Implementation Fidelity and Benefits of the Critical Care Pediatric Guideline Adherence and Outcomes Program in Traumatic Brain Injury
Phase: NA
Conditions: TBI (Traumatic Brain Injury)
Sponsor: University of Washington

v3 June 2020 
 
Coversheet 
 
Study title: Pediatric Guideline Adherence and Outcomes- Argentina (PEGASUS) 
NCT number: NCT03896789 
PI name: Monica Vavilala 
Document name: protocol_CTgov resubmit_2 
Initial IRB approval date: 9/28/2018 
Continuing IRB approval date: 8/15/2019 
Protocol modification and continuing IRB approval date: 8/7/2020 (of the protocol v3 June 2020) 
 
 

Protocol-PEGASUS Argentina 
2 
 
 
PEGASUS-Argentina 
Implementation Fidelity and Benefits of the Critical Care 
Pediatric Guideline Adherence and Outcomes Program in 
Traumatic Brain Injury-Argentina 
 
 
 
MPIs: Monica S Vavilala, MD and Michael J Bell, MD 
UW IRB# STUDY00005629 
Clinicaltrials.gov NCT 03896789 
Funded by NIH R01 NS1065001A1 
01/01/2019 to 12/31/2023 
 
 
 
 
 
 
 

Protocol-PEGASUS Argentina 
3 
 
Table of Contents 
 
Chapter 1. STUDY OVERVIEW ....................................................................................................................... 5 
1.1 Specific Aims ....................................................................................................................................... 5 
1.2 Funding ............................................................................................................................................... 6 
1.3 IRB Protocol ......................................................................................................................................... 6 
Chapter 2. STUDY ORGANIZATION AND RESPONSIBILITIES .......................................................................... 6 
2.1 Coordinating Center ............................................................................................................................ 6 
2.2 Secondary Centers .............................................................................................................................. 6 
2.3 Study Sites ........................................................................................................................................... 7 
2.4 Roster .................................................................................................................................................. 7 
CHAPTER 3. STUDY DESIGN ........................................................................................................................... 8 
3.1 Study Design ........................................................................................................................................ 8 
3.2 Governance Model.............................................................................................................................. 9 
3.3 Site Randomization Plan ................................................................................................................... 10 
3.4 Screening and Eligibility Criteria ....................................................................................................... 11 
3.5 Informed Consent ............................................................................................................................. 11 
3.6 Risks .................................................................................................................................................. 11 
3.7 Sample Size and Power ..................................................................................................................... 11 
3.8 Recruitment, Retention & Follow-up ................................................................................................ 11 
CHAPTER 4. INTERVENTION ........................................................................................................................ 12 
4.1 Intervention Model ........................................................................................................................... 12 
4.2 Implementation Readiness ............................................................................................................... 13 
4.3 TBI Guideline Adaptations ................................................................................................................ 13 
4.4 PEGASUS Pathway ............................................................................................................................. 13 
4.5 Case Review and Quality Improvement (QI) Intervention Cycle ...................................................... 14 
4.6 Focus Groups and MI Check-Ins ........................................................................................................ 14 
CHAPTER 5. SAFETY REPORTING & ADVERSE EVENTS ................................................................................ 14 
5.1 Complications Reporting ................................................................................................................... 14 
5.2 DSMB Committee .............................................................................................................................. 15 
CHAPTER 6. TRAINING PLAN ....................................................................................................................... 15 

Protocol-PEGASUS Argentina 
4 
 
6.1 Data Collection Training .................................................................................................................... 15 
6.2 Training Cycle for Intervention Implementation .............................................................................. 15 
6.3 PEGASUS Pathway Training............................................................................................................... 16 
6.4 Case Review and Quality Improvement Training Details .................................................................. 16 
6.5 Focus Group and Motivational Interviewing (MI) Informed Check-In Facilitation Training ............. 17 
CHAPTER 7. COMMUNICATIONS PLAN ....................................................................................................... 18 
CHAPTER 8. DATA COLLECTION, MANAGEMENT, & ANALYSIS .................................................................. 18 
8.1 Data Management ............................................................................................................................ 18 
8.2 Data Confidentiality .......................................................................................................................... 18 
8.3 Data Flow Model ............................................................................................................................... 18 
8.4 Data Collection Timeline ................................................................................................................... 19 
8.5 Missing Data ...................................................................................................................................... 20 
CHAPTER 9 STUDY COMPLETION AND CLOSEOUT PROCEDURES ............................................................... 20 
9.1 Study End .......................................................................................................................................... 20 
9.2 Dissemination Policy ......................................................................................................................... 20 
APPENDIX 1: REFERENCES ........................................................................................................................... 21 
APPENDIX 2: ABBREVIATIONS ..................................................................................................................... 21 
  
