The SIP Study: Simultaneously Implementing Pathways for Improving Asthma, Pneumonia, and Bronchiolitis Care for Hospitalized Children
Phase: NA
Conditions: Asthma, Pneumonia, Bronchiolitis
Sponsor: University of California, San Francisco

1 
 
 
 
The SIP Study: 
Simultaneously Implementing Pathways for Improving 
Asthma, Pneumonia, and Bronchiolitis Care for 
Hospitalized Children 
 
Study Protocol 
 
 
 
 
 
 
 
 
 
 
National Clinical Trial (NCT) Identified Number:  NCT05206695 
Principal Investigator: Sunitha Kaiser, MD MSc 
Sponsor: University of California, San Francisco 
Grant Number: R33HL157804 
 Funded by: National Heart, Lung, and Blood Institute 
Version Number:  v.1.6 
September 11, 2025 

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TABLE OF CONTENTS 
A 
INTRODUCTION ..................................................................................................................... 4 
A1 
STUDY ABSTRACT .............................................................................................................. 4 
A2 
PRIMARY HYPOTHESIS ....................................................................................................... 4 
B 
BACKGROUND ...................................................................................................................... 5 
B1 
PRIOR LITERATURE AND STUDIES ....................................................................................... 5 
B2 
RATIONALE FOR THIS STUDY .............................................................................................. 8 
C 
STUDY OBJECTIVES ............................................................................................................. 9 
C1 
PRIMARY AIM ..................................................................................................................... 9 
C2 
SECONDARY AIM ............................................................................................................... 9 
C3 
RATIONALE FOR THE SELECTION OF OUTCOME MEASURES .................................................. 9 
D 
INVESTIGATIONAL INTERVENTION .................................................................................... 9 
D1 
CLINICAL DATA TO DATE .................................................................................................... 9 
D2 
RISK/BENEFITS ................................................................................................................ 10 
E 
STUDY DESIGN .................................................................................................................... 11 
E1 
OVERVIEW AND STUDY DESIGN ........................................................................................ 11 
E2 
SUBJECT SELECTION ....................................................................................................... 12 
2.a 
Inclusion and Exclusion Criteria ................................................................................ 12 
2.b 
Subject Recruitment Plans and Consent Process ..................................................... 12 
2.c 
Randomization Method and Blinding ......................................................................... 13 
2.d 
Risks and Benefits ..................................................................................................... 13 
2.e 
Early Withdrawal of Subjects ..................................................................................... 13 
E3 
STUDY INTERVENTION ...................................................................................................... 13 
3.a 
Description ................................................................................................................. 13 
3.b 
Method for Assigning Subjects to Intervention Groups ............................................. 14 
3.c 
Fidelity Monitoring ..................................................................................................... 14 
3.d 
Prior and Concomitant Interventions ......................................................................... 14 
F 
STUDY PROCEDURES ........................................................................................................ 14 
F1 
SCREENING FOR ELIGIBILITY ............................................................................................. 14 
F2 
DATA COLLECTION/STUDY OUTCOME MEASUREMENT ........................................................ 15 
F3 
SAFETY MONITORING AND SERIOUS ADVERSE EVENT REPORTING ..................................... 15 
G 
STATISTICAL PLAN ............................................................................................................ 18 
G1 
SAMPLE SIZE DETERMINATION AND POWER ....................................................................... 18 
G2 
ANALYSIS PLAN AND STATISTICAL METHODS ..................................................................... 18 
G3 
MISSING OUTCOME DATA ................................................................................................. 19 
G4 
UNBLINDING PROCEDURES ............................................................................................... 20 
H 
DATA HANDLING AND RECORD KEEPING ...................................................................... 20 
H1 
CONFIDENTIALITY AND SECURITY ...................................................................................... 20 
H2 
TRAINING ........................................................................................................................ 20 
H3 
CASE REPORT FORMS AND SOURCE DOCUMENTS ............................................................. 20 
H4 
RECORDS RETENTION AND DATA SHARING ....................................................................... 20 
I 
STUDY MONITORING, AUDITING, AND INSPECTING ...................................................... 20 
I1 
STUDY MONITORING PLAN ................................................................................................... 20 
I2 
AUDITING AND INSPECTING ................................................................................................... 21 
J 
STUDY ADMINISTRATION .................................................................................................. 21 

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J1 
ORGANIZATION AND PARTICIPATING CENTERS ....................................................................... 21 
J2 
FUNDING SOURCE AND CONFLICTS OF INTEREST ................................................................... 22 
J3 
SUBJECT STIPENDS OR PAYMENTS ....................................................................................... 22 
J4 
STUDY TIMETABLE ............................................................................................................... 22 
K 
PUBLICATION PLAN ........................................................................................................... 23 
L 
ATTACHMENTS ................................................................................................................... 24 
L1 
INFORMED CONSENT DOCUMENTS ..................................................................................... 24 
L2 
DATA COLLECTION INSTRUMENTS ..................................... ERROR! BOOKMARK NOT DEFINED. 
M 
REFERENCES ...................................................................................................................... 24 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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A Introduction 
A1 Study Abstract 
 
Asthma, pneumonia, and bronchiolitis are the top causes of childhood hospitalization in the US, 
leading to over 350,000 hospitalizations and ≈$2 billion in costs annually. Poor guideline 
adoption by clinicians contributes to poor health outcomes for children hospitalized with 
these respiratory illnesses, including longer recovery time/hospital stay, higher rates of 
transfer to intensive care units, and increased risk of hospital readmission.      
 
General hospitals, such as community hospitals, primarily provide care for adults but also 
provide care for >70% of hospitalized children nationally. Unlike dedicated children’s hospitals, 
community hospitals face unique challenges to achieving guideline adoption and high-quality 
care for children, including less access to pediatric services and limited resources for pediatric 
care and quality improvement.  
 
Pathways have been shown to improve clinicians’ adoption of evidence-based 
practices/guidelines and health outcomes for children in community hospitals. Pathways are 
simple, visual diagrams that guide clinicians step-by-step through the evidence-based care of a 
specific medical condition (accessed via paper or electronically). Most hospitals implement 
pathways for a single medical condition at a time, but Seattle Children’s Hospital developed an 
intervention for simultaneously implementing multiple pathways for multiple pediatric conditions. 
This intervention led to sustained improvements in guideline adoption, decreases in length of 
stay, and decreases in costs. This multi-condition pathway intervention has not yet been 
studied in community hospitals, which face unique implementation barriers.  
 
Our objective is to identify and test pragmatic and sustainable strategies for implementing the 
multi-condition pathway intervention for children hospitalized with asthma, pneumonia, or 
bronchiolitis in community hospitals. In Aim 1, we will conduct a pragmatic, cluster-randomized 
trial in 36 community hospitals (1:1 randomization to intervention vs. wait-list control) to 
determine the effects of the multi-condition pathway intervention. Our primary outcome will be 
adoption of 2 evidence-based practices for each condition over a sustained period of 2 years. 
We will also determine length of stay, ICU transfer, and readmission.  During implementation, 
we will measure fidelity (use of implementation strategies as intended) in hospitals receiving 
the intervention. In Aim 2, we will use multi-level models to determine if these strategies are 
associated with guideline adoption (measured in Aim 1). Our expected outcomes will be a 
comprehensive understanding of how to pragmatically and sustainably implement the multi-
condition pathway intervention in community hospitals and an assessment of its effects. These 
outcomes will have an important positive impact by providing evidence on an intervention that 
can leverage implementation resources by tackling multiple pathways and rapidly improve care 
and outcomes for children with respiratory illnesses. 
A2 Primary Hypothesis 
 
Our hypothesis is that the multi-condition pathway intervention will be associated with 
significantly greater increases in adoption of evidence-based practices compared to control 
(standard care/practice). 
 

