Locally Applied Antibiotics for Infection Prophylaxis in Treatment of Open Fractures
Phase: PHASE3
Conditions: Fractures, Open
Sponsor: University of Virginia

 
 
 
 
 
 
Locally applied antibiotics for infection prophylaxis in treatment of open fractures 
 
NCT03705962 
 
06 Dec 2016 
 
Protocol with Statistical Analysis Plan 

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IRB-HSR PROTOCOL 
Investigator Agreement 
 
BY SIGNING THIS DOCUMENT, THE INVESTIGATOR CONFIRMS: 
1. I am not currently debarred by the US FDA from involvement in clinical research studies. 
2. I am not involved in any regulatory or misconduct litigation or investigation by the FDA. 
3. That if this study involves any funding or resources from an outside source, or if you will be sharing data 
outside of UVA prior to publication that you will contact the Dean’s office regarding the need for a 
contract and letter of indemnification.  If it is determined that either a contract or letter of indemnification 
is needed, subjects cannot be enrolled until these documents are complete. 
4. The proposed research project will be conducted by me or under my close supervision.  It will be 
conducted in accordance with the protocol submitted to and approved by the IRB including any 
modifications, amendments or addendums submitted and approved by the IRB throughout the life of the 
protocol.  
5. That no personnel will be allowed to work on this protocol until they have completed the IRB-HSR On-line 
training and the IRB-HSR has been notified. 
6. That all personnel working on this protocol will follow all IRB-HSR Policies and Procedures as stated on the 
IRB-HSR Website http://www.virginia.edu/vprgs/irb/ and on the School of Medicine Clinical Trials Office 
Website:  http://knowledgelink.healthsystem.virginia.edu/intranet/hes/cto/sops/sop_index.cfm 
7. I will ensure that all those delegated tasks relating to this study, whether explicitly or implicitly, are 
capable through expertise, training , experience or credentialing to undertake those tasks.   
8. I confirm that the implications of the study have been discussed with all Departments that might be 
affected by it and have obtained their agreement for the study to take place.  
9. That no subjects will be recruited or entered under the protocol until the Investigator has received the 
signed IRB-HSR Approval form stating the protocol is open to enrollment 
10. That any materials used to recruit subjects will be approved by the IRB-HSR prior to use.  
11. That all subjects will sign a copy of the most current consent form that has a non-expired IRB-HSR approval 
stamp. 
12. That any modifications of the protocol or consent form will not be initiated without prior written approval 
from the IRB-HSR, except when necessary to eliminate immediate hazards to the subjects. 
13. Any significant findings that become known in the course of the research that might affect the willingness 
of subjects to enroll or to continue to take part, will be promptly reported to the IRB.   
14. I will report immediately to the IRB any unanticipated problems involving risk to subjects or to others 
including adverse reactions to biologics, drugs or medical devices.   
15. That any serious deviation from the protocol will be reported promptly to the Board in writing. 
16. That any data breach will be reported to the  IRB, the UVa Corporate Compliance and Privacy Office , UVa 
Police as applicable.  
17. That the continuation status report for this protocol will be completed and returned within the time limit 
stated on the form. 
18. That the IRB-HSR office will be notified within 30 days of a change in the Principal Investigator or of the 
closure of this study. 

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19. That a new PI will be assigned if the current PI will not be at UVA for an extended period of time.  If the 
current PI is leaving UVa permanently, a new PI will be assigned PRIOR to the departure of the current PI.  
20. All study team members will have access to the current protocol and other applicable documents such as 
the IRB-HSR Application, consent forms and Investigator Brochures. 
21. Signed consent forms and other research records will be retained in a confidential manner.  Records will 
be kept at least 6 years after completion of the study.  
22. No data/specimens may be taken from UVa without a signed Material Transfer Agreement between 
OSP/SOM Grants and Contracts Office and the new institution.  Original study files are considered 
institutional records and may not be transferred to another institution. I will notify my department 
administration regarding where the originals will be kept at UVa.  The material transfer agreement will 
delineate what copies of data, health information and/or specimens may be taken outside of UVa.  It will 
also approve which HIPAA identifiers may be taken outside of UVa with the health information or 
specimens. 
23. If any member of study team leaves UVa, they are STRONGLY ENCOURAGED to use Exit Checklist found on 
IRB-HSR website at http://www.virginia.edu/provost/facultyexit.pdf. 
 
The IRB reserves the right to terminate this study at any time if, in its opinion, (1) the risks of further 
experimentation are prohibitive, or (2) the above agreement is breached. 
 