 
 
 
 
 
 
 

Protocol-PEGASUS Argentina 
5 
 
Chapter 1. STUDY OVERVIEW 
Globally, over three million children sustain a traumatic brain injury (TBI) each year, with an estimated 
3-7% being classified as having a severe TBI (Glasgow Coma Scale (GCS) score ≤8). Long-term TBI-related 
disability and high health care costs are a significant burden to individuals and society, although data are 
limited outside of the United States and Europe.1,2 The Brain Trauma Foundation (BTF) Guidelines for 
Management of Pediatric Severe TBI represent the most comprehensive synthesis of evidence-based 
care for children with severe TBI,3 but they are not systematically implemented4 and are also almost 
exclusively based on evidence from research in the United States and Europe.  
Pediatric Guideline Adherence and Outcomes (PEGASUS) Argentina is a National Institutes of Health 
(NIH)-funded, multi-site randomized controlled trial (RCT) currently testing implementation of best 
practice care for children with severe TBI in South America.5 In prior work, we found that adherence to 
the TBI guidelines was associated with 6% better outcomes in 5 leading U.S. academic centers. The 
single center PEGASUS program pilot at Harborview Medical Center (Level-1 pediatric trauma center in 
Seattle, Washington) demonstrated improved adherence to key performance indicators of the BTF 
guidelines and patient outcomes, while not increasing in-hospital costs.6,7 However, TBI guideline 
adherence remains low, and the guidelines have limitations related to recommendation applicability 
across health care systems and across countries. While feasible, acceptable, and efficacious in the pilot 
study, the next step is to test PEGASUS intervention effectiveness more broadly. Focus on our 
partnership with experienced TBI researchers in Argentina at the Centro de Informática e Investigación 
Clínica (CIIC), and implementation at South American hospital sites will expand evidence of which 
guidelines are most important contributors to three-month patient outcomes and examine 
generalizability of the PEGASUS program.  
The study hypothesis is that the PEGASUS program improves TBI guideline adherence during the first 3 
days of intensive care in all children severe pediatric TBI and stratified by extracranial injury status. 
Sixteen hospitals throughout Argentina (14), Chile (1), and Paraguay (1) are participating in this study 
(Chapter 3.2). 
1.1 Specific Aims 
 
1) Determine the relationship between PEGASUS program implementation and TBI guideline 
adherence (Aim 1a) and assess system, provider, patients, implementation, and guideline 
factors associated with TBI guideline adherence (Aim 1b). 
 
2) Create a value stream map (VSM) that readily identify value added process of care associated 
with TBI guideline adherence. 
 
3) Use computer simulation to develop and disseminate a real-world best practices blueprint for 
TBI guideline adherence.  
This is a necessary advance and a step towards implementing guideline-based TBI care for 
children who suffer from TBI. 

Protocol-PEGASUS Argentina 
6 
 
 
**A cost analysis component is also included, although it is not a separate aim. 
1.2 Funding 
Research is supported by the National Institute of Neurological Disorders and Stroke of the National 
Institutes of Health under award number R01NS106560 (PIs: Vavilala, MS and Bell, MJ). Primary award is 
to the University of Washington (UW), subcontracts awarded to support CIIC, CNH, and WSU. Study 
hospitals receive funding through CIIC based on patient enrollment as well as subsidized travel. 
The sponsor and funder had no role in the design of this study and will not be involved in the 
implementation, analyses, interpretation of data, or writing of manuscripts for publication. 
1.3 IRB Protocol 
The study protocol (UW IRB# STUDY00005629) was initially approved by the UW Institutional Review 
Board (IRB) on 09/28/2018 as minimal risk. Study design revision was approved on August 7, 2020 and 
modification assessed as minimal risk. Approval was obtained at the IRBs for each of the local study 
hospitals for local recruitment, consent, and activities. 
Chapter 2. STUDY ORGANIZATION AND RESPONSIBILITIES 
2.1 Coordinating Center 
The University of Washington is the Coordinating Center. Roles and responsibilities include: 
 