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B Background 
B1 Prior Literature and Studies 
 
Overview of Prior Literature:  
Asthma, pneumonia, and bronchiolitis are the 
top 3 causes of childhood hospitalization.1,2 An 
estimated 370,000 children are hospitalized each 
year in the US for these conditions, leading to ≈$2 
billion in direct healthcare costs.1,2 
Tremendous delays and barriers to clinicians’ 
guideline adherence lead to poor health 
outcomes for hospitalized children. Clinicians 
face many challenges adhering to guidelines (e.g., 
lack of familiarity, low confidence in ability to 
adhere),3 and these challenges cause up to 17-
year delays in achieving high guideline 
adherence.4 There is unnecessary variability in 
guideline adherence and health outcomes for 
children in hospital settings across a wide range of 
conditions, including respiratory illnesses. Even 
after adjusting for clinical severity, there is 
significant heterogeneity across hospitals in 
children receiving recommended medications, 
having prolonged length of stay and associated 
high costs, being transferred to intensive care 
units, and being readmitted to the hospital.5-8  
Pathways are a critical tool for improving 
guideline adherence and outcomes. Guidelines 
are lengthy and difficult to access and review 
efficiently while providing clinical care. Pathways 
are visual, step-by-step diagrams that are 
accessed via paper or electronically (Figure 1). 
They facilitate quick, easy guidance on evidence-
based practices. Rigorous studies, including 
randomized-controlled trials, have shown single-
condition pathways improve guideline adherence 
in children’s and community hospitals (Table 1).9-21 
These studies illustrate the current state of low 
guideline adherence, but also show: 1) pediatric asthma pathways increase use of 
recommended medications, and decrease unnecessary tests and medications, length of stay, 
costs, and hospital readmissions;9,13,16,17,19-21 2) pediatric pneumonia pathways increase 
appropriate antimicrobial use, and decrease radiation exposure, surgical procedures, and 
readmissions;10,15,18 and 3) pediatric bronchiolitis pathways decrease unnecessary tests and 
medications, length of stay, costs, and readmissions.11,12,14 Pathways also have the potential to 
improve current disparities22,23 in pediatric respiratory illness care and outcomes by 
standardizing care for all children.24 
Recently, Seattle Children’s Hospital developed an intervention that required similar 
implementation resources (e.g., clinician time, support for electronic integration) to 
simultaneously implement multiple pathways for multiple conditions. This intervention  
Figure 1.  
Multi-condition Pathway Intervention:  
Clinicians select the appropriate pathway 
based on the child’s illness 

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demonstrated improvements in clinicians’ guideline adherence comparable to those described 
for single-condition pathway implementation, and these results were sustained.9-12,25-27   
Simultaneously implementing pathways for multiple conditions is a higher-value 
approach- this approach leverages similar resources to potentially achieve sustained 
improvements in guideline adherence and health outcomes for more children more 
efficiently (compared to single-condition pathway implementation).  
Community hospitals face unique challenges in pediatric quality improvement (QI) efforts 
and pathway implementation. General hospitals, such as community hospitals, care for >70% 
of hospitalized children,2 but face unique and formidable barriers in pediatric QI efforts 
compared to dedicated children’s hospitals. Dedicated children’s hospitals have resources 
explicitly devoted to improving and sustaining clinicians’ guideline adherence and high-quality 
care for children (e.g., QI staff, data collection systems, support for electronic health record 
[EHR] modifications). Community hospitals primarily provide care to adults, and as a 
consequence, pediatric QI efforts have limited access to such QI resources.28,29 Additionally, 
community hospitals have less availability of pediatric-focused staff (e.g., emergency 
physicians, respiratory therapists, nurses) and services (e.g., pediatric intensive care units), low 
volumes of pediatric patients, and more varied staffing models for pediatric units.2,30 These and 
other factors contribute to substantially different uptake and effectiveness of pediatric QI 
interventions, lower adherence to pediatric guidelines, and differences in health outcomes for 
children in community hospitals.31-34 Reflective of these barriers, we found community hospitals 
have lower utilization of pediatric pathways (asthma pathway use 44% vs. 75% in community 
vs. children’s hospitals).9  
Community hospitals may be able to overcome these barriers and achieve rapid, 
widespread improvements in guideline adherence and health outcomes across the full 
spectrum of care. Our group and others have demonstrated that community hospitals can 
successfully overcome these barriers and implement pathways for a single condition at a time,9-
11 and our preliminary data indicates the multi-condition pathway intervention is feasible and 
acceptable in community hospitals (see Details on Prior Literature, below). 
Table 1. Baseline Adherence to Evidence-Based Practices & Increases Associated with Single-
Condition Pathways 
 
Evidence-Based Practice 
Rationale 
Baseline 
Adoption 
Absolute 
Increase 
Pneumonia 
Administration of narrow-
spectrum antibiotic in 
hospital 
Reduces antibiotic-associated 
side effects and emergence of 
multi-resistant organisms 
32% 
+ 30% 
No prescription of macrolide 
antibiotic at discharge 
Reduces antibiotic-associated 
side effects and emergence of 
multi-resistant organisms 
62% 
+ 27% 
Asthma 
Prescription of ICS for 
children >5 years 
ICS (daily or just when using 
rescue inhaler) prevents future 
severe exacerbations 
70% 
 +20% 
Use of metered-dose 
inhalers (MDIs) 
MDIs are cost-effective, 
promote asthma education, 
and promote asthma control. 
43% 
+ 25% 
Placement of an asthma 
pathway order 
Use of a pathway associated 
with decreased LOS, costs 
56% 
+ 8% 
Bronchiolitis 
No administration of 
albuterol during admission* 
Bronchodilators do not reduce 
symptoms or length of stay 
54% 
+ 13% 
Avoidance of chest 
radiographs 
Radiography leads to 
unnecessary radiation 
exposure and costs 
55% 
+9 

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Details on Prior Literature: The preliminary studies described below provide evidence that: #1) 
the multi-condition pathway intervention tested in Seattle Children’s Hospital can rapidly, 
broadly, and sustainably improve care quality for hospitalized children; #2) single-condition 
pathways can be successfully implemented and improve care quality for children in community 
hospitals; and #3) the multi-condition pathway intervention is feasible, acceptable, and 
appropriate in community hospitals. 
#1) As mentioned above, Seattle Children’s Hospital developed an intervention to 
simultaneously implement multiple pathways for multiple conditions. This multi-condition 
pathway intervention (pathways and key implementation strategies) demonstrated significant 
improvements in clinicians’ guideline adherence, length of stay, and costs that were comparable 
to those described for single-condition pathway implementation, and these results were 
sustained over 5 years.9-12,25-27 
#2) PIPA (Pathways for Improving Asthma Care): We successfully implemented and tested a 
pediatric asthma pathway intervention (single condition: asthma) in both children’s and 
community hospitals using a hybrid effectiveness-implementation study design,9 which is also 
proposed here. The PIPA study included 85 hospitals from around the US- 40 children’s 
hospitals and 45 community hospitals.  
PIPA Study- Effectiveness: Figure 2 illustrates our prior study findings. In our evaluation of 
effectiveness,9 we found pathways improved use of metered-dose inhalers (MDIs) during 
hospitalizations. MDIs are recommended by guidelines because they are more cost-effective 
and have fewer side effects than nebulizers,35,36 and MDI use promotes asthma education and 
better chronic asthma control.37-39 We also found pathways improved rates of referral of 
caretakers to smoking cessation resources- this is recommended by evidence-based guidelines 
because secondhand tobacco 
exposure worsens asthma 
outcomes in children.35,40,41 We 
evaluated sustainability in 
community hospitals, and we 
found improvements in both of 
these outcomes were sustained 
over 2 years. In addition, we 
found an 8% decrease in length 
of hospital stay for children who 
had pathway orders placed in 
the EHR.9 This study illustrates 
the effectiveness of asthma 
pathways (single-condition) in 
community hospitals. In Aim 1, 
we propose to build on this prior 
single-condition pathway work 
by determining the effectiveness 
of the multi-condition pathway 
intervention, specifically in 
community hospitals. 
Other prior studies indicate 
single-condition pathways for 
pneumonia and bronchiolitis are 
also effective in community 
hospitals. A 2017 study by 
Parikh et. al. that included a total 
of 48 hospitals (n=3802) 
demonstrated signficant 
Figure 2. Guideline Adherence Before and After Pediatric 
Asthma Pathway Implementation 