Investigators Experience 
 
The PI of this study, Seth Yarboro MD is Assistant Professor of Orthopedic Surgery, Division of Trauma at 
University of Virginia. He has extensive experience with treatment of Orthopedic Trauma cases and clinical 
research.  He studied the application of local antibiotics to open wounds in rat model with favorable results 
and is now planning to conduct a clinical trial using aqueous tobramycin for infection prophylaxis in open 
fractures. Such extensive experience and knowledge base puts him at a unique position to undertake the 
current study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Signatures 
 
Principal Investigator 
 
____________________________ 
____________________________ 
_______ 
Principal Investigator 
Principal Investigator 
Date 
Signature 
Name Printed 
 
 
The Principal Investigator signature is ONLY required if this is a new protocol, a 5 year update or a modification 
changing the Principal Investigator. 
 
 
Department Chair 
BY SIGNING THIS DOCUMENT THE DEPARTMENT CHAIR AGREES: 
1. To work with the investigator and with the board as needed, to maintain compliance with this 
agreement. 
2. That the Principal Investigator is qualified to perform this study. 
3. That the protocol is scientifically relevant and sound. 
 
___________________________ 
_______________________  
_________ 
Department Chair or Designee  
Department Chair or Designee 
Date 
Signature 
Name Printed 
 
 
The person signing as the Department Chair cannot be the Principal Investigator or a sub-investigator on this 
protocol. 
The Department Chair or Designee signature is ONLY required if this is a new protocol or a modification 
changing the Principal Investigator. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Brief Summary/Abstract 
The primary objective of this study is to investigate the effectiveness of local antibiotic versus placebo 
in the prevention of infections in open fractures.  The study will assess whether local treatment of open 
fractures with the antibiotic  tobramycin (in addition to standard systemic antibiotics) will decrease the risk 
and rate of infection, time to fracture union, and rate of re-operation. This will be studied using a randomized 
controlled clinical trial design in adult population of age 18-70 years who present with open fractures.  About   
133subjects will be recruited in this study at UVA.  There will also be similar studies performed at University of 
Florida- Jacksonville and Medical University of South Carolina and we will be performing a collaborative site 
analysis study with those centers and we will be sharing demographic, infection and treatment information (at 
either 2 or 6 weeks), and any adverse events that occur.   
 
Note:  Standard protocols at UVA will be followed for systemic antibiotic administration. No specimens will be 
collected for research purposes.  The patient will otherwise receive the standard of care treatment for their 
fractures.  
 
SAFETY SUMMARY: 
 
•  Local tissue safety: 80mg/40mL is 2 mg/mL (which is 2000micrograms / mL). This level was 
found to be safe in Rathbone/Wenke study (1). Further, the local level is expected to decrease 
quickly, as opposed to the sustained levels seen in tissue culture in that study. 
 
• Systemic safety: Gentamicin/tobramycin is routinely given as a single IV dose at 4-7mg/kg 
(depending on severity of infection). For a 70kg patient treated with 5mg/kg dose, 350mg 
would be given IV (thus immediately available systemically). The dose we administer is only 
80mg, a much lower dose, and is administered in the wound (thus more similar to IM than IV). 
Peak levels are not routinely checked at UVA for short courses of even the higher doses of IV 
tobramycin/gentamicin, and we find no safety issue or support for obtaining peak levels in this 
study. Systemic levels high enough to cause side effects are typically associated with dosing 
that is higher than recommended or too frequent to allow adequate renal clearance. 
 
• In cases of renal impairment, dosing is typically spaced out further to allow time for renal 
clearance (see attached below from Stanford Guidelines 2013). This would not create a safety 
issue in our study, as a single 80mg dose is administered. If ongoing therapy with a systemic 
aminoglycoside is required (either gentamicin or tobramycin), the patient’s primary team would 
be made aware of the intra-operative dose and follow serum levels as appropriate based on 
repeated dosing. 
 
• This route of administration of local tobramycin represents the current standard of care in my 
practice. I have treated all open fractures this way since starting at UVA in 2012, and have 
observed no adverse effects. In fact, my impression is that the infection rate is lower as a 
result of this practice. 

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Unpublished pilot data from a single trauma surgeon at UNC Chapel Hill demonstrated a significantly 
lower infection rate in patients treated with local aminoglycoside (initially gentamicin, then changed to 
tobramycin once above Wenke data showing lower potential for local toxicity was published). In the 
comparison group (received no local antibiotics) the overall incidence of deep infection was 4.8% 
(11/243) while in the current group it was 0.6% (2/343, p=0.0025). Looking specifically at patients 
treated with ORIF found a historical deep infection rate of 6% (8/134) versus 1.2% (2/170, p=0.0247) 
in the local antibiotic group. Tibia fractures had a historical deep infection rate of 10% (3/30), and 
there were no infections in the local antibiotic group (0/56, p=0.0397). For open fractures, the 
historical group had 19% (5/26) infection rate versus none (0/34) in the local antibiotic group 
(p=0.012). 
 