Development of the randomization scheme and procedures 
 
Development of intervention plan 
 
Development of the data flow and data management procedures, including data entry, error 
identification, and correction 
 
Development of data collection forms 
 
Development of value stream mapping app 
 
Communications with secondary centers, scheduling of meetings, and responding to ad hoc 
communications 
 
Quality control procedures 
 
Statistical analysis 
 
Subject matter expertise 
 
Reports (e.g. enrollment, participant status, site performance, quality control, DSMB) 
 
Distribution of updates, documents, and reports to secondary sites, study sites, DSMB, IRB, 
FITBIR, NIH, as necessary 
2.2 Secondary Centers 
Centro de Informática e Investigación Clínica (CIIC) is responsible for: 
 
Communications with study sites, study IRBs, and coordinating center 
 
Co-development of intervention, procedures, and forms 

Protocol-PEGASUS Argentina 
7 
 
 
Training of study sites 
 
Site visits to ensure adherence to protocol and procedures 
 
Database development and management 
 
Data entry and cleaning 
 
Subject matter expertise 
 
Translation 
Children’s National Hospital (CNH) provided: 
 
Subject matter expertise 
 
Co-development of intervention, procedures, and forms 
Washington State University (WSU) provided: 
 
Cost analysis and utilization 
2.3 Study Sites 
The study sites (site PI and site coordinators) are responsible for: 
 
Participation in the protocol finalization and preparation of study materials 
 
Compliance with protocol and IRB regulations 
 
Recruitment, screening, and enrollment of participants 
 
Protection of participants’ rights 
 
Training of pediatric intensive care unit (ICU) staff and intervention implementation 
 
Data collection and participant follow-up through study completion 
 
Transfer of data to secondary center (CIIC) 
 
Communication of questions, concerns, and observations to secondary and coordinating 
centers. 
2.4 Roster 
Name 
Role 
Affiliation 
Phone 
Email 
Dr. Monica 
Vavilala 
Project Director/ 
Principal 
Investigator (PI) 
University of Washington, 
Seattle, WA 
206-744-9454 
vavilala@uw.edu  
Dr. Michael 
Bell 
Project 
Director/Principal 
Investigator (PI) 
Children’s National 
Hospital, Washington, DC 
202-476-2037 
mbell@childrensnational.org  
Dr. Gustavo 
Petroni 
Co-Investigator 
Centro de Informática e 
Investigación Clínica (CIIC), 
Rosario, Argentina 
+54.341.0471030 
gustavopetroni@gmail.com 
Dr. Silvia 
Lujan 
Co-Investigator 
Centro de Informática e 
Investigación Clínica (CIIC), 
Rosario, Argentina 
+54.341.4721030 
silviablujan@gmail.com 

Protocol-PEGASUS Argentina 
8 
 
Dr. Linda 
Boyle 
Co-Investigator, 
Value Stream 
Mapping 
University of Washington, 
Seattle, WA 
 
linda@uw.edu 
Dr. Charles 
Mock 
Co-Investigator, 
Quality 
Improvement 
University of Washington, 
Seattle, WA 
 
cmock@uw.edu 
Dr. Megan 
Moore 
Co-Investigator, 
Qualitative 
University of Washington, 
Seattle, WA 
 
mm99@uw.edu 
Dr. Ali 
Rowhani-
Rahbar 
Co-Investigator, 
Epidemiologist 
University of Washington, 
Seattle, WA 
 
rowhani@uw.edu 
Dr. Jin Wang 
Injury Statistician 
University of Washington, 
Seattle, WA 
 
wangji@uw.edu 
Dr. Bryan 
Weiner 
Co-Investigator, 
Implementation 
Science 
University of Washington, 
Seattle, WA 
 
bjweiner@uw.edu 
Dr. Janessa 
Graves 
Co-Investigator, 
Cost Analysis 
Washington State 
University, Pullman, WA 
 
janessa.graves@wsu.edu  
Julia 
Velonjara, 
MPH 
Research 
Coordinator 
University of Washington, 
Seattle, WA 
 
