Defining Normal Postoperative Magnetic Resonance Imaging and Muscle Enzyme Levels After Total Knee Arthroplasty Associated With Continuous Adductor Canal Block
Conditions: Local Anesthetic Complication, Local Anesthetic Drug Adverse Reaction
Sponsor: Benaroya Research Institute

Original Protocol and Amendments
March 8, 2018 - May 29, 2018
NCT04821245
ID: BRI IRB18-008
Deﬁning Normal Postoperative Magnetic Resonance Imaging after Total Knee Arthroplasty 

 
IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: March 23, 2021
Personnel Information
1
Subject Checklist
3
Study Location
4
General Checklist
4
Funding
5
Application Type Checklist
6
Expedited Paragraphs
6
Summary, Purpose, Procedures
8
Background and additional procedures
9
Subject Population
10
Recruitment Process, Subject Compensation and Costs
11
Risks
13
Benefits
14
Confidentiality
14
Consent Information
16
Assent Background
17
HIPAA
18
Drugs and Devices
20
Potential Conflict of Interest
21
Attachments
21
Obligations
22

 
IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: March 23, 2021
Event History
23

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IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: March 23, 2021
Protocol Title:
Defining Normal Postoperative Magnetic Resonance Imaging after Total
Knee Arthroplasty
Date Submitted:
03/08/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval.
Please check the comments section of the online protocol.
Questions that appear to not have been answered may not have been required
for this submission. Please see the system application for more details.
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* * * Personnel Information * * *
Click "Help" (upper right corner of screen) for guidance regarding who to include below (Key Personnel) and what
CITI Training is needed.  See the Clinical Research Glossary for definitions.  Questions:  Contact the Research
Protections Department
Principal Investigator
Client defines "Investigator" as an individual who conducts a research study. If the study is conducted by a team
of individuals, the Investigator is the responsible leader of the team.
Name of Principal Investigator*
Degree (MD/PhD/BSN/etc.)
Title
Neal, Joseph
MD
ANESTHESIOLOGIST
Email*
Phone
Fax
Joseph.Neal@virginiamason.org
206-223-6980
VM/BRI Department
Investigator Affiliation Check ALL
that apply*
Mailstop
Anesthesiology
X
VM personnel
B2-AN
BRI personnel
Zip code
Other
98101
Training Details
No training data is available.
Sub-Investigator(s)
Sub-Investigator
Degree
(MD/PhD/BSN/etc.)
Title
Research Department
Blackmore, Craig
MD
RADIOLOGIST
Radiology MD Admin
Verdin, Peter
MD
ORTHOPEDIC
SURGEON
Orthopedics - Outpatient
Sub-Investigator(s)
Name of Sub-Investigator(s)
Degree (MD/PhD/BSN/etc.)
Title
Blackmore, Craig
MD
RADIOLOGIST
Email*
Phone
Fax
Craig.Blackmore@virginiamason.org
206-223-6851
VM/BRI Department
Investigator Affiliation Check ALL
that apply*
Mailstop
Radiology MD Admin
X
VM personnel
R3-324
BRI personnel
Zip code
Other
98101
Role in Study
Radiologist

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Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: March 23, 2021
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Training Details
No training data is available.
Sub-Investigator(s)
Name of Sub-Investigator(s)
Degree (MD/PhD/BSN/etc.)
Title
Verdin, Peter
MD
ORTHOPEDIC SURGEON
Email*
Phone
Fax
Peter.Verdin@virginiamason.org
206-223-7530
X6-ORT
VM/BRI Department
Investigator Affiliation Check ALL
that apply*
Mailstop
Orthopedics - Outpatient
X
VM personnel
BRI personnel
Zip code
Other
98101
Role in Study
Training Details
Course
UserID
CourseCompletionDate
CourseExpirationDate
CITI Good Clinical
Practice
peter.verdin
11/14/2016 3:34:28 PM
11/14/2019 3:34:28 PM
Study Coordinator
Study Coordinator
Degree
(MD/PhD/BSN/etc.)
Title
Research Department
Neal, Joseph
MD
ANESTHESIOLOGIST
Anesthesiology
Study Coordinator
Name of Study Coordinator
Degree (MD/PhD/BSN/etc.)
Title
Neal, Joseph
MD
ANESTHESIOLOGIST
Email*
Phone
Fax
Joseph.Neal@virginiamason.org
206-223-8822
VM/BRI Department
Investigator AffiliationCheck ALL
that apply*
Mailstop
Anesthesiology
X
VM personnel
B2-AN
BRI personnel
Zip code
Other
98101
Training Details
No training data is available.
Regulatory Contact (Primary IRB contact if not PI or Study Coordinator)
Name of Regulatory Contact
Degree (MD/PhD/BSN/etc.)
Title
Email*
Phone
Fax

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Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: March 23, 2021
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VM/BRI Department
Investigator Affiliation Check ALL
that apply*
Mailstop
VM personnel
BRI personnel
Zip code
Other
Training Details
No training data is available.
Additional Personnel Information: (Use the area below if necessary to provide additional information
regarding the personnel on this protocol)
Dr. Lauren Steffel, Puget Sound VA Health Services, will participate in manuscript writing and data analysis. She will have no contact
with Virginia Mason subjects. The data that she will have access to will be de-identified with regard to subject PHI.
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* * * Subject Checklist * * *
Subject Checklist
Select all that apply:
Retrospective medical records   (e.g. Chart Review)
Tissue, blood, other specimens (e.g. repository)
X
Individuals with underlying medical conditions
X
Healthy individuals
Select all vulnerable groups:
Check all targeted or possibly included subjects.  This also applies to retrospective chart reviews.
Some groups (e.g. prisoners, pregnant women, or children) may require additional IRB oversight per
federal regulations.
Prisoners
45CFR46 Subpart C (Should be excluded unless you know subject(s) will be "in prison" at the time of
enrollment.  Notify IRB immediately if a subject becomes incarcerated after enrollment.  This population
can not be reviewed exempt.)
Pregnant women
45CFR46 Subpart B
Females of childbearing potential
Children (under 18)
45CFR46 Subpart D
Persons incompetent to give consent (e.g., dementia, comatose, have legally authorized representative)
Economically/educationally disadvantaged.
Illiterate
Non-English speaking
See:  VM Interpreter Services
Are any other subjects outside of the above targeted or possibly included in this study?
N

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If yes, describe below:
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* * * Study Location * * *
Study Location
1.
Click "add" and create a separate row in the table below for each unique VM / BRI study location.
VM/BRI  Table
VM Location
Other VM Location:
VM location Study
Activities
Other Activities
Main Campus Seattle -
Clinic / Hospital
Blood draw, Informed
consent discussion,
Ongoing study visits,
Screening visits, Specific
procedures associated
with the study
VM/BRI  Table
Location
Main Campus Seattle - Clinic / Hospital
Activity
Blood draw,Informed consent discussion,Ongoing study visits,Screening
visits,Specific procedures associated with the study
2)
Are there any locations outside of VM / BRI that are involved in any way with this study?  If yes, explain
below.  If no, proceed to the next section.
N
i.
Are any outside locations "engaged"with this research study?  If yes, explain: (click on "Help" for
more information regarding engagement)
N
ii.
Will the BRI IRB be responsible for oversight (IRB of Record) for any study procedures
conducted at outside locations? If yes, describe in the table below (click "add"). If no, confirm
who is the IRB of Record for engaged activities outside of VM in the space below and then
proceed to the next section.
N
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* * * General Checklist * * *
General Checklist
Select All That Apply:  At least 1 box must be checked to proceed.  If none are applicable contact the IRB at
IRB@benaroyaresearch.org  Use the attachment section to add separate documents or forms.
X
Protected Health Information (PHI) will be viewed, created, accessed, used, or disclosed by VM/BRI
personnel or others.  (Checking this box activates the HIPAA section)

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Questionnaire/Survey
Tissues or data to be stored for future research projects (e.g. registry or repository)
Tissues or data to be sent out of VM / BRI as part of a research agreement - Material Transfer Agreement
(MTA)- Data Use Agreement (DUA)
X
FDA regulated device (Investigational or otherwise)- This includes Humanitarian Use Devices (HUD)
FDA regulated drugs, reagents, or chemicals (Investigational or otherwise)
This study is or will be posted on ClinicalTrials.gov
If checked, specify number:
Radioisotopes/radiation-producing machines, even if standard of care (Radiation Safety)
VM/BRI Institutional Biosafety Committee (IBC) Review Required- Clinical research involving recombinant
and/or synthetic nucleic acid
Request to Rely on Another IRB - Please upload completed Request to Rely and associated documents in
attachment section (This applies for Cooperative Review studies.)
IRB Authorization Agreement (IAA), Memorandum Of Understanding (MOU), etc.(attach in the
Attachments section (This only applies to studies where the Client IRB is the "Reviewing" IRB).
X
A stand-alone protocol already exists.
Checking this box doesn't reduce the number of questions you need to answer.  However, you can be
brief with your answers and include references to the stand-alone protocol (e.g. section, page #) for
more information.  Use the attachment section  to include the stand-alone protocol with your
submission.
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* * * Funding * * *
Funding / Resources
1)
Is there funding or other resources required for this project?
Y
No means absolutely no internal or external funds, services, skills, or products (e.g., statistical services, database
warehousing, free test article) are provided.  If no, proceed to the next section.
If yes, Click "add" and create a separate row in the table below for each unique funding source.
Funding / Resources Table
Funding
Name
BRI Funding
#
Restricted
BRI Funds
Unrestricted
BRI Funds
Federal
Grant
Federal
Funding #,
Grant #
Non-Profit
Foundation
Industry
Funding
Washington
State
Society of
Anesthesiol
ogists
Seafair
Grant
Award
Through VM
Foundation
N
N
N
Y
N
Funding / Resources Table

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Name of Funding Entity
Washington State Society of Anesthesiologists Seafair Grant
Award
BRI Funding Number
Through VM Foundation
BRI restricted funds?
N
BRI unrestricted funds?
N
Federal Grant funds?
N
Non-Profit Foundation?
Y
Industry Funding
N
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* * * Application Type Checklist * * *
Please check one of the boxes below to determine how to move forward with your project. The US Office of
Human Research Protections (OHRP) has created graphic aids to help with deciding if your research requires
IRB oversight.  In addition, please contact the BRI Research Protections Department with questions.
Application type checklist
Not Human Subjects Research (This form is not currently available through eProtocol.  Please click
"https://www.benaroyaresearch.org/sites/default/files/Human%20Subjects%20Determination%20Form.doc"
target=_blankhere if applicable.)
Exempt
X
Expedited/Full Board (This includes Cooperative and Chart Reviews.)
Indicate what level of review you anticipate for this protocol:
Full Board (greater than minimal risk)
X
Expedited (minimal risk)
 "https://www.benaroyaresearch.org/our-research/clinical-research/for-investigators/starting-
study/cooperative-trials" target=_blankCooperative (approval by another IRB of record, regardless of
risk level)
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* * * Expedited Paragraphs * * *
EXPEDITED REVIEW CATEGORIES If this is a FULL BOARD study, or COOPERATIVE (IRB of Record is not
BRI), then proceed to next section.
For expedited review all aspects of the research must be: (1) Minimal Risk (2) Involve one or more categories
listed below.  Select all that apply (Click Help for more information):
1.
Clinical studies of drugs and medical devices only when condition (a) and (b) are met.
a)
Research on drugs for which an investigational new drug application (21 CFR Part 312) is not
required. (Note: Research on marketed drugs that significantly increases the risks or decreases
the acceptability of the risks associated with the use of the product is not eligible for expedited
review.)
b)
Research on medical devices for which
i)
An investigational device exemption application (21 CFR Part 812) is not required; or
ii)
The medical device is cleared/approved for marketing and the medical device is being used
in accordance with its cleared/approved labeling.
X
2.
Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:
a)
From healthy, non-pregnant adults who weigh at least 110 pounds. For these subjects, the

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amounts drawn may not exceed 550 ml in an 8 week period and collection may not occur more
frequently than 2 times per week; or
b)
From other adults and children, considering the age, weight, and health of the subjects, the
collection procedure, the amount of blood to be collected, and the frequency with which it will be
collected. For these subjects, the amount drawn may not exceed the lesser of 50 ml or 3 ml per
kg in an 8 week period and collection may not occur more frequently than 2 times per week.
3.
Prospective collection of biological specimens for research purposes by non-invasive means.
Examples:
a)
Hair and nail clippings in a non-disfiguring manner.
b)
Deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction.
c)
Permanent teeth if routine patient care indicates a need for extraction.
d)
Excreta and external secretions (including sweat).
e)
Uncannulated saliva collected either in an unstimulated fashion or stimulated by chewing
gumbase or wax or by applying a dilute citric solution to the tongue.
f)
Placenta removed at delivery.
g)
Amniotic fluid obtained at the time of rupture of the membrane prior to or during labor.
h)
Supra- and subgingival dental plaque and calculus, provided the collection procedure is not
more invasive than routine prophylactic scaling of the teeth and the process is accomplished in
accordance with accepted prophylactic techniques.
i)
Mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings.
j)
Sputum collected after saline mist nebulization.
X
4.
Collection of data through non-invasive procedures (not involving general anesthesia or sedation)
routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. Where
medical devices are employed, they must be cleared/approved for marketing. (Studies intended to
evaluate the safety and effectiveness of the medical device are not generally eligible for expedited
review, including studies of cleared medical devices for new indications.)
Examples:
a)
Physical sensors that are applied either to the surface of the body or at a distance and do not
involve input of significant amounts of energy into the subject or an invasion of the subject's
privacy.
b)
Weighing or testing sensory acuity.
c)
Magnetic resonance imaging.
d)
Electrocardiography, electroencephalography, thermography, detection of naturally occurring
radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow,
and echocardiography.
e)
Moderate exercise, muscular strength testing, body composition assessment, and flexibility
testing where appropriate given the age, weight, and health of the individual.
X
5.
Research involving materials (data, documents, records, or specimen) that have been collected, or will
be collected solely for non-research purposes (such as medical treatment or diagnosis). (NOTE: Some
research in this paragraph may be exempt from the HHS regulations for the protection of human
subjects. 45 CFR 46.101(b)(4). This listing refers only to research that is not exempt.)
6.
Collection of data from voice, video, digital, or image recordings made for research purposes.
7.
Research on individual or group characteristics or behavior (including, but not limited to, research on