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improvements in use of narrow-spectrum antibiotics and avoidance of uneccessary macrolide 
antibiotics with pediatric pneumonia pathway implementation.10 A 2016 study by Ralston et. al. 
that included 21 hospitals (n=1869) demonstrated significant improvements in avoidance of 
uneccessary bronchodilators and corticosteroids, as well as decreased length of stay with 
bronchiolitis pathway implementation.11  
PIPA Study- Quantitative Evaluation of Implementation Strategy Utilization: During the 
PIPA study, we prospectively collected quantitative data on the utilization of key implementation 
strategies (via monthly survey of local implementation leaders and field visits).42 We found that 
site leaders conducted an average of 6 audit and feedback meetings with clinicians and 4 Plan-
Do-Study-Act (PDSA) cycles over 12 months at each site. Over 90% of hospitals that completed 
the study reported successful integration of pathways into the EHR. This study illustrates the 
feasibility of our proposed implementation strategies and our team’s experience with collecting 
prospective data on the utilization of implementation strategies (proposed in Aim 2). In Aim 2, 
we propose to build on this prior work by determining if these strategies are associated with 
increases in guideline adherence. 
PIPA Study- Qualitative Evaluation of Barriers and Facilitators of Implementation: Our 
team was the first to identify barriers, facilitators, contextual factors that influence pediatric 
asthma pathway implementation (single condition) in community hospitals.29 We found 
significant barriers included developing consensus on evidence-based practices, obtaining the 
needed QI resources, and training adult-focused clinicians (e.g., respiratory therapists). 
Facilitators included engaging a multi-disciplinary implementation team and devising solutions 
with external QI facilitators.29  
#3) We conducted a survey of implementation leaders from all 36 community hospitals recruited 
for this proposal using validated instruments,43 including the “Feasibility of Intervention 
Measure” (sample question: “This intervention seems easy to use”). Our results indicate high 
feasibility (mean score 4.1/5), high acceptability (mean score= 4.4/5), and high appropriateness 
(mean score 4.3/5) of the multi-condition pathway intervention. Scores ranged from 4 (“agree”) 
to 5 (“completely agree”) on all survey items. 
B2 Rationale for this Study 
 
Our proposal addresses critical 
gaps that prevent achievement of 
broad-scale improvements in care 
and outcomes for all hospitalized 
children (Table 2). We know 
single-condition pathways improve 
guideline adoption and health 
outcomes across a variety of settings.9-21 Simultaneous implementation of pathways for multiple 
conditions has been successfully demonstrated in 1 children’s hospital.12,22-24 However, this 
intervention has not yet been studied in community hospitals, which face unique implementation 
barriers (Table 2, Box D).28,29  
Understanding how to successfully implement the multi-condition pathway intervention 
in community hospitals will fill a critical knowledge gap that can enable broad-scale 
improvements in guideline adoption and health outcomes for hospitalized children 
across a wide range of common conditions.25,44 
Table 2. Critical Gap in Prior Research 
 
Children’s 
Hospitals 
Community 
Hospitals 
Single-Condition Pathway 
Interventions9-21 
A: Tested, 
effective 
B: Tested, 
effective 
Multi-Condition Pathway 
Intervention12,22-24 
C: Tested, 
effective 
D: GAP IN PRIOR 
RESEARCH 

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C Study Objectives 
C1 Primary Aim 
We will determine the effects of the intervention compared to control via chart reviews of 
children hospitalized with asthma, pneumonia, or bronchiolitis. Our primary outcome will be 
adoption of evidence-based practices35,40,45,46 (2-3 for each condition) over a sustained period 
of 2 years (e.g., use of narrow-spectrum antibiotics for pneumonia). We will also determine 
length of stay, ICU transfer, and readmission/emergency revisit. 
C2 Secondary Aim 
We will measure fidelity (use of implementation strategies as intended25,47) via monthly surveys 
of site leaders and field visits to intervention hospitals. We will use multi-level models to 
determine if these strategies are associated with guideline adoption (measured in Aim 1/primary 
aim). If the intervention is successful, we will use these and other study findings to create and 
disseminate an implementation toolkit. 
C3 Rationale for the Selection of Outcome Measures 
Our primary outcome will be adoption of evidence-based practices. We selected 7 evidence-
based practices (Table 1),35,40,45,46 based on the following criteria: 1) there are low baseline rates 
and significant variability in adoption of the practice in community hospitals,9-11 2) pathways are 
associated with significantly increased adoption of the practice,9-11,15,19,27 and 3) improved 
adoption is associated with improvements in patient-centered outcomes, such as length of stay 
or hospital readmission.9,11-17,19,27,48 Secondary study outcomes will include length of hospital 
stay in hours, transfer to an intensive care unit, and 30-day hospital readmission or emergency 
revisit. These outcomes align with national quality measures, including the PRIMES guideline 
adoption measures,72,74 and the National Quality Forum-endorsed 30-day pediatric respiratory 
illness readmission measure.49 
D Investigational Intervention  
D1 Clinical Data to Date  
General hospitals, such as community hospitals, care for >70% of hospitalized children2 but 
face unique barriers in efforts to improve care quality for children. Our prior work demonstrated 
that community hospitals have lower utilization of pediatric pathways (asthma pathway use 44% 
in community hospitals versus 75% in children’s hospitals)9 and face unique barriers to pathway 
implementation, including delays in integrating pathway content into the electronic health record 
(EHR), less quality improvement (QI) infrastructure and support, and fewer resources prioritized 
for pediatric care.28,29 However, our group and others have demonstrated that community 
hospitals can overcome these barriers and successfully implement pathways for a single 
condition at a time (Table 1 in B1 Prior Literature and Studies).9-11  
Recently, Seattle Children’s Hospital developed an intervention that required similar 
implementation resources (e.g., clinician time, support for electronic integration) to 
simultaneously implement multiple pathways for multiple conditions. This intervention 
demonstrated improvements in guideline adoption, length of stay, and costs comparable to 
those described for single-condition pathway implementation, and these results were 
sustained.9-12,25-27 

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D2 Risk/Benefits  
Risks 
This proposed research involves a cluster-randomized controlled trial of a multi-condition 
pathway intervention in general/community hospitals (1:1 randomization to intervention vs. wait-
list control). The pathway intervention is designed to provide clinicians with step-by-step 
guidance on the evidence-based care of children hospitalized with asthma, pneumonia, or 
bronchiolitis. The pathway intervention provides decision support to clinicians to promote current 
standards of care; the intervention does not involve any new therapies or diagnostic tests in 
participants.  
 
For Aim 1/primary aim, chart reviewers will extract data from electronic health records into 
REDCap (Research Electronic Data Capture), a secure electronic data management tool. 
Reviewers will obtain a list of eligible patients (based on ICD-10 primary diagnosis codes), and 
this list will be destroyed after data entry into REDCap. No Protected Health Information will be 
collected for this study. The data recorded in REDCap will include the patient’s age, sex, need 
for supplemental oxygen on admission, race, primary insurance type, prior prescription of an 
inhaled corticosteroid, and presence of any other comorbidities. Data collection will also include 
our outcomes of interest, including evidence-based care practices, length of hospital stay, 
transfer to intensive care (yes/no), and 30-day hospital readmission or emergency revisit 
(yes/no). For Aim 2, data on use of implementation strategies (e.g., audit and feedback 
meetings) and potential unintended negative consequences of implementation will be collected 
via monthly surveys entered into REDCap. These data will specify hospital/study site. 
 
