Comparative Effectiveness Trial of Bowel Ultrasound and Abdominal Radiograph Versus Abdominal Radiograph Alone for Diagnosis of Necrotizing Enterocolitis
Phase: NA
Conditions: Necrotizing Enterocolitis
Sponsor: Children's Mercy Hospital Kansas City

SHORT TITLE: BUS for NEC 
Page 1 of 32 
 
PROTOCOL TITLE: Multicenter Randomized Control Trial of Bowel Ultrasound for 
Diagnosis of Necrotizing Enterocolitis 
 
PRINCIPAL INVESTIGATOR: 
Sherwin Chan (PI) 
Department of Radiology 
(816) 458-3841 
sschan@cmh.edu 
 
Alain Cuna (Co-PI) 
Department of Pediatrics 
Division of Neonatology 
(816) 458-3842 
accuna@cmh.edu  
 
IND/IDE NUMBER: N/A 
 
VERSION NUMBER/DATE 
07 – 15OCT2025 
 
REVISION HISTORY 
 
Revision 
# 
Version Date 
Summary of Changes 
Consent 
Change? 
01 
20MAY2022 
Initial Creation 
 
02 
22DEC2022 
Changing inclusion criteria from preterm 
infants to include all infants concerned for NEC 
 
03 
07MAR2023 
Updating to increase enrollment numbers to 
80 neonates and 80 neonatologists 
 
04 
21JUL2023 
Increasing enrollment numbers from 40 to 80 
at KUMC 
 
05 
25DEC2023 
Increasing CMH enrollment numbers from 80 
to 120 
 
06 
17DEC2024 
Adding UMKC as a study site 
 
07 
15OCT2025 
Adding this revision history table as it was 
missing initially 
 
 
 

SHORT TITLE: BUS for NEC 
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Table of Contents 
STUDY INFORMATION 
1.0 Study Summary 
2.0 Objectives 
3.0 Background 
4.0 Study Endpoints 
5.0 Study Design 
6.0 Study Intervention/Investigational Agent 
PARTICIPANT MANAGEMENT 
7.0 Inclusion and Exclusion Criteria 
8.0 Local Number of Participants 
9.0 Screening and Recruitment Methods 
10.0 Procedures 
11.0 Surveys and Psychometric Testing 
12.0 Follow-Up 
13.0 Genetic Analysis Information 
14.0 Sharing of Results with Participants 
15.0 Risks to Participants 
16.0 Potential Benefits 
17.0 Investigator Assessment of Risk/Benefits Ratio 
18.0 Payment, Reimbursement and Tangible Property Provided to Participants 
19.0 Compensation for Research-Related Injury 
20.0 Economic Burden to Participants 
21.0 Parental Permission and Adult Consent Process 
22.0 Assent of Pediatric Participants 
23.0 HIPAA and Confidentiality 
24.0 Provisions to Protect the Privacy Interests of Participants 
25.0 Withdrawal of Participants 
DATA MANAGEMENT 
26.0 Data Collection 
27.0 Adverse Events and Unanticipated Problems 
28.0 Statistical Analysis 
29.0 Data and Specimen Management 

SHORT TITLE: BUS for NEC 
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30.0 Storage/Banking of Data and Specimens for Future Research 
31.0 Provisions to Monitor the Data to Ensure the Safety of Participants 
DATA MANAGEMENT 
32.0 Settings and Locations 
33.0 Multi-Site Research 
34.0 International Research 
ADDENDUMS 
Addendum A: Waiver of Documentation of Permission/Consent 
Addendum B: Waiver/Alteration of Permission/Assent/Consent 
Addendum C: Non-English Speaking Participants 
Addendum D: Surrogate Decision Maker Consent 
Addendum E: Waiver/Alteration of HIPAA Authorization 
 
 
 

SHORT TITLE: BUS for NEC 
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STUDY INFORMATION 
1.0 
Study Summary* 
 
The diagnosis of necrotizing enterocolitis (NEC) – an acute and life-threatening intestinal disease 
that affects 5-10% of infants – can be challenging. Traditionally, neonatologists rely on abdominal 
radiographs (AXR) to evaluate infants with concern for NEC. In recent years, bowel ultrasound 
(BUS) has been proposed as a helpful adjunct to AXR for NEC evaluation. In centers where BUS 
expertise is available, clinicians now have the option of using BUS in addition to AXR in their 
diagnostic evaluation for NEC. However, significant variability remains on whether 
neonatologists would use or not use BUS in this clinical setting. An important reason for this 
variability is the lack of evidence regarding whether BUS improves patient outcomes or not. 
Additionally, BUS expertise generally is available only in highly specialized children’s hospitals. 
Thus, in centers with limited BUS availability, AXR remains the standard imaging modality for 
NEC. The lack of rigorous and robust clinical trials conducted in diverse NICU settings is an 
important gap in knowledge that needs to be addressed before the routine use of add-on BUS 
for NEC evaluation.  
 
To help address these limitations, we propose to conduct comparative effectiveness research to 
evaluate the benefits of add-on BUS on patient outcomes. Our study design will be a pragmatic 
randomized clinical trial (RCT) of AXR versus AXR + BUS in infants with suspected NEC. We 
propose to conduct this study in two diverse sites. The first site will be the level IV NICU of 
Children's Mercy Kansas City (CMKC), which already has expertise in BUS for NEC. The second site 
will be the level III NICU of University of Kansas Medical Center (KUMC), an adult hospital with 
less experience in BUS. The rationale for this study is that infants at high risk for NEC are cared 
for in diverse settings including level III NICUs in adult hospitals that have little experience in using 
BUS to evaluate NEC. Our study has two specific aims.  
 
Specific aim #1: To determine the impact of add-on BUS for NEC evaluation on patient 
outcomes in two different NICU settings. We hypothesize that adding BUS to NEC 
evaluation changes differential diagnosis, therapy plan and patient outcomes. 
Specific aim #2: To determine the capability of implementing BUS for NEC evaluation in a 
level III NICU within an adult hospital. We hypothesize that BUS timeliness, quality, and 
inter-rater reliability are comparable between level III and IV NICUs.   
 
The addition of BUS to the diagnostic repertoire of infants with suspected NEC is an important 
contribution to neonatology. Before widespread adoption can be realized, however, strong 
evidence is needed to determine whether the addition of BUS would lead to actual clinical 
benefits, including in level III NICUs in adult hospitals. We anticipate that our study will help 
address this critical gap in knowledge and provide important insights as to the safe and effective 
use of BUS for NEC. 
 