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perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and
social behavior) or research employing survey, interview, oral history, focus group, program evaluation,
human factors evaluation, or quality assurance methodologies. (NOTE: Some research in this category
may be exempt from the HHS regulations for the protection of human subjects - 45 CFR 46.101(b)(2)
and (b)(3). This listing refers only to research that is not exempt.)
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* * * Summary, Purpose, Procedures * * *
 BRI Study ID Number - From the Clinical Research Program (e.g.
CRP170XX)
CRP18023
Unit / Department -  Administrative Oversight of Research
Protocol Title
Defining Normal Postoperative Magnetic Resonance Imaging after Total Knee Arthroplasty
1.
Summary
Provide a summary of the scope of work of this protocol.
Recent reports(1) describe sentinel cases of presumed local anesthetic-induced myotoxicity occurring after continuous adductor
canal blocks (CACB) that were placed to provide analgesia after total knee arthroplasty (TKA). Crucial to the diagnosis, management,
and eventual understanding of this newly described anesthetic complication is elucidating what constitutes normal postoperative
magnetic resonance imaging (MRI) after TKA. A recent retrospective review of MRIs obtained for various indications within a week of
TKA failed to identify a consistent pattern of MR findings that might have defined "normal MRI imaging" after TKA (BRI 16092,
Magnetic Resonance Imaging of the Quadriceps Muscle After Total Knee Arthroplasty). The logical next step in this investigation
would be to obtain MRIs in TKR patients just prior to hospital discharge after an otherwise normal postoperative course.
2.
Purpose
Describe the purpose for the proposed project as well as the hypotheses/research questions to be
examined.
This study aims to define normal quadriceps imaging in 20 asymptomatic volunteers two days after undergoing TKA. A secondary
aim is to investigate alterations in creatine phosphokinase (CPK) and aldolase levels coincident with TKA. The aim of this
observational study is to define what constitutes a normal MRI appearance and normal CPK / aldolase alterations in postoperative
TKA patients. This knowledge is crucial for proper diagnosis and further understanding of this sentinel complication.
3.
Procedures
a)
Describe the activities/procedures to be conducted in chronological order (e.g. pull charts/data from Cerner,
screening,  interventions/interactions with subjects, data collection, photographing, audio and video
recording, follow-up.)
-Patients of various age and sex that are scheduled for unilateral TKR will be approached by VM orthopedic surgeons to ascertain
their willingness to volunteer for this study
-Identified patients will be consented for study participation by the PI at least 24 hours prior to their entry into the study
-All patients will undergo the standard VMMC TKA clinical pathway, which includes a 2 day continuous adductor canal block
-If their postoperative course has been normal, 10 volunteers will undergo unilateral thigh MRI prior to discharge home on the
morning of postoperative day 2. These patients will have pre- and post-op CPK and aldolase levels analyzed.
-Leg MRIs will be graded using a standardized checklist by a supervised radiology resident who is unaware of the study's purpose.
b)
Explain who will conduct the procedures.  Include where and when they will take place.
-MRIs will be obtained as scheduled cases at VMMC
-CPK and aldolase will be obtained and analyzed by VMMC laboratory
-MRIs will be assessed using a standardize template by a radiologist who is unaware of the study's purpose
c)
Will you be conducting procedures directly with patients?  If yes, answer the questions below.  If no (e.g.
chart review only), proceed to question 4.0 Study Duration.
Y
i)
Are there any procedures considered experimental and outside standard of care or established
practices at Virginia Mason, including follow-up procedures?
Y

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If yes, explain.
Lower extremity MRIs are standard, but are not a routine part of postoperative TKA care. CPK and aldolase analyses before
and after TKA is non-standard.
ii)
Will blinding be involved with this study?
Y
If yes, explain.
-The interpreting radiologist will be blinded as to the study's purpose
iii)
Will deception be used?
N
If yes, provide a rationale and describe debriefing procedures. Submit a debriefing script in
attachments section.
iv)
Will audio, photographs, or video taping of individuals occur?
N
If yes, describe and clarify what will become of the tapes/photographs (e.g., shown at scientific
meetings, erased, etc.).
4.
Study Duration
What is the anticipated start date and duration of the proposed study?
We plan to start immediately after IRB approval. We anticipate all 20 volunteers should be recruited and studied within a 3 month
period
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* * * Background and additional procedures * * *
5.
Background and additional procedures
a.
Relevant Background: Discuss the present knowledge, appropriate literature and rationale for conducting
the research.
Local anesthetics consistently induce myotoxicity in animal models and in up to 0.5% of humans after ophthalmic blocks, yet clinically
apparent myotoxicity in patients undergoing peripheral nerve blocks was heretofore believed to be nearly non-existent.(2) This
changed after introduction of continuous adductor canal blocks (ACB) at Virginia Mason Medical Center when 4 patients developed
symptoms, MRI findings, and neurophysiologic testing compatible with local anesthetic-induced myotoxicity. In short order, other
cases were reported from the Swedish Orthopedic Institute, 3 from retrospective analysis of other post-TKA MRIs obtained at Virginia
Mason, and anecdotally from practices throughout the United States. These sentinel complications have resulted in major morbidity
for the affected patients. After a normal early postoperative course, the patients rapidly developed flaccid quadriceps muscles and the
inability to lift the operative lower extremity against gravity, with consequent halting of their rehabilitative trajectory. While fortunate
patients recovered fully or nearly so after weeks to a few months as the unaffected myoblasts regenerated, less fortunate patients
have never recovered to baseline.
Because non-ophthalmic myotoxicity has never been described to this degree in humans, little is known about its etiology, diagnosis,
and treatment. Definitive diagnosis of myositis requires muscle biopsy, but this invasive and expensive intervention is unlikely to
occur. All patients in our series had MRI signals consistent with edema and inflammation, consistent with myositis. However, the
radiologic literature is silent with regard to what constitutes normal MRI findings immediately after TKA. Therefore, the MRI pathology
that we observed, while clearly demonstrating inflammatory changes in the anterior compartment of the leg, could conceivably
represent normal postoperative findings. We have attempted to study this question by retrospectively reviewing MRIs of patients who
underwent leg MRI within a week of TKA. While we could identify several patients with clinical presentations consistent with
undiagnosed myotoxicity, we were unable to confidently discern pathological findings versus 'normal' postoperative changes on
imaging.
b.
If applicable, please describe statistical methods of the research and plans for analysis of the data (i.e.
planned statistics, justification of sample size, etc.).
Observational convenience sample, therefore N/A
c.
Are there any alternative treatments to participating in this research (e.g., standard of care treatment,
etc.)?
N

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If yes, describe.  Any standard treatment that is being withheld must be disclosed. This information must be
included in the consent form.
d.
Can subjects receive alternative treatment outside of enrolling in this study?
N/A
e.
Will subjects be followed after their participation is complete?
N
If yes, explain why and describe how:
f.
Is this a cooperative study (e.g. UW, FHCRC is IRB of record)?
N
(If yes, answer the questions below.  If no, proceed to the next section.  Click here for more information.)
i.
Has this study been approved by the IRB of record?  (NOTE:  BRI IRB cannot review any
COOP study not currently approved by the IRB of record)
If yes, when did the initial approval for this study occur?
ii.
Has this study undergone Continuing Review (CR) at the IRB of record?
If yes, what are the current approval dates?
iii.
Will there be any costs to VM for study procedures (e.g. lab costs, etc.)?
If yes, how will these costs be paid to VM? (e.g., direct billing to your grant, etc.)
iv.
Will potential subjects from VM be approached?
(Note:  Refer to Non-VM Investigator Patient Approach Procedures for the correct procedures.)
If yes, describe how subjects will be approached and by whom.
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* * * Subject Population * * *
6.
Subject Population
a)
Complete the projected subject enrollment information below:List multiple subject groups/cohorts as
appropriate.(e.g.  retrospective, prospective, children, adult, controls, treatment, etc.)
Subject Enrollment
Subject Group
(DEFINE:
cases/controls/records/
specimens etc.)
Age Range
Expected Number at
End of Study (locally)
Expected Number at
End of Study (Total if
multi-site)
Expected Enrollment
next 12 months
20
50-75
20
20
b)
Complete the vulnerable subject table below:

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Potentially Vulnerable Subject Populations
Targeted
Possible
Inclusion
Excluded
N/A
Prisoners: FAQ  (Note:  should be excluded unless you know
subjects will be "in prison" at the time of enrollment.  Notify
IRB immediately if a subject becomes incarcerated after
enrollment.)
X
Pregnant Women:  (45CFR Subpart B)
X
Children (under 18): 45CFR46 Subpart D
X
People not competent to provide informed consent
X
If the above populations are targeted or possibly included,
explain:  (Give rationale and specific steps to protect those
populations)
Female of childbearing potential:
X
If excluded, explain:
Non-English Speaking:  VM Interpreter Services
X
If Non-English Speaking subjects are targeted or possibly
included, give rationale and specific steps to protect those
populations.  If excluded, explain.
Concern regarding not fully understanding through the
translator that this study involves the acquisition of MRI and
enzyme tests that are not part of a standard knee
replacement hospitalization
New Description
New
Description
New
Description
New
Description
New
Description
New Description
New
Description
New
Description
New
Description
c)
Are any other potentially vulnerable subjects (sight impaired, illiterate, etc.) targeted or possibly included
in this study?  If yes, explain and provide steps to protect this population:
N
d)
Inclusion and Exclusion Criteria (e.g., Participants must have 20/20 vision, Participants must be 30-45
years of age, etc.)
i.
Identify inclusion criteria.
-Anticipated unilateral TKA performed under the standard VMMC joint pathway, with 2 night stay postop
-Subjects will be operated by a single surgeon (Dr. Verdin) to eliminate possible confounders related to surgical technique
-Subjects must be willing to volunteer for MRI study and CPK and aldolase blood draws
ii.
Identify exclusion criteria.
-Any contraindication to use of spinal anesthesia or adductor canal-based analgesia
-History of muscle wasting or related disease
-History of auto-immune disorders that may affect the musculature
-History of pre-existing neurologic condition affecting the lower extremities
-Allergy to radiologic contrast
-Contraindications to MRI exam
e)
To provide support for your projected enrollment goals, how many patients at VMMC do you anticipate
would have met your eligibility criteria over the last 1-5 years?  If NA or no numbers available, explain why
and provide rationale to support your projections:
1000 per year
f)
How long do you anticipate it will take to complete accrual for this study?
3 months
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* * * Recruitment Process, Subject Compensation and Costs * * *
7.
Recruitment Process:
a)
Describe the step-by-step procedures for identifying and recruiting potential research subjects and/or
requesting their data or specimens.
-Patients of various age and sex that are scheduled for unilateral TKA will be approached by Dr. Verdin to ascertain their
willingness to volunteer for this study
-Identified patients will be consented for study participation by the PI (Dr. Neal) at least 24 hours prior to their surgery
b)
Identify who will contact prospective subjects. (complete request for waiver of consent if applicable)
Joseph M. Neal, MD
c)
Planned Subject Identification Methods:
VM Medical Records / Chart Review
Direct Advertising
From PI's own practice / department
Referrals
Records
Specific registries, specify IRB#:
Outside Institution, please specify:
X
Other, explain below:
From VMMC orthopedic surgical patients scheduled for TKA. Initial willingness to participate in the study will be ascertained by
Dr. Verdin or his physician assistant.
d)
Planned Recruitment Materials / Methods:
X
Face to face interactions
Flyers / posters
Phone Scripts
Letters to providers / schools / organizations
Television ads
Newspaper ads
Letters to prospective subjects
Radio ads
Oral Scripts
PowerPoint presentations
Internet ads / postings
Email
X
Other, please specify:
Phone conversation with PI
NA
Attach ALL recruitment information in its final form using the Attachments section of this IRB eProtocol
form.
See BRI IRB Recruitment Material Guidance.
8.
Subject Compensation and Costs:
a)
Will subjects or their health care providers be required to pay for any study related procedures or
products?
N
i.
If "Yes," explain.  Max out of pocket?  Are any funds available from the study if the subjects
insurance will not cover study-related procedures or products?
b)
Will subjects receive compensation in any manner for participation? If "Yes," complete the questions
below. If "No", skip to the next section.
N
i.
Will subjects receive monetary payment?  If yes, describe payment schedule including per visit
and total.

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ii.
Will any one payment be more than 40% of total compensation? If "Yes," explain and provide
rationale.
iii.
Will other forms of compensation be provided?   If yes, describe below.
Parking Voucher
Gifts
Transportation
Lodging
Gift card/certificate
Other (describe below)
---------------------------------------------------------------------------------------------
* * * Risks * * *
9.
Risks / Data Safety Oversight / Monitoring
(Click "Help" above for more information)
a)
PI's evaluation of the overall level of Risk. (Please check one: minimal, or greater than minimal.)  Minimal
risk:  The probability and magnitude of harm or discomfort anticipated in the research are not greater in and
of themselves than those ordinarily encountered in daily life, or during the performance of routine physical
or psychological examinations or tests.
X
Minimal risk
Greater than minimal risk
b)
Check all potential risks/side effects to subjects. Check only added potential risks/side effects that may
occur to subjects from the research and not those that would occur if subjects were to receive standard
treatment/procedures only. [Note: Virtually all research studies involve "breach of confidentiality" and
"invasion of privacy" as potential risks since several entities may have access to research records (e.g.,
FDA, NIH, IRB, etc.). Risks must be consistent with the consent form and protocol.]
Risk / Side Effects
Physical Harms
Psychological
Social Economical
Minor Pain
Depression
X
Breach of Confidentiality,
resulting in:
Discomfort
Confusion
X
Invasion of privacy
Serious Injury
Hallucination
Potential loss of employment or
insurability
Death
Stress
Potential criminal prosecution
Injury from invasive medical
procedure
Guilt
Harm from possible side effects
from drugs
Loss of self-esteem
None (only applicable if all data
is stripped of all identifiers and
not coded)
X
Rare allergic reaction to radiologic
contrast dye
Embarrassment
None
X
Possible anxiety or
claustrophobia during MRI exam
None
c)
Describe the procedures or safeguards in place to protect against or minimize potential risks (e.g., referral
to psychological counseling resources).
-Standard assessment of allergy or MRI-associated risk prior to MRI study