No Protected Health Information will be collected in any part of this study. To ensure 
confidentiality and compliance with the Health Insurance Portability and Accountability Act 
(HIPAA), all data and records will be kept confidential, all data will be stored on secure servers 
maintained by UCSF (see below), and access will be restricted to members of the IRB-approved 
research team. Any paper documents generated in the execution of this study will be stored in a 
locked filing cabinet in a locked office. Only the investigative team will have access to this 
information. Data collected through this research will be used only for the purposes discussed in 
this application. 
 
All research data, including that within REDCap, will be stored within UCSF MyResearch. 
MyResearch is a secure, HIPAA-compliant desktop environment hosted on servers at the UCSF 
Data Center. The MyResearch environment is hosted on 6 Dell PowerEdge R710s and 1 Dell 
EqualLogic SAN array, which are located inside a locked rack at the Data Center. There are two 
layers of physical redundant Juniper firewalls that protect the servers and SAN. The 
MyResearch environment utilizes VM Ware View Virtual Desktop, which must be logged into 
using UCSF Active Directory credentials. The servers are locked inside a rack locked with a 
combination lock. The rack is in a data center secured by two sets of locked doors with an air 
lock and unlocked via a biometric device. To reach the rack, one must progress through the two 
sets of locked doors and through an Operations Desk area which is staffed 24x7. The rack itself 
has a security camera mounted on it and is tied into the central security camera system to 
ensure that the feed is monitored 24x7. Study data will be stored in Dr. Kaiser’s group network 
folder in the remote MyResearch environment, where only the research team members are able 
to view the data and this access is audited. This folder is physically located in a data store on 
the SAN in the locked rack, and study staff will only access it through the VMWare remote 
desktop. Network traffic between MyResearch and the UCSF campus network traverses an SSL 
VPN tunnel in encrypted format. 
 

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The potential risks to the participants in this research will be no more than minimal risk. There 
are minor risks to privacy of individuals or confidentiality of data. The minimal risks of this study 
will be mitigated by strict adherence to proper data management and protection policies. 
 
Benefits 
Children hospitalized with respiratory illnesses may benefit from the intervention through 
improvements in clinicians’ adherence to evidence-based practices. Better guideline adherence 
may reduce time to recovery/hospital stay, risk of transfer to intensive care, and risk of hospital 
readmission. Clinicians who participate in implementation data collection (Aim 2) will not directly 
benefit from participating in these research activities. In the long term, patients/children and 
families, clinicians, and administrators stand to benefit from participating in this research as they 
and their families continue to receive care in the participating sites (after implementation of 
pathways).  
E Study Design  
E1 Overview and Study Design 
 
The multi-condition pathway intervention was previously studied at a 1 dedicated, free-standing 
children’s hospital.25 We propose to implement and test this intervention in a diverse sample of 
community hospitals across the US. We will conduct a type 3 hybrid effectiveness-
implementation trial, in which the primary goal is evaluating implementation and a secondary 
goal is determining effects on clinical outcomes.50 For Aim 1, we will conduct a cluster-
randomized trial of the multi-condition pathway intervention in community hospitals (1:1 
randomization to intervention versus wait-list control), and we will implement the intervention 
using the well-established mentored implementation framework.47 We will determine effects of 
the intervention compared to control via chart reviews of children hospitalized with asthma, 
pneumonia, or bronchiolitis. Our primary outcome will be adoption of 2-3 evidence-based 
practices35,40,45,46 for each condition over a sustained period of 2 years. During implementation, 
we will measure fidelity (use of implementation strategies as intended25,47) and in Aim 2 we will 
use multi-level models to determine if these strategies are associated with guideline adoption. 
Design: A parallel, cluster-randomized trial best addresses seasonal variation in outcomes for 
these respiratory illnesses by providing a concurrent control group and collecting data over 5 
respiratory viral seasons, 3 seasons prior to implementation and 2 seasons after 
implementation. We will stratify hospital randomization by geographic region (e.g., Northeast) to 
help ensure the effects of seasonal variation are similar across intervention and control groups. 
Figure 3 shows the study timeline. In Year 1, we will recruit and randomize hospitals to 
intervention versus wait-list control, and chart reviewers will collect baseline data (before 
implementation). In Year 2, we will begin implementation in the intervention hospitals. Hospitals 
in the wait-list control arm will wait/not implement pathways until Year 4. 
 
Figure 3. Study Timeline 

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E2 Subject Selection 
2.a 
Inclusion and Exclusion Criteria  
 
The study sample will include 
children admitted to the inpatient 
pediatric wards of study  
hospitals for asthma, pneumonia, 
or bronchiolitis during the study 
period. We will identify eligible 
children using ICD-10 codes that 
were developed and validated as 
part of the NHLBI-funded PRIMES 
Studies (Pediatric Respiratory 
Illness Inpatient Measurement 
System, R01HL121067 and 
R01HL088503).48,51 For asthma, 
codes include J4520, J4521, 
J4522, J4530, J4531, J4532, 
J4540, J4541, J4542, J4550, 
J4551, J4552, J45901, J45902, 
J45990, J45991, or J45998. For pneumonia, codes include J13, J14, J150, J151, J1520, 
J15211, J15212, J1529, J153, J154, J155, J156, J157, J158, J159, J160, J168, J17, J180, 
J181, J182, J188, J189 (focused on bacterial pneumonia). For bronchiolitis, codes include J210, 
J211, J218, J219. Inclusion and exclusion criteria and rationale are outlined in Table 3. Chart 
reviewers at each hospital will review all eligible admissions each month, to a maximum of 10 
per condition of interest (total 30 admissions per month, randomly selected).  
2.b 
Subject Recruitment Plans and Consent Process 
 
Data will be collected via chart review, as described above. Data collection will occur a minimum 
of 30 days after a patient is discharged from the hospital. No recruitment is required for this data 
collection process. In line with prior studies,9-11 we were granted waiver of consent by the UCSF 
IRB. An IRB may waive the requirements to obtain informed consent provided the IRB finds and 
documents that: 
 
(1) The research involves no more than minimal risk to the subjects 
 
This proposal meets criteria for minimal risk, as the intervention seeks to improve clinicians' 
adherence to current standard of care, and no PHI will be collected. 
 
(2) The waiver or alteration will not adversely affect the rights and welfare of the subjects 
 
This study involves no procedures for which written consent is normally required outside of the 
research context. It is unlikely that patients and their families would consider that this waiver has 
the potential to cause adverse consequences for their privacy, welfare, or general well-being. 
There is no collection of Protected Health Information planned, therefore collecting Protected 
Health Information in order to document informed consent increases the risk of privacy breach 
associated with this study. 
 
(3) The research could not practicably be carried out without the waiver or alteration 
Table 3. Study Inclusion/Exclusion Criteria 
Inclusion Criteria: 
Primary diagnosis of asthma AND age >2 to <18 years-old at time of 
admission to the hospital 
Primary diagnosis of pneumonia AND age >2 months and <18 years 
at time of admission to the hospital 
Primary diagnosis of bronchiolitis AND age <2 years at time of 
admission to the hospital 
Exclusion Criteria and Rationale: 
Secondary diagnosis of SARS-CoV-2 (due to lack of evidence-based 
guidelines on management) 
Transfer in from or out to an inpatient facility (due to inability to 
accurately determine length of hospital stay) 
Pre-existing chronic lung disease (other than asthma), cardiovascular 
disease, airway anomalies, immunodeficiency, or neurologic 
disorders*  
*The pathway intervention excludes these children because it is intended 
for routine management of the targeted respiratory conditions, not for 
children who are critically ill or have underlying chronic illness 

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It would not be practicable to perform the research (as it has been defined in the protocol by its 
specific aims and objectives) if consent was required for the following reasons: 
 
a. Scientific validity would be compromised if consent was required. The sample size required is 
so large that including only those patients for which consent can be obtained would prohibit 
conclusions to be drawn or bias the sample such that conclusions would be skewed. 
 
b. The disclosure of the study purpose as part of the consent process could impact the behavior 
of the staff caring for patients with respiratory illnesses, so that the results will not be 
meaningful. 
 
c. There is a risk of creating additional threats to privacy by having to link data that is otherwise 
free of identifiers in order to contact patients’ families to seek and document consent. 
 