 

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2.0 
Objectives* 
2.1 
Purpose, specific aims or objectives:   
The overall objective of our study is to determine the clinical usefulness of BUS for 
NEC evaluation in diverse NICU settings. We plan to accomplish this overall 
objective by completing the following specific aims: 
Specific aim #1: Determine the impact of add-on BUS for NEC evaluation on patient 
outcomes in two different NICU settings. 
Specific aim #2: Determine the capability of implementing BUS for NEC evaluation in a 
level III NICU within an adult hospital. 
2.2 
Hypothesis:  
Our hypothesis is that the addition of BUS to AXR can favorably change differential 
diagnosis, therapy plan, and patient outcomes of infants with suspected NEC; and 
that this beneficial impact extends to less specialized centers with little prior 
experience with BUS for NEC evaluation. 
3.0 
Background* 
3.1 
Gaps in knowledge. 
In reviewing the evidence supporting the use of BUS in the diagnostic imaging evaluation 
for NEC, several important limitations need to be considered. First, the best level of 
evidence regarding BUS for NEC has been limited to diagnostic accuracy studies. While 
appropriate for early investigation, diagnostic accuracy studies are insufficient in 
demonstrating the clinical utility of new diagnostic tests. Second, most of these diagnostic 
accuracy studies are small, single-center cohort studies that retrospectively assessed the 
authors’ experience with BUS following its adoption into the diagnostic pathway for NEC. 
Such studies have limited power, are subject to numerous confounders and biases, and 
are meant to generate hypotheses that can then be studied via larger, prospective 
studies. Third, most of the prior research on BUS has been conducted in the level IV NICUs 
of free-standing children’s hospitals with pediatric sonographers and radiologists. Most 
infants at greatest risk for NEC, however, are cared for in level III NICUs within adult 
hospitals staffed by adult sonographers and radiologists with little to no experience in 
how to perform and interpret BUS for NEC evaluation. This limitation raises the important 
question of generalizability beyond specialized pediatric centers.  
☒ Children/Minors (under 7 years of age) 
☐ Children/Minors (7-17 years of age) 
☒ Neonates (infants less than 30 days old) 
☐ Neonates of Uncertain Viability (infants 
less than 30 days old) 
☐ Non-Viable Neonates (infants less than 
30 days old) 
☐ Wards of the State 
☐ Fetuses 
☐ Pregnant Women  

SHORT TITLE: BUS for NEC 
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☐ Adults with impaired decision-making 
capacity         
☒ CM Employees 
☐ CM Students/Residents/ Fellows 
☐ Economically or Educationally 
Disadvantaged Persons 
☐ Prisoners 
 
 
• Neonates (infants less than 30 days old) will be included in the study as the 
peak onset of NEC in preterm infants is around 2 to 4 weeks of life. Thus, 
there is no other means to study the impact of BUS on infants with suspected 
NEC without including neonates. To assess potential risks of BUS in this 
vulnerable population, we reviewed the published clinical studies on BUS for 
NEC evaluation and confirm that BUS is safe and well-tolerated in this 
population. Furthermore, BUS is already used in clinical practice for the 
evaluation of NEC, and thus no added risk to the neonate will occur because 
of the proposed research.  
 
8.0 
Local Number of Participants 
 
 
Site 1  
(CMKC) 
Site 2 
(KUMC) 
Totals 
Enrollment Goal: (Neonates) 
Number of participants to be enrolled = the 
number of participants to be consented or to 
be screened for chart reviews. 
 120 
80 
200 
Enrollment Goal: (Neonatologists) 
Number of participants to be enrolled = the 
number of participants to be consented or to 
be screened for chart reviews. 
120 
80 
200 
 
 
 

SHORT TITLE: BUS for NEC 
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9.0 
Identification and Recruitment of Potential Participants* 
9.1 
Identification of Potential Participants:   
How will participants be identified? (Check all that apply) 
 
☒ Chart reviews  
 
☐ By their treating physician who will then provide the study team’s contact 
information to the potential participant/family 
☐ By their treating physician who will obtain patient/family permission to share 
contact information with the study team 
☐ Self-refer in response to IRB approved advertisements or websites  
☐ Through Cerner or other CM sources (e.g. databases, billing records, 
pathology reports, admission logs, etc.) May involve access of records by 
individuals not involved in the patient’s care. 
☐ List of candidates provided through the Data Report Request Form  
☐ Registry of individuals interested in research opportunities   
☐ Past participant list 
☐ Participants will roll-over from another research study: Study # 
☐ Other:  
9.2 
Pre-Screening prior to HIPAA Authorization 
Will any of the identification methods checked above involve 
access to Protected Health Information (PHI) prior to obtaining 
HIPAA Authorization? 
☒ Yes 
 
☐ No 
• If yes, a “Partial Waiver of HIPAA Authorization” is required.  Be sure to 
make this selection in the “HIPAA & Confidentiality” section below and 
complete Addendum E: Waiver/Alteration of HIPAA Authorization 
9.3 
Recruitment of Potential Participants:   
• All consecutive infants admitted during the study period at the 
NICUs of CMKC or KUMC who meet eligibility criteria for the study 
will be automatically included in the study.  

SHORT TITLE: BUS for NEC 
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10.0 Procedures 
10.1 
Inclusion 
Eligible infants who develop clinical concern for NEC for which the 
neonatologist decides to obtain imaging for further evaluation as part of 
usual clinical care will be included into the study. 
10.2 
Randomization 
Infants who meet inclusion criteria of NEC concern as above will be 
randomized to either AXR arm or AXR + BUS arm based on the calendar 
month the infant was born. A pre-generated randomization calendar will 
be posted in the NICU workroom to inform the care team which arm the 
infant will be randomized to, and consequently which imaging test will be 
ordered.  
10.3 
Intervention: AXR or AXR + BUS 
Infants randomized to AXR arm will have a portable abdominal x-ray 
ordered, performed, and interpreted per usual clinical workflow. Likewise, 
infants randomized to AXR + BUS intervention will have both a portable 
abdominal x-ray and add-on BUS ordered, performed, and interpreted per 
usual clinical workflow. Results of all imaging tests (AXR or AXR + BUS 
depending on randomization) will be available to the care team taking care 
of infants as per usual clinical care. 
10.4  
Post-AXR and Post-BUS Survey 
Neonatologists will receive surveys to determine changes in their clinical 
diagnostic and therapeutic thinking after results of AXR or AXR + BUS. 
10.5 
Cross-over 
Infants randomized to AXR only, but for whom the treating neonatologist 
deems a BUS is clinically warranted, will be allowed to cross-over and have 
BUS ordered. In our pilot study, only one infant randomized to AXR arm 
“cross-over” to AXR + BUS arm because of clinical concerns for an 
abdominal abscess (abdominal abscess is best evaluated by sonography). 
We had no instances in our pilot study of cross-over besides this isolated 
event, indicating clinical equipoise between AXR vs AXR + BUS. As such, 
although allowed in the study we anticipate cross-over to be rare. 
10.6 
Follow-up imaging 
Infants with suspected NEC may need additional follow-up imaging for 
ongoing concerns of NEC. If the treating neonatologist deems follow-up 
imaging is needed, study infants will continue to have either AXR or AXR + 
BUS performed as determined by their randomization arm.  
 