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-Standard care during phlebotomy
-Referral to psychological counseling if indicated
d)
Who will be monitoring the risks noted above to ensure the safety of subjects?
X
The Principal Investigator Describe your monitoring plan for reviewing interim results and/or safety
concerns during the study:
-Contact with the volunteer prior to obtaining the MRI
-Post-procedural contact (after MRI and blood draw) to ascertain any concerns
-Contact information of PI will be made available to the volunteers
A group representing the study sponsor State name of group and describe monitoring plan for
reviewing interim results and/or safety concerns during the study:
A Data Safety Monitoring Board (DSMB) State name of DSMB and describe procedures for
submitting summary reports from the DSMB to the IRB:
Other:
If multi-site trial, are DSMB report(s) available for research already conducted?If yes,
attach DSMB reports. (see clinical research glossary for "DSMB" clarification.  If you
think your study warrants DSMB oversight and you do not know of one to utilize,
please contact the IRB office.)
e)
Are there any stopping rules based on the risks noted above, or other study criteria?  If yes, describe
below and include study endpoints. (Click "Help" above for more information.)/
N
---------------------------------------------------------------------------------------------
* * * Benefits * * *
10.
Benefits(This section is not enabled for exempt or cooperative studies)/
a)
Are there any direct benefits to the research participants? Note: Direct benefit is a valued or desired
outcome; an advantage (please do not include monetary inducement or compensation).If yes, please
describe.
N
b)
Are there any anticipated benefits of this study to society, academic knowledge or both? If yes, please
describe.
Y
The results of this study should define the effectiveness of MRI and/or CPK / aldolase as diagnostic tools in future patients with
suspected local anesthetic-induced myotoxicity
c)
Explain how the potential benefits justify the potential risks involved in participation in this research.
For this previously unknown complication, new knowledge is critical for both understanding the proper diagnosis and for complication
management. We have tried other routes to understand the diagnostic paradigm, to no avail. The low risk and inconvenience of
postoperative MRI and CPK / aldolase studies will facilitate further knowledge related to this previously unknown complication.
---------------------------------------------------------------------------------------------
* * * Confidentiality * * *
11.
Confidentiality
a)
Which of the following types of data will be associated with this study.  Consider all aspects of the
study.(Click 'Help" above for more information)/

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X
Identifiable
Anonymous
X
De-identified
Coded
b)
Describe your protection method(s) in two or three sentences (e.g. coding system, limited access,
password protected, certificate of confidentiality, etc.).  Include safeguards to protect against direct or
indirect identification of subjects in any reporting of research results (e.g. publications):
-MRIs contain patient names and medical record numbers will be seen by the blinded radiologist
-CPK reports contain patient names and medical record numbers, but will be seen only by Dr. Neal and the patient's orthopedic team
-A password-protected spreadsheet housed on a VMMC password-protected computer will be used to link MRN to radiologist-
generated MRI standard reading and CPK levels
-MRNs will be removed from the spreadsheet prior to sharing with Dr. Steffel (at VA Puget Sound).
-Subject number, age, results of MRI and enzyme analysis, sex. No other identifiable information
c)
Other than study staff and BRI Regulatory & Compliance, what entities will have access to research records
and/or data that identify subjects (including coded data)?
NIH
Study Sponsor
Contracted monitor
FDA
Personal physician
X
None
Other:  (explain below)
d)
How will research data be recorded?
Case report forms
Remote data entry (e.g.
central database off site)
X
Local database (e.g. Excel spreadsheet)
REDCap database
Patient medical records
N/A
Other: (explain below)
e)
How will research records be stored locally?
X
VMMC/BRI server
X
Investigator's computer
Locked file cabinet
Locked office
N/A
Other: (explain below)
f)
How will specimens be stored?
Limited access refrigerator / freezer
Locked cabinet / office
X
N/A
Other: (explain below)
g)
After completion of this study, will you keep any data and/or specimens for future research purposes? N
if yes then answer the following questions:Describe why the information and/or specimens will be
retained (i.e., possible use for another research project[s], etc.).  Note:  Separate IRB applications must
be submitted for additional use of retained data and/or specimens outside the approved protocol:
Describe in two or three sentences how the confidentiality of the retained information and/or specimens
(whether directly identifiable or coded) will be maintained:

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h)
Indicate the length of time research records and/or specimens will be kept before EITHER all
identifiers/codes are removed OR the records and/or specimens are destroyed.  Describe the procedures
you will use.
Research records will be kept 1 year after publication of our results. After that, the spreadsheet will be turned over to BRI for
archiving.
---------------------------------------------------------------------------------------------
* * * Consent Information * * *
12.
Consent Information
 Consent Instructions and Checklist
Template Consent Forms and Guidance
a)
Click "Add" to enter information in the "Informed Consent" table below.  This includes translated consents
and waivers of consent.    Exempt Studies:  This table is disabled.  If a consent is used then attach in the
attachment section. Chart review:  If accessing medical charts without consent, a waiver of consent is
required. Oral Consent:  A waiver of signed consent is required. Subjects under 18 yrs old:  Go to the next
section. complete and attach assent information.   Enter information in the Informed Consent table
separately for each consent and/or waiver of consent.
Informed Consent Table
Title
Consent Type
Clean Consent - Vers. 04.09.18 - IRB18-008
Consent
IRB Stamped Approved Consent - Vers. 04.09.18 -
IRB18-008
Consent
Informed Consent Table
Title (e.g. main, screening, translated, oral,
information sheet, waiver request) *
Clean Consent - Vers. 04.09.18 - IRB18-008
Consent Information Type*
Consent
Consent Document*
X
Attachment
Clean Consent - Vers. 04.09.18 -
IRB18-008
Who will obtain subjects consent? (Check all that apply)
Principal Investigator
Co-Investigator
Study Coordinator
Research assistant(s)
Other research staff
Contracted Data Collection Firm
Other (please specify)
Informed Consent Table
Title (e.g. main, screening, translated, oral,
information sheet, waiver request) *
IRB Stamped Approved Consent - Vers. 04.09.18 - IRB18-008
Consent Information Type*
Consent
Consent Document*
X
Attachment
IRB Stamped Approved Consent -
Vers. 04.09.18 - IRB18-008

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Who will obtain subjects consent? (Check all that apply)
X
Principal Investigator
X
Co-Investigator
Study Coordinator
Research assistant(s)
Other research staff
Contracted Data Collection Firm
Other (please specify)
  If consenting human subjects answer the questions below.  If NOT consenting human subjects, leave blank and
skip to the next section.
b)
Describe the process used to consent all subjects on the study.
-Volunteer subjects will be identified in orthopedic office by Dr. Verdin or his staff
-Those interested in participating will be consented by Joseph M. Neal, MD at least 24 hours prior to their surgery. If possible, consent
will be obtained in person. If not possible, consent will be obtained via phone.
c)
Will subjects have as much time as they want between the explanation of the study and signing the
consent form?  If no, or N/A explain below.
Y
d)
If consent is being obtained from non-English speaking subjects, explain the translation process for all
documents seen by subjects, including consent documents. Describe the consent process in these
circumstances.
N/A
e)
Do you plan on having a Legally Authorized Representative (LAR) involved in the consent process?  If
yes, explain below and ensure the appropriate section is included in the consent form.
N
f)
Will you require an impartial third party witness be included in the consenting process?  If yes, explain
below and ensure the appropriate section is included in the consent form.
N
---------------------------------------------------------------------------------------------
* * * Assent Background * * *
13.
Assent Background  (Continue to the next section if no subjects under the age of 18 will be enrolled in this
study)
a)
Complete the "Assent" table below.   Attach assent documents and/or request assent waivers. Click "Help"
above for more information regarding assent and assent waiver.
You must check children (under 18) on the Subject Checklist section to activate this table.
b)
Complete the Regulatory Compliance worksheet below:
Regulatory Compliance - Subpart D - Children
Provide the specific age range for children (less than 18 years old) you wish to enroll in the study and what is

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your accrual goal:
Age Range:
Total Accrual
Goal:
Check the appropriate box below (only one) to indicate which category your study may be approved in light of 45
CFR 46 subpart D for research involving children.  Chlick on the links below for guidance.
Research not involving greater than minimal risk.  45 CFR 46.404
Research involving greater than minimal risk, but presenting the prospect of direct benefit to
the individual subjects. CFR 46.405
Research involving greater than minimal risk and no prospect of direct benefit to the individual
child subjects involved in the research, but likely to yield generalizable knowledge about the
subject's disorder or condition. 45 CFR 46.406
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
Will you be using an Assent Form?  (Required for subjects 7-11 years old per BRI IRB policies
- see 45 CFR 46.408 for reference)
Describe in the space below the details of your assent process for children in your study. (Include specific
approach(es) to subjects in various age ranges, how assent will be documented, who will be able to give
persimssion for each child (e.g. child's parent(s) or guardian), and how this permission will be recorded in the
file.)
Does your study involve an FDA regulated drug, device, or biologic? If yes, check the
appropriate box below (only one) to indicate which category your study may be approved in
light of 21 CFR 50 Subpart D for research involving children.  Click on the links below for
guidance.
Clinical investigations not involving greater than minimal risk 21 CFR 50.51
Clinical investigations involving greater than minimal risk, but presenting the prospect of direct
benefit to the individual subjects. 21 CFR 50.52
Clinical investigations involving greater than minimal risk and no prospect of direct benefit to
individual subjects.
Clinical investigations not otherwise approvable that present an opportunity to understand,
prevent, or alleviate a serious problem affecting the health or welfare of children.  21 CFR
50.53
Will you be using an Assent Form?  (Required for subjects 7-11 years old per BRI IRB policies
- see 45 CFR 46.408 for reference)
---------------------------------------------------------------------------------------------
* * * HIPAA * * *
14.
Health Insurance Portability and Accountability Act (HIPAA)
If you are using PHI and this page is not active you must return to the General
Checklist and check the box regarding the use of PHI in this research.
HIPAA Privacy Rule: Establishes the right of an individual to authorize a covered entity, such as health
plan, health care clearinghouse or health care provider, to use and disclose his/her Protected Health
Information (PHI) for research purposes.  The Privacy Rule defines the elements of individual
information that comprise PHI and establishes the conditions under which PHI may be used or disclosed
by covered entities for research purposes. It also includes provisions to allow an individual's PHI to be
disclosed or used in research without the person's authorization (i.e., IRB Waiver of HIPAA
Requirement Authorization).  For more information refer to the HIPAA Privacy Rule.

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Protected Health Information (PHI):Health information with one or more of the identifiers listed below.
For more information see the  NIH website.  Research which involves the use of de-identified data is
exempt from HIPAA requirements. In order to be de-identified data NONE of the subject identifiers listed
below can be collected, used, reviewed, recoded, accessed or disclosed.
For more information see the following:VM/BRI Protected Health Information Guidance Document
a)
How will you obtain approval to access PHI for this research?
X
HIPAA Authorization request from subject
X
Incorporated into consent form
Stand alone document
Waiver of Subject HIPAA Authorization (partial or complete)(complete question e. below)
Limited Data Set and Data Use Agreement
Other: (explain below)
c)
Will any non-VM/BRI personnel need access to PHI?  If yes, how and where will they access subject
PHI (e.g. on-site, remote via Cerner, etc.)?
N
d)
Review the following list and indicate if any of the information will be collected from any medical records for
the purpose of this research project.
Names
Social Security Numbers
Telephone Numbers
All geographic subdivisions smaller than a state, including street address, city, county, precinct, zip
code, and their equivalent geocodes, except for the initial three digits of a zip code, if according to the
current publicly available data from the Bureau of the Census;
i.
The geographic unit formed by combining all zip codes with the same three initial digits
contains more than 20,000 people; and
ii.
The initial three digits of a zip code for all such geographic units containing 20,000 or
fewer people is changed to 000.
All elements of dates (except year) for dates directly related to an individual, including birth date,
admission date, discharge date, date of death; and all ages over 89 and all elements of dates (including
year) indicative of such age, except that such ages and elements may be aggregated into a single
category of age 90 or older.
Fax Numbers
Electronic Mail Addresses (email)
X
Medical Record Numbers
i.
You must identify the data points being collected from MRN by attaching a separate data
collection sheet or listing them in the procedures section.
Health Plan Beneficiary Numbers
Account Numbers
Certificate/License Numbers
Vehicle Identifiers and Serial Numbers, including License Plate Numbers
Device Identifiers and Serial Numbers
Web Universal Resource Locations (URLs)
Internet Protocol (IP) Address Numbers
Biometric Identifiers, including Finger and Voice Prints

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Full Face Photographic Images and any Comparable Images
Any other unique identifying number, character, or code (note this does not mean the unique code
assigned by the Investigator(s) to code the research data)
e)
Are you requesting a HIPAA waiver?  (Required for any type of waiver of consent)If yes, answer the
following questions.  If no, proceed to the next section.
N
i.
Explain why the research cannot reasonably be conducted without the waiver of
authorization:
ii.
Explain why the research cannot reasonably be conducted without access to and use of
identifiable health information:
iii.
Describe the reasonable safeguards to protect idenifiable information from unauthorized use
or re-disclosure:
iv.
Describe the reasonable safeguards to protect against identification, directly or indirectly, any
patient in any report of the research:
v.
Describe the plan to destroy the identifiers at the earliest opportunity consistent with the
research.  If there is a health or research justification for retaining identifiers, or if law requires
you to keep such identifying information, please provide this information as well:
vi.
Provide written assurance that identifiable information will not be reused/disclosed to any
other person or entity, unless such use is required by law, for oversight of the research study,
or for other research permitted by law:
vii.
Explain why the research is of sufficient importance to outweigh the privacy intrusion:
viii.
Explain who the subject should contact to enforce patient rights, or to obtain an accounting of
the research disclosures (e.g. PI, sub-investigator, coordinator):
---------------------------------------------------------------------------------------------
* * * Drugs and Devices * * *
15.
Drugs and Devices
a)
Does this study involve a drug or device?  If YES, continue below.If NO, proceed to the next section.
Y
i)
Is the drug(s) or device(s) FDA approved?  If YES,  list drug / device name and explain in text
field below. (e.g. HDE, 510K, Compassionate Use, etc) If NO, click "add" and complete the
table below for each investigational drug(s) or device(s).
Y
MRI
(These tables are not activated unless a drug / device question is checked on the General
Checklist section)
b)
Briefly describe the drugs and devices listed above.  Include any relevant information that has not been

