with home supervision
or ED-dispensing with home and school supervision. All children will be treated with a
standardized medication regimen consisting of once-daily budesonide inhalation powder
supplemented by as-needed albuterol sulfate.
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4.2
Participant Screening and Enrollment
Research staﬀwill approach parents of children who are being treated for symptoms con-
sistent with an asthma attack. The research staﬀwill explain the study and will provide
parents with a brief written description. Written parental permission will be obtained
from parents; assent, as applicable, will be obtained from children. Given a 6-hour turn-
around between presentation and discharge within PECARN EDs, we anticipate adequate
time will be available to identify, recruit, and evaluate study participants. To ensure all
participants can complete 90 days of school-supervised treatment before summer break,
recruitment will commence at the beginning of the school year (e.g., September) and
cease in March.
To achieve our 90 participant goal, each site will be expected to enroll approximately
8 participants per month during the study enrollment windows.
4.3
Baseline Data Collection
Successful implementation of ED-SAMS will require EDs to distribute medication to
schools in a timely manner and schools to administer it daily. While we are conﬁdent that
schools will be willing and able to administer asthma medications at school, a number
of administrative barriers must be overcome before medication administration can be
initiated. For example, speciﬁc forms must be completed by parents and physicians and
medication with appropriate labeling must be supplied to the school. With the support of
the ED-SAMS outreach unit at the University of Arizona, ED personnel will complete all
required forms prior to the child’s discharge. These completed forms and the individually
labeled medication will then be couriered to the school’s health oﬃce within 5 business
days. We expect to accomplish this for ≥90% of participants. With the support of the
ED-SAMS outreach unit, phone contact will be made to each school’s health oﬃce to
ensure and document successful initiation of the ﬁrst medication dose.
A variety of data will be collected from multiple sources including, but not limited to,
recruitment and enrollment logs, the electronic medical record, parent and participant
surveys, and school medication administration records.
4.4
Follow-up Data Collection
Parent follow-up interviews (telephone) and a text message survey will commence approx-
imately 30 days after enrollment and will continue monthly until at least 120 days post
randomization. To help ensure ≥67% of parent interviews are completed at the 120-day
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mark, multiple calls will be attempted on home and cell-phone numbers at multiple times
including nights and weekends. Parents will also be provided $40 per completed call and
$1 for each text answered, a total of $10 if all texts are answered. The total compensation
is $190 if all phone interviews and texts are completed. Because the notion of asthma
control (or symptom reduction) remains an important outcome, we will ask parents about
their child’s asthma symptoms and albuterol use during each of the monthly telephone
interviews and text message surveys. We will ask parents about their child’s at-home
medication use during the telephone interviews, as well.
An important determinant of our success will be parent and ED provider satisfaction.
Parents who participated in either the “ED-dispensing with home and school supervision”
or the “ED-dispensing with home supervision” arm will be asked to rate their satisfaction
with the ED-SAMS program at the 120-day follow-up interview. School health personnel
responsible for medication administration will be asked to complete a survey to rate their
satisfaction with the ED-SAMS program. The survey will be made available near the end
of the study to ensure ample time is available to make multiple solicitation attempts. ED
providers will also be asked to complete a survey after the patient is discharged from the
ED.
To ensure that schools are able to consistently administer ICS, we will audit the
schools’ medication administration records. Schools are typically required to document
administration of all prescription medications.
4.5
PECARN Registry Data Review
The PECARN Registry, a continuously accruing multicenter clinical data repository of
electronic health record data from seven pediatric sites, is comprised of more than 4.4
million overall pediatric ED visits and 17,000 ED visits annually for children with asthma.
The University of Arizona will send aggregate summary data from 2016 and 2019
around how many asthma patients were seen in the ED, how many patients had insurance
coverage, and how many patients were on medication regimens speciﬁc to asthma. The
DCC will combine these aggregate summaries with the summaries produced through
PECARN Registry.
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5
Study Procedures
5.1
Randomization and Enrollment
Eligible participants will be randomly assigned on a 1:1 basis to receive either guideline
concordant care (ED-dispensing with home supervision) or ED-dispensing with home and
school supervision. The randomization protocol will be determined by the DCC using a
block permutation design to ensure balanced randomization given the small sample sizes
required at each site.
Within the ED, care will be provided at the sole discretion of the primary ED provider
including all tests, procedures, and treatments deemed appropriate to restore pulmonary
function and safely discharge the participant home. At discharge, participants will be
assigned to either:
• ED-dispensing with home supervision (control): Participants will receive 2-3
medications:
1. Oral prednisolone based on body weight to achieve a daily dose of 2mg/kg/day
not to exceed 40 mg per day for 5 days or its equivalent (provided in the
emergency department),
2. 360 µg of budesonide inhalation powder once-daily for at-home use, and
3. albuterol sulfate as needed for relief of acute respiratory symptoms.
Given 120 doses per budesonide inhaler at 2 puﬀs per day, two inhalers will be dis-
pensed therefore ensuring ≥90 days of medication coverage. Once-daily budesonide
at 360 µg per day has been shown to be safe and eﬃcacious by several randomized
controlled trials for the treatment of mild-to-moderate asthma. All participants
will be advised and/or scheduled to complete a follow-up visit with their child’s
healthcare provider within 7 days of ED discharge. The ED staﬀwill communicate
with healthcare providers to inform them of the child’s study participation and their
assigned medication regimen. Parents will also receive a copy of the letter to take to
their child’s follow-up visit. Each participant will receive general asthma education
including speciﬁc training on how to use the inhaler.
• ED-dispensing with home and school supervision (intervention): Partici-
pants will receive care as described above for home use and additional inhalers
will be couriered to the child’s school health oﬃce within 5 business days after
ED discharge. School health personnel will supervise the child’s use of once-daily
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budesonide each school day that the child is present. Parents will be instructed to
supervise their child’s at-home use only on weekends, holidays, and school absences.
Consenting participants may already be taking an inhaled corticosteroid at the
time of ED arrival. At ED discharge, their current inhaled corticosteroid will
be discontinued and replaced by the study’s budesonide inhalation powder.