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10.7 
 Multiple episodes of NEC concern 
Infants may also develop more than one episode of NEC concern during 
their admission. For such instances, study infants will remain in the same 
randomization arm throughout the study. 
10.8 
Diagnosis and treatment decisions 
All other diagnostic testing will be decided upon independently according 
to the treating neonatologist’s clinical judgment. All treatment decisions, 
including length of bowel rest and length of antibiotic treatment, will also 
be at the discretion of the treating neonatologist.  
10.9 
Blood and Other Specimen Collection: NA 
11.0 Surveys and Psychometric Testing: 
• 
We will conduct two surveys to determine change in clinician’s 
diagnostic and therapeutic thinking. The first survey (post-AXR 
survey), applicable to all infants, will be conducted after AXR is 
performed. The second survey (post-BUS survey), applicable 
only to infants randomized to AXR + BUS, will be conducted 
after BUS is performed. Surveys will be answered by the 
neonatologist taking care of the infants using a 5-point Likert 
scale from “not at all likely” to “extremely likely”.   
12.0 Follow-up 
• All study infants will be followed throughout their course in the 
NICU, from admission to discharge. All data will be collected 
through clinical chart review. Follow-up will end once infants 
are discharged from the NICU. We will collect the following data 
points: (1) baseline characteristics (gestational age, birth 
weight, sex, race, mode of delivery, Apgar scores; (2) clinical 
characteristics at time of NEC concern (clinical presentation, 
age at time of NEC concern, results of diagnostic tests for NEC 
concern, information on treatment including days to full 
enteral feeds and days on antibiotics); and clinical outcomes at 
discharge (total length of stay, age at discharge, co-morbidities 
during NICU admission).  
13.0 Genetic Analysis Information - NA 
 
14.0 Sharing of Results with Participants 
14.1 
Results of all AXR and BUS will be uploaded in the electronic 
medical record as per usual standard workflow for any imaging test 
ordered in clinical practice. These results will be accessible by 

SHORT TITLE: BUS for NEC 
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neonatologists, radiologists, and other members of the clinical team 
authorized to view the infant’s clinical chart as part of their duties in taking 
care of the infants in the study. Parents who are enrolled in the patient 
portal at CMH or KUMC will also have access to these results, just as they 
have access to all other results and health information of their infant. 
15.0 Risks to Participants* 
15.1 
This study involves no greater than minimal risk to the subjects 
enrolled. BUS is a noninvasive imaging tool currently used in standard of 
care procedures for premature infants in the NICU. It has no radiation, 
does not require infants to fast or any other special preparation before the 
procedure, and is well-tolerated even by sick infants. 
16.0 Potential Benefits* 
16.1 
There may be no direct benefit to the patient in the study. 
However, the BUS imaging done as part of the study will be available to 
any treating physician and may be helpful in medical management of the 
patient.   
16.2 
Knowledge gained from this study can potentially benefit future 
infants with NEC concern by providing strong evidence regarding the 
optimal use of BUS for NEC evaluation that is both safe and effective.  
17.0 Investigator Assessment of Risk/Benefits Ratio*  
17.1 
 
Select as applicable: 
Pediatric Risk Category: 
☒ 
Category 1  
Research not involving greater than minimal risk  
(45 CFR §46.404 and 21 CFR §50.51)   
☐ 
Category 2 
Research involving greater than minimal risk but 
presenting the prospect of direct benefit to the 
individual participants. (45 CFR §46.405 and 21 CFR 
§50.52) 
☐ 
Category 3 
Research involving greater than minimal risk and no 
prospect of direct benefit to individual participants, 
but 
likely to yield generalizable knowledge about the 
participant's disorder or condition.  
(45 CFR §46.406 and 21 CFR §50.53) 
☐ 
Category 4 
Research not otherwise approvable which presents 
an opportunity to understand, prevent, or alleviate a 
serious problem affecting the health or welfare of 
children. (45 CFR §46.407 and 21 CFR §50.54) 
Select if applicable: 
Adult Risk Category: 
☒ 
Not Greater than Minimal Risk 
☐ 
Greater than Minimal Risk 

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18.0 Payment, Reimbursement and Tangible Property provided to 
participants*  
Is payment, reimbursement, or tangible property part of the study?  
☐  Yes                 ☒  No (If No, delete the following subsections) 
19.0 Compensation for Research-Related Injury - NA 
 
20.0 Economic Burden to Participants 
20.1 
There will be no economic burden to participants of the study. All 
BUS imaging done as part of the study will be paid for by the study and 
will not be billed to participants. 
21.0  Parental Permission and Adult Consent Process* 
Written Informed Permission/Consent 
☐ Written informed permission of parent/LAR for pediatric participants 
 
Study group(s) to which this method applies: 
☐ Written informed consent of adult participants 
 
Study group(s) to which this method applies: 
☐ Written informed consent of participants turning 18 
This includes the continued access to and use of their PHI by the study team. 
 
Study group(s) to which this method applies: 
Waiver of Documentation of Permission/Consent 
Permission/Consent form provided but signature will NOT be obtained (e.g. verbal consent) 
Must complete Addendum A: Waiver of Documentation of Permission/Consent 
☐ Waiver of written documentation of permission of parent/LAR for pediatric 
participants  
 
Study group(s) to which this method applies: 
☒ Waiver of written documentation of consent of adult participants  
 
Study group(s) to which this method applies: Neonatologists taking part of the 
survey 
☐ Waiver of written documentation of consent of participants turning 18  

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Study group(s) to which this method applies: 
Waiver or Alteration of Permission/Consent 
Parent/LAR permission/adult consent will NOT be obtained, or an alteration to an element(s) of 
consent. 
Must complete Addendum B: Waiver of Permission/Assent/Consent 
 
☒ Waiver/Alteration of permission of parent/LAR for pediatric participants 
 
Study group(s) to which this method applies: AXR group and AXR + BUS group 
☐ Waiver/Alteration of consent of adult participants 
 
Study group(s) to which this method applies: 
☐ Waiver/Alteration of consent of participants turning 18 
 
Study group(s) to which this method applies: 
Additional Methods 
☐ Obtaining permission/assent/consent of non-English speaking parents or 
participants 
Must compete Addendum C: Non-English Speaking Participants 
 
Study group(s) to which this method applies: 
☐ Surrogate decision maker consent to be used when adults are not capable of 
consenting for themselves 
Must complete Addendum D: Surrogate Decision Maker Consent 
 
Study group(s) to which this method applies: 
22.0 Assent of Pediatric Participants 
 
22.1 
Select the option(s) that apply to the study: 
 
☐ Assent of pediatric participants WILL BE SOUGHT following assessment of 
ability to assent. 
 