Background 
1. Provide the scientific background, rationale and relevance of this project.   
Local antibiotics provide high local concentrations with lower systemic levels than parenterally 
administered antibiotics. The delivery of local antibiotics can both supplement and sometimes obviate the 
need for systemic antibiotics. In certain instances, the target area of treatment may be avascular, preventing 
systemic antibiotics from reaching the targeted site. In these scenarios, local antibiotics may serve as the only 
effective option in treating the infection. Perhaps the main advantage of local antibiotic therapy is the ability 
of an antibiotic to reach a high local concentration while simultaneously having a low or undetectable 
systemic concentration, thereby avoiding certain negative side effects such as nephrotoxicity and ototoxicity 
and decreasing the chances of developing pathogenic resistance.[2-4] At this high level of local concentration, 
many bacteria that might otherwise be normally resistant to an antibiotic fall within its spectrum of activity.[5] 
Antibiotics can be effectively administered in aqueous solution, and do not necessarily require a 
carrier. While antibiotic (as well as antiseptic) solutions have been used for many years, there is clinical data 
that suggest this method of delivery is effective. A significant positive impact was shown in a series of shoulder 
arthroplasty patients, where the rate of infection was decreased by one order of magnitude with intra-
articular injection of aqueous gentamicin performed after wound closure.[ 6] This method of administration 
has also been effective in a rat model, where aqueous gentamicin was significantly better for infection 
prophylaxis after placement of a metal implant and contamination with Staphylococcus aureus, and this effect 
was further improved by concomitant administration of systemic antibiotics.7,8] This method of delivery is 
distinct from antibiotic solution for irrigation, as the aqueous antibiotic is injected into the surgery site after 
the wound is closed. An 18 ga needle is used adjacent to the incision to inject the solution throughout the 
wound. This technique allows the solution to ideally infiltrate the interstices or depths of the wound. In 
practice, the solution has been made in a concentration of 2 mg/mL (80 mg aminoglycoside in 40 mL injectable 
saline). Recent data which suggested lower local cytotoxicity with  tobramycin compared to gentamicin [5] has 
led us to choose  tobramycin in this application. We will therefore use tobramycin as the study drug in this 
protocol. 
 
The advantages of delivering antibiotic in aqueous form are several, including cost, as there is no need 
for a specialized vehicle of delivery. The antibiotic drugs are approved and ready for use this time. Also, the 
wound encounters a higher maximum antibiotic concentration, potentially improving antibiotic efficacy. 
 
Drawbacks to this method may include poor sustained antibiotic level. However, other vehicles for 
delivery such as collagen sponge have been shown to elute the drug very quickly, then potentially become a 

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foreign body at the surgical site. Thus, this method of antibiotic delivery may be more effective in a situation 
where sustained delivery is not required, such as prophylaxis of surgical site infections. 
 
Regarding local toxicity and safety, Rathbone et al demonstrated levels of toxicity for many commonly 
used antibiotics.[ 1] This data is helpful for determining appropriate concentrations that are acceptable in the 
wound cavity, regardless of the delivery method. Upon evaluating osteogenic cell viability and activity as 
measured by alkaline phosphatase activity, wide variability was noted, even within families of antibiotics. 
Rifampin, tetracyclines, and ciprofloxacin were noted to be particularly cytotoxic, with considerable decrease 
in cell number and activity at concentrations of even 100mcg/mL.  Tobramycin, vancomycin, and amikacin 
were noted to be least cytotoxic.  Of note, cell number and activity were measured at time points of 10 and 14 
days for various concentrations of each antibiotic. While the response of osteogenic cells to these 
concentrations of antibiotics is useful information, it should be noted that these are measured in response to 
sustained levels of antibiotics, and in the clinical setting the antibiotics levels are highest at early time points 
then often decrease rapidly.  
Hypothesis to be Tested 
Local aqueous tobramycin used for infection prophylaxis injected into open fracture wounds following 
definitive closure prevent infections, and decreases re-operation rate in patients with open fractures within 6 
weeks of administration. 
 
Study Design: Biomedical 
1.  Will controls be used? Yes 
 
►IF YES, explain the kind of controls to be used. 
 We will use placebo controls who will receive 40 mL of 0.9% NS injected into the closed wound at the 
end of surgical treatment. 
 
2. What is the study design?  
Double blind 
 
3. 
Does the study involve a placebo?Yes 
 
►IF YES, provide a justification for the use of a placebo 
This study will need placebo group to evaluate the effectiveness of local injection of  tobramycin.  
 
Human Participants 
Ages:   18-70 
Sex: 
Both 
Race: All 
 
Subjects- see below 
1.  Provide target # of subjects (at all sites) needed to complete protocol. 133 
2.  Describe expected rate of screen failure/ dropouts/withdrawals from all sites.   