The school health oﬃce will also receive an Asthma Action Plan that details the partic-
ipant’s medication regimen, explains how to recognize and respond to worsening asthma
symptoms, and describes when to activate the emergency medical services system. The
Clinical Site PI’s name will be listed on the Asthma Action Plan and school health person-
nel will be encouraged to facilitate follow-up with this practitioner if needed. Training will
be made available to school nurses, health assistants, and/or administrative personnel that
provides general asthma knowledge and demonstrates proper inhaler technique. In our
experience, even after viewing the web-based training, school health personnel may have
remaining questions about proper inhaler technique or need reinforcement of appropriate
asthma management techniques. Therefore, we will establish a toll-free “hotline” staﬀed
during school hours for the clinical centers involved (eastern and central time zones)
by experienced school health research personnel at the ED-SAMS outreach unit at the
University of Arizona to address unanswered questions. Anticipated advice will include
proper inhaler technique and storage, communication strategies for engagement of the
child’s healthcare provider, and general asthma management. We will take care to ensure
school personnel do NOT use the hotline in lieu of 911 for the treatment of asthma
emergencies.
To ensure medication reaches the participant’s school in a timely manner, the ED
personnel will forward the information needed to initiate school-supervised treatment to
the ED-SAMS outreach unit at the University of Arizona. The ED personnel will also
complete the necessary steps to initiate medication administration including:
1. preparing the medication with a personalized label, administration instructions, and
the prescribing physician’s name and
2. completing the district’s required medication administration records which typically
require signatures from parents and sometimes physicians.
With the support of the ED-SAMS Outreach Unit sites will ensure that all necessary
forms are available at each ED. Within 5 business days of randomization, while school is
in session, the following will happen: the school health oﬃce will be contacted to:
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1. conﬁrm initiation of medication administration,
2. communicate the method and timing of medication delivery, and to
3. arrange web-training for personnel with administration authority.
Once conﬁrmation is received, medication will be released by hospital courier delivery to
the school’s health oﬃce. To accomplish these activities, we will rely on our experience
developing similar protocols in other populations and settings.6
5.2
Withdrawal From Study
Parents may withdraw their child from participation in this study at any time. We will
not be able to collect new information about their child, and they will be withdrawn from
the research study. However, we can continue to use information we have already started
to use in our research, as needed to maintain the integrity of the research.
6
Data Analysis
The hypothesis of this preliminary study is that ED-SAMS will be feasible to conduct,
and it will be acceptable to the providers, schools and families.
ED-SAMS is hypothesized to reduce exacerbation risk by increasing adherence with
daily controller medication. There are 4 major outcomes of interest: our ability to recruit
and retain participants, our ability to initiate school-supervised medication administration,
and participant satisfaction. We will also conduct a preliminary CEA to identify potential
cost-centers, reﬁne measurement procedures, and inform future decision modeling.
This pilot trial is intended to inform the design of a larger multi-center clinical trial
that capitalizes on the full experience, infrastructure, and reach of the 18 PECARN sites.
The future trial is anticipated to be a multi-center randomized controlled 3-arm trial
where children are randomized to receive ED-based prescribing with home supervision
(guideline concordant care and control arm) or ED-based dispensing with home supervision
or ED-based dispensing with home and school supervision. This design allows the impact
of dispensing to be diﬀerentiated from the mode of supervision. Because our current goal
is to determine feasibility, we have included the two intervention arms: ED-dispensing
with home supervision and ED-dispensing with home and school supervision.
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Ninety children (45 per arm) from 3 participating EDs will be randomized to receive
ED-dispensing with home supervision or ED-dispensing with home and school supervision.
The primary outcome, 90-day ED recidivism, will be obtained from medical record review;
60-day and 30-day recidivism will be evaluated as secondary outcomes. The purpose of
estimating the potential impact of the intervention on 90-day recidivism is three-fold:
ensure that recidivism can be accurately tracked among this population of children,
estimate which follow-up period is most sensitive to the intervention, and estimate a
plausible eﬀect size. These elements inform feasibility of ED-recidivism as an outcome
and help establish an appropriate sample size for a planned larger clinical trial.
6.1
Speciﬁc Aim Analyses
Speciﬁc Aim 1. Determine the feasibility and acceptability of dispensing inhaled cor-
ticosteroids in the emergency department and supervising its use in the school
setting.
There are 4 important areas of interest: recruitment feasibility, intervention feasibility,
participant retention, and intervention acceptability. Assessing the extent to which we
can accomplish our goals and successfully engage with families, schools, and clinicians
will help determine the appropriateness and design of a future multi-center randomized
controlled trial.
The PECARN Registry will be used to summarize school-aged asthma patients seen
in participating PECARN Registry Emergency Departments (EDs) for active asthma
exacerbations in years 2016 and 2019. The total number of asthma visits seen by each
ED will be summarized along with insurance status and current medications being taken
by patients. Information about controller medications collected in the Registry will be
evaluated and categorized in order to deﬁne the type of controller medication in use at
the time of the ED Visit. Data will be summarized for each ED using summary statistics
(means/medians and frequencies/percents). The primary outcome is whether or not a
child is on monotherapy at the time of ED arrival. Statistical tests (e.g., chi-square and
Cochran-Mantel-Haenszel tests stratiﬁed by ED) will compare characteristics of asthma
patients between the two years. Individual chi-square tests will be reported for the primary
outcome for each hospital. Sensitivity analyses will also be performed looking at the data
in aggregate.
Speciﬁc Aim 2. Estimate a range of plausible intervention eﬀect sizes to support the
development of a larger multi-center clinical trial.
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While the primary purpose of the ED-SAMS pilot is to determine the feasibility and
acceptability of the proposed intervention, we will also estimate the conﬁdence interval of
the intervention’s eﬀect size. We are aware that small samples such as this one yield large
standard errors and wide conﬁdence intervals. However, we still believe this pilot data
will be informative with regard to the intervention’s potential impact and whether future
trials are likely to hold promise. Furthermore, the results can inform future analytic
approaches and suggest a plausible range of potential eﬀect sizes. As such, the focus will
not be on signiﬁcance testing but rather on estimating eﬀect sizes and corresponding
conﬁdence intervals. Enrollment rate (subjects enrolled out of those eligible during
enrollment windows) will be estimated using the observed proportions and exact binomial
95% conﬁdence intervals. Rates of ED recidivism within 90 days and corresponding
conﬁdence intervals will be estimated in a similar fashion.