☒ Obtaining assent of pediatric participants is NOT POSSIBLE due to: 
☒  The capability of the participants (considering the ages, maturity, physical 
and/or psychological state) is so limited that they cannot reasonably be 
consulted. 

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☐  The intervention or procedure involved in the research holds out a prospect 
of direct benefit that is important to the health or well-being of the 
participants and is available only in the context of the research. 
 
☒ Obtaining assent of pediatric participants is NOT PRACTICLE given the 
context of this study (e.g., minimal risk, no direct contact with participants). 
Must complete Addendum B: Waiver/Alteration of 
Permission/Assent/Consent 
 
23.0 HIPAA and Confidentiality 
23.1 
HIPAA Authorization  
☐  Full Written HIPAA Authorization will be obtained (within the p/a/c form or 
standalone form) 
 
☒ Partial Waiver of HIPAA Authorization (e.g. waiver for recruitment and pre-
screening purposes only) 
Must complete Addendum E: Waiver/Alteration of HIPAA Authorization 
 
a) Describe what PHI must be accessed for recruitment/pre-screening 
purposes prior to obtaining HIPAA Authorization. 
 
☐ Alteration of HIPAA Authorization (some but not all required elements of an 
Authorization are present, e.g. signature will not be obtained) 
Must complete Addendum E: Waiver/Alteration of HIPAA Authorization 
 
a) Describe which proposed elements to be altered. 
 
☒ Waiver of HIPAA Authorization (authorization will NOT be obtained) 
 
☐ If Other, explain: 
23.2 Specify the PHI for which accessing (“viewing”) or recording 
(“writing down”) is necessary for the purpose of this research: 
1. Name/Initials 
☒ Accessed only 
☐ Recorded 
2. All elements of date (except year) directly 
related to an individual (e.g. date of birth, 
admission date, discharge date, date of 
death) 
☐ Accessed only 
☒ Recorded 
3. Medical record number 
☐ Accessed only 
☒ Recorded 
4. Account number 
☐ Accessed only 
☐ Recorded 
5. Health plan identification number 
☐ Accessed only 
☐ Recorded 
6. Social Security Number 
☐ Accessed only 
☐ Recorded 

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7. Device identifiers and serial number 
☐ Accessed only 
☐ Recorded 
8. Certificate/License number 
☐ Accessed only 
☐ Recorded 
9. Telephone number 
☐ Accessed only 
☐ Recorded 
10. Fax number 
☐ Accessed only 
☐ Recorded 
11. Email addresses 
☐ Accessed only 
☐ Recorded 
12. Web addresses (URLs); Internet IP addresses 
☐ Accessed only 
☐ Recorded 
13. Street address, city, county, precinct, zip 
code or equivalent geographical codes 
☐ Accessed only 
☐ Recorded 
14. Full face photographic images and any 
comparable images 
☐ Accessed only 
☐ Recorded 
15. Biometric identifiers, including finger and 
voice print 
☐ Accessed only 
☐ Recorded 
16. Vehicle identifiers and serial numbers, 
including license plate number 
☐ Accessed only 
☐ Recorded 
17. Any other unique identifying number, 
characteristic or code that may help identify 
individual participants including their initials 
(e.g. student or employee ID number) 
☐ Accessed only 
☐ Recorded 
18. Elements of date, including year, for persons 
90 years or older 
☐ Accessed only 
☐ Recorded 
19. Other: 
☐ Accessed only 
☐ Recorded 
 
23.3 
Patient information will be maintained in a REDCap application and 
will be housed within the CMH Data Center by the Division of Biomedical 
Informatics.  The hosting server has an internal failover two-node cluster.  
The CMH Data Center is constantly staffed by qualified personnel and 
physical access is limited to authorized personnel.  The Center has 
optimized conditions for the servers and stabilized electrical supply.  The 
database has a full backup.  The database server is located inside the CMH 
corporate firewall.  A person must have CMH system access to login.  
23.4 
Additional security for the study patient database restricts access 
to only those persons specifically granted authorization by the Principle 
Investigator. It is possible for data to be downloaded from REDCap.  
Individuals who lack authority to see confidential data can download 
reports with non‐identifiable data only. The core research group will have 
the ability to download sensitive fields and if such a download occurs, 
REDCap maintains a record of who, what, when, and to where copies of 
the database were imported.  
23.5 
A Certificate of Confidentiality has not been issued for this study.   
 

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24.0 Provisions to Protect the Privacy Interests of Participants* 
24.1 
Only IRB approved members of the study team will be granted access to 
the study folder located on the network drive or the REDCap database, which is 
password protected and encrypted. Additionally, study team members who are 
responsible for collected data only will be granted limited access to REDCap, 
allowing them to record data only.   
24.2 
PHI to be accessed and/or recorded for this research study includes: DOB, 
MRN, dates of service (AXR and BUS exams, dates and dates of severity milestones 
and death if applicable) will be recorded.  
 
25.0 Withdrawal of Participants* 
25.1 
A subject may be withdrawn from participation if they were 
transferred to another outside hospital or if they undergo exploratory 
laparotomy with ostomy and mucus fistula creation during the course of 
their admission as this procedure can preclude them from safely 
undergoing a BUS. 
25.2 
Subjects may also be discontinued from the study at the discretion 
of the site investigator as deemed appropriate for any reason. 
25.3 
If a subject withdraws from the research study, data that has 
already been collected may still be used; however, no new information will 
be collected except information related to adverse events or other safety 
issues. 
DATA MANAGEMENT 
26.0 Data Collection* 
26.1 
The study will collect baseline clinical characteristics, lab test 
results, AXR and BUS results, clinical diagnosis, treatment data, and survey 
results.  
• Clinical characteristics: gestational age at birth, weight at birth, sex, 
race/ethnicity, age at time of NEC concern,  
• Lab test results: complete blood cell count (CBC), C-reactive protein 
(CRP), blood culture 
• AXR and BUS results: time of order input in the chart, time of image 
acquisition, time of reporting, text of report and interpretation by 
radiologist 
• Clinical diagnosis: NEC, no NEC, food protein-induced enterocolitis, 
clinical sepsis, other diagnosis 

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• Treatment data: medical treatment of NEC including days of bowel 
rest, days to full enteral feeds, days on antibiotics; surgical 
treatment of NEC including peritoneal drainage or exploratory 
laparotomy 
• Survey results: post-AXR survey and post-BUS survey by 
neonatologists 
26.2 
Data will be obtained from the electronic medical record and 
surveys/questionnaires.  
26.3 
Sensitive Data:  We will not be collecting or accessing sensitive 
data. 
 
27.0 Adverse Events and Unanticipated Problems* 
27.1 
Monitoring:  The study team will meet bi-weekly to monitor study 
progress, review participants and data, and troubleshoot any questions or 
problems related to the study. As all study interventions are standard of care, we 
do not anticipate any adverse events or problems related to the study protocol of 
add-on BUS. 
 