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described in the protocol summary or background sections.
MRI will be used to obtain thigh scans
---------------------------------------------------------------------------------------------
* * * Potential Conflict of Interest * * *
16.
Potential Conflict of Interest(This section is not enabled for exempt studies)/
a)
Y
Is there funding for this study?
b)
N If yes, are there any positive financial disclosures related to this study for any key personnel?
c)
N Regardless of funding, are there any positive positional disclosures related to this study for any key
personnel?
d)
Y
I attest that I have read the
'https://brinet.benaroyaresearch.org/center/Documents/VM%20Research%20Conflicts%20of%20Interes
t.pdf#search=research%20conflict'target='blank'VM Conflict of Interest Policy and agree to abide by its
terms. I will update this protocol when new or changes in conflict of interest arise, and I will comply with
any conflict management plan required by the Institutional Review Board (IRB) to manage, reduce, or
eliminate any actual or potential conflict of interest for the duration of the research.
If Yes to b) or c) above, complete the table and answer the questions below concerning the potential conflict of
interest.  If No, then proceed to the next section.
Minimizing Risks and Disclosure to Subjects
e)
N Have you disclosed any actual, potential or perceived conflicts of interest in the consent form? Research
Personnel are required to disclose all such conflicts to all research participants in the research consent
form.
f)
What steps, if any, have you taken or will you take to manage the conflict of interest and minimize the risks
associated with any actual, potential or perceived conflicts of interest arising out of this research?
---------------------------------------------------------------------------------------------
* * * Attachments * * *
16.
Attachments
Attach relevant documents here. These could include:
-
Collaborating Investigator's IRB approval and approved documents
-
Conflict of Interest information
-
Debriefing Script; Grant/Sub-contract
-
HIPAA Authorization Form from HIPAA-covered entity
-
Interview/Focus Group Questions
-
Investigator's Brochure
-
Letters of Agreement/Cooperation from organizations who will help with recruitment
-
Questionnaires/Surveys
-
Radiation Control Office approval material
-
Recruitment Material (e.g., flyers, email text, verbal scripts)
-
Protocol
-
Patient Card
-
Other files associated with the protocol (you can upload most standard file formats: xls, pdf, jpg, tif,

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etc.)
Please be sure to attach all documents associated with your protocol. Failure to attach the necessary files may
result in this protocol being returned prior to review.
To update or revise any attachments, please delete the existing attachment and upload the revised document to
replace it.
Select from list
Attachment Name
Attached Date
Submitted Date
Data Collection Sheet
IRB18-008 Copy of Study
Data Sheet
03/08/2018
Other
IRB18-008 Neal Financial
Disclosure
03/08/2018
Data Collection Sheet
IRB18-008 Copy of MRI
Data Sheet
03/08/2018
Protocol
Clean Protocol - Vers.
04.09.18 - IRB18-008
04/13/2018
04/13/2018
---------------------------------------------------------------------------------------------
* * * Obligations * * *
Note:  The use of "I" below refers to the Principal Investigator (PI).  If someone other than the PI is completing
and submitting this application, that person is responsible to make sure the PI is aware of their obligation and
assurances cited below.  The PI is ultimately responsible for all conduct under this study and answers provided in
this IRB submission.
Research Obligations of the Principal Investigator Include the Following:
 Training - ALL key personnel, including any newly added personnel, must meet all IRB required training requirements (e.g. CITI Ethics, GCP,
Conflict of Interest).  Training refreshers must be completed at the appropriate intervals (i.e. every three (3) or four (4) years).
 Study Modifications - Changes to any aspect of the study (e.g. protocol, consent/assent forms, advertising materials, additional key
personnel, subject population, etc.) will be submitted to the IRB for approval before instituting the changes.
Final Report - The IRB will be notified when the study is complete, and must be closed out in eProtocol prior to expiration of the approval.
Investigator's Statement and Assurance of Confidentiality:
I certify that I have reviewed this application, including attachments, and all information contained herein is accurate to the best of my
knowledge.
I agree to not enroll any subject(s) or collect any data intended only for research use prior to issuance of an IRB approval.
I understand that I am fully responsible for the execution and management of this study, and I am responsible for the performance of any sub-
investigators or key personnel, including their adherence to all of the applicable policies and regulations.
I agree to report any substantive changes to the information contained in this application, unanticipated problems, or adverse events
encountered during the project immediately to the IRB.
I will ensure the names of any human subjects or any identifiable data from human subjects shall be treated as confidential information.  This
information will not be disclosed to anyone other than those directly connected with the research project unless the patient has given prior
approval in writing.
If this is a funded project, I certify that the funding source document is entirely consistent with the corresponding study protocol.
I certify I have not been barred from doing research by any regulatory agency or entity.  If I am a physician (or other licensed health care
professional), I certify that my medical (or other) license is current.
I further agree any failure to perform the undertaking specified above shall be good cause for termination of the research project.
When Closing Your Protocol:
I understand when I close this protocol with the IRB NO further data collection, follow-up with subjects, coding of data, data analysis, and
manuscript preparation that requires personal identifiable information (e.g. PHI) may be conducted.
I agree to retain all research materials for at least 10 years after closure of the research project and acknowledge these documents may be
subject to review by the Clinical Research Program and IRB, if deemed necessary.

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I further certify I will not take any PHI and/or specimens generated from this research with me if I leave BRI/VM, unless having first
established an agreement with VM legal in advance of my departure.
I confirm this study will not begin until the investigator receives written final approval or determination of exemption.
X
The Principal Investigator has read and agrees to abide by the above obligations.
 Continuing Review - You are responsible to complete and submit a Continuing Review form at least 30 days prior to the date of expiration.
You will be asked to note accomplishments of your project at that time.
 Protocol Deviations/Violations, Adverse Events (AEs)  that occur in the course of the protocol will need to be submitted in a prompt manner
from when they occurred.
X
The Principal Investigator has read and agrees to abide by the above obligations.
Please click "next" to continue to protocol Check for Completeness.  If the protocol is complete and ready for
submission, please click "Submit Form" to your left to submit your protocol for IRB Review.
---------------------------------------------------------------------------------------------
* * * Event History * * *
Event History
Date
Status
View Attachments
Letters
05/07/2020
CLOSED
05/07/2020
FINAL FORM
APPROVED
Y
N
04/27/2020
PROTOCOL EXPIRED
04/24/2020
CONTINUING REVIEW 1
FORM Fox, Ellie added in
CONTINUING REVIEW
04/23/2020
FINAL FORM
REVIEWER(S)
ASSIGNED
04/22/2020
FINAL FORM
SUBMITTED
Y
04/22/2020
FINAL FORM CREATED
05/30/2019
CONTINUING REVIEW 1
FORM Stevens, Leslie
added in CONTINUING
REVIEW
05/30/2019
CONTINUING REVIEW 1
FORM Chan, Christine
added in CONTINUING
REVIEW
04/25/2019
CONTINUING REVIEW 1
FORM APPROVED
Y
Y
04/22/2019
CONTINUING REVIEW 1
FORM REVIEWER(S)
ASSIGNED
04/19/2019
CONTINUING REVIEW 1
FORM PANEL
MANAGER REVIEW
04/19/2019
CONTINUING REVIEW 1
FORM SUBMITTED
Y

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04/19/2019
CONTINUING REVIEW 1
FORM CREATED
03/27/2019
REPORT 1 FORM
WITHDRAWN
03/27/2019
REPORT 1 FORM
PANEL MANAGER
REVIEW
03/22/2019
REPORT 1 FORM
SUBMITTED
Y
03/13/2019
AMENDMENT 3 FORM
APPROVED
Y
Y
03/01/2019
SAE REPORT 1 FORM
APPROVED
Y
N
03/01/2019
AMENDMENT 3 FORM
REVIEWER(S)
ASSIGNED
03/01/2019
SAE REPORT 1 FORM
REVIEWER(S)
ASSIGNED
03/01/2019
AMENDMENT 3 FORM
PANEL MANAGER
REVIEW
03/01/2019
REPORT 1 FORM
CREATED
03/01/2019
SAE REPORT 1 FORM
SUBMITTED
Y
03/01/2019
SAE REPORT 1 FORM
CREATED
02/06/2019
AMENDMENT 3 FORM
SUBMITTED
Y
02/06/2019
AMENDMENT 3 FORM
CREATED
05/31/2018
AMENDMENT 2 FORM
APPROVED
Y
Y
05/30/2018
AMENDMENT 2 FORM
REVIEWER(S)
ASSIGNED
05/29/2018
AMENDMENT 2 FORM
SUBMITTED
Y
05/29/2018
AMENDMENT 2 FORM
CREATED
05/24/2018
AMENDMENT 1 FORM
APPROVED
Y
Y
05/23/2018
AMENDMENT 1 FORM
REVIEWER(S)
ASSIGNED
05/22/2018
AMENDMENT 1 FORM
SUBMITTED
Y
05/17/2018
AMENDMENT 1 FORM
CREATED
04/30/2018
NEW FORM APPROVED
Y
Y

Page 25 of 25
 
25
IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: March 23, 2021
---------------------------------------------------------------------------------------------------------
04/30/2018
NEW FORM UNDO
APPROVED
04/30/2018
NEW FORM APPROVED
Y
Y
04/17/2018
NEW FORM
REVIEWER(S)
ASSIGNED
04/13/2018
NEW FORM
REVIEWER(S)
ASSIGNED
04/12/2018
NEW FORM PANEL
MANAGER REVIEW
03/08/2018
NEW FORM PANEL
ASSIGNED
03/08/2018
NEW FORM
SUBMITTED
Y
01/26/2018
NEW FORM CREATED

 
NOTICE OF IRB EXEMPTION
04/30/2018
Joseph Neal, MD
Anesthesiology
RE: IRB# IRB18-008 (NEW)
Study Title: Defining Normal Postoperative Magnetic Resonance Imaging after Total Knee Arthroplasty
Dear Joseph Neal, MD,
Thank you for submitting the above referenced study for review by the Benaroya Research Institute at Virginia
Mason Institutional Review Board (BRI IRB). Review was carried out in light of federal regulations on human
subjects and BRI IRB policies.
I am pleased to inform you the IRB Chair has determined your project presents no more than minimal risk to
human subjects and qualifies for a Certificate of Exemption under 45 CFR 46.101 (b), paragraph 2, 4, 5. In
accordance with BRI IRB policies, your exemption has been granted and is valid for five years from 04/27/2018
to 04/26/2019.
During the course of the study, if there are changes in the protocol that would alter this determination (e.g.
increased risk, additional non-exempt activity), including protocol termination, or if human subjects involved in
the study are subjected to unanticipated problems, please report these immediately to BRI IRB. Please include
the Protocol ID Number (IRB18-008) on all correspondence.
If your study received initial Feasibility Review, no study activity may occur until you receive a Clinical
Research Program letter to commence from the BRI Administrative Director of Clinical Research, Cheryl
Weaver. Her phone number is (206) 342-6911.
Please contact the Research Protections Department at irb@benaroyaresearch.org if you have any question
regarding your approval or the eProtocol system. Thank you.
Sincerely,
Bredfeldt, James, MD
IRB Chair
Items included with this submission are listed below under attachments:
Attachments
Clean Protocol - Vers. 04.09.18 - IRB18-008
Notes:
Additional approved documents: IRB Stamped Approved Consent - Vers. 04.09.18 - IRB18-008

Page 1 of 3
 
1
IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: March 01, 2019
Protocol Title:
Defining Normal Postoperative Magnetic Resonance Imaging after Total
Knee Arthroplasty
Date Submitted:
Draft
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval.
Please check the comments section of the online protocol.
Questions that appear to not have been answered may not have been required
for this submission. Please see the system application for more details.
-------------------------------------------------------------------------------------
* * * Adverse Event Report Form * * *
ADVERSE EVENT REPORT FORM
1.
Is this adverse event unexpected (in terms of nature, severity, or frequency) given (a) the research
procedures described in the protocol-related documents, such as the IRB-approved research protocol
and informed consent document, or the Investigator Brochure; and (b) the characteristics of the subject
population being studied?
Y
2.
Is this adverse event related or possibly related to participation in the research (possibly related means
there is a reasonable possibility the incident, experience, or outcome may have been caused by the
drugs, devices or procedures involved in the research)?
Y
3.
Does this adverse event suggest the research places subjects or others at a greater risk of harm
(including physical, psychological, economic, or social harm) than was previously known or recognized?
Y
(Note: "off-site" reports will not be accepted unless; (a) the event described is both serious and unexpected,(b)
the report identifies all previous safety reports concerning similar adverse experiences,(c) the report analyzes the
significance of the current adverse experience in light of the previous reports, and (d) the report outlines a
corrective action plan.  21_CFR_312.32)
If you answered "NO" to any of the above questions STOP.  You do not need to submit this event/report to the
IRB unless all three above criteria are met.
4.
What type of report is this?
X
Initial Report
Date of Initial Report:
03/01/2019
Follow up #
Follow up complete
Drug
Device
N/A [Name of test article(s)]:
5.
Describe in detail the Adverse Event you are reporting (e.g. Confusion, Vomiting, Hyponatremia, etc.):
Catheters used for continuous adductor canal block contain wire. According to the manufacturer's published information, these
catheters are deemed "MRI Conditional", with low to no risk from heating during an MRI scan.
Our first subject had their MRI on February 22, 2019 and reported a mild sensation of heating at the catheter site. The MRI was
aborted. The patient reported no harm.
Dr. Neal became aware of this issue on February 25, 2019. After consultation with Drs. Blackmore, Strodtbeck, Warren, and
Macdonald, it was agreed that the adductor canal catheter will be removed in subsequent patient volunteers that are recruited for this
study.
6.
Event Start date:
02/22/2019
7.
Date of Death (if applicable):
8.
Participant Study Identifier:
Number 6
9.
Why do you consider this event unexpected?
The manufacturer does not report significant heating to be an issue with these catheters. Furthermore, these catheters have indeed
been in place in some patients who underwent uneventful MRI studies at Virginia Mason.