Speciﬁc Aim 3. Conduct a preliminary cost-eﬀectiveness analysis (CEA).
The primary outcome will be dollars per averted ED visit. ED visits are an objective
measure of exacerbation risk that are salient to patients, payers, and policymakers. While
ED visits themselves represent only 5% of asthma-related health spending, the ED is
the primary access point to costly inpatient care. For example, the mean cost of an
asthma-related ED visit is approximately $600; however, about 15% of children treated
in the ED are admitted for inpatient care which costs about $4000 per inpatient stay.
Therefore, averting a single ED visit could yield $1200 in cost-oﬀsets ($600 plus 15% of
$4000).
To the extent possible, the analysis will follow the International Society for Phar-
macoeconomics and Outcomes Research best practices for CEA conducted alongside
clinical trials. However, this analysis will deviate from these recommendations in two
important ways. First, the primary outcome is not a comprehensive measure of well-being
(e.g., quality-of-life) that captures all of the relevant impacts of asthma. While this
recommendation is well-founded, there are no existing instruments that can reliably
capture quality-of-life, or more speciﬁcally, the preference-based utility weights needed
to derive quality-adjusted life-years. We (Joe K. Gerald and Lynn B. Gerald) have
considerable experience using the Pediatric Asthma Health Outcome Measure, a tool
designed to prospectively capture quality-adjusted life-years in children with asthma. We
have found it to be diﬃcult to administer and its measurement properties unsuited for its
intended role. Lacking a suitable alternative, we have chosen to rely instead on averted
ED visits. In a second major deviation, we have chosen to use the payer, rather than
societal perspective. The major implication of this decision is to ignore beneﬁts that
might accrue to patients and their families, meaning we will tend to underestimate the
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intervention’s cost-eﬀectiveness. We recognize this as an important limitation, but we also
recognize that society does not “write checks”. Our primary intention is to demonstrate
to third-party payers that their investment could be worthwhile. The time horizon will
comprise the 90-day treatment window as we anticipate all intervention beneﬁts and costs
will accrue during this window. Because of the short time horizon, it will not be necessary
to discount future costs or beneﬁts.
A decision-analytic model will be developed that incorporates not only the point
estimates of the various parameters but also the uncertainty surrounding them (e.g.,
95% conﬁdence interval). In addition to standard one-way and two-way deterministic
sensitivity analysis, the model will also use a probabilistic sampling strategy to estimate
overall model stability and generate a pseudo-95% conﬁdence interval based on multiple
iterations (e.g., 10,000 runs). This strategy will help identify the most inﬂuential model
assumptions and those parameters that if estimated with greater precision would mean-
ingfully improve the model’s predictive power.
All resources required to implement school-based supervision will be measured including
medication courier fees. Asthma-related medical costs (e.g., ED visits) will be estimated
using a gross-costing method where costs are bundled by service type (e.g. $600 per ED
visit) rather than micro-costing where costs are individually aggregated (e.g. nursing
time, medication, procedure costs at each ED visit). Gross-costing is more practical and
reliable than micro-costing when a wide variety of service events and locations are being
measured. Our primary source of cost data will come from medical record review to
identify asthma-related ED visits; however, this will be supplemented by research logs
(e.g. intervention-related personnel time and courier fees) and parent interviews (e.g.,
prescription ﬁlls for ICS albuterol among the control group). Where possible or needed
these data will be crosschecked against existing estimates from secondary sources such as
the published literature.
6.2
Sample Size Calculations and Statistical Power
Randomization of 90 patients allows estimation of consent and approach rates to within
8% (half-width of 95% conﬁdence interval). With 45 subjects in each arm, we will be able
to estimate recidivism to within approximately ±15%.
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6.3
Populations for Analysis
The subjects for the proposed research are children 6-12 years of age who are treated for
an asthma attack as determined clinically by the principal ED provider (e.g., shortness-
of-breath, cough, wheezing that improves following ≥1 dose of albuterol or equivalent
and ≥1 dose of systemic corticosteroids). The child’s symptoms must resolve so that
he/she can be safely discharged home. Children must have physician-diagnosed persistent
asthma as reported by the child’s parents and/or recorded in the clinical site’s electronic
medical record. Children must be enrolled full-time (5 days/week) in a participating
school and must be 6-12 years of age with a physician diagnosis of asthma. Parents and
children must speak English or Spanish. We expect the children to be 40% female, 30%
Hispanic, 54% black and 45% white (30% are Hispanic White).
We expect children to be 40% female as is the national population of asthma among
children; therefore, females will be adequately represented. We expect that approximately
84% of the children who enroll will be minorities: including approximately 54% black and
30% Hispanic. Therefore, minorities will be well represented in this research.
7
Data Management
7.1
Clinical Site Selection
In this pilot study, children treated within 3 of 18 participating PECARN EDs will be
targeted for recruitment. These sites were selected based on their ability to demonstrate
feasibility within a diverse geographic locale, setting, and/or population. Each of these
sites will be collaborating with the largest public school system in their catchment area.
7.2
Electronic Data Capture System
Under the direction of the DCC PI and biostatistician, and in collaboration with study
investigators, the DCC will be involved with the development of electronic data capture
systems to collect information on screening and enrollment, survey responses, safety mea-
sures, and medical chart review. The DCC uses a web-based interface designed speciﬁcally
for clinical trials and observational studies. The DCC has developed a sophisticated
software system for managing data discrepancy queries. This Query Management System
allows for data checks on individual data ﬁelds (e.g., for missing or out-of-range data) in
addition to the validation of data between diﬀerent forms. This helps ensure that data
will be complete and valid.
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7.3
Study Monitoring
The investigators recognize the importance of ensuring data of excellent quality. The
DCC will plan to perform remote monitoring activities during the study period to ensure
regulatory compliance, patient safety, and the quality of the data collected. Remote
monitoring will involve a detailed review of the data entered by the Clinical Center and
consultations with the Clinical Center investigator and/or research coordinator. Regula-
tory documents, data collection forms and parts of the medical record may be reviewed
to compare those materials against the data recorded in the electronic data capture system.