27.2 
Reporting:  We confirm that Policy 5.11 Reportable Events of the CM 
Research Program Policies and Procedures will be followed in regard to reporting 
adverse events and other unanticipated problems to the CM IRB. 
 
28.0 Statistical Analysis* 
28.1 
We will use two-tailed McNemar’s test with paired measures to 
analyze differences in diagnostic thinking efficacy and therapeutic efficacy 
from pre- and post-BUS surveys. Comparison of duration of antibiotics, 
bowel rest, and days to full enteral feeds will be performed using Student’s 
t-test. Kaplan-Meier curve will be used to analyze time to full feeds 
between the 2 groups, censoring for death, discharge/transfer out of the 
hospital, or 30 days following initial NEC concern. Analyses of patient 
outcomes (duration of bowel rest, duration of antibiotics, time to full 
feeds) will follow the intention-to-treat principle, with statistical 
significance set at a P value of < 0.05. 
28.2 
We will use t-test to analyze differences in mean time of BUS image 
acquisition and reporting. Chi-square test will be used to compare 
differences in proportion of BUS studies that were performed and 
reported per standardized protocol. Inter-rater reliability for BUS studies 
will be assessed by Cohen’s kappa statistics. 
 

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28.3 
Sample size was calculated based on our pilot study which 
demonstrated a mean ± SD of duration to full enteral feeds of 16 ± 9 days 
per episode of NEC concern. Using this information, we generated Table 1, 
which shows sample sizes for a range of possible means and standard 
deviations, with significance level of 0.05 and 80% power. For a 1-year 
study with 67 to 81 distinct episodes, for an SD of +8 days, we anticipate 
having sufficient sample size to detect a 5- to 6-day difference in mean 
duration to full feeds (highlighted in gray in Table 1).  
Difference 
of means 
between 
groups  
Expected 
Standard 
Deviation  
±8  ±9  ±10 
4 days  126  160  198 
5 days  
81  102  126 
6 days  
56  72  88  
 
29.0 Data and Specimen Management* 
29.1 
Data Management:   
• 
Data will be collected and stored in REDCap.  
• 
Data will be stored for at least five years after final publication of 
results.   
• 
Only IRB-approved study members will have access to the data.  
• 
The Principal Investigator will be responsible for receipt or 
transmission of the data.    
• 
Data will primarily be transferred via secure e-mail within CMH’s 
internal email servers only. Data can also be transferred via password-
protected, encrypted, CMH approved USB thumbdrives. 
29.2 
Specimen Management: NA 
29.3 
Biosafety Information 
Will this study involve handling, transporting, or shipping any 
potentially hazardous biological material at/from a Children’s 
Mercy location (e.g., blood, stool, saliva, tissue)? 
☐ Yes 
☒ No 

SHORT TITLE: BUS for NEC 
Page 18 of 32 
 
Will this study involve processing any potentially hazardous 
biological material at a Children’s Mercy location (e.g., blood, 
stool, saliva, tissue)? 
☐ Yes 
☒ No 
If processing potentially hazardous biological materials, where will 
this work be conducted? 
☐ Pediatric Clinical Research Unit (PCRU) 
☐ Children's Mercy Research Institute Biorepository (CRIB) 
☐ Children’s Mercy Research Institute labs (mySafety 
ID#:__________) 
☐ Other location 
If “Other location,” identify the location and mySafety ID# of the 
corresponding IBC protocol: 
Location: ____________________ 
mySafety ID#: ___________________________  
 
30.0 Storing of Data and/or Banking of Specimens for Future Research 
30.1 
If this study involves storing of data or banking of leftover 
specimens for future research, indicate how the use will be managed: 
☐  Contributing data and/or leftover specimens to an existing CM 
repository protocol (myIRB#___________________________) 
☐  Contributing data and/or leftover specimens to an existing non-CM 
repository (Institution/Repository Name: _________________________) 
☒  Not contributing to an existing repository for the management of 
data/specimens for future research use.   
☐  Other: 
30.2 
If not contributing to an existing repository, describe: 

SHORT TITLE: BUS for NEC 
Page 19 of 32 
 
• To maximize potential impact, de-identified clinical and imaging 
data collected from the study will be stored for potential use for for 
future research.  
• De-identified data will be archived in Redcap and will be housed 
within the CMH Data Center by the Division of Biomedical 
Informatics as described before in section 23 (HIPPA) and section 
29 (Data management). 
• Data will be accessed through Redcap. Access will be restricted to 
only those persons specifically granted authorization by the 
Principal Investigator.  
• Data will be stored for at least five years after final publication of 
study results.  
• A formal request for release of de-identified data will be required, 
preferably by e-mail. Approval for release will be by the Principal 
Investigator. Both CM researchers and external researchers can 
request access for the data. Only de-identified data will be 
available.  
31.0 Provisions to Monitor the Data to Ensure the Safety of Participants 
– NA (no more than minimal risk research) 
 
STUDY MANAGEMENT 
32.0 Setting & Locations* 
32.1 
The NICU at CMKC is an 87-bed level IV NICU. Majority of infants 
admitted at the NICU are born at other hospitals and are typically 
transferred to CMKC due to need for specialized care. Neonatologists are 
in-house 24/7. As a children’s hospital, radiology staff at CMKC are 
composed of pediatric sonographers and pediatric radiologists. BUS for 
NEC evaluation has been available at CMKC since 2015. Despite its 
availability, current use of BUS for NEC evaluation at CMKC remains highly 
variable, often dependent upon the individual preferences of the treating 
neonatologist. 
32.2 
The NICU at KUMC is a 32-bed level III NICU. Majority of infants 
admitted at the NICU are born at KUMC. Neonatology coverage at KUMC 
is provided by CMKC neonatologists who are also in-house 24/7. As a 
general adult hospital, radiology staff at KUMC are composed primarily of 
adult sonographers and adult radiologists. Currently, only one radiologist 
at KUMC has the expertise to perform BUS for NEC evaluation. Because of 
this limited availability, BUS for NEC evaluation is infrequently performed 
at KUMC. However, as part of our study’s aim of investigating 

SHORT TITLE: BUS for NEC 
Page 20 of 32 
 
generalizability of BUS in NICUs of adult hospitals, pre-study training will 
be done to standardize performance and availability of BUS between 
CMKC and KUMC.  
32.3 
Close research collaboration exists between the NICUs of CMKC 
and KUMC. Several research protocols done at CMKC are also done at 
KUMC. In fact, KUMC is such an active site for collaborative research that 
a CMKC-employed neonatology research coordinator (Miah Ruffin) is 
dedicated solely for recruitment of participants at KUMC-NICU. Although 
KUMC has its own IRB, majority of the research done at KUMC NICU is 
approved via reliance on the IRB at CMKC.  
33.0 Multi-Site or Collaborative Research 
Choose ALL relationship types that apply:  
☒    Multi-Site Research: Multiple sites will be engaged in this human research 
project. Sites will use the same protocol to conduct the same human research 
activities (except for minor variations due to local context considerations).   
☒    Collaborative Research: Multiple sites will be engaged in this human 
research project. Sites will not be performing the same research activities. The 
Site submission will specify the specific research activities each site will perform.   
☐    Student(s):  Student(s) will help with this project and will be engaging their 
home institution.  
☒    Visiting Resident(s) / Visiting Fellow(s):  Visiting Resident(s) / Visiting 
Fellow(s) will help with this project and will be engaging their home institution.  
Complete the Chart (Add a new row for each site): 
Site Name 
Enrollment Goal for 
Site(s) 
Choose One 
Relying on CM IRB?  
KUMC 
☐  Site will not rely 
on the CM IRB 
 