Page 2 of 3
 
2
IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: March 01, 2019
---------------------------------------------------------------------------------------------------------
10.
Relationship to research:
Definite
Probable
Possible (possibly related means there is a reasonable probability that the incident, experience, or
outcome may have been caused by the drugs, devices or procedures involved in the research.)
11.
Why do you consider this event related or possibly related to participation in the research?
Warming at the catheter site is consistent with MRI effects on metallic objects
12.
What changes do you propose to the consent form and/or the protocol in order to protect the rights, welfare
and safety of the research subjects?  If none are proposed, provide the rationale for why changes are not
needed?
Future subjects will have the adductor canal catheter removed prior to entering the MRI suite
13.
Where did the unanticipated Adverse Event occur? (i.e. on site or off site) If "ON SITE" (e.g. occurred to
VM/BRI subject) where did the AE occur? (e.g. VM, BRI, at home etc.):
VMMC 5th floor MRI scanner
14)
Choose an adverse event category:
Death
Life-Threatening
Disability
Hospitalization
Congenital
Anomaly
X
Required
intervention to
prevent damage /
impairment
Medically
Important Event
Other: (explain below)
Because the patient reported heating, the MRI was terminated. The heating immediately dissipated and the patient reported no further harm.
15)
Date the PI/study staff became aware of this event:
2/25/19
16)
Description of event:
As noted above
17)
Has this event been reported to all appropriate agencies as defined in the protocol, grant, contract, or
clinical trial agreement?  Check all that apply and provide date reported:
Sponsor:
N/A
Date Notified:
FDA (if BRI/VM PI holds the IND/IDE):
N/A
Date Notified:
Coordinating Center:
N/A
Date Notified:
18)
Has this type of event been reported previously to the BRI IRB?  If yes, explain.
N
I am unaware of any previous reports
19)
Do you consider the frequency higher than expected?  If yes, explain.
Y
The event was unexpected based on previous experience and manufacturer report. What is unclear is the precise intensity of the
heating reported by the patient. It is possible that other patients have experienced similar sensations, but have not reported them.
20)
Is this study closed to new accrual at VM (and its affiliated sites)?
N

Page 3 of 3
 
3
IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: March 01, 2019
---------------------------------------------------------------------------------------------------------
i.
If yes, is at least one (1) participant at VM (and/or its affiliated sites) still receiving study
treatment/intervention?
21)
Is your intent to modify the consent and/or protocol based on this event?  if "yes" you will need to also
complete an amendment form and attach the revised protocol and/or consent form with all changes
underlined?
Y
---------------------------------------------------------------------------------------------

 
IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: May 29, 2018
Amendment
1
Personnel Information
2
Subject Checklist
5
Study Location
5
General Checklist
6
Funding
7
Application Type Checklist
8
Expedited Paragraphs
8
Summary, Purpose, Procedures
10
Background and additional procedures
11
Subject Population
12
Recruitment Process, Subject Compensation and Costs
13
Risks
15
Benefits
16
Confidentiality
16
Consent Information
18
Assent Background
20
HIPAA
21
Drugs and Devices
23
Potential Conflict of Interest
23

 
IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: May 29, 2018
Attachments
24
Obligations
25
Event History
26

Page 1 of 26
 
1
IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: May 29, 2018
Protocol Title:
Defining Normal Postoperative Magnetic Resonance Imaging after Total
Knee Arthroplasty
Date Submitted:
05/29/2018
Approval Period:
Draft
Important Note:
This Print View may not reflect all comments and contingencies for approval.
Please check the comments section of the online protocol.
Questions that appear to not have been answered may not have been required
for this submission. Please see the system application for more details.
-------------------------------------------------------------------------------------
* * * Amendment * * *
Protocol Amendment 1) Complete the questions below.2) Update your approved protocol including any
attachments.3) Electronically "sign" your application by clicking the check box in the Obligations section.4)
Remember to click "Submit Form" so the IRB staff will receive your request.5) For Cooperative studies
(see help above).  Answer all questions below from BRI/VM specific perspective.
1.
Does this amendment change the status of your study?If yes, check one of the boxes below and
complete the table.  If no, continue to question 2.
N
Study Status Change
Temporary Closure to Accrual
Date Effective:
Reason:
Permanent Closure to Accrual, Study
Particpation/Intervention Continues
Date Effective:
How many subjects were ever enrolled at
this site?
How many subjects are still on treatment at
this site?
How many subjects (total of all sites) were
enrolled in this study (if applicable and
know)?
Permanent Closure to Accural, Only Long-
Term Follow-Up and/or Data
Collection/Analysis Continues (no active
participation/intervention continues)
Date Effective:
How many subjects were ever enrolled at
this site?
How many subjects (total of all sites) were
enrolled in this study (if applicable and
know)?
2.
Describe all changes being proposed  including any modifications to the attached documents.  (If
referencing attachments cite page numbers)
1. Inclusion of stipend for participants
2. Modification of obtaining MRI and discharge lab work either the afternoon of Day 1 or the morning of Day 2
3.
Will the requested modifications change the scope or research objectives (e.g. change in specific aims,
change from previously approved use of human subjects, etc.)?   If yes, describe below.
N
4.
Are any NEW potentially vulnerable subjects being added as targeted or possibly included in this study
(e.g. children, pregnant women, illiterate, etc.) ?
N
If yes, define your new study population and provide steps to protect the population. (Update the assent
section if children are being added.)

Page 2 of 26
 
2
IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: May 29, 2018
---------------------------------------------------------------------------------------------------------
5.
Were changes made to the Consent Form? (If no consent, or no changes check "No" and proceed to
question 6)
Y
If yes, describe changes below and provide justification regarding your plan to re-consent subjects.  Then,
check the appropriate box(es) below.  Once this modification is approved, the IRB will hold the researcher
responsible to "re-consent" all subjects as indicated.
Inclusion of stipend and modification of MRI timing
Re-consent not required
X
Consent all new subjects with modified consent form(s)
Re-consent active participants at next visit
Re-consent all subjects including those who have completed the study
Other:  (explain)
6.
Indicate level of risk involved with the changes proposed.
(If level of risk has changed, update the "Risk" section in the protocol.)
Increase
X
No Change
Decreased
7.
If this study was originally reviewed Expedited, do you attest this project continues to present no more
than minimal risk of harm to subjects? See the Help section for more information.
Y
If no, your study may be reviewed by the Full Board IRB.
 Approval Includes
List of sections (and questions) that have been changed/modified
---------------------------------------------------------------------------------------------
* * * Personnel Information * * *
Click "Help" (upper right corner of screen) for guidance regarding who to include below (Key Personnel) and what
CITI Training is needed.  See the Clinical Research Glossary for definitions.  Questions:  Contact the Research
Protections Department
Principal Investigator
Client defines "Investigator" as an individual who conducts a research study. If the study is conducted by a team
of individuals, the Investigator is the responsible leader of the team.
Name of Principal Investigator*
Degree (MD/PhD/BSN/etc.)
Title
Neal, Joseph
MD
ANESTHESIOLOGIST
Email*
Phone
Fax
Joseph.Neal@virginiamason.org
206-223-6980
VM/BRI Department
Investigator Affiliation Check ALL
that apply*
Mailstop
Anesthesiology
X
VM personnel
B2-AN
BRI personnel
Zip code
Other
98101
Training Details

Page 3 of 26
 
3
IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: May 29, 2018
---------------------------------------------------------------------------------------------------------
No training data is available.
Sub-Investigator(s)
Sub-Investigator
Degree
(MD/PhD/BSN/etc.)
Title
Research Department
Blackmore, Craig
MD
RADIOLOGIST
Radiology MD Admin
Verdin, Peter
MD
ORTHOPEDIC
SURGEON
Orthopedics - Outpatient
Jackson, Dane
MD
RESIDENT -
RADIOLOGY
Graduate Medical
Education
Sub-Investigator(s)
Name of Sub-Investigator(s)
Degree (MD/PhD/BSN/etc.)
Title
Blackmore, Craig
MD
RADIOLOGIST
Email*
Phone
Fax
Craig.Blackmore@virginiamason.org
206-223-6851
VM/BRI Department
Investigator Affiliation Check ALL
that apply*
Mailstop
Radiology MD Admin
X
VM personnel
R3-324
BRI personnel
Zip code
Other
98101
Role in Study
Radiologist
Training Details
No training data is available.
Sub-Investigator(s)
Name of Sub-Investigator(s)
Degree (MD/PhD/BSN/etc.)
Title
Verdin, Peter
MD
ORTHOPEDIC SURGEON
Email*
Phone
Fax
Peter.Verdin@virginiamason.org
206-223-7530
X6-ORT
VM/BRI Department
Investigator Affiliation Check ALL
that apply*
Mailstop
Orthopedics - Outpatient
X
VM personnel
BRI personnel
Zip code
Other
98101
Role in Study
Training Details
Course
UserID
CourseCompletionDate
CourseExpirationDate
CITI Good Clinical
Practice
peter.verdin
11/14/2016 3:34:28 PM
11/14/2019 3:34:28 PM
Human Research
peter.verdin
11/8/2015 4:18:51 PM
11/7/2018 9:00:00 PM
Sub-Investigator(s)
Name of Sub-Investigator(s)
Degree (MD/PhD/BSN/etc.)
Title
Jackson, Dane
MD
RESIDENT - RADIOLOGY

Page 4 of 26
 
4
IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: May 29, 2018
---------------------------------------------------------------------------------------------------------
Email*
Phone
Fax
Dane.Jackson@virginiamason.org
206-583-6079
VM/BRI Department
Investigator Affiliation Check ALL
that apply*
Mailstop
Graduate Medical Education
X
VM personnel
BRI personnel
Zip code
Other
Role in Study
Masked assessment of MRI results
Training Details
Course
UserID
CourseCompletionDate
CourseExpirationDate
CITI Good Clinical
Practice
dane.jackson
10/21/2017 3:19:35 PM
10/20/2020 3:19:35 PM
Human Research
dane.jackson
10/20/2017 2:09:36 PM
10/19/2020 2:09:36 PM
Study Coordinator
Study Coordinator
Degree
(MD/PhD/BSN/etc.)
Title
Research Department
Neal, Joseph
MD
ANESTHESIOLOGIST
Anesthesiology
Study Coordinator
Name of Study Coordinator
Degree (MD/PhD/BSN/etc.)
Title
Neal, Joseph
MD
ANESTHESIOLOGIST
Email*
Phone
Fax
Joseph.Neal@virginiamason.org
206-223-8822
VM/BRI Department
Investigator AffiliationCheck ALL
that apply*
Mailstop
Anesthesiology
X
VM personnel
B2-AN
BRI personnel
Zip code
Other
98101
Training Details
No training data is available.
Regulatory Contact (Primary IRB contact if not PI or Study Coordinator)
Name of Regulatory Contact
Degree (MD/PhD/BSN/etc.)
Title
Email*
Phone
Fax
VM/BRI Department
Investigator Affiliation Check ALL
that apply*
Mailstop
VM personnel
BRI personnel
Zip code

Page 5 of 26
 
5
IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: May 29, 2018
---------------------------------------------------------------------------------------------------------
Other
Training Details
No training data is available.
Additional Personnel Information: (Use the area below if necessary to provide additional information
regarding the personnel on this protocol)
Dr. Lauren Steffel, Puget Sound VA Health Services, will participate in manuscript writing and data analysis. She will have no contact
with Virginia Mason subjects. The data that she will have access to will be de-identified with regard to subject PHI.
---------------------------------------------------------------------------------------------
* * * Subject Checklist * * *
Subject Checklist
Select all that apply:
Retrospective medical records   (e.g. Chart Review)
Tissue, blood, other specimens (e.g. repository)
X
Individuals with underlying medical conditions
X
Healthy individuals
Select all vulnerable groups:
Check all targeted or possibly included subjects.  This also applies to retrospective chart reviews.
Some groups (e.g. prisoners, pregnant women, or children) may require additional IRB oversight per
federal regulations.
Prisoners
45CFR46 Subpart C (Should be excluded unless you know subject(s) will be "in prison" at the time of
enrollment.  Notify IRB immediately if a subject becomes incarcerated after enrollment.  This population
can not be reviewed exempt.)
Pregnant women
45CFR46 Subpart B
Females of childbearing potential
Children (under 18)
45CFR46 Subpart D
Persons incompetent to give consent (e.g., dementia, comatose, have legally authorized representative)
Economically/educationally disadvantaged.
Illiterate
Non-English speaking
See:  VM Interpreter Services
Are any other subjects outside of the above targeted or possibly included in this study?
N
If yes, describe below:
---------------------------------------------------------------------------------------------

Page 6 of 26
 
6
IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: May 29, 2018
---------------------------------------------------------------------------------------------------------
* * * Study Location * * *
Study Location
1.
Click "add" and create a separate row in the table below for each unique VM / BRI study location.
VM/BRI  Table
VM Location
Other VM Location:
VM location Study
Activities
Other Activities
Main Campus Seattle -
Clinic / Hospital
Blood draw, Informed
consent discussion,
Ongoing study visits,
Screening visits, Specific
procedures associated
with the study
VM/BRI  Table
Location
Main Campus Seattle - Clinic / Hospital
Activity
Blood draw,Informed consent discussion,Ongoing study visits,Screening
visits,Specific procedures associated with the study
2)
Are there any locations outside of VM / BRI that are involved in any way with this study?  If yes, explain
below.  If no, proceed to the next section.
N
i.
Are any outside locations "engaged"with this research study?  If yes, explain: (click on "Help" for
more information regarding engagement)
N
ii.
Will the BRI IRB be responsible for oversight (IRB of Record) for any study procedures
conducted at outside locations? If yes, describe in the table below (click "add"). If no, confirm
who is the IRB of Record for engaged activities outside of VM in the space below and then
proceed to the next section.
N
---------------------------------------------------------------------------------------------
* * * General Checklist * * *
General Checklist
Select All That Apply:  At least 1 box must be checked to proceed.  If none are applicable contact the IRB at
IRB@benaroyaresearch.org  Use the attachment section to add separate documents or forms.
X
Protected Health Information (PHI) will be viewed, created, accessed, used, or disclosed by VM/BRI
personnel or others.  (Checking this box activates the HIPAA section)
Questionnaire/Survey
Tissues or data to be stored for future research projects (e.g. registry or repository)
Tissues or data to be sent out of VM / BRI as part of a research agreement - Material Transfer Agreement