Remote monitoring will take place depending on grant budget, site enrollment and
compliance issues identiﬁed. Each site will be provided with a written report, and sites
will be required to follow up on any deﬁciencies.
Remote monitoring documents will be retained in accordance with federal requirements.
Safety of subjects will be monitored and ensured in accordance with the Data and Safety
Monitoring Board (DSMB) plan.
7.3.1
Pharmacy Monitoring
The Clinical Center pharmacy must maintain adequate records of all dispensed study
drug. Each pharmacy will be monitored and may be requested to send copies of these
documents to the DCC.
7.4
Data Coordinating Center
7.4.1
Data Center Description
The DCC in the Department of Pediatrics at the University of Utah School of Medicine
provides data coordination and management services for a variety of national research
networks. Anchoring these services is a new state-of-the-art, energy-eﬃcient data center
completed in 2013. The data center facility supports more than 1400 users around the
world and provides a secure, reliable, enterprise-wide infrastructure for delivering critical
DCC systems and services. The new data center was built using high industry standards
and energy-eﬃcient cooling solutions. The data center is cooled by Rittal’s LCP inline
cooling technology, providing eﬃciency, redundancy and modularity. Cooling is based
upon a hot/cold aisle design that allows for even air distribution with minimal hot spots.
The data center electrical power system contains a redundant Mitsubishi uninterruptible
power system with a diesel backup generator. The data center is protected with a FM200
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ﬁre suppression system, early warning smoke detectors and a heat detection warning
system to act as a secondary system to the smoke detectors. Security guards are on-site
conducting access control and rounds 24/7/365. Entry into the data center is restricted
by card access and layered security measures and controls. The data center and external
building access points are monitored with video surveillance.
In 2011 the data center began a large scale VMware server virtualization deployment.
Currently, the data center has virtualized about 99% of its environment. The virtual
environment consists of more than 200 virtual servers. The data center’s virtualization
solution provides key advantages:
• high availability – in the event of hardware failure, virtual servers automatically go
back online in a seamless process.
• ﬂexible infrastructure – disk storage, memory and processor capacity can be increased
or reallocated at any time.
• rapid deployment – servers can be provisioned on-demand with minimal waiting on
hardware or software.
The data center also enhanced its storage resources by implementing a networked
storage system to support its virtualized environment. The data center currently manages
over 50 terabytes of data. The storage solution consists of Dell’s EqualLogic PS Series
Storage system for providing a virtualized storage area network. Some of the beneﬁts
that are realized through this technology are:
• storage architecture is no longer a bottleneck for IT services;
• performance is better than with the previous architecture;
• tiered storage is now possible;
• provisioning and reclamation of storage area network disk will be much easier; and
most important,
• the new architecture includes a redesign of the storage area network fabric to include
complete redundancy.
Production servers running critical applications are clustered and conﬁgured for failover
events. Servers are backed up with encryption through a dedicated backup server that
connects across an internal 10 gigabit network to a tape drive. DCC storage area net-
working applications, clusters, and switch-to-switch links are also on a 10 gigabit network.
Incremental backups occur hourly Monday through Friday from 6 am to 6 pm. Incremental
backups also are performed each night with full system backups occurring every Friday.
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Tapes are stored in a ﬁreproof safe inside the data center facility, and full backups are
taken oﬀsite on a weekly basis to an oﬀ-site commercial storage facility.
In the event of catastrophic failure, such as a ﬁre in the server facility, daily backups
would probably survive because of the ﬁre suppression system and ﬁreproof safe, but there
would be obvious delay in re-establishing data center function because the servers will not
survive such a disaster. Total destruction of the data center facility could cause the loss
of up to one week’s data. In future investments, the data center is making co-location,
disaster recovery and business continuity solutions a top priority.
DCC information systems are available 24 hours a day, 7 days a week to all users
unless a scheduled maintenance interruption is required. If this occurs, we notify all users
of the relevant systems, and data entry can be deferred until after the interruption is over.
Critical systems availability has exceeded 99.9% for the past two years, and there has
been no unscheduled downtime in over ﬁve years.
7.4.2
Security and Conﬁdentiality
The data center coordinates the network infrastructure and security with the Health
Sciences Campus information systems at the University of Utah. This provides us with
eﬀective ﬁrewall hardware, automatic network intrusion detection, and the expertise of
dedicated security experts working at the University. Network equipment includes four
high-speed switches. User authentication is centralized with two Windows 2012 domain
servers. Communication over public networks is encrypted with virtual point-to-point
sessions using transport layer security or virtual private network technologies, both of
which provide at least 128 bit encryption. All of our Web-based systems use the transport
layer security protocol to transmit data securely over the Internet. Direct access to data
center machines is only available while physically located inside our oﬃces, or via a virtual
private network client.
All network traﬃc is monitored for intrusion attempts, security scans are regularly run
against our servers, and our IT staﬀis notiﬁed of intrusion alerts. Security is maintained
with Windows 2012 user/group domain-level security. Users are required to change their
passwords every 90 days, and workstations time out after 5 minutes of inactivity. All ﬁles
are protected at group and user levels; database security is handled in a similar manner
with group-level access to databases, tables, and views in Microsoft SQL Server. Finally,
all laptop computers in use in the DCC or in the Department of Pediatrics are whole-disk
encrypted.
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The data center uses control center tools to continuously monitor systems and failure
alerts. Environmental and network systems are also monitored to ensure up time. Highly
trained system administrators on staﬀare available to respond in high risk emergency
events.
All personnel involved with the DCC have signed conﬁdentiality agreements concerning
data encountered in the course of their daily work. All personnel (including administrative
staﬀ) have received Human Subjects Protection and Health Information Portability and
Accountability Act (HIPAA) education. We require all users to sign speciﬁc agreements
concerning security, conﬁdentiality, and use of our information systems, before access is
provided.
The limited PHI in the PECARN registry analysis database (month, year) is used in
order to direct performance measure reports, and the month and year of visit will not be
included in the database produced for sharing with other researchers.