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Approximately, 20% of subjects will be lost to follow up 
3.  How many subjects will be enrolled at all sites?     133 
 
4.  How many subjects will sign a consent form under this UVa protocol?    133 
 
5. Provide an estimated time line for the study.2 years 
Inclusion/Exclusion Criteria 
1.  List the criteria for inclusion  
- 
Ages 18 – 70 years 
- 
Gustilo Type I,II,IIIa open fracture (s) 
- 
Ability to provide informed consent (or proxy consent in cases where subject is temporarily impaired 
when intubated and sedated) 
- 
Subject should be able to follow up at the scheduled times following surgery 
- 
Subjects who may have compartment syndrome, renal insufficiency, and those who are 
immunosuppressed regardless of antibiotic administration will also be included in the study 
- 
 
 
2.  List the criteria for exclusion 
- 
Closed fracture 
- 
Severe injury requiring flap coverage or vascular reconstruction (Gustilo-Anderson Type IIIB and C 
respectively) 
- 
Aminoglycoside allergy 
- 
Presentation greater than 48 hours after injury 
- 
Pathologic fracture 
- 
Preexisting infection in bone with an open fracture 
- 
Patients with multiple trauma involving liver, kidney, or brain  
- 
Pregnancy (self-reported) 
- 
Current status as prisoner 
 
3.  List any restrictions on use of other drugs or treatments. 
Any other antibiotic not related to open fracture is prohibited during the study, which could mask wound 
infection. 
Statistical Considerations 
1. 
Is stratification/randomization involved?Yes 
 
►IF YES, describe the stratification/ randomization scheme. 
Subjects will be randomized prior to surgical treatment.  Randomization will be double blind. Neither 
the subject nor the surgeon injecting the antibiotic or placebo know which arm the subject belongs to. 
The Medical Pharmacist or Joe Hart PhD will have the key to randomization, at UVA.  The other sites 
involved will be expected to manage their randomization scheme.  UVA will not oversee the other 
sites.  

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►IF YES, who will generate the randomization scheme?  
__X___ Other:  Wendy Novicoff PhD  
 
2.  What are the statistical considerations for the protocol?  
- 
This is a prospective, randomized double blind study.  Subjects will be randomized to antibiotic (80mg 
tobramycin/40mL saline) or placebo arm (40mL of 0.9% saline).  
 
- 
The primary objective of this study is to evaluate the efficacy of local antibiotics in decreasing incidence 
of infection.  The primary outcome will include evidence of infection in the first 6 weeks of surgery.  
Infection will be defined as major and minor, with major indicated by return to the operating room for 
irrigation and debridement.  Minor infection is represented by documentation of cellulitis or superficial 
infection  at surgical site and administration of oral antibiotics.  .  
 
- 
Superficial infection as indicated by documentation of cellulitis at surgical site and administration of 
oral antibiotics with the indication of wound problems.  The primary purpose of this study is to 
document infection rates in the first 6 weeks after surgery.  If an infection is found, it will be cared for 
per standard clinical care; however, it will not be followed for research purposes.   
 
- 
There will be no contingencies for early stopping as the patients are receiving a single dose of 
antibiotics. There will be no interim analysis or stratification factors 
 
- 
We expect approximately - 60 – 65 open fractures within a year to be treated at UVA based on 
historical records.  
 
We will use a one-sided test for proportions to compare the control and experimental groups for the primary 
endpoint (presence of infection) and the secondary endpoint of evidence of non-union.  A p-value less than 
0.05 will be considered a significant result.   
 
 
 
 
3.  Provide a justification for the sample size used in this protocol.   
 
A sample size analysis was completed for different alpha and power levels.  A one-sided test for proportions 
was chosen to compare the baseline (no treatment) group to the hypothesized proportion (treatment group); 
based on historical data, we assumed that the no treatment group would have a 10% infection rate, and the 
treatment group would have a 1% infection rate.  Using an alpha of 0.05 and power of 70%, we would need to 
have 60 patients in each group. 
 
With an expected accrual rate of 65 patients per year, we would expect to enroll 130 patients in two years.  In 
order to maintain the sample size needed to ensure statistically valid results, we would want to enroll 
approximately 133 patients over the study period to end up with at least 120 patients in the analysis. 

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4.  What is your plan for primary variable analysis? 
One-sided test for proportions 
 
5.  What is your plan for secondary variable analysis?  
N/A. We are only conducting a primary analysis. 
 
6. Have you been working with a statistician in designing this protocol? Yes 
IF YES, what is their name?  Joe Hart 
 
Will data from multiple sites be combined during analysis?  Yes 
 
 
Information from Outside Institution 
INSTRUCTIONS: 
You will need to submit an IRB approval or documentation from the outside institution documenting that they 
approve of this study being done at their site and info being shared with UVa.  
In order to obtain information from other sites in the future, you will be required to submit a modification of 
this protocol to the IRB-HSR.   
 
