Early Administration of Steroids in the Ambulance Setting: An Observational Design Trial
Phase: PHASE4
Conditions: Asthma in Children
Sponsor: University of Florida

7/9/2019 
Study title: Early Administration of Steroids in the Ambulance Setting: An Observational Design 
Trial “EASI-AS-ODT” 
NCT03962894 
Study Protocol and Statistical Analysis Plan 
 
 

Title 
Early Administration of Steroids In the Ambulance Setting: An Observational Design Trial  
“EASI-AS-ODT” 
Study Location 
 
Lee County EMS: Lee EMS serves Florida’s Lee County, located in southwestern Florida. Lee 
County’s division of EMS operates under a license by the Florida Department of Health. Lee 
County serves a population estimated by the US Census Bureau as 739,000, 18% of whom are 
under 18 years of age, and 5% of whom are under 5 years of age. Lee County EMS responds to 
over 70,000 annual emergencies from 36 EMS stations, and the workforce is comprised of both 
EMT-paramedics and EMT-Basics. Per usual dispatch protocol and Lee EMS treatment protocol, 
the pediatric asthma patients experiencing an acute exacerbation (and all respiratory distress 
patients, for that matter) are treated and transported by EMT-paramedics (i.e., advanced life 
support (ALS)-level care), the highest level of care in the Lee County EMS system). 
Nassau County Fire Rescue Department: Nassau County Fire Rescue Department serves’ 
Florida’s Nassau County, the northeastern most county in Florida.  Nassau’s estimated population 
under 18 years of age is 16,544 according to the US Census Bureau. Nassau County is comprised 
solely of EMT-Paramedics (approximately 120), and contains a specific standard operating 
protocol for pediatric asthma exacerbations. 
Sarasota County EMS:  Sarasota County EMS serves a Southwest Florida population of over 
400,000 people, 14% of whom are under the age of 18. Sarasota EMS employs over 20 
ambulance stations to serve that growing population. 
Leon County EMS: Leon County EMS serves a population in Florida’s panhandle of nearly 
300,000, of whom 18% are under the age of 18. Leon County uses 19 ambulance crews to cover 
671 square miles and serve an annual call volume of over 30,000. 
Walton County Sheriff’s Office Fire and Rescue Division: Walton County serves a rural population 
of over 70,000 persons (20% of whom are under the age of 18 years) in Florida’s panhandle with 
over 100 providers.  
Cincinnati Children’s Hospital Medical Center: Investigators in Cincinnati have compiled a 
database of pediatric EMS encounters that include encounters before and after an EMS guideline 
change they performed in 2016 that added an oral steroid option (prednisolone) for children 
treated by EMS with an asthma exacerbation. 
Baylor College of Medicine, Houston, TX: Investigators in Houston have compiled a dataset of 
pediatric EMS encounters that include encounters before and after an EMS guideline change 
performed in 2014 which added an oral steroid option (dexamethasone) for children treated by 
Houston EMS with an asthma exacerbation who were transported to Texas Children’s Hospital. 
Study Type 
Observational study 

This study is an observational study administered by EMS to pediatric asthma patients ages 2 to 
18 years. In a pediatric asthma protocol update, all agencies are adding an oral steroid option 
for all asthma patients except for those who meet certain exclusion criteria, including those who 
are not stable to take an oral medication. Therefore, we will analyze outcomes from patients 
who do and do not receive oral steroids from EMS. 
Table 1: Inclusion and Exclusion Criteria 
Inclusion 
Exclusion 
Ages 2-18 years 
Unconscious, hemodynamically unstable, or critically ill -> EMS will 
proceed with usual critical care (includes IV methylprednisolone as per 
protocol) 
Primary 
problem: 
asthma attack 
Daily or every other day CS therapy, CS given for this exacerbation at 
home by legal guardian or in office by medical practitioner 
Safe to take an oral 
medication 
Allergy to prednisolone or another CS  
Transported by EMS 
to an ED 
Chronic lung disease besides asthma, airway anatomic abnormalities, 
tracheostomy, immunocompromised, traumatic injury, pregnancy, law 
enforcement custody, non-English speaking 
 
Data for 12 months before and 12 months after each EMS agency adds an oral CS option to their 
existing IV CS option will be abstracted from the EMS and ED EMR records. All sites will send de-
identiﬁed data already linked to ED outcomes from their pre-existing EMS database via RedCap. 

 
Study Data Variables 
EMS Identification of Study 
Patients
Age 2-18 years
Primary Problem: Asthma 
Exacerbations
Otherwise meets 
inclusion/exclusion criteria
Safe to take oral medication (if 
critically ill, exclude and proceed 
with usual critical care)
Treatment & Transport
EMS usual care per protocol (albuterol 
nebulizer, other medications, etc.)
Give oral steroid (dosing per protocol), 
if protocol change implemented in 
station
Transport mode and destination as 
usual
After EMS / ED Encounter
EMS Enrollment Report for Study Team
EMS and ED Record Abstraction 
Begins (either study team or in-house 
at EMS agency)

PHI is only collected to accomplish EMS to ED record linkage. PHI variables used for linkage are 
marked below. PHI will be used by local sites to accomplish this linkage. PHI will not be recorded 
in RedCap nor transmitted to the main site. 
 