julialv@uw.edu 
 
Dr. Brianna 
Mills 
Research Scientist 
University of Washington, 
Seattle, WA 
 
bmills@uw.edu 
 
Karen Segar, 
MA 
Database 
Manager 
University of Washington, 
Seattle, WA 
 
ksegar@uw.edu 
 
Dr. Nahuel 
Guadagnoli 
Research 
Coordinator 
Centro de Informática e 
Investigación Clínica (CIIC), 
Rosario, Argentina 
 
nahuelguadagnoli21@gmail.co
m 
 
Daniel 
Giordano 
Data Systems 
Analyst 
Centro de Informática e 
Investigación Clínica (CIIC), 
Rosario, Argentina 
 
danielestebangiordano@gmail.c
om 
 
Alejandra 
DePetris 
Translator/Admini
strative 
Centro de Informática e 
Investigación Clínica (CIIC), 
Rosario, Argentina 
 
info@ciic.org.ar 
 
 
CHAPTER 3. STUDY DESIGN 
3.1 Study Design 
This study is an open-label, multicenter, phase 3, superiority, pragmatic, parallel cluster randomized 
controlled trial (RCT) including 16 South American hospitals to provide usual care (n=8 sites) or the 
PEGASUS intervention (n=8 sites). This final design resulted after two iterations: the first iteration was a 
parallel cluster RCT with twelve sites (6 intervention, 6 control). In response to site requests for 
receiving the PEGASUS Pathway intervention, a stepped wedge design was developed and approved by 
the sponsor. However, the final study design was again updated in August 2020 after approvals from site 
PIs and sponsor from a stepped-wedge design due back to a parallel cluster RCT with sixteen sites (8 
intervention, 8 control) due to COVID-19 pandemic challenges.8   

Protocol-PEGASUS Argentina 
9 
 
 
3.2 Governance Model 
The University of Washington and Children’s National Hospital supports CIIC’s coordination of the 
sixteen hospital study sites for translation, project implementation, data management, data analysis, 
and data safety monitoring components. 
 
 
 

Protocol-PEGASUS Argentina 
10 
 
3.3 Site Randomization Plan 
Sixteen study sites were recruited by CIIC based on willingness to participate and annual severe TBI 
admissions. Sites were added after the original proposal to increase the potential patient recruitment 
population. All sites receive compensation for data submission. Prior to randomization on July 13, 2020, 
three sites who had no or one enrolled patient during ten months of baseline usual care data collection 
were removed from the pool. The remaining sixteen sites participating were ranked by median monthly 
baseline enrollment, number of zero recruiting months, and total number of recruited patients and 
divided into four groups (Group A=highest enrollment group, Group D=lowest enrollment group). The 
study statistician performed computer block randomization within each group to assign to control and 
intervention arms at a 1:1 ratio. Participant assignment was dependent on the intervention or control 
arm assignment of the study hospital to which they were admitted.  
Due to the nature of the intervention study team, site staff, and patients’ families are aware of the site’s 
arm assignment. 
 
 

Protocol-PEGASUS Argentina 
11 
 
3.4 Screening and Eligibility Criteria  
All pediatric patients who admitted to the ICU at a study hospital site with a TBI are screened and their 
families/guardians are approached to enroll. Patients who are not eligible at admission but deteriorate 
are included at the time deterioration is assessed. No other exclusions. 
 
To be included the patient must be: 
 
Age < 18 years 
 
Mechanism or CT evidence of TBI 
 
Glasgow Coma Scale (GCS ) Score ≤ 8 (if intubated, motor GCS ≤ 5) 
 
Admitted to ICU at any point in the hospital stay 
 
An enrollment log will be kept in the secure database. Reasons for non-enrollment (does not meet 
eligibility criteria, death before consent, consent refusal, withdrawal) will be documented. 
 