1. List the names of outside institutions that will be supplying data and/or specimens for this study.   
Answer/Response:  University of Florida-Jacksonville.  Medical University of South Carolina 
 
2. Describe the type of information you will receive from each site.   
Answer/Response:  We will receive de-identified subject demographics, infection information, pertinent 
dates, surgical procedures performed, and information re: treatment 
 
3.  Does the outside institution have an IRB?  
Answer/Response:  Yes. 
 
IF NO, list the names of the individuals who will be supplying the data and/or specimens.  
INSTRUCTIONS:  You will be required to submit a signed Unaffiliated Investigator Agreement for each 
person listed.  
Answer/Response: 
 
Biomedical Research 
 
1.  What will be done in this protocol?    

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 Patients who present with open fractures to UVA Health System will be approached for participation in the 
study.  After obtaining Informed consent, subjects will be randomized to Antibiotic Arm (experimental) or 
Placebo.  Administration of the local antibiotic in this study is being done solely for answering a research 
question on the efficacy of the antibiotic tobramycin in decreasing the risk and rate of infection. 
 
Subjects will be randomized to the experimental group, who will be injected locally at the wound cavity (i.e. 
fracture site, surrounding soft tissue which include muscle, and subcutaneous space) with 80mg/40mL of  
tobramycin after wound closure, and placebo group who will be injected locally with 40 mL 0.9% NS after 
wound closure. Systemic antibiotic will not be withheld and will be done along side the local injection of 
tobramycin.  If patient returns to the OR for repeat debridement procedures, the injection will be repeated.  If 
patient returns to the OR for repeat debridement procedures, the injection will be repeated.  The second 
injection will only be given if the subject undergoes a repeat procedure, and will be given two days later than 
the first injection.  By this time, serum tobramycin levels would have normalized, given the low does and time 
interval. . Dose volume will not be adjusted because the safety of this antibiotic assumes that the patient 
weights at least 16 kg, and any patient 18 years or older will weigh more than that. While systemic antibiotic 
treatment is standard of care, animal studies and early clinical case series data indicated that injection of 
aqueous aminoglycoside after wound closure locally could be a highly effective technique for wound infection 
prophylaxis[1].  In this study protocol, other aminoglycosides (eg. Gentamycin) will be allowed as part of 
standard systemic prophylaxis.  
 
Follow up data will be collected at 2 weeks, 6 weeks.  Clinical data will be collected from medical records  
2. List the procedures, in bullet form, that will be done for RESEARCH PURPOSES as stipulated in this 
protocol. 
• Medical record review at baseline and all subsequent study weeks up to 1 year after surgery 
• Randomization to Antibiotic ( tobramycin) arm or Placebo before surgery by clinical pharmacy program 
at UVA.  
• Experimental group will have the close wound injected with 80 mg/40mL of  tobramycin at the END of 
surgery 
• Control group will have 40 mL 0.9%NS injected into the closed wound at the end of the case 
• Follow up at 2 and 6 weeks at the clinic.  These visits to the clinic will coincide with the follow up as in 
standard of care for open fracture management.  
 
3. Will you be using data/specimens in this study that were collected previously, with the use of a research 
consent form, from another research study? NO 
 
4.  Will any of the procedures listed in item # 2 have the potential to identify an incidental finding? This 
includes ALL procedures, assessments and evaluations that are being done for RESEARCH PURPOSES that 
may or may not be considered investigational. yes 
 
►IF YES, check one of the following two options:  
___x__The examination(s) utilize(s) the same techniques, equipment, etc., that would be used if the 
subject were to have the examination(s) performed for clinical care.  There exists the potential for 
the discovery of clinically significant incidental findings.   

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• The PI takes full responsibility for the identification of incidental findings:  
• The PI will inform the subjects verbally of all incidental findings that are of clinical 
significance or are of questionable significance.   
• A follow-up letter describing the finding should be provided to the subject with 
instructions to either show the letter to their PC or if the subject has no PCP, the subject 
should be instructed to make an appointment at UVa or at the Free Clinic.   
 
5.  Do any of the procedures listed above, under question # 2, utilize any imaging procedures for RESEARCH 
PURPOSES? No 
 
6. Will you be using viable embryos? NO 
Will you be using embryonic stem cells? NO 
 
7.  Are any aspects of the study kept secret from the participants?  NO 
 
Is any deception used in the study?    NO 
  
If this protocol involves study treatment, explain how a subject will be transitioned from study treatment 
when they have completed their participation in the study.  NA 
 
 
 
 
 
Collaborative Site Analysis Studies 
 
1.  List the sites that will be sharing data/specimens.  
• University of Florida- Jacksonville  
• Medical University of South Carolina (MUSC) 
 
2. Will any data/specimens be sent to UVa for analysis from the sites outside of UVa? 
Only data.  There will be no data sent from UVA to other sites, data will only flow TO UVA. 
►IF YES, do you confirm you will have received a copy of the IRB approval from the outside 
site before receiving data/specimens from them?  Yes, confirmed. 
 