Database access database is managed in accordance with PECARN data sharing
policies and applicable Federal laws. The registry data will be de-identiﬁed and it will
not be permissible for any investigator to attempt to re-identify data within the registry.
7.5
Record Access
The medical record and study ﬁles (including informed consent, permission, and assent
documents) must be made available to authorized representatives of the DCC, upon
request, for source veriﬁcation of study documentation. In addition, medical information
and data generated by this study must be available for inspection upon request by
representatives (when applicable) of the Food and Drug Administration (FDA), NIH,
other Federal funders or study sponsors, and the Institutional Review Board (IRB) for
each study site.
8
Protection of Human Subjects
8.1
Institutional Review Board Approval
The University of Utah IRB is the IRB of record for ED-SAMS. Each clinical center
will seek approval from their local IRB to defer oversight to the University of Utah IRB.
The DCC will track IRB approval status at all participating centers and will not permit
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subject enrollment without documentation of initial IRB approval and maintenance of
that approval throughout subsequent years of the project.
8.2
Informed Consent
We will recruit children from the 3 participating EDs. Research staﬀwill approach parents
of children between the ages of 6 and 12 who are being treated for acute respiratory
distress consistent with an asthma attack. The research staﬀwill explain the study and
will provide parents with a brief written description. Written consent will be obtained
from parents; assent will be obtained from children as applicable. Copies of the consent
and assent will be provided to the parents. Recruitment and study procedures will occur
during down times to avoid interfering with clinical care. Given a 6-hour turn-around
window (time from ED presentation to discharge) within PECARN EDs, we anticipate
adequate time will be available to identify, recruit, and evaluate study participants. To
ensure all participants can complete 90 days of school-supervised treatment before summer
break, recruitment will commence at the beginning of the school year (e.g., September)
and cease in March. Schools will be approached at the district level for initial support.
Parents will provide consent for us to contact the school on their behalf and will complete
the necessary paperwork for the school to initiate supervised therapy.
Parental Permission
Subjects who are eligible for this study are at most 12 years of age, and written permission
from parents or legal guardians will be required for participation. After determining
that a subject is eligible, the site investigator or designee will approach the parent or
legal guardian to oﬀer participation for their child to be in the study. The parent or
legal guardian will be informed about the objectives of the study and the potential risks
and beneﬁts of participation. If the parent or legal guardian refuses permission for their
child to participate, then all clinical management will be provided by the clinical staﬀin
accordance with institutional practice and judgment.
Child Assent
Assent will be obtained, as applicable from children who are eligible for this study.
8.3
Potential Risks
The major risk to the study is loss of conﬁdentiality. However, we will minimize these
risks through appropriate protection of all study data (see protection against risk).
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There are risks related to prescribed asthma medications, however, these risks are
associated with standard of care. The majority of children receiving daily medication
at school will likely have previously used inhaled corticosteroids. The primary risk from
inhaled corticosteroids is a yeast infection in the mouth, commonly known as thrush.
Children and parents will be taught that the child should rinse his/her mouth after taking
their inhaled steroid to reduce this risk and school health personnel will also be instructed
about this risk during the web-based training.
Other adverse events with a ≥1% occurrence reported by patients include colds, sore
throat, nasal congestion, sinusitis (sinus infection), headache, nausea, upset stomach, voice
changes, back pain, fever, indigestion, and ear infections. Rare instances of glaucoma,
increased pressure inside the eye, and cataracts have also been reported with long-term
use. Studies have also shown that inhaled corticosteroids may cause a reduction in the
rate of growth in children. The potential for growth eﬀects of prolonged treatment should
be weighed against the clinical beneﬁts obtained and the risks and beneﬁts associated with
alternative therapies. Growth should be monitored in children who receive corticosteroids.
Rare side eﬀects of ICS include: immediate and delayed hypersensitivity reactions
including a red, itchy rash, hives, swelling of the face and lips, and diﬃculty breathing,
symptoms of hypocorticism (extreme fatigue, weight loss, abdominal pain), and hypercor-
ticism (weight gain, easy bruising of the skin); psychiatrics symptoms including depression,
aggressive reactions, irritability, anxiety, and psychosis.
Children will also be taking quick relief medication (albuterol) as needed. Albuterol
is very commonly prescribed for children with asthma (almost always). Albuterol may
cause jitteriness, dizziness and can raise the heart rate after administration. Parents and
school health personnel will be educated on the risks of all asthma medications to reduce
risks to the children.
8.3.1
Known Potential Beneﬁts
The beneﬁts for the children may include an increased knowledge about their asthma and
how to control it as well as reduced asthma exacerbations.
8.3.2
Assessment of Potential Risks and Beneﬁts
All study information will be conﬁdential. Privacy risks will be minimized by appropriate
protection of all study data. Paper data will be stored in a locked ﬁle cabinet and
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computerized data will be stored on a secure server with password protection. Access to
study data will only be given to study personnel. Data will only be published in aggregate
form such that no individuals can be identiﬁed. Because the study is a multi-site clinical
trial, the National Heart, Lung and Blood Institute (NHLBI) requires a DSMB. This
Board will set the rules and protocols for medical intervention.
The beneﬁts for society include increased knowledge about methods that may reduce
asthma exacerbations. The project will also provide information regarding the cost of
this program.
8.4
Adverse Events, Serious Adverse Events and Unanticipated
Problems
8.4.1
Adverse Events
This study is using guideline concordant care for asthma. The study intervention is not
related to the drugs used in the study, rather the eﬃcacy of school-based supervision.
The PIs, DCC, and Clinical Coordinating Center will monitor the study for any trends,
but adverse events would likely be attributed to the underlying disease of asthma, not
the school-based supervision.
Deﬁnition: An adverse event (AE) is any untoward medical occurrence experienced
by a subject. An event constitutes a disease, a set of related signs or symptoms, or a
single sign or symptom. The site investigators will evaluate all adverse events. The study
staﬀwill obtain information on symptoms and adverse events on scheduled follow up calls
and text message surveys. Adverse events not previously documented in the study will
be recorded on the adverse event record form. The nature of each experience, date and
time (where appropriate) of onset, outcome, course, and relationship to treatment should
be established.