(4) Whenever appropriate, the subjects will be provided with additional pertinent information 
after participation. 
2.c 
Randomization Method and Blinding 
 
We will cluster-randomize participating hospitals to 2 different intervention start dates as 
described above in “E1 Overview and Study Design.” Patients, families, and clinicians will be 
unblinded to the exposure to the intervention. Study analysts will be blinded as to intervention 
status. 
2.d 
Risks and Benefits 
 
See above section “D2 Risks/Benefits.” 
2.e 
Early Withdrawal of Subjects  
 
Early withdrawal is not applicable in this study, as all study data is collected at one time point, 
after a hospitalization. 
 
E3 Study Intervention 
3.a 
Description  
 
The multi-condition pathway intervention consists of pathways clinicians select from to guide the 
care of children with asthma, pneumonia, or bronchiolitis (Figure 1). Our overall implementation 
plan integrates the implementation strategies outlined in the prior single-center study of the 
intervention25 and implementation strategies specified for mentored implementation, a well-
established framework for multi-site implementation of healthcare interventions.47 Our prior 
research on asthma pathway implementation in community hospitals demonstrated the 
importance of these strategies.29 For instance, audit and feedback was critical to motivating 
clinicians and overcoming practice change inertia. Implementation strategies occurring during 
this R33 phase include: 
- Audit and feedback: Chart reviewers at each site will collect data (described below in “Data 
Collection”). We will use these data to produce monthly run charts/performance reports on the 

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proportion of eligible patients with pathway-based order sets accessed (process measure) and 
guideline adoption outcomes (Table 1). Reports will contain hospital-specific performance and 
aggregate performance across all intervention sites. Local implementation teams will hold 
monthly meetings with all clinicians and staff involved in the care of children with respiratory 
illnesses. In the meetings, they will use these reports to review local performance. 
- PDSA cycles: Local implementation teams will review clinical workflows in relation to current 
performance and plan PDSA cycles, in which teams identify and test workflow changes to 
improve performance.52 PDSA cycles facilitate progressive, structured, and iterative change.  
- Integration of pathway content into electronic order sets: In order to promote sustainability, 
local implementation teams will integrate guidance on evidence-based practices into electronic 
order sets. The Core Investigator Team will provide these teams order set templates to guide 
this process and mentors will support site leaders in planning and addressing barriers. 
- Mentor meetings/facilitation: Monthly meetings of the mentors and implementation teams will 
involve: 1) reviewing performance reports on adoption of evidence-based practices, 2) 
developing project plans with key milestones/targets and monitoring progress, and 3) planning 
PDSA cycles.  
- Learning Collaborative: Monthly mentor calls will periodically involve implementation leaders 
from all 2-3 sites the mentor is assisting. These group calls will facilitate cross-site problem 
solving and sharing of insights on barriers and facilitators of implementing the multi-condition 
pathway intervention. 
3.b 
Method for Assigning Subjects to Intervention Groups  
 
We will cluster-randomize participating hospitals to 2 different intervention start dates as 
described above in “E1 Overview and Study Design.” All children hospitalized after a hospital’s 
intervention start date will be considered “exposed” to the intervention. 
3.c 
Fidelity Monitoring 
 
During the first 12 months of intervention implementation, we will collect data via monthly 
electronic survey of local implementation leaders. Surveys will measure utilization (yes/no) of 
implementation strategies25 in the prior month. Each month, mentors will verbally verify these 
yes/no survey responses (during scheduled mentor meetings). In addition, during scheduled 
field visits to sites in month 4 after start of the intervention period, mentors will visually verify the 
integration of pathways into electronic order sets. Surveys will inquire about prior or concomitant 
interventions to improve pediatric respiratory illness care quality. Surveys will also collect 
quantitative estimates of the monthly time costs of implementation for local implementation 
leaders; and qualitative, free-text responses on any unintended negative consequences of 
implementation. 
3.d 
Prior and Concomitant Interventions  
 
See above section “E3 3.c Fidelity Monitoring.” 
 
F Study Procedures  
F1 Screening for Eligibility 
 
See above section “E2 2.a Inclusion and Exclusion Criteria.” 

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F2 Data Collection/Study Outcome Measurement 
 
Chart reviewers at each hospital will collect data through monthly chart review of the electronic 
health records of enrolled patients. All hospitals (both intervention and wait-list control) will 
collect baseline data in Year 1 and then continue data collection in Years 2-3, while intervention 
hospitals implement pathways and control hospitals continue to wait. Only wait-list control 
hospitals will collect data in Year 4, when they implement the intervention. We will collect data 
on the outcomes described in Table 1 as well as several patient characteristics known to be 
associated with the severity of these respiratory illnesses in children (see below in “Primary 
Analysis”).  
 
Dr. Kaiser and the UCSF Project Manager will train chart reviewers at each study site based on 
the Medical Record Abstraction Quality Assurance and Control Framework.53 Principles of the 
framework include: 1) quality assurance- prospective actions taken such as abstractor training, 
standard procedures, and job aids to assure adequate accuracy, and 2) quality control- 
measurement of error or discrepancy rates and use of the measurements to guide adjustments 
to controllable inputs to the abstraction process, such as abstraction tools, procedures, and 
training. A second chart reviewer will review a subset of charts (10%) each month at each site 
for quality control, providing feedback to the primary reviewer, Dr. Kaiser, and the UCSF Project 
Manager about any discrepancies (to facilitate additional training).  
 
Reviewers will enter data into the REDCap electronic database, accessible from all study sites. 
To maximize data quality, we will use REDCap data validation algorithms, which restrict input to 
plausible values and check for potentially erroneous outliers. The UCSF Project Manager will 
check for suspicious or missing data weekly and contact chart reviewers to make any needed 
corrections. We will store all data securely (see Protection of Human Subjects, Facilities). Our 
team has extensive experience using these methods of chart reviewer training and quality 
control/assurance in community hospitals.9,54 For any issues with REDCap, our central study 
team should be contacted (SIP@ucsf.edu).  
 