Page 7 of 26
 
7
IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: May 29, 2018
---------------------------------------------------------------------------------------------------------
(MTA)- Data Use Agreement (DUA)
X
FDA regulated device (Investigational or otherwise)- This includes Humanitarian Use Devices (HUD)
FDA regulated drugs, reagents, or chemicals (Investigational or otherwise)
This study is or will be posted on ClinicalTrials.gov
If checked, specify number:
Radioisotopes/radiation-producing machines, even if standard of care (Radiation Safety)
VM/BRI Institutional Biosafety Committee (IBC) Review Required- Clinical research involving recombinant
and/or synthetic nucleic acid
Request to Rely on Another IRB - Please upload completed Request to Rely and associated documents in
attachment section (This applies for Cooperative Review studies.)
IRB Authorization Agreement (IAA), Memorandum Of Understanding (MOU), etc.(attach in the
Attachments section (This only applies to studies where the Client IRB is the "Reviewing" IRB).
X
A stand-alone protocol already exists.
Checking this box doesn't reduce the number of questions you need to answer.  However, you can be
brief with your answers and include references to the stand-alone protocol (e.g. section, page #) for
more information.  Use the attachment section  to include the stand-alone protocol with your
submission.
---------------------------------------------------------------------------------------------
* * * Funding * * *
Funding / Resources
1)
Is there funding or other resources required for this project?
Y
No means absolutely no internal or external funds, services, skills, or products (e.g., statistical services, database
warehousing, free test article) are provided.  If no, proceed to the next section.
If yes, Click "add" and create a separate row in the table below for each unique funding source.
Funding / Resources Table
Funding
Name
BRI Funding
#
Restricted
BRI Funds
Unrestricted
BRI Funds
Federal
Grant
Federal
Funding #,
Grant #
Non-Profit
Foundation
Industry
Funding
Washington
State
Society of
Anesthesiol
ogists
Seafair
Grant
Award
Through VM
Foundation
N
N
N
Y
N
Funding / Resources Table
Name of Funding Entity
Washington State Society of Anesthesiologists Seafair Grant
Award
BRI Funding Number
Through VM Foundation
BRI restricted funds?
N

Page 8 of 26
 
8
IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: May 29, 2018
---------------------------------------------------------------------------------------------------------
BRI unrestricted funds?
N
Federal Grant funds?
N
Non-Profit Foundation?
Y
Industry Funding
N
---------------------------------------------------------------------------------------------
* * * Application Type Checklist * * *
Please check one of the boxes below to determine how to move forward with your project. The US Office of
Human Research Protections (OHRP) has created graphic aids to help with deciding if your research requires
IRB oversight.  In addition, please contact the BRI Research Protections Department with questions.
Application type checklist
Not Human Subjects Research (This form is not currently available through eProtocol.  Please click
"https://www.benaroyaresearch.org/sites/default/files/Human%20Subjects%20Determination%20Form.doc"
target=_blankhere if applicable.)
Exempt
X
Expedited/Full Board (This includes Cooperative and Chart Reviews.)
Indicate what level of review you anticipate for this protocol:
Full Board (greater than minimal risk)
X
Expedited (minimal risk)
 "https://www.benaroyaresearch.org/our-research/clinical-research/for-investigators/starting-
study/cooperative-trials" target=_blankCooperative (approval by another IRB of record, regardless of
risk level)
---------------------------------------------------------------------------------------------
* * * Expedited Paragraphs * * *
EXPEDITED REVIEW CATEGORIES If this is a FULL BOARD study, or COOPERATIVE (IRB of Record is not
BRI), then proceed to next section.
For expedited review all aspects of the research must be: (1) Minimal Risk (2) Involve one or more categories
listed below.  Select all that apply (Click Help for more information):
1.
Clinical studies of drugs and medical devices only when condition (a) and (b) are met.
a)
Research on drugs for which an investigational new drug application (21 CFR Part 312) is not
required. (Note: Research on marketed drugs that significantly increases the risks or decreases
the acceptability of the risks associated with the use of the product is not eligible for expedited
review.)
b)
Research on medical devices for which
i)
An investigational device exemption application (21 CFR Part 812) is not required; or
ii)
The medical device is cleared/approved for marketing and the medical device is being used
in accordance with its cleared/approved labeling.
X
2.
Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:
a)
From healthy, non-pregnant adults who weigh at least 110 pounds. For these subjects, the
amounts drawn may not exceed 550 ml in an 8 week period and collection may not occur more
frequently than 2 times per week; or
b)
From other adults and children, considering the age, weight, and health of the subjects, the

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IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: May 29, 2018
---------------------------------------------------------------------------------------------------------
collection procedure, the amount of blood to be collected, and the frequency with which it will be
collected. For these subjects, the amount drawn may not exceed the lesser of 50 ml or 3 ml per
kg in an 8 week period and collection may not occur more frequently than 2 times per week.
3.
Prospective collection of biological specimens for research purposes by non-invasive means.
Examples:
a)
Hair and nail clippings in a non-disfiguring manner.
b)
Deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction.
c)
Permanent teeth if routine patient care indicates a need for extraction.
d)
Excreta and external secretions (including sweat).
e)
Uncannulated saliva collected either in an unstimulated fashion or stimulated by chewing
gumbase or wax or by applying a dilute citric solution to the tongue.
f)
Placenta removed at delivery.
g)
Amniotic fluid obtained at the time of rupture of the membrane prior to or during labor.
h)
Supra- and subgingival dental plaque and calculus, provided the collection procedure is not
more invasive than routine prophylactic scaling of the teeth and the process is accomplished in
accordance with accepted prophylactic techniques.
i)
Mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings.
j)
Sputum collected after saline mist nebulization.
X
4.
Collection of data through non-invasive procedures (not involving general anesthesia or sedation)
routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. Where
medical devices are employed, they must be cleared/approved for marketing. (Studies intended to
evaluate the safety and effectiveness of the medical device are not generally eligible for expedited
review, including studies of cleared medical devices for new indications.)
Examples:
a)
Physical sensors that are applied either to the surface of the body or at a distance and do not
involve input of significant amounts of energy into the subject or an invasion of the subject's
privacy.
b)
Weighing or testing sensory acuity.
c)
Magnetic resonance imaging.
d)
Electrocardiography, electroencephalography, thermography, detection of naturally occurring
radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow,
and echocardiography.
e)
Moderate exercise, muscular strength testing, body composition assessment, and flexibility
testing where appropriate given the age, weight, and health of the individual.
X
5.
Research involving materials (data, documents, records, or specimen) that have been collected, or will
be collected solely for non-research purposes (such as medical treatment or diagnosis). (NOTE: Some
research in this paragraph may be exempt from the HHS regulations for the protection of human
subjects. 45 CFR 46.101(b)(4). This listing refers only to research that is not exempt.)
6.
Collection of data from voice, video, digital, or image recordings made for research purposes.
7.
Research on individual or group characteristics or behavior (including, but not limited to, research on
perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and
social behavior) or research employing survey, interview, oral history, focus group, program evaluation,
human factors evaluation, or quality assurance methodologies. (NOTE: Some research in this category

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may be exempt from the HHS regulations for the protection of human subjects - 45 CFR 46.101(b)(2)
and (b)(3). This listing refers only to research that is not exempt.)
---------------------------------------------------------------------------------------------
* * * Summary, Purpose, Procedures * * *
 BRI Study ID Number - From the Clinical Research Program (e.g.
CRP170XX)
CRP18023
Unit / Department -  Administrative Oversight of Research
Protocol Title
Defining Normal Postoperative Magnetic Resonance Imaging after Total Knee Arthroplasty
1.
Summary
Provide a summary of the scope of work of this protocol.
Recent reports(1) describe sentinel cases of presumed local anesthetic-induced myotoxicity occurring after continuous adductor
canal blocks (CACB) that were placed to provide analgesia after total knee arthroplasty (TKA). Crucial to the diagnosis, management,
and eventual understanding of this newly described anesthetic complication is elucidating what constitutes normal postoperative
magnetic resonance imaging (MRI) after TKA. A recent retrospective review of MRIs obtained for various indications within a week of
TKA failed to identify a consistent pattern of MR findings that might have defined "normal MRI imaging" after TKA (BRI 16092,
Magnetic Resonance Imaging of the Quadriceps Muscle After Total Knee Arthroplasty). The logical next step in this investigation
would be to obtain MRIs in TKR patients just prior to hospital discharge after an otherwise normal postoperative course.
2.
Purpose
Describe the purpose for the proposed project as well as the hypotheses/research questions to be
examined.
This study aims to define normal quadriceps imaging in 20 asymptomatic volunteers one to two days after undergoing TKA. A
secondary aim is to investigate alterations in creatine phosphokinase (CPK) and aldolase levels coincident with TKA. The aim of this
observational study is to define what constitutes a normal MRI appearance and normal CPK / aldolase alterations in postoperative
TKA patients. This knowledge is crucial for proper diagnosis and further understanding of this sentinel complication.
3.
Procedures
a)
Describe the activities/procedures to be conducted in chronological order (e.g. pull charts/data from Cerner,
screening,  interventions/interactions with subjects, data collection, photographing, audio and video
recording, follow-up.)
-Patients of various age and sex that are scheduled for unilateral TKR will be approached by VM orthopedic surgeons to ascertain
their willingness to volunteer for this study
-Identified patients will be consented for study participation by the PI at least 24 hours prior to their entry into the study
-All patients will undergo the standard VMMC TKA clinical pathway, which includes a 1 to 2 day continuous adductor canal block
-If their postoperative course has been normal, 20 volunteers will undergo unilateral thigh MRI prior to discharge home on the
afternoon of postoperative day 1 or the morning of postoperative day 2. These patients will have pre- and post-op CPK and aldolase
levels analyzed.
-Leg MRIs will be graded using a standardized checklist by a supervised radiology resident who is unaware of the study's purpose.
b)
Explain who will conduct the procedures.  Include where and when they will take place.
-MRIs will be obtained as scheduled cases at VMMC
-CPK and aldolase will be obtained and analyzed by VMMC laboratory
-MRIs will be assessed using a standardize template by a radiologist who is unaware of the study's purpose
c)
Will you be conducting procedures directly with patients?  If yes, answer the questions below.  If no (e.g.
chart review only), proceed to question 4.0 Study Duration.
Y
i)
Are there any procedures considered experimental and outside standard of care or established
practices at Virginia Mason, including follow-up procedures?
Y
If yes, explain.
Lower extremity MRIs are standard, but are not a routine part of postoperative TKA care. CPK and aldolase analyses before

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and after TKA is non-standard.
ii)
Will blinding be involved with this study?
Y
If yes, explain.
-The interpreting radiologist will be blinded as to the study's purpose
iii)
Will deception be used?
N
If yes, provide a rationale and describe debriefing procedures. Submit a debriefing script in
attachments section.
iv)
Will audio, photographs, or video taping of individuals occur?
N
If yes, describe and clarify what will become of the tapes/photographs (e.g., shown at scientific
meetings, erased, etc.).
4.
Study Duration
What is the anticipated start date and duration of the proposed study?
We plan to start immediately after IRB approval. We anticipate all 20 volunteers should be recruited and studied within a 3 month
period
---------------------------------------------------------------------------------------------
* * * Background and additional procedures * * *
5.
Background and additional procedures
a.
Relevant Background: Discuss the present knowledge, appropriate literature and rationale for conducting
the research.
Local anesthetics consistently induce myotoxicity in animal models and in up to 0.5% of humans after ophthalmic blocks, yet clinically
apparent myotoxicity in patients undergoing peripheral nerve blocks was heretofore believed to be nearly non-existent.(2) This
changed after introduction of continuous adductor canal blocks (ACB) at Virginia Mason Medical Center when 4 patients developed
symptoms, MRI findings, and neurophysiologic testing compatible with local anesthetic-induced myotoxicity. In short order, other
cases were reported from the Swedish Orthopedic Institute, 3 from retrospective analysis of other post-TKA MRIs obtained at Virginia
Mason, and anecdotally from practices throughout the United States. These sentinel complications have resulted in major morbidity
for the affected patients. After a normal early postoperative course, the patients rapidly developed flaccid quadriceps muscles and the
inability to lift the operative lower extremity against gravity, with consequent halting of their rehabilitative trajectory. While fortunate
patients recovered fully or nearly so after weeks to a few months as the unaffected myoblasts regenerated, less fortunate patients
have never recovered to baseline.
Because non-ophthalmic myotoxicity has never been described to this degree in humans, little is known about its etiology, diagnosis,
and treatment. Definitive diagnosis of myositis requires muscle biopsy, but this invasive and expensive intervention is unlikely to
occur. All patients in our series had MRI signals consistent with edema and inflammation, consistent with myositis. However, the
radiologic literature is silent with regard to what constitutes normal MRI findings immediately after TKA. Therefore, the MRI pathology
that we observed, while clearly demonstrating inflammatory changes in the anterior compartment of the leg, could conceivably
represent normal postoperative findings. We have attempted to study this question by retrospectively reviewing MRIs of patients who
underwent leg MRI within a week of TKA. While we could identify several patients with clinical presentations consistent with
undiagnosed myotoxicity, we were unable to confidently discern pathological findings versus 'normal' postoperative changes on
imaging.
b.
If applicable, please describe statistical methods of the research and plans for analysis of the data (i.e.
planned statistics, justification of sample size, etc.).
Observational convenience sample, therefore N/A
c.
Are there any alternative treatments to participating in this research (e.g., standard of care treatment,
etc.)?
N
If yes, describe.  Any standard treatment that is being withheld must be disclosed. This information must be
included in the consent form.