Side Eﬀects: Study staﬀwill obtain information about side eﬀects on scheduled
follow up calls and text message surveys.
Relatedness: The suspected relationship between study interventions and any adverse
event will be determined by the site investigator using the following criteria.
Related-
ness may not be assessed by a research coordinator, and must be assessed by an investigator.
Not Related: The event is clearly related to other factors, such as the subject’s
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clinical state, therapeutic interventions, or concomitant drugs administered to the subject.
Possibly Related: The event follows compatible temporal sequence from the time
of beginning the assigned study intervention, but could have been produced by other
factors such as the subject’s clinical state, therapeutic interventions, or concomitant drugs
administered to the subject.
Probably Related: The event follows a reasonable temporal sequence from the time
of beginning the assigned study intervention, and cannot be reasonably explained by
other factors such as the subject’s clinical state, therapeutic interventions, or concomitant
drugs administered to the subject.
Seriousness: The severity of clinical adverse events and laboratory abnormalities
will be recorded by the site investigator and categorized. A serious adverse event (SAE)
is an adverse event that:
• results in death; or
• is life-threatening (the patient was, in the view of the site investigator, in immediate
danger of death from the event as it occurred); or
• requires inpatient hospitalization or prolongs an existing hospitalization; or
• results in persistent or signiﬁcant disability or incapacity; or
• results in congenital anomaly/birth defect; or
• any other event that, based upon appropriate medical judgment, may jeopardize
the subject’s health and may require medical or surgical intervention to prevent one
of the other outcomes listed in this deﬁnition.
Expectedness of the Event: All adverse events, including serious adverse events,
will be evaluated as to whether their occurrence was expected or unexpected. An adverse
event is considered expected if it is known to be associated with acute asthma, other
underlying medical conditions of the subject, is directly related to study outcome, or is
otherwise mentioned in the protocol, informed consent, investigator brochure, or other
study documents. Expected complications of asthma treatment include yeast infection
in the mouth, commonly known as thrush, jitteriness and dizziness after administration
of ICS, elevated heart rate, respiratory infection, pharyngitis, sinusitis, voice alteration,
headache, ﬂu syndrome, pain, back pain, fever, dyspepsia, gastroenteritis, and nausea.
Rare instances of glaucoma, increased intraocular pressure, and cataracts have been
reported following the administration of corticosteroids. Rare side eﬀects of ICS include:
immediate and delayed hypersensitivity reactions including rash, contact dermatitis,
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urticaria, angioedema and bronchospasm, symptoms of hypocorticism and hypercorticism;
psychiatric symptoms including depression, aggressive reactions, irritability, anxiety, and
psychosis.
Treatment or Action Taken: For each adverse event, the site investigator will
record whether an intervention was required:
• Intervention: Surgery or procedure
• Other Treatment: Medication initiation, change, or discontinuation
• None: No action taken
Outcome of Event: Finally, the site investigator will record the clinical outcome of
each adverse event as follows:
• Death
• Recovered and the patient returned to baseline status
• Recovered with permanent sequelae
• Symptoms continue
The following adverse and serious adverse events are expected:
Adverse Events
• Evidence of coercion to participants
• Oral Thrush (white tongue)
• Worsening of respiratory symptoms (i.e., coughing, wheezing, shortness of breath,
tightness in the chest during the day, waking up from sleep at night) requiring
healthcare evaluation
Serious Adverse Events
• Hospitalization due to asthma
• Death for any reason
8.4.2
Time Period for Adverse Events
Serious adverse events, unexpected medically attended events, and new onset chronic
illnesses will be recorded following randomization through 120 days. Speciﬁcally, events
that occur following parental permission to participate in the study, but prior to actual
randomization, are not adverse events.
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8.4.3
Data Collection Procedures for Adverse Events
After patient randomization, all adverse events (including serious adverse events), whether
anticipated or unanticipated, will be recorded according to the date of ﬁrst occurrence,
severity, and their duration, as well as any treatment prescribed. Any medical condition
present at the time of randomization, recorded at study entry, which remains unchanged
or improves, will not be recorded as an adverse event at subsequent evaluations. However,
worsening of a medical condition that was present at the time of randomization will be
considered a new adverse event and reported.
Adverse events will be coded using the MedDRA coding vocabulary. Coding will be
done centrally at the DCC because this requires speciﬁc training.
8.4.4
Unanticipated Problems
Unanticipated problems (UP) are deﬁned as incidents, experiences, or outcomes that are
unexpected, related to participation in the study, and suggest that the research places
subjects at a greater risk of harm than was previously known or recognized. The site
investigator will report unanticipated problems to the DCC within 24 hours. A detailed
completed report will be required to be sent to the DCC within 3 working days of the
event. After receipt of the complete report, the DCC will report these unanticipated
problems to the NHLBI Program Oﬃcial or Project Oﬃcer in an expedited manner
(within 24 hours). In accordance with local IRB requirements, the site investigator may
be required to report such unanticipated problems to the IRB in addition to notifying the
DCC. In the event that the medical monitor believes that such an event warrants emergent
suspension of enrollment in the trial, and NHLBI staﬀcannot be reached expeditiously,
the DCC will notify the study investigators and all site investigators to cease enrollment
in the trial. Resumption of enrollment will not occur without consent of the NHLBI staﬀ
after discussion with the DSMB.
8.4.5
Monitoring Serious Adverse Events
The Principal Investigator of the DCC (Dr. Dean) will act as the medical monitor for
this study. If Dr. Dean is unavailable, a qualiﬁed physician will be designated to fulﬁll
this function. Site investigators and/or research coordinators will report serious adverse
events to the DCC within 24 hours. A detailed completed report will be required to be
sent to the DCC within 3 working days of the event, and the medical monitor will assess
all serious adverse events reported from site investigators.
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For each of these serious adverse events, the site investigator will provide suﬃcient
medical history and clinical details for a safety assessment to be made with regard to
continuation of the trial. The medical monitor will sign each SAE report after review. All
SAE reports will be retained at the DCC, and all SAE reports will be available for review
by DSMB members and NHLBI staﬀ. In the unlikely event that the medical monitor
believes an unexpected and study-related SAE warrants emergent cessation of enrollment
in the trial, NHLBI staﬀand the DSMB chairperson will be immediately consulted. If
these individuals concur with the judgment of the medical monitor, or if the NHLBI staﬀ
and the DSMB chairperson cannot be reached expeditiously, the DCC will notify the study
investigators and all site investigators to cease enrollment in the trial. Resumption of en-
rollment will not occur without consent of the NHLBI staﬀafter discussion with the DSMB.