SHM will create a project website in which all project materials will be stored in the WorkZone 
platform. All site leaders and chart reviewers will be provided individual usernames and 
passwords to access this website at anytime throughout the study. The SHM team can be 
contacted to help with access (sthompson@hospitalmedicine.org). Project materials will include 
chart review training and reference materials (including site-specific REDCap data entry links), 
the multi-condition pathway implementation toolkit, performance reports, mentor/facilitator 
meeting notes, educational videos, and project timeline.  
F3 Safety Monitoring and Serious Adverse Event Reporting  
 
The Data and Safety Monitoring Plan for this grant application incorporates the Policies on Data 
and Safety Monitoring specified by the Department of Pediatrics at the University of California, 
San Francisco. 
Monitoring the Progress of the Study  
The progress of the study will be monitored by the Data Safety Monitoring Board (DSMB) on a 
semi-annual basis. The DSMB chair is Dr. Eyal Cohen, and additional members include Dr. 
Stephen Teach and Dr. Matthew Hall. On a semi-annual basis, the Project Leaders (Drs. Kaiser, 
Auerbach, Gonzales, McCulloch, and Howell), the Project Manager, and Project Analyst will 
prepare a written report on the progress of the study including data on enrollments, comparison 

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of target to actual enrollment, overall status of the study patients, information on race/ethnicity 
and sex, and information on any serious adverse events. Following review of these reports, the 
DSMB will recommend any modifications that are required to enhance recruitment and retention 
of study patients. Participating hospitals each have designated safety officers as well, who will 
help ensure the safety of participants. This protocol presents minimal risks to participants and 
interim analyses of trial outcomes are not considered crucial for the protection of human subjects. 
- Overview of the DSMB 
The purpose of the DSMB is to provide the oversight and monitoring necessary to ensure the 
safety of the study participants and the validity and integrity of the trial data.  The study 
governance provided by the DSMB is distinct from the review and approval by an Institutional 
Review Board (IRB) or any independent adjudication committee.  The members of the DSMB 
have relevant expertise in the operational, medical, and biostatistical aspects of a clinical trial. 
The DSMB will advise the principal investigator (PI) and the study sponsor (NHLBI) regarding 
the continuing safety of study participants, the ongoing validity and scientific merit of the trial 
and whether or not the study should continue.  
- DSMB Membership and Chair 
The ability of the DSMB to provide additional assurance of participant safety and scientific 
validity depends on the appropriate selection of its Board members. The DSMB will be 
composed of Board members with expertise in pediatrics, pediatric respiratory illnesses, 
pediatric hospital care, quality and safety, and clinical trials. The DSMB will have a designated 
Chair. The role of the DSMB Chair is to provide leadership on administrative and scientific 
issues. The chair will: facilitate discussions on trial related topics; integrate differing points of 
view from the Board members; and establish a consensus on recommendations to the study 
sponsor.   
Any concerns noted will be brought to the attention of the DSMB Chair who will take 
appropriate action. The DSMB will review on a semi-annual basis the reports prepared by the 
study PI, statistician, and programmer/analyst on the progress of the project, including: data 
on enrollments; comparison of target to actual enrollment; overall status of the study 
participants; information on race/ethnicity; gender; and serious adverse events. The DSMB 
will also determine whether additional effort is required to foster the progress of the study, and 
whether serious adverse events were immediately reported to the UCSF Committee on 
Human Research and dealt with appropriately. The DSMB will determine whether the study 
should continue, be terminated, or be modified based on observed beneficial or adverse 
effects. 
- DSMB Responsibilities 
Prior to implementation of the trial, the DSMB will evaluate the study design, review informed 
consent documents and plans for recruitment, adherence, interventions, data quality and 
safety monitoring. At periodic intervals during the course of the trial, the responsibilities of the 
DSMB are to:  
• Evaluate the progress of the study, including, adequacy and timeliness of participant 
recruitment, adherence to the interventions protocol, data quality and timeliness, 
participant safety, and other factors that can affect study outcome; 
• Consider factors external to the study when relevant information, such as scientific 
developments, may have an impact on the safety of the participants or the ethical 
conduct of the trial;  
• Ensure data integrity;   
• Ensure confidentiality of data and the results of monitoring; 

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• Report to the study sponsor and investigators on the scientific progress of the trial and 
the safety of participants;  
• Make recommendations to the study sponsors and Investigators and Institutional 
Review Boards on continuation, termination, or other modifications of the trial. 
- DSBM Process 
The DSMB will meet semi-annually by videoconference. Agendas for the meetings will be 
developed by the PI and the DSMB Chair. The first meeting should take place before initiation 
of the study to discuss protocol, interventions, safety measures and to establish guidelines for 
monitoring. Following the initial meeting, the DSMB should meet semi-annually. An 
emergency meeting of the DSMB may be called at any time by the Chair or study sponsor 
should questions of participant safety arise. 
DSMB meetings will consist of an open and a closed session. The open session may be 
attended by investigators and study sponsor staff, and they should always include the principal 
investigator and the study biostatistician. Issues discussed at the open session will include 
conduct and progress of the study, recruitment, adherence with the visit and interventions 
protocols, data quality and timeliness, problems encountered and aggregate outcome data. 
The closed session will be attended only by DSMB members and appropriate study sponsor 
staff representative(s), but others may attend if requested by the DSMB. All discussion at the 
closed session is completely confidential. 
Should the DSMB decide to issue a recommendation to terminate or alter the study protocol, 
a full vote of the DSMB will be required. In the event of a split vote, a simple majority vote will 
rule and a minority report should be appended. The DSMB will review the protocol of approved 
and funded studies ancillary to the study, but they will not review the conduct and outcomes 
of these studies. 
- DSMB Recommendations 
The DSMB Chair will prepare minutes of the open and closed sessions, including any 
recommendations for changes in the study protocol that are approved by the Board and sent 
to study sponsor. The study sponsor Project Scientist will distribute minutes of the open 
session to the Principal Investigators within four weeks of each meeting. The minutes of each 
DSMB closed session should conclude with a recommendation to continue, terminate or alter 
the study. A recommendation to terminate the study or alter the study protocol may be made 
by the DSMB at any time by majority vote. Such recommendations will be transmitted to the 
study sponsor. Recommendations of the DSMB that are accepted by the study sponsor will 
be transmitted by the Project Scientist to the Principal Investigator as rapidly as possible. In 
the event of a split vote in favor of continuation, a minority report should be included in the 
regular DSMB closed report. 
 
Plans for Assuring Compliance with Requirements Regarding the Reporting of Serious 
Adverse Events  
This trial intervention consists of clinical pathways that remind clinicians of current standards of 
care. It does not involve experimental treatments or diagnostic tests. Given the nature of this 
intervention, serious adverse events (SAEs) have been defined and will be monitored as 
follows. SAEs are defined as: 1) events that lead to patient harm/morbidity (reported via hospital 
safety/incident reporting systems), or 2) death/mortality. Local Project Leaders at participating 
hospitals will be notified to contact the UCSF Core Study Team immediately should SAEs occur, 
and they will also be contacted monthly throughout the trial period via survey to inquire about 
any SAEs. If any SAEs are reported, the PI and Project Manager are responsible for reporting to 

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the Core Investigator Team, DSMB, and the UCSF Human Subjects Committee within 48 hours. 
The Core Investigator Team, DSMB, local Project Leader, and Local Safety Officers will then 
use root cause analysis (RCA) methods to review any events to determine attribution to the SIP 
intervention. A central tenet of RCA is to identify underlying problems that increase the 
likelihood of errors while avoiding the trap of focusing on mistakes by individuals. RCA thus 
uses the systems approach to identify both active errors (errors occurring at the point of 
interface between humans and a complex system) and latent errors (the hidden problems within 
health care systems that contribute to serious adverse events). 
G Statistical Plan  
G1  Sample Size Determination and Power 
For sample size calculations, we used an alpha of 0.05, effect size estimates based on prior 
literature (see Table), and intra-class correlation coefficients (ICCs) specific to each outcome. 
ICCs were calculated based on our baseline period data (12-month period prior to trial 
intervention). We identified 40 hospital sites, and we accounted for up to 20% drop out of 
hospitals over the course of the trial (n=32 hospitals). We found that with volumes of 10 children 
with asthma, 15 children with pneumonia, and 15 children with bronchiolitis per year per 
hospital, we have >80% power to detect previously reported effect sizes in mean adherence to 
these evidence-based practice measures. If 32 hospitals (80%) remain from the 40 hospitals we 
have enrolled, we will have estimated minimal sample size of 3,840 admissions in the study (32 
hospitals X 40 admissions per year X 3 years [1-year baseline and 2-year intervention period]). 
G2  Analysis Plan and Statistical Methods 
Primary Outcome: 
Our primary outcome will be mean adherence to the 7 evidence-based practices of focus (in 
aggregate, Table 1). In our primary analysis, we will compare changes in mean adherence to 
evidence-based practices from the baseline to intervention period between the pathway 
intervention and control groups (difference-in-differences analysis). This design best addresses 
the seasonal variation in outcomes for the target respiratory illnesses by providing a concurrent 
control group and collecting data over 5 respiratory viral seasons, including three seasons prior 
to implementation and 2 viral seasons/years after implementation.  
The unit of analysis is each patient, who will have 2-3 of the evidence-based practices 
applicable to their care during the hospitalization. We will analyze the primary outcome, mean 
adherence, using multi-level linear regression models. We will include hospital-specific random 
effects to account for clustering within hospitals. We will include patient-level covariates that 
have been associated with severity of respiratory illnesses: age,55,56 sex,56 need for 
supplemental oxygen on admission,57 and prior prescription of an inhaled corticosteroid (applies 
only to admissions for asthma).78,79 We will also include hospital-level covariates including 
hospital size, teaching status, and geographic region. We will not include clustering effects by 
clinician, because multiple clinicians are commonly involved in a patient’s care during a hospital 
admission. We will exclude data from months 1-3 of the implementation period from all analyses 
to allow for intervention implementation. However, we will collect outcome data throughout the 
intervention period to help guide implementation efforts. 
 