3.5 Informed Consent 
If eligible, the 24-hour-on-call study coordinator is notified to begin a culturally appropriate consent 
process. Written informed consent for study procedures is obtained from legal guardians of patients by 
each participating site in Spanish. Verbal assent of the patient is also sought by ICU discharge if the 
patient is capable. Enrolled participants at the control sites consent to data collection from their medical 
records. Enrolled participants at the intervention sites consent to data collection and receive the 
intervention delivered by the trained ICU staff delivering their care. A patient or family/guardians can 
withdraw consent at any time. Should a patient or their family withdraw their consent, any previously 
collected data is removed from analysis and, if they are a patient at an intervention site, the PEGASUS 
clinical pathway is no longer used at the bedside, and they receive needed, usual care. The CIIC served 
as the regional coordinating center and storage warehouse for documentation. This protocol was 
performed according to the updated Declaration of Helsinki and all patients provided informed consent 
per local protocols for trial participation. 
3.6 Risks 
There are minimal risks associated with the proposed study. The main risk for participants is loss of 
confidentiality, which will be protected as described in Chapter 8. Anticipated and unanticipated health 
risks will be reviewed and assessed as described in Chapter 5. There are no provisions for post-trial care. 
3.7 Sample Size and Power 
A sample size of 432 participants is targeted for the planned parallel cluster study, which would have 
80% power to detect a 18.7% higher ICU TBI guideline adherence rate with program implementation at 
the site level, with a two-sided alpha of 5%, and an intraclass coefficient of 0.05. Calculations included 
58.6% guideline adherence rate estimate based on prior pilot work in Argentina and assumed no change 
in adherence rate at control sites. The study will not be sufficiently powered for secondary outcomes of 
patient mortality, discharge outcomes, or three-month follow-up outcomes. 
3.8 Recruitment, Retention & Follow-up 

Protocol-PEGASUS Argentina 
12 
 
Recruitment is limited to eligible patients admitted and consented at study sites. Based on baseline 
recruitment levels, the target sample size of 432 is feasible with about 9 participants per site per year. 
This is an in-patient intervention for the first 7 days of ICU care where intervention ICU staff are trained 
on intervention delivery as part of their patient care. Other data will be obtained from the health 
records. Follow-up data collection will be attempted at three months post-admission and can be 
completed in-person, via telephone, or from the health record. If unable to complete follow-up by four 
months, the participant will be designated lost-to-follow-up, but in-hospital data will be included. There 
is no incentive for participation offered to patients at any stage. 
 
CHAPTER 4. INTERVENTION 
The PEGASUS program intervention has multi-level components to increase TBI guideline adherence. It 
will be implemented from October 2020-September 2023. The patient level clinical care pathway is 
implemented for each eligible, consented patient at an intervention site for up to seven days of their ICU 
stay. Intervention site care providers supply perspectives and knowledge elements quarterly. At the 
hospital level, intervention sites participate in quarterly focus groups, morbidity and mortality case 
reviews and quality improvement efforts, and regular motivational interviewing informed (MI) check-ins 
with site PIs facilitated by CIIC.  
4.1 Intervention Model 

Protocol-PEGASUS Argentina 
13 
 
 
4.2 Implementation Readiness  
The four overarching program attributes are intent to benefit children with severe TBI (the who), 
inclusion of evidence-based acute care severe TBI recommendations (the what), program flexibility (the 
how), and capacity building (the goal). Multilevel refers to outer setting, inner setting, individual, and 
implementation process. The PEGASUS program meets criteria for innovation domain of the 
Consolidated Framework for Implementation Research constructs. Actions are given in chronological 
order. Process times may vary but ranged from 2-3 months. Timeline for process completion may vary 
depending on local needs. 
4.3 TBI Guideline Adaptations 
During the baseline study period, the full study team, including the sites provided input on TBI 
guidelines in the local context and impact on the relevant indicators in the guideline adherence 
calculation scorecard.  
4.4 PEGASUS Pathway 
The PEGASUS pathway does not prescribe specific drug doses or treatments but provides guidelines that 
inform the clinical assessment and treatment for individual patients. The PEGASUS program has been 
iteratively refined for use in the South American context and includes additional nursing resources for 
rounding and family education guides to encourage engagement.  
As a pragmatic implementation science study with quality improvement efforts, the components of the 
study are designed to be adaptable to support sites’ needs and to evaluate process measures to address 
reach (number of patients), dose (% processes implemented), and fidelity (variance from recommended 

Protocol-PEGASUS Argentina 
14 
 
processes and timely clinical pathway adoption). The Theoretical Domain Framework (TDF) and the 
Determinants of Implementation Behavior Questionnaire (DIBQ) guide these efforts.9 
4.5 Case Review and Quality Improvement (QI) Intervention Cycle 
This QI Cycle is used to support intervention implementation. Intervention sites will select a PEGASUS 
case to review quarterly with their ICU team. The case review form and follow-up corrective actions will 
be assessed by the CIIC/UW team. 
 