In accordance with local IRB requirements, the site investigator may be required to
report such events to the IRB in addition to notifying the DCC. After notiﬁcation of
the NHLBI Program Oﬃcial or Project Oﬃcer, and the DSMB chairperson, of serious,
unexpected, and study-related AEs or UPs, decisions will be made whether to continue
the study without change, and whether to convene the entire DSMB for an emergent
meeting. If a decision is made to suspend enrollment in the trial, this will be reported to
the study investigators and all clinical investigators, who will be instructed to report this
to their local IRB.
The DSMB will review all adverse events (not necessarily serious, unexpected, and
study-related) during scheduled DSMB meetings. The DCC will prepare a Summary
Report of Adverse Events for the DSMB meetings, classiﬁed with the MedDRA coding
system.
8.4.6
Follow-up of Serious, Unexpected and Related Adverse Events
All serious, unexpected and related adverse events, that are unresolved at the time of the
patient’s termination from the study or discharge from the hospital, will be followed by
the Clinical Center investigators until the events are resolved, subject is lost to follow-up,
the adverse event is otherwise explained or has stabilized.
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9
Data and Safety Monitoring Plan
9.1
Data Safety Monitoring Board
The purpose of the DSMB is to advise the Federal funding agency NHLBI, the ED-SAMS
PIs (Dr. Gerald and Dr. Denninghoﬀ), and the PECARN Executive Committee re-
garding the continuing safety of study subjects and the continuing validity and scientiﬁc
merit of the study. The DSMB will be responsible for monitoring accrual of study sub-
jects, adherence to the ED-SAMS protocol, assessments of data quality, performance of
individual clinical sites, and review of serious adverse events and other subject safety issues.
DSMB meetings to evaluate study protocols, prior to study implementation, may be
open or closed according to the decision of the DSMB members. We suggest that these
meetings should be open to members of the ED-SAMS investigative team, as there are
no conﬁdential components to these proceedings, and it will facilitate the review and
appropriate alterations of the protocol in response to DSMB concerns.
9.2
Planned Interim Analysis
At the current time no interim analysis is planned. This is a pilot study involving
recruitment over a short period of time. There would be insuﬃcient time or data to
analyze, present, then act upon. If the DSMB and their charter require an interim analysis,
we will do so.
9.3
Study Discontinuation and Closure
Based on prospectively deﬁned guidelines to be outlined in the DSMB charter, as well as
any additional information available to DSMB members, the DSMB should recommend
whether to terminate enrollment in ED-SAMS because of potential safety concerns.
In the unlikely event that the DSMB recommends emergent cessation of enrollment in
ED-SAMS because of safety concerns, this communication will be made during the debrief-
ing segment of the DSMB meeting. If the NHLBI staﬀconcur with this recommendation,
the DCC will notify all ED-SAMS clinical sites to cease enrollment immediately.
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10
Study Training
10.1
Study Training
A formal training program for investigators and research staﬀwill be held prior to the
start of enrollment. The training program will cover regulatory topics and Good Clinical
Practice. The training will also provide in depth explanations regarding study procedures,
clinical care, adverse event reporting, data entry procedures, quality assurance, site
monitoring, and the informed consent process. A manual of operations will be provided
to each investigator prior to the start of enrollment. The manual will detail speciﬁc
information about the study procedures, regulatory information, safety reporting, and
other necessary information. Updates and revisions to the manual will be made available
electronically. The DCC, in collaboration with the study investigator (Dr. Gerald), will
be the main contact for study questions.
11
Regulatory Issues
11.1
Food and Drug Administration
Pulmicort ICS (budesonide) is indicated for twice-daily use; however, for this study we
are testing the hypothesis that once-daily supervision of ICS (budesonide) will improve
asthma related outcomes. We are requesting an IND exemption for the following reasons:
• This study is NOT intended to be reported to the FDA in support of a new
indication.
• This drug is lawfully marketed as a prescription drug product.
• This study is NOT intended to support a signiﬁcant change in advertising for the
product.
• The study does NOT involve a route of administration or dosage or population
that signiﬁcantly increases the risks (or decreases the acceptability of the risks)
associated with the use of the drug. This study will change the administration
of drug from twice a day to once a day, however, the daily dose will remain as
approved. This will not signiﬁcantly increase the risk.
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11.2
Health Insurance Portability and Accountability Act
Data elements collected include the date of birth, date of medical care and contact informa-
tion (including names). Prior to statistical analyses, dates will be used to calculate patient
age at the time of the study events. The ﬁnal data sets (used for study analyses and
archived at the end of the study) will be de-identiﬁed, and will exclude these speciﬁc dates.
Data elements for race, ethnicity, and gender are also being collected. These demo-
graphic data are required for Federal reporting purposes to delineate subject accrual by
race, ethnicity, and gender.
For purposes of the DCC handling potential protected health information (PHI) and
producing the de-identiﬁed research data sets that will be used for analyses, all study
sites will be oﬀered a Business Associate Agreement with the University of Utah. Copies
of executed Business Associate Agreements are maintained at the DCC.
11.3
Inclusion of Women and Minorities
There will be no exclusion of patients based on gender, race, or ethnicity.
11.4
ClinicalTrials.gov Requirements
This trial will be registered at ClinicalTrials.gov in accordance with Federal regulations.
11.5
Retention of Records
For federally funded studies subject to the Common Rule, records relating to the research
conducted shall be retained for at least 3 years after completion of the research, or
in accordance with State law. Completion of the research for this protocol should be
anticipated to include planned primary and secondary analyses, as well as subsequent
derivative analyses. Completion of the research also entails completion of all publications
relating to the research. All records shall be accessible for inspection and copying by
authorized representatives of the regulatory authorities at reasonable times and in a
reasonable manner [45 CFR §46.115(b)].