3.  Do you confirm you will have a Material Transfer Agreement (MTA) through the Grants and 
Contracts office prior to sending or receiving data/specimens? Yes, confirmed 
 
4. Describe the process for sharing safety concerns. We will have conference calls no less than twice per 
year.  If a SAE occurs and if it is deemed unexpected AND related there will be a conference call within 
5 days with the site-PI’s. 
INSTRUCTIONS 
• e.g. weekly conference calls, use of SAE forms, overall safety monitor etc.  

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• include frequency of communication 
• identify participants ( by role) in this process 
 
Collaborative Site Analysis Studies DSMP 
Type of Event 
To whom will it be 
reported: 
Time Frame for 
Reporting 
How reported? 
*Serious, unexpected 
and related or possibly 
related adverse events 
All Research Sites 
Within 15 days after 
the site PI receives 
knowledge of the 
event.   
IND/IDE Safety Report 
(Cover letter, copy of 
MedWatch/narrative) 
*Unanticipated Problem 
All Research Sites 
Within 15 calendar 
days from the time 
the Site PI receives 
knowledge of the 
event. 
Letter to Participating PIs, 
Copy of MedWatch or narrative 
Protocol 
Violations/Noncompliance 
The IRB-HSR only requires 
that MAJOR violations be 
reported, unless otherwise 
required by the sponsor. 
 
All Research Sites  
 
 
Within 7 calendar 
days from the time 
the study team 
received knowledge 
of the event.  
 
Protocol Violation, 
Noncompliance and Enrollment 
Exception Reporting Form 
http://www.virginia.edu/vprgs/ir
b/hsr_forms.html 
Go to 3rd bullet from the bottom. 
  
*as defined in each sites protocol  
 
 
 
 
Data and Safety Monitoring Plan. 
1.  Definition: 
1.1 How will you define adverse events (AE)) for this study?  
___X__An adverse event will be considered any undesirable sign, symptom or medical or 
psychological condition even if the event is not considered to be related to the investigational 
drug/device/intervention. Medical condition/diseases present before starting the investigational 
drug/intervention will be considered adverse events only if they worsen after starting study 
treatment/intervention.  An adverse event is also any undesirable and unintended effect of 
research occurring in human subjects as a result of the collection of identifiable private information 
under the research.  Adverse events also include any problems associated with the use of an 
investigational device that adversely affects the rights, safety or welfare of subject s. 
1.2 How will you define serious adverse events? 
_X___A serious adverse event will be considered any undesirable sign, symptom, or medical 
condition which is fatal, is life-threatening, requires or prolongs inpatient hospitalization, results 
in persistent or significant disability/incapacity, constitutes a congenital anomaly or birth 

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defect, is medically significant and which the investigator regards as serious based on 
appropriate medical judgment. An important medical event is any AE that may not result in 
death, be life-threatening, or require hospitalization but may be considered an SAE when, 
based upon appropriate medical judgment, it may jeopardize the patient and may require 
medical or surgical intervention to prevent one of the outcomes listed in the definitions of SAEs.  
1.3 What is the definition of an unanticipated problem?  
Do not change this answer 
An unanticipated problem is any event, experience that meets ALL 3 criteria below: 
 Is unexpected in terms of nature, severity or frequency given the research procedures that 
are described in the protocol-related documents AND in the characteristics of the subject 
population being studies 
 Related or possibly related to participation in research.  This means that there is a 
reasonable possibility that the incident may have been caused by the procedures involved 
in the research study. 
 The incident suggests that the research placed the subject or others at greater risk of harm 
than was previously known or recognized OR results in actual harm to the subject or others 
 
1.4 What are the definitions of a protocol violation and/or noncompliance?  
Do not change this answer 
A protocol violation is defined as any change, deviation, or departure from the study design or 
procedures of research project that is NOT approved by the IRB-HSR prior to its initiation or 
implementation.  Protocol violations may be major or minor violations.   
 
Noncompliance can be a protocol violation OR deviation from standard operating procedures, 
Good Clinical Practices (GCPs), federal, state or local regulations.   Noncompliance may be serious 
or continuing.  
Additional Information: see the IRB-HSR website at  
http://www.virginia.edu/vpr/irb/HSR_docs/Forms/Protocol_Violations_%20Enrollment_Exceptions
_Instructions.doc 
 
1.5 If pregnancy occurs how will this information be managed? 
___X__  Adverse Event- will follow adverse event recording and reporting procedures outlined in 
section 3.  
 