EMS EMR: 
• 
Date of Service (for linkage) 
• 
Name (for linkage) 
• 
EMS Record Identifier (ID) (for linkage) 
• 
Date of Birth (for linkage) 
• 
Home Address (for linkage) 
• 
Age 
• 
Race 
• 
Ethnicity 
• 
Gender 
• 
EMS Scene Location Address  
• 
Any medications given prior to EMS Arrival 
• 
All EMS vital signs and clinical assessments 
• 
All other EMS-administered medications 
• 
All EMS procedures 
• 
EMS Times: Dispatch to scene arrival, scene time, transport time, ED turnaround 
time 
• 
Dispatch Complaint 
• 
Provider Primary Impression 
• 
Provider Secondary Impression 
• 
Injury (Yes/No) 
• 
ED destination facility name 
• 
Date and Time of arrival at destination facility 
 
ED EMR: (duplicate demographic information is collected for record linkage purposes) 
• 
Date of Service (for linkage) 
• 
Name (for linkage) 
• 
Date of Birth (for linkage) 
• 
Home Address (for linkage) 
• 
Age 
• 
Gender 
• 
Race 
• 
Ethnicity 
• 
Insurance (for economic analysis) 
• 
Mode of Arrival 
• 
Vital Signs 
• 
All ED administered medications 
• 
All ED procedures 
• 
ED diagnoses 
• 
ED LOS (minutes) 
• 
ED Disposition (Admit -  Yes/No/Transfer) 
o If Yes – Floor vs. ICU 

o If No – any discharge prescriptions 
o If Transfer – to where and why 
 
Data and Safety Monitoring Plan (DSMP) and Data and Safety Monitoring Board 
(DSMB) 
Per potential study sponsor (NIH/NHLBI) guidelines and at the specific request of the NHLBI’s 
human subjects officer during administrative review, this study will employ a DSMP and charter 
a DSMB (see attachment DSMB charter). 
 
OVERSIGHT RESPONSIBILITIES 
Trial Oversight is provided by the Principal Investigator (PI), Dr. Jennifer Fishe, MD, and co-
investigators. 
The DSMB members are: Dr. Jason Lang, MD (Pediatric Pulmonologist, Duke University), Dr. 
Sfurti Nath, MD (UF Jacksonville Neonatologist), and Dr Jeff Harman, PhD (Health Economist / 
Biostatistician Florida State University), Dr. Arveen Bhasin, MD (Allergy/Pulmonology, Mayo 
Clinic Jacksonville) and Morgan Henson, BSH, CPH, MPH (executive secretary). 
 
MONITORING PROCEDURES 
Dr. Fishe is responsible for oversight and conduct of the study, including that the study is 
conducted according to the IRB-approved research plan. The IRB has approved this study with 
waiver of informed consent. Study data will be accessible at all times for the PI and co-
investigators to review. The PI and co-investigators will review study conduct including 
participant accrual, loss to follow-up, and EMS treatment guideline deviations on a monthly 
basis, and prepare data for reports for quarterly DSMB meetings. The DSMB members will 
review SAEs individually in real-time once they are discovered, and AEs plus all SAEs in 
aggregate on a quarterly basis. The PI ensures all protocol deviations, AEs, and SAEs are 
reported to the IRB, treating EMS agency, and study sponsor (if applicable) according to the UF 
IRB requirements and those requested by the DSMB as specified in the study DSMB charter. 
The DSMB members will elect a chair during their first meeting. 
 
COLLECTION, SPECIFICATION, AND REPORTING OF SAEs AND AEs 
Specification of Safety Variables  
Safety assessments will consist of monitoring and reporting adverse events (AEs) and serious 
adverse events (SAEs) that are considered related to EMS administration of oral steroids, all 
events of death, and any study specific issue of concern. 
 
 
Adverse Events 

An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with 
the EMS administration of oral steroids. Specific AE/SAEs that will be closely monitored for 
include nausea or vomiting after oral steroid administration, allergic reaction to the steroid (mild, 
moderate, or severe (anaphylaxis), or suspected aspiration of oral steroid. The study-specific 
definition of “temporally related” includes within 60 minutes of oral steroid administration. 
 