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12
References
References
[1] L. J. Akinbami, A. E. Simon, and L. M. Rossen. Changing trends in asthma prevalence
among children. Pediatrics, 137(1), 2016.
[2] L. J. Akinbami, J. E. Moorman, A. E. Simon, and K. C. Schoendorf. Trends in racial
disparities for asthma outcomes among children 0 to 17 years, 2001-2010. J Allergy
Clin Immunol, 134(3):547–553 e5, 2014.
[3] L. Y. Wang, Y. Zhong, and L. Wheeler. Direct and indirect costs of asthma in
school-age children. Prev Chronic Dis, 2(1):A11, 2005.
[4] H. Rappaport. The direct expenditures and indirect costs associated with treating
asthma in the united states. J Aller Ther, 3(2), 2012.
[5] S. Kamble and M. Bharmal. Incremental direct expenditure of treating asthma in
the united states. J Asthma, 46(1):73–80, 2009.
[6] C. Crump, D. Rivera, R. London, M. Landau, B. Erlendson, and E. Rodriguez.
Chronic health conditions and school performance among children and youth. Ann
Epidemiol, 23(4):179–84, 2013.
[7] K. A. Liberty, P. Pattemore, J. Reid, and M. Tarren-Sweeney. Beginning school with
asthma independently predicts low achievement in a prospective cohort of children.
Chest, 138(6):1349–55, 2010.
[8] S. A. Moonie, D. A. Sterling, L. Figgs, and M. Castro. Asthma status and severity
aﬀects missed school days. J Sch Health, 76(1):18–24, 2006.
[9] C. E. Basch. Asthma and the achievement gap among urban minority youth. J Sch
Health, 81(10):606–13, 2011.
[10] J. K. Schmier, R. Manjunath, M. T. Halpern, M. L. Jones, K. Thompson, and G. B.
Diette. The impact of inadequately controlled asthma in urban children on quality
of life and productivity. Ann Allergy Asthma Immunol, 98(3):245–51, 2007.
[11] S. Burgess, P. Sly, and S. Devadason. Adherence with preventive medication in
childhood asthma. Pulm Med, 2011:973849, 2011.
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Protocol Version Date: March, 18, 2020
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Page 38 of 39
Protocol 038 (Gerald/Denninghoﬀ)
[12] M. Desai and J. J. Oppenheimer. Medication adherence in the asthmatic child and
adolescent. Curr Allergy Asthma Rep, 11(6):454–64, 2011.
[13] S. Pando, C. Lemiere, M. F. Beauchesne, S. Perreault, A. Forget, and L. Blais. Sub-
optimal use of inhaled corticosteroids in children with persistent asthma: inadequate
prescription, poor drug adherence, or both? Pharmacotherapy, 30(11):1109–16, 2010.
[14] J. Gamble, M. Stevenson, E. McClean, and L. G. Heaney.
The prevalence of
nonadherence in diﬃcult asthma. Am J Respir Crit Care Med, 180(9):817–22, 2009.
[15] A. C. Wu, M. G. Butler, L. Li, V. Fung, E. O. Kharbanda, E. K. Larkin, W. M.
Vollmer, I. Miroshnik, R. L. Davis, T. A. Lieu, and S. B. Soumerai. Primary adherence
to controller medications for asthma is poor. Ann Am Thorac Soc, 12(2):161–6, 2015.
[16] J. B. Herndon, S. Mattke, A. Evans Cuellar, S. Y. Hong, and E. A. Shenkman.
Anti-inﬂammatory medication adherence, healthcare utilization and expenditures
among medicaid and children’s health insurance program enrollees with asthma.
Pharmacoeconomics, 30(5):397–412, 2012.
[17] R. A. Nathan, C. A. Sorkness, M. Kosinski, M. Schatz, J. T. Li, P. Marcus, J. J.
Murray, and T. B. Pendergraft. Development of the asthma control test: a survey
for assessing asthma control. J Allergy Clin Immunol, 113(1):59–65, 2004.
[18] M. Schatz, C. A. Sorkness, J. T. Li, P. Marcus, J. J. Murray, R. A. Nathan,
M. Kosinski, T. B. Pendergraft, and P. Jhingran. Asthma control test: reliability,
validity, and responsiveness in patients not previously followed by asthma specialists.
J Allergy Clin Immunol, 117(3):549–56, 2006.
[19] L. K. Williams, E. L. Peterson, K. Wells, B. K. Ahmedani, R. Kumar, E. G.
Burchard, V. K. Chowdhry, D. Favro, D. E. Lanfear, and M. Pladevall. Quantifying
the proportion of severe asthma exacerbations attributable to inhaled corticosteroid
nonadherence. J Allergy Clin Immunol, 128(6):1185–1191 e2, 2011.
[20] A. Schlender, P. E. Alperin, H. L. Grossman, and E. R. Sutherland. Modeling the
impact of increased adherence to asthma therapy. PLoS One, 7(12):e51139, 2012.
[21] R. B. Haynes, E. Ackloo, N. Sahota, H. P. McDonald, and X. Yao. Interventions for
enhancing medication adherence. Cochrane Database Syst Rev, (2):CD000011, 2008.
[22] H. K. Reddel, E. D. Bateman, A. Becker, L. P. Boulet, A. A. Cruz, J. M. Drazen,
T. Haahtela, S. S. Hurd, H. Inoue, J. C. de Jongste, Jr. Lemanske, R. F., M. L. Levy,
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Protocol 038 (Gerald/Denninghoﬀ)
Page 39 of 39
P. M. O’Byrne, P. Paggiaro, S. E. Pedersen, E. Pizzichini, M. Soto-Quiroz, S. J.
Szeﬂer, G. W. Wong, and J. M. FitzGerald. A summary of the new gina strategy: a
roadmap to asthma control. Eur Respir J, 46(3):622–39, 2015.
[23] M. M. Cloutier, M. Schatz, M. Castro, N. Clark, H. W. Kelly, R. Mangione-Smith,
J. Sheller, C. Sorkness, S. Stoloﬀ, and P. Gergen. Asthma outcomes: composite
scores of asthma control. J Allergy Clin Immunol, 129(3 Suppl):S24–33, 2012.
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