 
4.6 Focus Groups and MI Check-Ins 
The purpose of the quarterly focus groups and primarily bi-monthly (adaptive) MI check-ins as part of 
the intervention is to: 
 
Facilitate engagement in the study 
 
Promote adherence with PEGASUS protocols 
 
Address unmet needs while promoting site PI and clinician autonomy 
It utilizes adaptable discussion guides based on the TDF and DIBQ domains to maintain engagement to 
promote changes in the behavior of the site PI and coordinators that translates into improved 
implementation of the PEGASUS Pathway and the goal of increasing BTF guideline adherence. 
CHAPTER 5. SAFETY REPORTING & ADVERSE EVENTS 
5.1 Complications Reporting 
The UW IRB has determined that the study and the intervention pose minimal risk to participants. 
However, due to the nature of severe TBI injuries and ICU hospitalization it is anticipated that adverse 
events and complications, including death, will occur. Site PIs will report to a complications form in the 
database. The complications form tracks the occurrences, type, and severity (grave, moderate, or mild) 
of complications that occur. Shock, pneumonia, peritonitis, intraparenchymal hemorrhage, and 

Protocol-PEGASUS Argentina 
15 
 
arrhythmia are specifically identified, and other complications are noted as free text. We have pre-
intervention baseline data to assess adverse events related to patient safety or concerning trends in 
recruitment or follow-up data and we do not expect higher than baseline adverse events during the 
implementation of the intervention. If concerned about the impact of the study on an adverse event, 
site PIs will notify CIIC directly and the concern will be reviewed and escalated. 
5.2 DSMB Committee 
This study has an internal Data Safety and Monitoring Board (DSMB) comprised of a small group of 
experts who are not part of the study team. Study PIs, CIIC co-investigators, and the research 
coordinator will meet with them twice per year to review study status, recruitment, and adverse events, 
or in the event of an escalation.  
The DSMB will review participant recruitment, mortality, surgery type and frequency, and adverse 
events from the complications form. The study team will categorize complications according to body 
system. The DSMB will remain blinded to study arms unless a specific, unanticipated concern needs to 
be address. Reports from the meetings will also be submitted to the UW IRB to comply with IRB 
requirements. 
CHAPTER 6. TRAINING PLAN 
The overarching methodology of training for this study is a train-the-trainer model. The University of 
Washington (MSV) and Children's National Hospital (MJB) trained CIIC (NG, SBL, GP) partners and CIIC 
investigators trained site PIs in study procedures. Materials were co-developed by the study team. 
Questions from sites were first fielded in real time and per schedule by CIIC and escalated to MSV and 
MJB, as deemed necessary by CIIC. 
6.1 Data Collection Training 
Prior to participant enrollment for baseline data collection, all sites are trained in screening and 
consenting study participants. Training is conducted in medical record abstraction for patient level usual 
care data. After introducing the database and data collection forms, sites abstract a medical record from 
a sample patient as practice. Additional organizational level forms are also reviewed and the first round 
of these repeated forms are completed. Annually, data collection will be covered during booster 
trainings and other individual data entry issues will be addressed within the communications with the 
sites.  
UW trains CIIC on concept of process flow and value stream mapping through app demonstration and 
real-world examples. CIIC trains all site PIs on concepts of process flow and value stream mapping 
(VSM). Process flows are workshopped by site PIs who provided annual surveys of the ICU workflow.  
6.2 Training Cycle for Intervention Implementation 
Below is the PEGASUS Training Cycle for Intervention Implementation describing the timing and steps of 
implementation training for the intervention sites prior to intervention implementation. Annually, 

Protocol-PEGASUS Argentina 
16 
 
common intervention concerns will be covered during booster trainings and other individual issues will 
be addressed within the communications with the intervention sites. 
 