1.6 What is the definition of a Protocol Enrollment Exception?   
___X__NA- No outside sponsor 
 
1.7 What is the definition of a data breach? 
Do not change this answer 

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A data breach is defined in the HITECH Act (43 USC 17932) as an unauthorized acquisition, access, 
or use of protected health information (PHI) that compromises the security or privacy of such 
information. 
Additional Information may be found on the IRB-HSR Website: Data Breach 
2.  Identified risks and plans to minimize risk 
 
2.1 What risks are expected due to the intervention in this protocol? 
 
Expected Risks related to study 
participation. 
Frequency 
 
  Nephrotoxicity 
____Occurs frequently 
____Occurs infrequently 
_X___Occurs rarely 
____Frequency unknown 
Neurotoxicity manifested by 
ototoxicity – vestibular and 
auditory 
____Occurs frequently 
____Occurs infrequently 
_X___Occurs rarely 
____Frequency unknown 
Neurotoxicity manifested by 
numbness, skin tingling, 
muscle twitching and 
convulsions (in patients with 
preexisting renal damage 
and normal renal function 
with prolonged exposure to  
tobramycin  
__ X  Occurs frequently 
____Occurs infrequently 
_ ___Occurs rarely 
____Frequency unknown 
Nephrotoxicity in patients 
with impaired renal function 
and in those who received 
high dose of  tobramycin for 
prolonged period 
__X__Occurs frequently 
____Occurs infrequently 
_ ___Occurs rarely 
____Frequency unknown 
Violation of subject’s privacy and 
confidentiality 
Minimized due to the requirements of 
the privacy plan in this protocol 
 
2.2   List by bullet format a summary of safety tests/procedures/observations to be performed that will 
minimize risks to participants:   
 
• Renal and eighth cranial nerve function will be closely monitored, especially in patients with 
known or suspected reduced renal function at onset of therapy and also in those whose renal 
function is initially normal but who develop signs of renal dysfunction during therapy. 
• Urine will be examined for decreased specific gravity, increased excretion of protein and the 
presence of cells or casts. 

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• Blood urea nitrogen (BUN), serum creatinine or creatinine clearance will be determined per 
standard of care during hospitalization.   
• Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears or hearing loss) or 
cephrotoxicity will prompt closer monitoring and consultation of ENT and/or the nephrology 
teams.  
• Concurrent and/or sequential systemic or topical use of other potentially neurotoxic and 
nephrotoxic drugs including: cisplatin, cephaloridine, kanamycin, amikacin, neomycin, 
polymyxin B, colistin, paromomycin, streptomycinvancomycin, and viomycin will be avoided.  
Age and dehydration which increase the risk of toxicity will be monitored. Concurrent use of 
tobramycin with potent diuretics such as ethacrynic acid or furosemide will be avoided.  All 
patients on diuretics will have them held on the day prior to surgery to avoid complications.  
Diuretics will be withheld after subject signs Informed consent 
• Injecting the drug directly into the fracture site will pose no greater than risk than 
intramuscular injection of tobramycin. 
Clinical care team will be notified of the need to avoid other potentially nephrotoxic or neurogenic 
agents. A note will be put in Epic to this effect. 
 
2.3 Under what criteria would an INDIVIDUAL SUBJECT’S study treatment or study participation be stopped 
or modified 
 
__X___Treatment would be stopped if the subject had a serious adverse event deemed related to 
study, or study drug will be increased if the subject tolerates dosing 
 
2.4 Under what criteria would THE ENTIRE STUDY need to be stopped.   
__X___Per IRB, PI, DSMB, or sponsor discretion 
 
2.5 What are the criteria for breaking the blind/mask? 
 
__X___Other: Confidentially compromised 
 
2.6 How will subject withdrawals/dropouts be reported to the IRB prior to study completion? 
__X___IRB-HSR continuation status form  
 
3.  Adverse Event / Unanticipated Problem Recording and Reporting 
 
3.1 Will all adverse events, as defined in section 1.1, be collected/recorded? no 
►IF NO, what criteria will be used?  
 
___X__Only adverse events deemed related/possibly related to study  
 
3.2 How will adverse event data be collected/recorded?  
_____Paper AE forms/source documents  
__X___Spreadsheet: paper or electronic 

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3.3. How will AEs be classified/graded? Check all that apply 
_X_ Serious/Not serious Required for all protocols 
 
 
3.4 What scale will the PI use when evaluating the relatedness of adverse events to the study 
participation?   
 
__X___The PI will determine the relationship of adverse events to the study 
 using the following scale: 
 
Related:      
 
AE is clearly related to the intervention 
Possibly related: 
AE may be related to the intervention 
Unrelated:  
 