Serious Adverse Events 
An AE should be classified as an SAE if: 
• 
It results in death (i.e., the AE actually causes or leads to death).  
• 
It is life threatening (i.e., the AE, in the view of the investigator, places the subject at 
immediate risk of death.  It does not include an AE that, had it occurred in a more severe 
form, might have caused death.). 
• 
It requires or prolongs inpatient hospitalization. 
• 
It results in persistent or significant disability/incapacity (i.e., the AE results in substantial 
disruption of the subject’s ability to conduct normal life functions). 
• 
It is considered a significant medical event by the investigator based on medical 
judgment (e.g., may jeopardize the subject or may require medical/surgical intervention 
to prevent one of the outcomes listed above). 
 
Methods and Timing for Assessing AND Recording Safety variables 
The investigator is responsible for ensuring that all AEs and SAEs that are observed or reported 
during the study are collected and reported to the UF IRB, treating EMS agency, and study 
sponsor (if applicable) in accordance with CFR 312.32 (IND Safety Reports).  
 
Adverse Event Reporting Period 
The reporting period for all study-defined adverse events will begin when the EMS data are 
abstracted (approximately weekly). AEs are reported to DSMB for their regular quarterly 
meetings, SAEs must be reported to the DSMB and IRB within 24 hours of becoming aware of 
the event.  
 
Assessment of Adverse Events 
Each reported SAE will be described by its duration (i.e., start and end dates), regulatory 
seriousness criteria if applicable, suspected relationship to oral steroids, actions taken, and 
patient outcomes. To ensure consistency of SAE causality assessments, investigators will apply 
the following general guideline: 
 
AEs are graded according to the following severity scale: 
  

Mild: An experience that is transient, and requires no special treatment or intervention. The 
experience does not generally interfere with usual daily activities. This includes transient 
laboratory test alterations. 
 
Moderate: An experience that is alleviated with simple therapeutic treatments. The experience 
impacts usual daily activities. Includes laboratory test alterations indicating injury, but without 
long-term risk. 
 
Severe: An experience that requires therapeutic intervention. The experience interrupts usual 
daily activities. If hospitalization (or prolongation of hospitalization) is required for treatment it 
becomes an SAE. 
 
The study uses the following AE attribution scale: 
 
Not related: the AE is clearly not related to the EMS administration of an oral steroid (i.e., 
another cause of the event is most plausible and/or a clinically plausible temporal sequence is 
inconsistent with the onset of the event). 
 
Possibly related: an event that follows a reasonable temporal sequence from the EMS 
administration of an oral steroid, but that could readily have been produced by a number of 
other factors.  
 
Related: The AE is clearly related to EMS administration of oral steroids. 
 
Asthma Exacerbation Related Exempted Events  
The following signs, symptoms, observations and events are frequently observed in association 
with asthma exacerbations and are exempted from regulatory reporting unless known to be 
caused by the study drug: dyspnea, chest pain, fever, hypoxemia, rapid pulse, rapid respiratory 
rate, dizziness, nausea, vomiting, anxiety, altered mental status, shortness of breath, difficulty 
breathing, hypokalemia (associated with administration of bronchodilators), dehydration. 
 
AE Management 
Should any patient experience an adverse event, they are in the care of emergency 
professionals (EMS providers who then treat and transport to ED providers) who are trained in 
the management of unexpected and potentially serious adverse events. 
 

Procedures for eliciting, recording, and reporting adverse events 
Specific Instructions for Recording Adverse Events 
Investigators will use correct medical terminology/concepts when reporting AEs or SAEs.  Avoid 
colloquialisms and abbreviations. 
a. 
Diagnosis vs. Signs and Symptoms 
If known at the time of reporting, a diagnosis will be reported rather than individual 
signs and symptoms. However, if a constellation of signs and/or symptoms cannot 
be medically characterized as a single diagnosis or syndrome at the time of 
reporting, it will be reported based upon the information that is currently available.  If 
a diagnosis is subsequently established, it will be reported as follow-up information. 
b. 
Deaths 
All deaths that occur during the protocol-specified AE reporting period, regardless of 
attribution, will be reported to the appropriate parties. 
When recording a death, the event or condition that caused or contributed to the 
fatal outcome will be reported as the single medical concept.  If the cause of death 
is unknown and cannot be ascertained at the time of reporting, report “Unexplained 
Death”. 
c. 
Preexisting Medical Conditions 
A preexisting medical condition is one that is present at the start of the study.  Such 
conditions will be reported as medical and surgical history. 
A preexisting medical condition will be reported as an AE or SAE only if the 
frequency, severity, or character of the condition worsens as a direct result of EMS 
administration of oral steroids.  When reporting such events, it is important to 
convey the concept that the preexisting condition has changed by including 
applicable descriptors (e.g., “more frequent vomiting”). 
d. 
Hospitalizations for Medical or Surgical Procedures 
Any AE that results in prolonged hospitalization will be documented and reported as 
an SAE. If a subject is hospitalized to undergo a medical or surgical procedure as a 
result of an AE, the event responsible for the procedure, not the procedure itself, will 
be reported as the SAE.   
Hospitalizations for the following reasons do not require reporting: Prolonged 
hospitalization for diagnostic or elective surgical procedures for preexisting 
conditions, or hospitalization or prolonged hospitalization for scheduled therapy of 
the target disease of the study.  
 