Secondary Outcomes: 
Secondary outcomes will include adherence for each evidence-based practice, length of 
hospital stay in hours, transfer to intensive care, and 30-day hospital readmission or emergency 

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revisit. We will analyze secondary outcomes using multi-level regression models with hospital-
specific random effects and the same hospital and patient characteristics included in the primary 
outcome analysis (see above). We will analyze each evidence-based practice using linear 
regression, length of stay using gamma regression, and transfer to intensive care and 30-day 
hospital readmissions/emergency revisits using logistic regression. 
 
Subgroup Analyses: 
For our primary outcome, we will perform exploratory subgroup analyses to understand effects 
by different subgroups: 1) hospital type [community hospital, nested children’s hospital], and 2) 
additional demographic characteristics [race, ethnicity, primary language, and primary 
insurance]. We will conduct these analyses to quantify and understand effects sizes across 
these important subgroups. We will also test interaction terms to see if any differences in effect 
sizes by subgroup are significant. 
 
Sensitivity Analyses: 
In our primary analysis, we will adjust for patient age, sex, need for supplemental oxygen, and 
prior prescription of inhaled corticosteroid (applies only to admissions for asthma). In a 
sensitivity analysis, we will incorporate additional demographic factors including race, ethnicity, 
primary language, and primary insurance [proxy for socioeconomic status]. This will be done to 
make sure our effects are robust even if these covariates were imbalanced by randomization. 
Additionally, we will examine an “all-or-nothing” outcome across all conditions (asthma, 
pneumonia, and bronchiolitis), where we analyze if all 2-3 evidence-based practices that apply 
for a given admission were adhered to or not. Although our difference-in-differences approach 
should account for differential adherence to evidence-based practices before the intervention, if 
we find significant discrepancy in baseline adherence in control versus intervention hospitals 
such that we would be concerned about floor/ceiling effects (limited ability to improve), we will 
perform an additional sensitivity analysis in which we formally incorporate mean adherence to 
evidence-based practices at baseline/before the intervention at the hospital level into our 
models. Lastly, we have also collected prospective data on intervention fidelity and interventions 
that could lead to potential contamination in the control arm. If we find low fidelity in the 
intervention arm or potential contamination in control arm hospitals, we will also incorporate 
these data into a sensitivity analysis.  
 
Fidelity/Aim 2 Analysis: 
We will summarize the degree of utilization of implementation strategies aggregated over 12 
months (e.g., mean number of audit and feedback episodes) and time costs of implementation 
using descriptive statistics. We will link data on hospital-level utilization of implementation 
strategies to hospital-level data on changes in mean adherence to evidence-based practices 
from the baseline to intervention period. We will use multi-level linear regression models to 
determine associations between degree of utilization of implementation strategies and changes 
in adherence by testing for interactions between the strategies and time. We will include 
hospital-specific random effects to account for clustering within hospitals. We will use the same 
patient-level and hospital-level covariates for these models as described in the primary analysis. 
G3  Missing Outcome Data 
We will monitor for missingness throughout the study as described above in “F2 Data 
Collection/Study Outcome Measurement.” We will determine overall proportion of missingness 
of each co-variate and outcome variable and, if any variable is missing in >5% of participant 
records, we will apply multiple imputation methods. We will report all missingness and analytic 
strategies to address missingness in any publications or reports. 

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G4  Unblinding Procedures  
 
Patient, families, and clinicians will be unblinded to the intervention throughout the study. The 
DSMB and study team will work in concert to review study progress and any adverse events as 
described above in “F3 Safety Monitoring and Serious Adverse Event Reporting.” If the DSMB 
determines unblinding of the DSMB, study team, and/or study analyst is needed at any time, 
this will be done.  
 
H Data Handling and Record Keeping  
H1 Confidentiality and Security 
 
See above section, “D2 Risks/Benefits” for a detailed description of data confidentiality and 
security procedures. 
H2 Training  
 
See above section “F2 Data Collection/Study Outcome Measurement” for a detailed description 
of chart reviewer training methods. 
H3 Case Report Forms and Source Documents 
 
All study data will be collected from participating hospitals’ electronic health records and entered 
into case report forms within the UCSF REDCap database as described above in “F2 Data 
Collection/Study Outcome Measurement.” 
H4 Records Retention and Data Sharing 
 
Data generated under this project will be administered in accordance with the policies of the 
University of California San Francisco (UCSF) and NIH/NHLBI. The proposed research will 
generate quantitative and qualitative data from community hospitals that care for children 
hospitalized with respiratory illnesses. Aim 1 generates quantitative data about adherence to 
evidence-based practices in the care of these conditions as well as patients’ length of hospital 
stay, transfer to intensive care, and hospital readmissions/emergency department revisits. Aim 2 
generates a combination of qualitative and quantitative data about the multi-condition pathway 
implementation process. The Final Research Data (the dataset necessary to document and 
support research findings) will be made available for sharing after the main research findings 
from the final data set have been accepted for publication in a peer-reviewed journal. Prior to 
sharing, data will be redacted to strip all direct identifiers of hospitals (no identifiers of 
patients/individuals will be collected).  
 
I Study Monitoring, Auditing, and Inspecting  
 
I1 
Study Monitoring Plan  
 
See details in above section “F3 Safety Monitoring and Serious Adverse Event Reporting.” 

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I2 
Auditing and Inspecting  
 
See details in above section “F3 Safety Monitoring and Serious Adverse Event Reporting.” 
J Study Administration 
J1 Organization and Participating Centers 
 
Figure 3 displays the organizational structure for the proposed study. Our proposed 
interdisciplinary Core Investigator Team at the University of California, San Francisco will 
oversee all aspects of the proposed research. Members include Sunitha Kaiser, MD MSc (PI), 
Andrew Auerbach, MD MPH (Co-I), Ralph Gonzales, MD MSPH (Co-I) and Charles McCulloch, 
PhD (Co-I). The team is supported by Project Manager Yeelen Edwards, MSc.   
A team from Society of Hospital Medicine will oversee all aspects of implementation using the 
mentored implementation framework.47 SHM team members include Dr. Eric Howell, Ms. Jenna 
Goldstein, and Sara Thompson.  
We have also recruited local site leaders from community hospitals (participating centers). 
These leaders are physicians with QI expertise. They will recruit multidisciplinary 
implementation teams at each site that will assist in identifying barriers, refining the intervention, 
and overseeing implementation at participating sites. Expert QI mentors/facilitators will support 
these local teams.  
We have also assembled a multidisciplinary National Advisory Board that will help guide 
successful completion of the proposed grant. These 8 members include Dr. Casey Lion, Dr. 
Michael Cabana, Dr. Kavita Parikh, Dr. Shawn Ralston, Dr. Christopher Landrigan, Dr. Judy 
Shaw, Dr. Leonard Bacharier. Several advisory board members hold leadership roles with our 
dissemination partners, and they will advise us on how best to provide these organizations with 
the needed information on the intervention for future dissemination and replication. Our 5 
dissemination partners are the leading national organizations involved in the care of hospitalized 
children.  
 