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d.
Can subjects receive alternative treatment outside of enrolling in this study?
N/A
e.
Will subjects be followed after their participation is complete?
N
If yes, explain why and describe how:
f.
Is this a cooperative study (e.g. UW, FHCRC is IRB of record)?
N
(If yes, answer the questions below.  If no, proceed to the next section.  Click here for more information.)
i.
Has this study been approved by the IRB of record?  (NOTE:  BRI IRB cannot review any
COOP study not currently approved by the IRB of record)
If yes, when did the initial approval for this study occur?
ii.
Has this study undergone Continuing Review (CR) at the IRB of record?
If yes, what are the current approval dates?
iii.
Will there be any costs to VM for study procedures (e.g. lab costs, etc.)?
If yes, how will these costs be paid to VM? (e.g., direct billing to your grant, etc.)
iv.
Will potential subjects from VM be approached?
(Note:  Refer to Non-VM Investigator Patient Approach Procedures for the correct procedures.)
If yes, describe how subjects will be approached and by whom.
---------------------------------------------------------------------------------------------
* * * Subject Population * * *
6.
Subject Population
a)
Complete the projected subject enrollment information below:List multiple subject groups/cohorts as
appropriate.(e.g.  retrospective, prospective, children, adult, controls, treatment, etc.)
Subject Enrollment
Subject Group
(DEFINE:
cases/controls/records/
specimens etc.)
Age Range
Expected Number at
End of Study (locally)
Expected Number at
End of Study (Total if
multi-site)
Expected Enrollment
next 12 months
20
50-75
20
20
b)
Complete the vulnerable subject table below:
Potentially Vulnerable Subject Populations

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Date Printed: May 29, 2018
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Targeted
Possible
Inclusion
Excluded
N/A
Prisoners: FAQ  (Note:  should be excluded unless you know
subjects will be "in prison" at the time of enrollment.  Notify
IRB immediately if a subject becomes incarcerated after
enrollment.)
X
Pregnant Women:  (45CFR Subpart B)
X
Children (under 18): 45CFR46 Subpart D
X
People not competent to provide informed consent
X
If the above populations are targeted or possibly included,
explain:  (Give rationale and specific steps to protect those
populations)
Female of childbearing potential:
X
If excluded, explain:
Non-English Speaking:  VM Interpreter Services
X
If Non-English Speaking subjects are targeted or possibly
included, give rationale and specific steps to protect those
populations.  If excluded, explain.
Concern regarding not fully understanding through the
translator that this study involves the acquisition of MRI and
enzyme tests that are not part of a standard knee
replacement hospitalization
New Description
New
Description
New
Description
New
Description
New
Description
New Description
New
Description
New
Description
New
Description
c)
Are any other potentially vulnerable subjects (sight impaired, illiterate, etc.) targeted or possibly included
in this study?  If yes, explain and provide steps to protect this population:
N
d)
Inclusion and Exclusion Criteria (e.g., Participants must have 20/20 vision, Participants must be 30-45
years of age, etc.)
i.
Identify inclusion criteria.
-Anticipated unilateral TKA performed under the standard VMMC joint pathway, with 1 to 2 night stay postop
-Subjects will be operated by a single surgeon (Dr. Verdin) to eliminate possible confounders related to surgical technique
-Subjects must be willing to volunteer for MRI study and CPK and aldolase blood draws
ii.
Identify exclusion criteria.
-Any contraindication to use of spinal anesthesia or adductor canal-based analgesia
-History of muscle wasting or related disease
-History of auto-immune disorders that may affect the musculature
-History of pre-existing neurologic condition affecting the lower extremities
-Allergy to radiologic contrast
-Contraindications to MRI exam
e)
To provide support for your projected enrollment goals, how many patients at VMMC do you anticipate
would have met your eligibility criteria over the last 1-5 years?  If NA or no numbers available, explain why
and provide rationale to support your projections:
1000 per year
f)
How long do you anticipate it will take to complete accrual for this study?
3 months
---------------------------------------------------------------------------------------------
* * * Recruitment Process, Subject Compensation and Costs * * *

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Date Printed: May 29, 2018
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7.
Recruitment Process:
a)
Describe the step-by-step procedures for identifying and recruiting potential research subjects and/or
requesting their data or specimens.
-Patients of various age and sex that are scheduled for unilateral TKA will be approached by Dr. Verdin to ascertain their
willingness to volunteer for this study
-Identified patients will be consented for study participation by the PI (Dr. Neal) at least 24 hours prior to their surgery
b)
Identify who will contact prospective subjects. (complete request for waiver of consent if applicable)
Joseph M. Neal, MD
c)
Planned Subject Identification Methods:
VM Medical Records / Chart Review
Direct Advertising
From PI's own practice / department
Referrals
Records
Specific registries, specify IRB#:
Outside Institution, please specify:
X
Other, explain below:
From VMMC orthopedic surgical patients scheduled for TKA. Initial willingness to participate in the study will be ascertained by
Dr. Verdin or his physician assistant.
d)
Planned Recruitment Materials / Methods:
X
Face to face interactions
Flyers / posters
Phone Scripts
Letters to providers / schools / organizations
Television ads
Newspaper ads
Letters to prospective subjects
Radio ads
Oral Scripts
PowerPoint presentations
Internet ads / postings
Email
X
Other, please specify:
Phone conversation with PI
NA
Attach ALL recruitment information in its final form using the Attachments section of this IRB eProtocol
form.
See BRI IRB Recruitment Material Guidance.
8.
Subject Compensation and Costs:
a)
Will subjects or their health care providers be required to pay for any study related procedures or
products?
N
i.
If "Yes," explain.  Max out of pocket?  Are any funds available from the study if the subjects
insurance will not cover study-related procedures or products?
b)
Will subjects receive compensation in any manner for participation? If "Yes," complete the questions
below. If "No", skip to the next section.
Y
i.
Will subjects receive monetary payment?  If yes, describe payment schedule including per visit
and total.
Y
$50 stipend will be paid after the participant has completed the study (paid as gift card)

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ii.
Will any one payment be more than 40% of total compensation? If "Yes," explain and provide
rationale.
N
iii.
Will other forms of compensation be provided?   If yes, describe below.
Y
Parking Voucher
Gifts
Transportation
Lodging
X
Gift card/certificate
Other (describe below)
As noted above
---------------------------------------------------------------------------------------------
* * * Risks * * *
9.
Risks / Data Safety Oversight / Monitoring
(Click "Help" above for more information)
a)
PI's evaluation of the overall level of Risk. (Please check one: minimal, or greater than minimal.)  Minimal
risk:  The probability and magnitude of harm or discomfort anticipated in the research are not greater in and
of themselves than those ordinarily encountered in daily life, or during the performance of routine physical
or psychological examinations or tests.
X
Minimal risk
Greater than minimal risk
b)
Check all potential risks/side effects to subjects. Check only added potential risks/side effects that may
occur to subjects from the research and not those that would occur if subjects were to receive standard
treatment/procedures only. [Note: Virtually all research studies involve "breach of confidentiality" and
"invasion of privacy" as potential risks since several entities may have access to research records (e.g.,
FDA, NIH, IRB, etc.). Risks must be consistent with the consent form and protocol.]
Risk / Side Effects
Physical Harms
Psychological
Social Economical
Minor Pain
Depression
X
Breach of Confidentiality,
resulting in:
Discomfort
Confusion
X
Invasion of privacy
Serious Injury
Hallucination
Potential loss of employment or
insurability
Death
Stress
Potential criminal prosecution
Injury from invasive medical
procedure
Guilt
Harm from possible side effects
from drugs
Loss of self-esteem
None (only applicable if all data
is stripped of all identifiers and
not coded)
X
Rare allergic reaction to radiologic
contrast dye
Embarrassment
None
X
Possible anxiety or
claustrophobia during MRI exam
None
c)
Describe the procedures or safeguards in place to protect against or minimize potential risks (e.g., referral
to psychological counseling resources).
-Standard assessment of allergy or MRI-associated risk prior to MRI study

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-Standard care during phlebotomy
-Referral to psychological counseling if indicated
d)
Who will be monitoring the risks noted above to ensure the safety of subjects?
X
The Principal Investigator Describe your monitoring plan for reviewing interim results and/or safety
concerns during the study:
-Contact with the volunteer prior to obtaining the MRI
-Post-procedural contact (after MRI and blood draw) to ascertain any concerns
-Contact information of PI will be made available to the volunteers
A group representing the study sponsor State name of group and describe monitoring plan for
reviewing interim results and/or safety concerns during the study:
A Data Safety Monitoring Board (DSMB) State name of DSMB and describe procedures for
submitting summary reports from the DSMB to the IRB:
Other:
If multi-site trial, are DSMB report(s) available for research already conducted?If yes,
attach DSMB reports. (see clinical research glossary for "DSMB" clarification.  If you
think your study warrants DSMB oversight and you do not know of one to utilize,
please contact the IRB office.)
e)
Are there any stopping rules based on the risks noted above, or other study criteria?  If yes, describe
below and include study endpoints. (Click "Help" above for more information.)/
N
---------------------------------------------------------------------------------------------
* * * Benefits * * *
10.
Benefits(This section is not enabled for exempt or cooperative studies)/
a)
Are there any direct benefits to the research participants? Note: Direct benefit is a valued or desired
outcome; an advantage (please do not include monetary inducement or compensation).If yes, please
describe.
N
b)
Are there any anticipated benefits of this study to society, academic knowledge or both? If yes, please
describe.
Y
The results of this study should define the effectiveness of MRI and/or CPK / aldolase as diagnostic tools in future patients with
suspected local anesthetic-induced myotoxicity
c)
Explain how the potential benefits justify the potential risks involved in participation in this research.
For this previously unknown complication, new knowledge is critical for both understanding the proper diagnosis and for complication
management. We have tried other routes to understand the diagnostic paradigm, to no avail. The low risk and inconvenience of
postoperative MRI and CPK / aldolase studies will facilitate further knowledge related to this previously unknown complication.
---------------------------------------------------------------------------------------------
* * * Confidentiality * * *
11.
Confidentiality
a)
Which of the following types of data will be associated with this study.  Consider all aspects of the

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Date Printed: May 29, 2018
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study.(Click 'Help" above for more information)/
X
Identifiable
Anonymous
X
De-identified
Coded
b)
Describe your protection method(s) in two or three sentences (e.g. coding system, limited access,
password protected, certificate of confidentiality, etc.).  Include safeguards to protect against direct or
indirect identification of subjects in any reporting of research results (e.g. publications):
-MRIs contain patient names and medical record numbers will be seen by the blinded radiologist
-CPK reports contain patient names and medical record numbers, but will be seen only by Dr. Neal and the patient's orthopedic team
-A password-protected spreadsheet housed on a VMMC password-protected computer will be used to link MRN to radiologist-
generated MRI standard reading and CPK levels
-MRNs will be removed from the spreadsheet prior to sharing with Dr. Steffel (at VA Puget Sound).
-Subject number, age, results of MRI and enzyme analysis, sex. No other identifiable information
c)
Other than study staff and BRI Regulatory & Compliance, what entities will have access to research records
and/or data that identify subjects (including coded data)?
NIH
Study Sponsor
Contracted monitor
FDA
Personal physician
X
None
Other:  (explain below)
d)
How will research data be recorded?
Case report forms
Remote data entry (e.g.
central database off site)
X
Local database (e.g. Excel spreadsheet)
REDCap database
Patient medical records
N/A
Other: (explain below)
e)
How will research records be stored locally?
X
VMMC/BRI server
X
Investigator's computer
Locked file cabinet
Locked office
N/A
Other: (explain below)
f)
How will specimens be stored?
Limited access refrigerator / freezer
Locked cabinet / office
X
N/A
Other: (explain below)
g)
After completion of this study, will you keep any data and/or specimens for future research purposes? N
if yes then answer the following questions:Describe why the information and/or specimens will be
retained (i.e., possible use for another research project[s], etc.).  Note:  Separate IRB applications must
be submitted for additional use of retained data and/or specimens outside the approved protocol:
Describe in two or three sentences how the confidentiality of the retained information and/or specimens
(whether directly identifiable or coded) will be maintained:

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Protocol: IRB18-008
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h)
Indicate the length of time research records and/or specimens will be kept before EITHER all
identifiers/codes are removed OR the records and/or specimens are destroyed.  Describe the procedures
you will use.
Research records will be kept 1 year after publication of our results. After that, the spreadsheet will be turned over to BRI for
archiving.
---------------------------------------------------------------------------------------------
* * * Consent Information * * *
12.
Consent Information
 Consent Instructions and Checklist
Template Consent Forms and Guidance
a)
Click "Add" to enter information in the "Informed Consent" table below.  This includes translated consents
and waivers of consent.    Exempt Studies:  This table is disabled.  If a consent is used then attach in the
attachment section. Chart review:  If accessing medical charts without consent, a waiver of consent is
required. Oral Consent:  A waiver of signed consent is required. Subjects under 18 yrs old:  Go to the next
section. complete and attach assent information.   Enter information in the Informed Consent table
separately for each consent and/or waiver of consent.
Informed Consent Table
Title
Consent Type
Clean Consent - Vers. 04.09.18 - IRB18-008
Consent
IRB Stamped Approved Consent - Vers. 04.09.18 -
IRB18-008
Consent
Revised Consent 5.17.18
Consent
Consent 5.29.18 revision
Consent
Informed Consent Table
Title (e.g. main, screening, translated, oral,
information sheet, waiver request) *
Clean Consent - Vers. 04.09.18 - IRB18-008
Consent Information Type*
Consent
Consent Document*
X
Attachment
Clean Consent - Vers. 04.09.18 -
IRB18-008
Who will obtain subjects consent? (Check all that apply)
Principal Investigator
Co-Investigator
Study Coordinator
Research assistant(s)
Other research staff
Contracted Data Collection Firm
Other (please specify)
Informed Consent Table

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Date Printed: May 29, 2018
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Title (e.g. main, screening, translated, oral,
information sheet, waiver request) *
IRB Stamped Approved Consent - Vers. 04.09.18 - IRB18-008
Consent Information Type*
Consent
Consent Document*
X
Attachment
IRB Stamped Approved Consent -
Vers. 04.09.18 - IRB18-008
Who will obtain subjects consent? (Check all that apply)
X
Principal Investigator
X
Co-Investigator
Study Coordinator
Research assistant(s)
Other research staff
Contracted Data Collection Firm
Other (please specify)
Informed Consent Table
Title (e.g. main, screening, translated, oral,
information sheet, waiver request) *
Revised Consent 5.17.18
Consent Information Type*
Consent
Consent Document*
X
Attachment
Revised5.17.18.Consent Document -
IRB18-008
Who will obtain subjects consent? (Check all that apply)
X
Principal Investigator
X
Co-Investigator
Study Coordinator
Research assistant(s)
Other research staff
Contracted Data Collection Firm
Other (please specify)
Informed Consent Table
Title (e.g. main, screening, translated, oral,
information sheet, waiver request) *
Consent 5.29.18 revision
Consent Information Type*
Consent
Consent Document*
X
Attachment
IRB18-008 Consent Document.Rev
5.29.18
Who will obtain subjects consent? (Check all that apply)
X
Principal Investigator
X
Co-Investigator
Study Coordinator
Research assistant(s)
Other research staff
Contracted Data Collection Firm
Other (please specify)

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  If consenting human subjects answer the questions below.  If NOT consenting human subjects, leave blank and
skip to the next section.
b)
Describe the process used to consent all subjects on the study.
-Volunteer subjects will be identified in orthopedic office by Dr. Verdin or his staff
-Those interested in participating will be consented by Joseph M. Neal, MD at least 24 hours prior to their surgery. If possible, consent
will be obtained in person. If not possible, consent will be obtained via phone.
c)
Will subjects have as much time as they want between the explanation of the study and signing the
consent form?  If no, or N/A explain below.
Y
d)
If consent is being obtained from non-English speaking subjects, explain the translation process for all
documents seen by subjects, including consent documents. Describe the consent process in these
circumstances.
N/A
e)
Do you plan on having a Legally Authorized Representative (LAR) involved in the consent process?  If
yes, explain below and ensure the appropriate section is included in the consent form.
N
f)
Will you require an impartial third party witness be included in the consenting process?  If yes, explain
below and ensure the appropriate section is included in the consent form.
N
---------------------------------------------------------------------------------------------
* * * Assent Background * * *
13.
Assent Background  (Continue to the next section if no subjects under the age of 18 will be enrolled in this
study)
a)
Complete the "Assent" table below.   Attach assent documents and/or request assent waivers. Click "Help"
above for more information regarding assent and assent waiver.
You must check children (under 18) on the Subject Checklist section to activate this table.
b)
Complete the Regulatory Compliance worksheet below:
Regulatory Compliance - Subpart D - Children
Provide the specific age range for children (less than 18 years old) you wish to enroll in the study and what is
your accrual goal:
Age Range:
Total Accrual
Goal:
Check the appropriate box below (only one) to indicate which category your study may be approved in light of 45
CFR 46 subpart D for research involving children.  Chlick on the links below for guidance.
Research not involving greater than minimal risk.  45 CFR 46.404
Research involving greater than minimal risk, but presenting the prospect of direct benefit to
the individual subjects. CFR 46.405