☒  If relying on the 
CM IRB: Site 
Enrollment Goal: 80 
neonates and 80 
Neonatologists 
 
☐  Site will not 
enroll  
☒  External Site will rely on the CM IRB as 
the IRB of Record using a reliance 
agreement. (Required for non-Exempt NIH 
or other Federally Funded research) 
☐  External Site will utilize their home 
institution’s IRB for IRB approval. A reliance 
agreement will not be sought. 
☐  Not Applicable. Site will not interact or 
intervene with human participants or their 
identifiable data / identifiable biospecimens.  
UMKC 
☐  Site will not rely 
on the CM IRB 
☒  External Site will rely on the CM IRB as 
the IRB of Record using a reliance 

SHORT TITLE: BUS for NEC 
Page 21 of 32 
 
 
☐  If relying on the 
CM IRB: Site 
Enrollment Goal: 
Click or tap here to 
enter text. 
 
☒  Site will not 
enroll 
agreement. (Required for non-Exempt NIH 
or other Federally Funded research) 
☐  External Site will utilize their home 
institution’s IRB for IRB approval. A reliance 
agreement will not be sought. 
☐  Not Applicable. Site will not interact or 
intervene with human participants or their 
identifiable data / identifiable biospecimens. 
 
34.0 International Research - NA 
Addendum A: Waiver of Documentation of Permission/Consent 
 
Regulatory Criteria: To qualify for a waiver of documentation of parental permission or 
adult consent, the study must fit into at least one of the three scenarios below. Indicate 
which scenario(s) applies. 
 
☐ The only record linking the participant and the research would be the 
permission/consent form and the principal risk is potential harm resulting from a 
breach of confidentiality. Each parent/LAR or adult participant will be asked whether 
they want documentation linking the participant with the research, and the 
parent/LAR’s or adult participant’s wishes will govern. 
 
OR 
 
☒ The research presents no more than minimal risk of harm to participants and 
involves no procedures for which written parental permission or adult consent is 
normally required outside of the research context. 
 
OR 
 
☐ The parent(s)/LAR or adult participants are members of a distinct cultural group or 
community in which signing forms is not the norm, the research presents no more 
than minimal risk of harm to participants and an appropriate alternative mechanism 
for documenting that informed parental/LAR permission or adult consent was 
obtained will be provided. Describe the alternative mechanism provided: 

SHORT TITLE: BUS for NEC 
Page 22 of 32 
 
 
Addendum B: Waiver/Alteration of Permission/Assent/Consent 
 
What’s the difference between a “waiver” and an “alteration” of parental permission, 
child assent, or adult consent?   
 
• A “waiver” of parental permission, child assent, or adult consent is when all 9 
required elements of permission/consent are waived. If the IRB approves a 
waiver then the study team does not need to obtain the parental permission or 
adult consent in order to include a participant in the study. 
 
• An “alteration” of parental permission, child assent, or adult consent is when 
one or more of the 9 required elements are waived because they are not 
relevant to the research activity. If the IRB approves an alteration, then the study 
team must still obtain parental permission or adult consent in order to include a 
participant in the study, but certain elements may not be required in the 
form/discussion. 
 
 
 
NOTE: If requesting a waiver of parental/LAR permission because parental permission is 
not a reasonable requirement to protect the participants [e.g. research on neglected or 
abused children], contact irb@cmh.edu to discuss additional regulatory requirements. 
 
Regulatory Criteria: To qualify for a waiver or alteration of parental permission or adult 
consent, ALL of the following must apply.  Explain how the study meets each of the 
regulatory criteria below.   
 
Criteria 
Explain how the study meets the criteria 
The research involves no more than 
minimal risk to the participants 
Add-on BUS involves no more than minimal risk to 
participants for the following reasons: 
(1) BUS is non-invasive, free from radiation, does not 
require any special preparation before the 
procedure, and is well tolerated even in sick, infants.  
(2) BUS is an accepted imaging option for the diagnostic 
evaluation of infants with suspected NEC.  
(3) The workflow for obtaining BUS in the study will be 
the same as the workflow for obtaining BUS in 
routine clinical care. Thus, the BUS images acquired 
by the sonographer and the report provided by the 
radiologist will be securely stored in the infant’s 
electronic medical record.  
 

SHORT TITLE: BUS for NEC 
Page 23 of 32 
 
(4) There is clinical equipoise for the diagnostic imaging 
evaluation of NEC (AXR vs AXR+BUS). This is 
evidenced by the fact that the diagnostic imaging 
algorithm for neonates for whom there is NEC 
suspicion is more based on the staff present that day 
than any other factor. 
The research could not practicably be 
carried out without the requested 
waiver/alteration (i.e., explain why the 
study could not be done if 
permission/assent/consent were 
required) 
We initially conducted a pilot study to determine the 
feasibility of a RCT study design of BUS for NEC evaluation. 
While the RCT study design itself was feasible, we found 
that the process of obtaining consent was not practicable. 
The reasons why the proposed research could not be 
practicably carried out without the requested waiver are 
detailed below and in Fig 3: 
(1) NEC is an emergency, making traditional parental 
consent at time of NEC concern impossible. Because 
NEC can rapidly deteriorate, infants with suspected 
NEC require “stat” evaluation with imaging and 
other laboratory tests. Families approached for 
research during emergency situations are often 
unable to give proper informed consent because of 
physical and emotional distress. Obtaining consent 
at time of NEC concern would also increase the risk 
of delaying evaluation. For these reasons, traditional 
parental informed consent at time of NEC concern is 
not possible for our study. 
(2) Obtaining consent prior to NEC concern will require 
impractically large numbers to meet sample size 
demands. To overcome the emergency nature of 
NEC, we elected in our pilot study to seek consent 
from all infants who meet eligibility criteria, follow 
consented infants over time, and randomize only 
consented infants who develop concern for NEC. The 
problem with this approach is that only 36% (20/56) 
of consented infants developed NEC concern for 
randomization into the study. Based on these 
numbers, we will need to successfully consent 222 
infants to achieve our target sample size of 80 
infants. Although mathematically possible, it would 
require implausibly high approach and consent rates 
to successfully enroll 222 infants over the 2 years of 
the proposed study, making this approach of 
obtaining consent prior to NEC concern 
impracticable. This approach would also intrude on 
many families who would not need and may not 