Sunitha Kaiser, MD MSc 
Yeelen Edwards, MSc 
Jenna Goldstein, MA 
Principal Investigator, who 
handles all scientific and 
clinical inquiries related to 
the study 
 
UCSF Project Manager, 
who leads all administrative 
and logistical aspects of the 
study 
 
SHM Project Manager, who 
leads all aspects of Mentored 
Implementation of the 
intervention 
 
Figure 3. Organizational Structure  

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sunitha.kaiser@ucsf.edu 
yeelen.edwards@ucsf.edu 
jgoldstein@hospitalmedicine.org 
 
J2 Funding Source and Conflicts of Interest 
 
The funding source for the study is the National Heart, Lung, and Blood Institute. The PI and 
Co-Is have no conflicts of interest relevant to this proposal to disclose. 
 
J3 Subject Stipends or Payments  
 
None. 
J4  Study Timetable 
 
 
Timeline: Year 1 
Study Month 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Hire UCSF Project Manager and staff  
 
 
 
 
 
 
 
 
 
 
 
 
Complete the UCSF Single IRB approval process 
 
 
 
 
 
 
 
 
 
 
 
 
Recruit community hospitals and randomize to 
intervention versus wait-list control groups 
 
 
 
 
 
 
 
 
 
 
 
 
Issue reliance agreements and data use agreements (if 
needed) for each participating site 
 
 
 
 
 
 
 
 
 
 
 
 
Train chart reviewers at each site, then reviewers enroll 
participants/perform baseline chart review  
 
 
 
 
 
 
 
 
 
 
 
 
Assess organizational readiness for change 
 
 
 
 
 
 
 
 
 
 
 
 
Finalize plans for implementation strategies, 
operationalizing the implementation framework, and skills 
development (to occur during Mentor University) 
 
 
 
 
 
 
 
 
 
 
 
 
Finalize the unit of intervention, comparison groups, and 
outcome measures (with targets) 
 
 
 
 
 
 
 
 
 
 
 
 
Plan elements of the implementation strategy designed to 
foster sustainability and re-use  
 
 
 
 
 
 
 
 
 
 
 
 
Finalize study infrastructure and documents (e.g., data 
safety monitoring plans, informed consent documents, 
study protocol) 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct mentor/facilitator monthly meetings with sites 
(discuss performance, identify targets, plan 
implementation efforts) 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct meetings with Dr. Kaiser, UCSF Project 
Manager, and UCSF staff (weekly) 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct meetings with Dr. Kaiser, UCSF Project 
Manager, UCSF staff, and SHM team (bi-weekly) 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct meetings with Dr. Kaiser, UCSF Project 
Manager, UCSF staff, SHM team, and other Core 
Investigators  (monthly) 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct meetings with Dr. Kaiser, UCSF Project 
Manager, UCSF staff, SHM team, other Core 
Investigators, and National Advisory Board (quarterly) 
 
 
 
 
 
 
 
 
 
 
 
 
Timeline: Years 2-5 

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K Publication Plan  
 
We have engaged the 5 leading national organizations involved in the care of hospitalized 
children in dissemination efforts (see Letters of Support J-N). These include the Society of 
Hospital Medicine (SHM, national organization representing over 40,000 hospitalists), the 
American Academy of Pediatrics (national organization of 67,000 pediatricians, pediatric 
medical subspecialists, and pediatric surgical specialists), the Pediatric Research in Inpatient 
Settings Network (pediatric hospitalist network representing over 120 hospitals and 400 
pediatric hospitalists in the US and Canada), America’s Hospital Essentials (national network of 
over 300 safety-net hospitals), and the National Improvement Partnership Network (national 
quality improvement network that includes hospitals in 20 states).  
Study Quarter 
Q1 
Q2 
Q3 
Q4 
Q5 
Q6 
Q7 
Q8 
Q9 
Q10 
Q11 
Q12 
Q13 
Q14 
Q15 
Q16 
Aim 1: Intervention hospitals implement 
intervention and perform chart review* 
 
25% 
 
50% 
 
75% 
 
100
% 
 
 
 
 
 
 
 
 
Aim 1: Control hospitals wait to 
implement, but perform chart review* 
 
25% 
 
50% 
 
75% 
 
100
% 
 
 
 
 
 
 
 
 
Aim 1: Control hospitals implement 
intervention and continue chart review  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aim 1: Analyze data (cluster RCT) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aim 1: Prepare manuscript (cluster 
RCT) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aim 1: Analyze data (effects in wait-list 
group) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aim 1: Prepare manuscript (effects in 
wait-list group) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aim 2: Collect data (surveys, field 
visits) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aim 2: Analyze data (with Aim 1 data) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aim 2: Prepare manuscript  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Develop a plan to support sustainability 
beyond the research study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Close out study  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Develop implementation toolkit (if 
intervention is successful) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Disseminate findings +/- toolkit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct meetings with Dr. Kaiser, 
UCSF Project Manager, and UCSF 
staff (weekly) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct meetings with Dr. Kaiser, 
UCSF Project Manager, UCSF staff, 
and SHM team (bi-weekly) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct meetings with Dr. Kaiser, 
UCSF Project Manager, UCSF staff, 
SHM team, and other Core 
Investigators (monthly) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct meetings with Dr. Kaiser, 
UCSF Project Manager, UCSF staff, 
SHM team, other Core Investigators, 
and National Advisory Board 
(quarterly) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* Percentages within timeline boxes indicate cumulative enrollment in the cluster RCT 

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These partners have all committed to disseminate our study findings via organizational 
websites, e-mail listservs, social media (e.g., Twitter), newsletters, and national seminars. If the 
multi-condition pathway intervention is effective, we will assemble an implementation toolkit for 
dissemination by these national organizations. The toolkit will contain all necessary materials for 
future implementation efforts, including a brief/overall summary of our findings; the multi-
condition pathways; details about mentored implementation; educational seminar materials; 
specifications on measuring evidence-based practice adoption outcomes; and guidance on 
implementation strategies, barriers and facilitators, and adaptions to the intervention. SHM will 
distribute this toolkit, and prior SHM projects have each had 400-800 downloads of such toolkits 
and widespread use. Also, the American Academy of Pediatrics will consider using this toolkit to 
support a future national project to scale the multi-condition pathway intervention more broadly 
to hospitals across the country (as they have done in several prior successful projects). In 
addition, we will share order sets via the Agency for Healthcare Research and Quality’s Clinical 
Decision Support Repository. 
We will also seek to publish our findings in peer-reviewed manuscripts, present them at 
academic meetings, and present them to national, regional, and local clinician, health 
administrator, and QI audiences. Our Core Investigator Team has experience with the rapid 
publication of research findings and have collaborated on prior research publications. In 
addition, there are a number of resources at UCSF to support dissemination, including a 
network of affiliated community hospitals, the Clinical and Translational Science Institute’s 
(CTSI) consultation services on scientific writing and dissemination, and CTSI’s 
Communications Team. 
L  Attachments  
L1  Informed consent documents 
 
We were approved for waiver of consent for Aim 1. For Aim 2, we have provided the consent 
document as Appendix A. 
L2  Data Collection Instrument 
 
The chart review data collection instrument is provided as Appendix B. 
 
M References 
 
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Appendix A: Consent Form 
 

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Appendix B: Chart Review Tool 

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