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Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: May 29, 2018
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Research involving greater than minimal risk and no prospect of direct benefit to the individual
child subjects involved in the research, but likely to yield generalizable knowledge about the
subject's disorder or condition. 45 CFR 46.406
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
Will you be using an Assent Form?  (Required for subjects 7-11 years old per BRI IRB policies
- see 45 CFR 46.408 for reference)
Describe in the space below the details of your assent process for children in your study. (Include specific
approach(es) to subjects in various age ranges, how assent will be documented, who will be able to give
persimssion for each child (e.g. child's parent(s) or guardian), and how this permission will be recorded in the
file.)
Does your study involve an FDA regulated drug, device, or biologic? If yes, check the
appropriate box below (only one) to indicate which category your study may be approved in
light of 21 CFR 50 Subpart D for research involving children.  Click on the links below for
guidance.
Clinical investigations not involving greater than minimal risk 21 CFR 50.51
Clinical investigations involving greater than minimal risk, but presenting the prospect of direct
benefit to the individual subjects. 21 CFR 50.52
Clinical investigations involving greater than minimal risk and no prospect of direct benefit to
individual subjects.
Clinical investigations not otherwise approvable that present an opportunity to understand,
prevent, or alleviate a serious problem affecting the health or welfare of children.  21 CFR
50.53
Will you be using an Assent Form?  (Required for subjects 7-11 years old per BRI IRB policies
- see 45 CFR 46.408 for reference)
---------------------------------------------------------------------------------------------
* * * HIPAA * * *
14.
Health Insurance Portability and Accountability Act (HIPAA)
If you are using PHI and this page is not active you must return to the General
Checklist and check the box regarding the use of PHI in this research.
HIPAA Privacy Rule: Establishes the right of an individual to authorize a covered entity, such as health
plan, health care clearinghouse or health care provider, to use and disclose his/her Protected Health
Information (PHI) for research purposes.  The Privacy Rule defines the elements of individual
information that comprise PHI and establishes the conditions under which PHI may be used or disclosed
by covered entities for research purposes. It also includes provisions to allow an individual's PHI to be
disclosed or used in research without the person's authorization (i.e., IRB Waiver of HIPAA
Requirement Authorization).  For more information refer to the HIPAA Privacy Rule.
Protected Health Information (PHI):Health information with one or more of the identifiers listed below.
For more information see the  NIH website.  Research which involves the use of de-identified data is
exempt from HIPAA requirements. In order to be de-identified data NONE of the subject identifiers listed
below can be collected, used, reviewed, recoded, accessed or disclosed.
For more information see the following:VM/BRI Protected Health Information Guidance Document
a)
How will you obtain approval to access PHI for this research?
X
HIPAA Authorization request from subject
X
Incorporated into consent form
Stand alone document

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IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: May 29, 2018
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Waiver of Subject HIPAA Authorization (partial or complete)(complete question e. below)
Limited Data Set and Data Use Agreement
Other: (explain below)
c)
Will any non-VM/BRI personnel need access to PHI?  If yes, how and where will they access subject
PHI (e.g. on-site, remote via Cerner, etc.)?
N
d)
Review the following list and indicate if any of the information will be collected from any medical records for
the purpose of this research project.
Names
Social Security Numbers
Telephone Numbers
All geographic subdivisions smaller than a state, including street address, city, county, precinct, zip
code, and their equivalent geocodes, except for the initial three digits of a zip code, if according to the
current publicly available data from the Bureau of the Census;
i.
The geographic unit formed by combining all zip codes with the same three initial digits
contains more than 20,000 people; and
ii.
The initial three digits of a zip code for all such geographic units containing 20,000 or
fewer people is changed to 000.
All elements of dates (except year) for dates directly related to an individual, including birth date,
admission date, discharge date, date of death; and all ages over 89 and all elements of dates (including
year) indicative of such age, except that such ages and elements may be aggregated into a single
category of age 90 or older.
Fax Numbers
Electronic Mail Addresses (email)
X
Medical Record Numbers
i.
You must identify the data points being collected from MRN by attaching a separate data
collection sheet or listing them in the procedures section.
Health Plan Beneficiary Numbers
Account Numbers
Certificate/License Numbers
Vehicle Identifiers and Serial Numbers, including License Plate Numbers
Device Identifiers and Serial Numbers
Web Universal Resource Locations (URLs)
Internet Protocol (IP) Address Numbers
Biometric Identifiers, including Finger and Voice Prints
Full Face Photographic Images and any Comparable Images
Any other unique identifying number, character, or code (note this does not mean the unique code
assigned by the Investigator(s) to code the research data)
e)
Are you requesting a HIPAA waiver?  (Required for any type of waiver of consent)If yes, answer the
following questions.  If no, proceed to the next section.
N
i.
Explain why the research cannot reasonably be conducted without the waiver of
authorization:

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IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: May 29, 2018
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ii.
Explain why the research cannot reasonably be conducted without access to and use of
identifiable health information:
iii.
Describe the reasonable safeguards to protect identifiable information from unauthorized use
or re-disclosure:
iv.
Describe the reasonable safeguards to protect against identification, directly or indirectly, any
patient in any report of the research:
v.
Describe the plan to destroy the identifiers at the earliest opportunity consistent with the
research.  If there is a health or research justification for retaining identifiers, or if law requires
you to keep such identifying information, please provide this information as well:
vi.
Provide written assurance that identifiable information will not be reused/disclosed to any
other person or entity, unless such use is required by law, for oversight of the research study,
or for other research permitted by law:
vii.
Explain why the research is of sufficient importance to outweigh the privacy intrusion:
viii.
Explain who the subject should contact to enforce patient rights, or to obtain an accounting of
the research disclosures (e.g. PI, sub-investigator, coordinator):
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* * * Drugs and Devices * * *
15.
Drugs and Devices
a)
Does this study involve a drug or device?  If YES, continue below.If NO, proceed to the next section.
Y
i)
Is the drug(s) or device(s) FDA approved?  If YES,  list drug / device name and explain in text
field below. (e.g. HDE, 510K, Compassionate Use, etc) If NO, click "add" and complete the
table below for each investigational drug(s) or device(s).
Y
MRI
(These tables are not activated unless a drug / device question is checked on the General
Checklist section)
b)
Briefly describe the drugs and devices listed above.  Include any relevant information that has not been
described in the protocol summary or background sections.
MRI will be used to obtain thigh scans
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* * * Potential Conflict of Interest * * *
16.
Potential Conflict of Interest(This section is not enabled for exempt studies)/
a)
Y
Is there funding for this study?

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IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: May 29, 2018
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b)
N If yes, are there any positive financial disclosures related to this study for any key personnel?
c)
N Regardless of funding, are there any positive positional disclosures related to this study for any key
personnel?
d)
Y
I attest that I have read the
'https://brinet.benaroyaresearch.org/center/Documents/VM%20Research%20Conflicts%20of%20Interes
t.pdf#search=research%20conflict'target='blank'VM Conflict of Interest Policy and agree to abide by its
terms. I will update this protocol when new or changes in conflict of interest arise, and I will comply with
any conflict management plan required by the Institutional Review Board (IRB) to manage, reduce, or
eliminate any actual or potential conflict of interest for the duration of the research.
If Yes to b) or c) above, complete the table and answer the questions below concerning the potential conflict of
interest.  If No, then proceed to the next section.
Minimizing Risks and Disclosure to Subjects
e)
N Have you disclosed any actual, potential or perceived conflicts of interest in the consent form? Research
Personnel are required to disclose all such conflicts to all research participants in the research consent
form.
f)
What steps, if any, have you taken or will you take to manage the conflict of interest and minimize the risks
associated with any actual, potential or perceived conflicts of interest arising out of this research?
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* * * Attachments * * *
17.
Attachments
Attach relevant documents here. These could include:
-
Collaborating Investigator's IRB approval and approved documents
-
Conflict of Interest information
-
Debriefing Script; Grant/Sub-contract
-
HIPAA Authorization Form from HIPAA-covered entity
-
Interview/Focus Group Questions
-
Investigator's Brochure
-
Letters of Agreement/Cooperation from organizations who will help with recruitment
-
Questionnaires/Surveys
-
Radiation Control Office approval material
-
Recruitment Material (e.g., flyers, email text, verbal scripts)
-
Protocol
-
Patient Card
-
Other files associated with the protocol (you can upload most standard file formats: xls, pdf, jpg, tif,
etc.)
Please be sure to attach all documents associated with your protocol. Failure to attach the necessary files may
result in this protocol being returned prior to review.
To update or revise any attachments, please delete the existing attachment and upload the revised document to
replace it.
Select from list
Attachment Name
Attached Date
Submitted Date

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IRB Protocol
Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: May 29, 2018
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Data Collection Sheet
IRB18-008 Copy of Study
Data Sheet
03/08/2018
05/22/2018
Other
IRB18-008 Neal Financial
Disclosure
03/08/2018
05/22/2018
Data Collection Sheet
IRB18-008 Copy of MRI
Data Sheet
03/08/2018
05/22/2018
Protocol
Clean Protocol - Vers.
04.09.18 - IRB18-008
04/13/2018
04/13/2018
Protocol
IRB18-008 Protocol.Rev
5.29.18
05/29/2018
05/29/2018
---------------------------------------------------------------------------------------------
* * * Obligations * * *
Note:  The use of "I" below refers to the Principal Investigator (PI).  If someone other than the PI is completing
and submitting this application, that person is responsible to make sure the PI is aware of their obligation and
assurances cited below.  The PI is ultimately responsible for all conduct under this study and answers provided in
this IRB submission.
Research Obligations of the Principal Investigator Include the Following:
 Training - ALL key personnel, including any newly added personnel, must meet all IRB required training requirements (e.g. CITI Ethics, GCP,
Conflict of Interest).  Training refreshers must be completed at the appropriate intervals (i.e. every three (3) or four (4) years).
 Study Modifications - Changes to any aspect of the study (e.g. protocol, consent/assent forms, advertising materials, additional key
personnel, subject population, etc.) will be submitted to the IRB for approval before instituting the changes.
Final Report - The IRB will be notified when the study is complete, and must be closed out in eProtocol prior to expiration of the approval.
Investigator's Statement and Assurance of Confidentiality:
I certify that I have reviewed this application, including attachments, and all information contained herein is accurate to the best of my
knowledge.
I agree to not enroll any subject(s) or collect any data intended only for research use prior to issuance of an IRB approval.
I understand that I am fully responsible for the execution and management of this study, and I am responsible for the performance of any sub-
investigators or key personnel, including their adherence to all of the applicable policies and regulations.
I agree to report any substantive changes to the information contained in this application, unanticipated problems, or adverse events
encountered during the project immediately to the IRB.
I will ensure the names of any human subjects or any identifiable data from human subjects shall be treated as confidential information.  This
information will not be disclosed to anyone other than those directly connected with the research project unless the patient has given prior
approval in writing.
If this is a funded project, I certify that the funding source document is entirely consistent with the corresponding study protocol.
I certify I have not been barred from doing research by any regulatory agency or entity.  If I am a physician (or other licensed health care
professional), I certify that my medical (or other) license is current.
I further agree any failure to perform the undertaking specified above shall be good cause for termination of the research project.
When Closing Your Protocol:
I understand when I close this protocol with the IRB NO further data collection, follow-up with subjects, coding of data, data analysis, and
manuscript preparation that requires personal identifiable information (e.g. PHI) may be conducted.
I agree to retain all research materials for at least 10 years after closure of the research project and acknowledge these documents may be
subject to review by the Clinical Research Program and IRB, if deemed necessary.
I further certify I will not take any PHI and/or specimens generated from this research with me if I leave BRI/VM, unless having first
established an agreement with VM legal in advance of my departure.
I confirm this study will not begin until the investigator receives written final approval or determination of exemption.
X
The Principal Investigator has read and agrees to abide by the above obligations.

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Protocol: IRB18-008
PI Name: Neal,Joseph
Date Printed: May 29, 2018
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 Continuing Review - You are responsible to complete and submit a Continuing Review form at least 30 days prior to the date of expiration.
You will be asked to note accomplishments of your project at that time.
 Protocol Deviations/Violations, Adverse Events (AEs)  that occur in the course of the protocol will need to be submitted in a prompt manner
from when they occurred.
X
The Principal Investigator has read and agrees to abide by the above obligations.
Please click "next" to continue to protocol Check for Completeness.  If the protocol is complete and ready for
submission, please click "Submit Form" to your left to submit your protocol for IRB Review.
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* * * Event History * * *
Event History
Date
Status
View Attachments
Letters
05/29/2018
AMENDMENT 2 FORM
SUBMITTED
Y
05/29/2018
AMENDMENT 2 FORM
CREATED
05/24/2018
AMENDMENT 1 FORM
APPROVED
Y
Y
05/23/2018
AMENDMENT 1 FORM
REVIEWER(S) ASSIGNED
05/22/2018
AMENDMENT 1 FORM
SUBMITTED
Y
05/17/2018
AMENDMENT 1 FORM
CREATED
04/30/2018
NEW FORM APPROVED
Y
Y
04/30/2018
NEW FORM UNDO
APPROVED
04/30/2018
NEW FORM APPROVED
Y
Y
04/17/2018
NEW FORM REVIEWER(S)
ASSIGNED
04/13/2018
NEW FORM REVIEWER(S)
ASSIGNED
04/12/2018
NEW FORM PANEL
MANAGER REVIEW
03/08/2018
NEW FORM PANEL
ASSIGNED
03/08/2018
NEW FORM SUBMITTED
Y
01/26/2018
NEW FORM CREATED