SHORT TITLE: BUS for NEC 
Page 24 of 32 
 
want the information provided. A secondary concern 
would be the excessive personnel time and cost 
requirements to consent 222 families to meet the 
targeted enrollment of 80 infants.  
(3) The inherent differences in families able to be 
consented versus not consented in the study may 
result in underrepresentation, selection bias, 
reduced generalizability, and erroneous 
conclusions. In our pilot study, majority of infants 
were unable to be consented for two reasons. The 
first reason (40% of infants) was that the infants 
were very sick at the time of transfer and their NEC 
concern episode happened very early in their 
hospitalization, resulting in very limited time to 
consent the parents. The second reason (also 40% of 
infants) was that infants were transferred from 
faraway hospitals. As a level IV NICU, infants 
admitted at CMH are referred from the whole of 
Kansas and western half of Missouri. Similarly, as a 
tertiary referral hospital for high-risk pregnancies, 
KUMC admits and delivers pregnant moms from all 
over Kansas. Such families who live farther away 
from Kansas City are often not able to be present as 
often in the NICU to be approached for research. 
Thus, because of these two reasons for limited 
availability to obtain consent, we believe our pilot 
study sample was biased by overrepresentation of 
healthier infants and infants from the Kansas City 
metropolitan area. Limited availability to consent for 
research is also known from prior studies to be 
higher among families that have transportation 
issues, speak a different language other than English 
or Spanish, unable to pay their phone bills, etc. 
Together, these barriers can systematically prevent 
the inclusion of at-risk families in research studies, 
decreasing generalizability of our results. If this 
selection bias were to persist in our larger study, it 
would weaken the scientific validity of our research 
by increasing the likelihood of missing important 
benefits or hazards and reaching erroneous 
conclusions.  
 
 

SHORT TITLE: BUS for NEC 
Page 25 of 32 
 
(4) Complexity of following consented infants for 
development of NEC concern result in missed 
randomization, loss of study participants, and 
insufficient power. In our pilot study, 20% of 
consented infants who developed concern for NEC 
(4/20) were not randomized into the study. The 
complexity of following consented infants 
prospectively for development of NEC concern is a 
major contributing factor for missed randomization. 
This is because NEC concern, which by itself is 
already a relatively rare event, can occur at any time 
of the day or night, and can occur several weeks 
from the time of informed consent. The loss of even 
a few subjects from complex consent process and 
missed randomization would negatively impact the 
power and validity of our proposed study. Instead, 
we propose including all consecutive infants who 
develop NEC concern into the study with waiver of 
consent to simplify the study process, eliminate 
errors related to missed randomization, and 
maximize sample size and power for the study. 
 
Figure 3. A hypothetical example of 100 eligible patients to demonstrate how traditional consent 
process prior to NEC concern is not practicable. Using estimates based on our pilot study, the 
traditional consent process would have only successfully randomized 13 infants (green box). The red 
boxes indicate reasons why the traditional consent process would not be practicable for our study. In 
contrast, a waiver of informed consent would have successfully randomized 36 infants (green box + 
yellow boxes).  
 
100 eligible infants
unable to approach for 
consent = 36 (36%)
did not develop 
NEC concern     
= 23 (64%)
developed 
NEC concern 
= 13 (36%)
approached for 
consent = 64 (64%)
refused consent        
= 20 (32%)
did not 
develop NEC 
concern        
= 13 (64%)
developed 
NEC 
concern      
= 7 (36%)
agreed to study    
= 44 (68%)
did not develop 
NEC concern     
= 28 (64%)
developed NEC 
concern              
= 16 (36%)
missed 
randomization        
= 3 (20%)
successfully 
randomized        
= 13 (80%)
Selection bias 
Insufficient power 
Need for 
impracticably 
large 
numbers 

SHORT TITLE: BUS for NEC 
Page 26 of 32 
 
If the research involves using 
identifiable private information or 
identifiable biospecimens, the research 
could not practicably be carried out 
without using such information or 
biospecimens in an identifiable format 
PHI is required to identify subjects and data from all 
participants is needed to describe aims of the study.     
The waiver/alteration will not 
adversely affect the rights and welfare 
of the participants 
The waiver will not adversely affect subjects for the 
following reasons:  
(1) The allowance of cross-over in the study ensures 
that participants will not be deprived from obtaining 
BUS should the treating neonatologist deem it is 
clinically warranted to do so. Thus, the availability of 
BUS as an option remains the same regardless of 
research participation or not. 
(2) BUS will be performed for proper clinical indication 
of NEC concern and not for research purposes only. 
Results of BUS will be available to clinical care team 
per routine clinical care. Thus, research participation 
will not affect the regular care of infants with NEC 
concern, nor will it negatively affect infant’s welfare.  
(3) BUS results will be performed per routine clinical 
workflow, ensuring information from BUS will be 
kept secure and confidential in the patient’s 
electronic medical record. Thus, research 
participation will not affect patient confidentiality. 
Whenever appropriate, the 
participants or legally authorized 
representatives will be provided with 
additional pertinent information after 
participation 
NA – no additional disclosure of information is needed as 
families will be updated and provided with the information 
from BUS during family-centered patient care rounds as 
part of routine care. Additionally, results of BUS will be 
freely available in the infant’s electronic medical record.  
 
Proposed Alteration (if applicable):  
Select which required elements of permission are to be omitted. 
☐ A statement that the study involves research, an explanation of the purposes of 
the research and the expected duration of the participant's participation, a 
description of the procedures to be followed, and identification of any 
procedures that are experimental; 
 
☐ A description of any reasonably foreseeable risks or discomforts to the 
participant; 
 
☐ A description of any benefits to the participant or to others that may reasonably 
be expected from the research; 

SHORT TITLE: BUS for NEC 
Page 27 of 32 
 
 
☐ A disclosure of appropriate alternative procedures or courses of treatment, if any, 
that might be advantageous to the participant; 
 
☐ A statement describing the extent, if any, to which confidentiality of records 
identifying the participant will be maintained; 
 
☐  For research involving more than minimal risk, an explanation as to whether any 
compensation and an explanation as to whether any medical treatments are 
available if injury occurs and, if so, what they consist of, or where further 
information may be obtained; 
 
☐  An explanation of whom to contact for answers to pertinent questions about the 
research and research participants' rights, and whom to contact in the event of a 
research-related injury to the participant; 
 
☐  A statement that participation is voluntary, refusal to participate will involve no 
penalty or loss of benefits to which the participant is otherwise entitled, and the 
participant may discontinue participation at any time without penalty or loss of 
benefits to which the participant is otherwise entitled; and 
 
☐  One of the following statements about any research that involves the collection 
of identifiable private information or identifiable biospecimens: 
 
☐  A statement that identifiers might be removed from the identifiable private 
information or identifiable biospecimens and that, after such removal, the 
information or biospecimens could be used for future research studies or 
distributed to another investigator for future research studies without 
additional informed consent from the participant or the legally authorized 
representative, if this might be a possibility; or 
 
☐  A statement that the participant's information or biospecimens collected as 
part of the research, even if identifiers are removed, will not be used or 
distributed for future research studies. 
 