6.3 PEGASUS Pathway Training 
CIIC will lead training with intervention sites prior to implementation to review BTF guidelines and show 
how they integrate with the PEGASUS Pathway using an example case. Additional nursing resources and 
rounding tool and a family guide, co-developed by UW and CIIC, will be introduced and provided to 
support training of ICU nursing staff and for families, respectively. 
Intervention sites (site PIs and site coordinators) will then lead training for their ICU staff who care for 
eligible participants. 
6.4 Case Review and Quality Improvement Training Details 
The case review training module is adapted from World Health Organization (WHO) trauma quality 
improvement guidelines by UW with CIIC input. CIIC (SL) attended a Pan-American Health Organization 
(PAHO)-led training on the topic in 2019. The goal of the case review and QI training is to build capacity 
at sites for local QI processes. Part One is a case review module consisting of a self-directed training 
module (recorded presentation) and Part Two, a group case review training activity led by CIIC of three 

Protocol-PEGASUS Argentina 
17 
 
local cases (deidentified) at the implementation training to be conducted prior to implementation at 
intervention sites. Annually, QI topics were revisited in booster trainings. 
 
 
6.5 Focus Group and Motivational Interviewing (MI) Informed Check-In Facilitation Training 
Using the train-the-trainer model, UW provides initial facilitation trainings (two sessions) to CIIC on the 
use of motivational interviewing methods for the regular check-in communication at intervention sites 
and for focus groups with site PIs, coordinators, and ICU staff. The study team provides support on 
facilitation to CIIC as needed. 
The primary components of this training include: 
 
Principles of MI 
 
Basic Principles of a Person-Centered Approach to Behavior Change 
 
The Flow of MI 
 
Reveal Discrepancies and Respond to Resistance 

Protocol-PEGASUS Argentina 
18 
 
 
Strengthen Commitment and Make a Change Plan 
 
Review and Role Play of the Focus Group and Check-In Discussion Guides 
CHAPTER 7. COMMUNICATIONS PLAN 
UW communicates internally and with CIIC at least weekly. Study PIs and CIIC meet biweekly, and the 
PEGASUS Argentina study team meets monthly. Meeting minutes will be maintained. Other sub-
meetings and ad hoc communications for specific tasks facilitate activities in-between regular meetings. 
All-team meetings with PIs, study team, CIIC, and site PIs and coordinators (separated by study arm) are 
annual, via Zoom or in-person, as feasible. 
CIIC conducts day-to-day management of intervention delivery and implementation of activities, data 
entry support, training of study site staff, and direct weekly communication with study sites. Site 
communication and monitoring is conducted by CIIC to educate, support, and solve problems with data 
collection, intervention implementation, and quality improvement, with additional input from study PIs 
and co-investigators as necessary. In-person site visits are conducted as feasible due to travelling 
restrictions. 
CHAPTER 8. DATA COLLECTION, MANAGEMENT, & ANALYSIS 
8.1 Data Management 
The purpose-built, password-protected database is maintained on a dedicated server and has logic 
coding and input parameters to ensure legal variable values. Qualitative data for the provider- and 
hospital-level intervention support include free text response in questionnaires and case reviews, notes, 
and summaries of focus groups and MI check-ins. Data completion is assessed monthly by UW and CIIC 
study staff.  
8.2 Data Confidentiality 
Participant identification codes are assigned at the sites at the time of screening. Hospital site PIs and 
study coordinators have access to personal identifiers of their site’s enrolled patients and medical 
records through their dual roles as researchers and care providers. CIIC and U.S.-based study staff have 
access to the full dataset through the PEGASUS database, but without protected personal information 
like names, birth dates, or contact information.  
8.3 Data Flow Model 
The Data Flow Model below shows the procedures and responsibilities for data collection, data checks, 
and analysis. 

Protocol-PEGASUS Argentina 
19 
 
 
 
8.4 Data Collection Timeline 
Baseline data collection will occur at all participating sites from September 2019-September 2020. From 
October 2020-September 2023, interventions sites will collect additional data associated with the 
intervention implementation. The Data Collection Timeline below shows the data types collected 
(leftmost column) and the intervals of repeated measures. 

Protocol-PEGASUS Argentina 
20 
 
 
8.5 Missing Data 
Missing data identified during data checks will be followed-up and resolved with site PIs. Participants 
with missing data will be included in relevant analyses unless they specifically withdraw from the study. 
CHAPTER 9 STUDY COMPLETION AND CLOSEOUT PROCEDURES 
9.1 Study End 
After the study intervention and data collection periods are completed, the study team will share results 
with all site PIs and engage them throughout the analysis and manuscript writing process and provide 
sites who participated in the control arm with a training and materials package aimed to facilitate 
implementation should they desire. 
9.2 Dissemination Policy 
Access to a cleaned, deidentified dataset and code may be requested after the study is completed and 
accompanying manuscripts are published. As required by NIH, data will be submitted to FITBIR. The 
primary aim is a study-wide analysis and will be disseminated as such. We do not expect to have 
sufficient data for publication at the level of individual sites. Any publications and presentations prior to 
the release of the primary results will not impede the integrity of those results. 
 