Data Quality Assurance and Monitoring Plan 
Accurate, consistent, and reliable data will be ensured through the use of standard practices 
and procedures. All study data will be deidentified as soon as possible (following EMS to ED 

record linkage), and stored in password protected files on password protected computers in 
locked offices only in IRB approved phile drives. The study PI will be responsible for data quality 
assurance, and for timely data submission for preparation of quarterly DSMB meetings. 
 
Safety Monitoring 
This study will charter a DSMB (see DSMB charter) to monitor the study. 
 
Human Subjects Protections 
Waiver of Informed Consent 
The data collected from this research study relates to data that would have already been collected 
on care the children would have already received based on the existing / planned future protocols 
for care as defined by the EMS agency contributing data for the study. It is not practical for EMS 
to consent patients during emergency treatment to have their data collected, nor is it practical to 
ask legally authorized representatives who may or may not be present during the EMS encounter 
for consent in the midst of emergency treatment for data collection. Further to this, the study is 
not altering any aspect of EMS treatment, and therefore is retrospectively collecting data AFTER 
THE ENCOUNTER HAS OCCURRED.  
 
The use of PHI involves no more than minimal risk to the individuals because multiple steps will 
be taken (as noted in other sections above and below) to prevent loss of confidentiality. Also, the 
PHI will not be used for data reporting, since this information will be removed prior to analysis, 
and the subjects will be coded with a study number. Accessing the patient's records does not 
otherwise affect their rights or welfare, since personal information will not be released.  The data 
collected from the pediatric population in this research study relates to care that children would 
have already received based on the existing protocols for care as defined by the EMS agency 
involved. The investigators/study team will not be directly interacting with the EMS patients. 
Access to the PHI (incident run number, date of birth, etc.) is necessary, in order to calculate age 
accurately and link separate records for the same patient encounter in the EMS and ED EMRs. 
The principal investigator has performed similar previous and ongoing IRB-approved pediatric 
EMS studies with waiver of consent. Therefore, this study could not be done without obtaining 
this PHI, because there would be no other way to match link the EMS to ED records or calculate 
age in an accurate manner.  
 
Obtaining consent from these patients will not be feasible or practical because the care will have 
already been provided as defined by the EMS agencies, obtaining consent will not affect the care 
they already received in the prehospital settings, and attempting to obtain consent after care has 
already been provided would require intentionally searching the EMS database for additional 
personally identifying information, which would be more intrusive as this is not required for data 
analysis for the study. 

 
These subjects are not likely to be encountered again by the investigators in the clinical setting, 
so there is no other means to provide additional information to the subjects except to contact them 
via mail or phone. Providing subjects with additional pertinent information after participation would 
not be appropriate, since it would require gathering additional personal information from the 
charts, such as address or telephone number, in order to communicate with them. In addition, 
contacting the subjects in this manner may be perceived by the subjects as an intrusion of their 
privacy, since gathering addresses and telephone numbers is not required to conduct this 
retrospective study. 
 
Potential Risks 
 
PHI 
Research procedures also include abstracting patient data from the EMS and ED/hospital EMR. 
PHI must be collected in order to link EMS and ED/hospital records, after which the data will be 
de-identified. Linkage of EMS and ED records will commence once study personnel are notified 
in the daily morning report of a EMS pediatric asthma patient. Once EMS and ED records are 
linked, for each pediatric asthma patient (oral steroid or no oral steroid), the REDCap™ database 
system will be used to record data variables for analysis. REDCap™ will not contain any patient 
identifiers. Data will be abstracted from the patient’s electronic medical record (EMR) for both the 
EMS and ED encounter. Data will be collected prospectively by trained study investigators 
(including the participating EMS agency’s medical directors) and research assistants who are 
listed on the study IRB. Only the study investigators, research assistants, and research 
coordinators named on the study IRB will have access to PHI.  
 
 
 

Statistical Analysis Plan 
We will perform descriptive statistics using frequencies and percentages for categorical 
variables, and mean with standard deviation and median with interquartile range for continuous 
variables. We will perform univariate analyses with chi-square testing for categorical variables, 
and Wilcoxon rank sum for continuous variables comparing between the steroids and no 
steroids groups for equivalence testing. A p value of > 0.05 will be considered statistically 
signiﬁcant. We will report 95% conﬁdence intervals.  
We will build hierarchical generalized linear mixed models for the primary outcome of 
hospitalization. For the models, we will use only complete observations and did not perform any 
imputations. We will report model performance using the Akaike Information Criterion (AIC).