Provide the rationale for omitting the item(s) selected: 
 
 

SHORT TITLE: BUS for NEC 
Page 28 of 32 
 
Addendum C: Non-English Speaking Participants 
 
There are special considerations that must be made when obtaining 
permission/assent/consent from participants who prefer to communicate in a language 
other than English. To ensure that adequate processes are in place to obtain effective 
permission/assent/consent from these participants address each of the items below. 
 
Indicate which language(s) other than English are understood by prospective 
participants or representatives. 
 
☐  Spanish 
☐  Arabic 
☐  Burmese 
☐  Somali 
☐  Vietnamese 
☐  Other:_______________________________________________ 
 
 
Describe the plan for enrolling non-English speaking participants (e.g. fully translated 
consent forms, use of Qualified Bilingual Study Staff or interpreters): 
 
 
 
If providing fully translated consent forms, explain if the ORI Translation Program for 
internally and/or federally funded studies will be used, or if translation services will be 
obtained through the study sponsor or some other service. 
NOTE: If using ORI Translation Program services for an industry sponsored study, contact 
Research Business Operations staff to get this negotiated in the study 
agreement/contract. 
 
 

SHORT TITLE: BUS for NEC 
Page 29 of 32 
 
Addendum D: Surrogate Decision Maker Consent 
 
Assessment of Decision-Making Capacity:   
• Describe the process to determine whether an individual is capable of consent. 
See CM Research Policy 9.10 Incapacity, Temporary or Fluctuating Decision-
Making Capacity for more information on the proper procedures for enrolling 
adults who are not able to consent for themselves. 
 
Identification of Surrogate Decision Maker 
• List the individuals from whom permission will be obtained in order of priority, 
e.g. durable power of attorney for health care, court appointed guardian for 
health care decisions, spouse, and adult child. 
• For research conducted in the states of Missouri and/or Kansas, review  CM 
Research Policy 9.10 Incapacity, Temporary or Fluctuating Decision-Making 
Capacity to be aware of which individuals in the state meet the definition of 
“legally authorized representative.” 
• For research conducted outside of Missouri and/or Kansas, provide information 
that describes which individuals are authorized under applicable law to consent 
on behalf of a prospective participant to their participation in the procedure(s) 
involved in this research. One method of obtaining this information is to have a 
legal counsel review the protocol. 
 
Assent of Adult Participant 
• Describe the process for assent of the adult participants who are unable to 
consent for themselves. Indicate whether: 
o Assent will be required of all, some, or none of the participants. If some, 
indicate which participants will be required to assent and which will not. 
o If assent will not be obtained from some or all participants, an 
explanation of why not. 
o Describe whether assent of the participants will be documented and the 
process to document assent. The IRB allows the person obtaining assent 
to document assent on the consent document and does not routinely 
require assent documents or require participants to sign assent 
documents. 
o Describe how participants will be closely monitored.  
o Describe whether participants will be withdrawn if they appear to be 
unduly distressed. 
 
 

SHORT TITLE: BUS for NEC 
Page 30 of 32 
 
 
 
Addendum E: Waiver/Alteration of HIPAA Authorization 
 
 
What’s the difference between a “waiver” and an “alteration” of HIPAA 
Authorization? 
 
• A “waiver” of HIPAA Authorization is when the requirement to obtain 
authorization is completely waived. If the IRB approves a waiver then the study 
team does not need to obtain HIPAA Authorization in order to include a 
participant in the study. 
 
• An “alteration” of HIPAA Authorization is when one or more of the required 
elements of authorization are waived.  If the IRB approves an alteration then 
the study team must still obtain HIPAA Authorization in order to include a 
participant in the study, but certain elements may not be required in the 
form/discussion. 
 
 
 
Regulatory Criteria: To qualify for a waiver/alteration of HIPAA Authorization, ALL of the 
following must apply to a study. Explain how the study meets each of the regulatory 
criteria below.   
 
Criteria 
Explain how the study meets the 
criteria 
The use or disclosure of PHI involves no 
more than minimal risk to the privacy of 
individuals based upon the following:  
a. Plan to protect PHI from 
improper use and disclosure: 
b. Plan to destroy PHI at the 
earliest opportunity, unless 
there is a health or research 
justification for retaining the 
PHI: 
c. Assurance that PHI will not be 
reused or disclosed to any 
other person or entity: 
 
a. We plan to protect identifiers 
by the following plan: 
- Only trained research personnel 
who have been educated on 
HIPAA regulations and who have 
been given password-protected 
access to clinical health systems 
and medical records will have 
access to this information. 
- All databases into which the data 
will be stored will be housed on 
secure networks with password-
protection.  

SHORT TITLE: BUS for NEC 
Page 31 of 32 
 
- The electronic data will be 
stored on a server managed by 
Children’s Mercy. Access to the 
server is restricted to only those 
with IRB approval for the study, 
and it is password protected. 
 
b.  All PHI collected during the 
study will be removed once 
complete research data has been 
collected and validated through 
quality assurance review. We will 
only maintain de-identified data 
for potential use in future 
research. 
c. PHI will not be reused or 
disclosed to any person or entity 
other than those listed in this 
application, except as required by 
law, for authorized oversight of 
this research study, or as 
specifically approved for use in 
another study by an IRB. 
 
The research cannot practicably 
be conducted without the 
waiver/alteration, i.e. explain why 
a signature for HIPAA 
Authorization cannot be obtained. 
A signature for HIPPA 
Authorization cannot practically 
be obtained because we are 
requesting to waive parental 
consent for the study. Without a 
corresponding HIPPA waiver, we 
would have to approach the 
families of every single patient 
treated in the NICU at the time of 
the study, which would be 
contrary to our request for waiver 
of parental consent. See Appendix 
B for reasons why a waiver of 
parental consent is requested for 
the study. 
The research cannot practicably 
be conducted without access to 
and use of the PHI, i.e. explain 
Access to and use of PHI is needed 
for the study for the following 
reasons: 
 

SHORT TITLE: BUS for NEC 
Page 32 of 32 
 
 
why access to PHI is needed for 
this study. 
(1) The month of birth will be 
used to determine 
randomization. Other 
elements of date will be 
used to calculate duration 
of antibiotic treatment and 
days to full enteral feeds.  
(2) Name and MRN will be 
used to track infant’s 
course throughout NICU 
admission and access 
electronic medical records 
for data collection.