Protocol-PEGASUS Argentina 
21 
 
APPENDIX 1: REFERENCES 
1. Dewan MC, Mummareddy N, Wellons JC, Bonfield CM. Epidemiology of Global Pediatric Traumatic 
Brain Injury: Qualitative Review. World Neurosurg. 2016;91:497-509.e1. 
2. Maas AIR, Menon DK, Adelson PD, Andelic N, Bell MJ, Belli A, et al. Traumatic brain injury: integrated 
approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017;16(12):987-1048. 
3. Kochanek PM, Tasker RC, Carney N, Totten AM, Adelson PD, Selden NR, et al. Guidelines for the 
Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma 
Foundation Guidelines. Pediatr Crit Care Med. 2019;20(3S Suppl 1):S1-S82. 
4. Vavilala MS, Kernic MA, Wang J, Kannan N, Mink RB, Wainwright MS, et al. Acute care clinical 
indicators associated with discharge outcomes in children with severe traumatic brain injury. Crit Care 
Med. 2014;42(10):2258-66. 
5. Vavilala MS, Bell MJ. Pediatric Guideline Adherence and Outcomes-Argentina, NCT03896789. 
ClinicalTrials.gov. Bethesda, MD: U.S. National Library of Medicine. 
https://clinicaltrials.gov/ct2/show/NCT03896789. 2019 Apr 1. Accessed 2021 Dec 10. 
6. Vavilala MS, King MA, Yang JT, Erickson SL, Mills B, Grant RM, et al. The Pediatric Guideline Adherence 
and Outcomes (PEGASUS) programme in severe traumatic brain injury: a single-centre hybrid 
implementation and effectiveness study. Lancet Child Adolesc Health. 2019;3(1):23-34. 
7. Graves JM, Kannan N, Mink RB, Wainwright MS, Groner JI, Bell MJ, et al. Guideline Adherence and 
Hospital Costs in Pediatric Severe Traumatic Brain Injury. Pediatr Crit Care Med. 2016;17(5):438-43. 
8. Velonjara J, Mills B, Lujan S, Petroni G, Bell MJ, Guadagnoli N, et al. The Pediatric Guideline Adherence 
and Outcomes (PEGASUS Argentina) program in severe traumatic brain injury: study protocol 
adaptations during the COVID-19 pandemic for a multisite implementation-effectiveness cluster 
randomized controlled trial. Trials. 2022 Dec 5;23(1):980.  
9. Huijg JM, Gebhardt WA, Dusseldorp E, et al. Measuring determinants of implementation behavior: 
psychometric properties of a questionnaire based on the theoretical domains framework. Implement 
Sci. 2014 Mar 19;9:33. 
 
APPENDIX 2: ABBREVIATIONS 
AIS-Abbreviated Injury Score 
BTF-Brain Trauma Foundation 
CIIC-Centro de Informática e Investigación Clínica 
CNH-Children’s National Hospital 

Protocol-PEGASUS Argentina 
22 
 
DIBQ-Determinants of Implementation Behavior Questionnaire 
DSMB-Data and Safety Monitoring Board 
FITBIR-Federal Interagency Traumatic Brain Injury Research 
GCS-Glasgow Coma Scale 
GOS-Glasgow Outcome Scale 
GOSE-Peds-Glasgow Outcome Scale Extended Pediatric 
ICU-Pediatric Intensive Care Unit 
IRB-Institutional Review Board 
ISS-Injury Severity Score 
ITT-Intent-To-Treat 
MI-Motivational Interview 
MPI-Multiple Principal Investigator 
NIH-National Institutes of Health 
NINDS-National Institute of Neurological Disorders and Stroke 
PAHO-Pan-American Health Organization 
 
PEGASUS-Pediatric Guideline Adherence and Outcomes 
PI-Principal Investigator 
RCT-Randomized Controlled Trial 
TBI-Traumatic Brain Injury 
TDF-Theoretical Domain Framework 
UW-University of Washington 
VSM-Value Stream Map 
WHO-World Health Organization 
WSU-Washington State University