AE is clearly not related to intervention 
 
3.5 When will recording/reporting of adverse events/unanticipated problems begin? 
__X___After subject begins study drug/ device placement/intervention /study-related 
procedure/specimen collection 
 
3.6 When will the recording/reporting of adverse events/unanticipated problems end? 
__X___ Subject completes intervention and follow up period of protocol 
 
3.7 How will Adverse Events, Unanticipated Problems, Protocol Violations and Data Breaches be 
reported?  Complete the table below to answer this question 
 
Type of Event 
To whom will it 
be reported: 
Time Frame for 
Reporting 
How reported? 
Any internal event resulting 
in death that is deemed 
DEFINITELY related to (caused 
by) study participation 
An internal event is one that 
occurs in a subject enrolled in 
a UVa protocol 
IRB-HSR 
Within 24 hours 
IRB Online and phone call 
 
www.irb.virginia.edu/ 
 
Internal, Serious, 
related/possibley related 
Unexpected adverse event  
 
  
IRB-HSR 
Within 7 calendar 
days from the 
time the study 
team received 
knowledge of the 
event. 
 
Timeline includes 
submission of 
signed hardcopy 
of AE form. 
IRB Online 
 
www.irb.virginia.edu/ 
 
Unanticipated Problems that 
are not adverse events or 
IRB-HSR 
 
Within 7 calendar 
days from the 
Unanticipated Problem report form.  
 

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protocol violations  
This would include a Data 
Breach.   
 
time the study 
team received 
knowledge of the 
event.  
http://www.virginia.edu/vprgs/irb/HSR_d
ocs/Forms/Reporting_Requirements-
Unanticipated_Problems.doc ) 
Protocol 
Violations/Noncompliance 
The IRB-HSR only requires that 
MAJOR violation be reported, 
unless otherwise required by 
your sponsor, if applicable. 
 
OR 
 
Enrollment Exceptions 
See definition- only allowed if 
there is a commercial sponsor 
or a DSMB that has granted 
the enrollment exception.  
IRB-HSR 
 
 
Within 7 calendar 
days from the 
time the study 
team received 
knowledge of the 
event.  
 
Protocol Violation, Noncompliance and 
Enrollment Exception Reporting Form 
 
 
http://www.virginia.edu/vprgs/irb/hsr_fo
rms.html 
 
Go to 3rd bullet from the bottom. 
  
Data Breach  
The UVa 
Corporate 
Compliance and 
Privacy Office, a 
 
 
 
ITC:  if breach 
involves  
electronic data-  
 
 
 
 
Police if breach 
includes items 
that are stolen: 
 
Stolen on UVA 
Grounds 
 
OR  
 
Stolen off UVa 
Grounds- contact 
police 
department of 
jurisdiction of last 
known location of 
PHI 
As soon as 
possible and no 
later than 24 
hours from the 
time the incident 
is identified. 
 
As soon as 
possible and no 
later than 24 
hours from the 
time the incident 
is identified. 
 
IMMEDIATELY.  
 
 
UVa Corporate Compliance and Privacy Office- 
Phone 924-9741 
 
 
 
 
ITC:  Information Security Incident Reporting 
procedure,  
http://www.itc.virginia.edu/security/reporting.ht
ml 
 
 
 
 
UVa Police-Phone- (434) 924-7166 
  
 
4.    How will the endpoint data be collected/recorded.  
__X___Protocol specific case report forms  

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_____Source documents 
_____Database: Specify   Answer/Response:  
_____Other: Specify   Answer/Response: excel spreadsheet with de-identified data from other 
institutions will be combined with the excel spreadsheets at UVA.  The University of Virginia will not be 
transferring data to other institutions, only receiving data. 
 
5. Data and Safety Oversight Responsibility 
 
5.1. Who is responsible for overseeing safety data for this study?  
 
__X___No additional oversight body other than PI at UVa Skip question 5.2 
_____All site PI’s (for protocols in which there is no common protocol but data from  multiple sites will be 
combined for analysis: Collaborative Site Analysis Studies)  
 
_____The UVa Cancer Center Data and Safety Monitoring Committee   
If your study involves cancer patients, see Question # 6 to help you decide if you should 
check this option. 
 
_____Medical Monitor   
This could include such things as the overall PI of a multisite trial. 
 
_____DSMB/ DSMC 
 
If your study is NIH funded, check with the center to determine if they require a DSMB for this study. 
The following groups/individuals are NOT considered a DSMB: 
DO NOT CHECK THIS BOX 
•  Members of the study team  
• Medical monitors from a commercial drug company  
•  Safety review committee within a commercial drug company  
•  UVa Cancer Center Data and Safety Monitoring Committee  
•  The overall PI of a multi-site trial or a single individual who may serve as the medical monitor. 
 
The following groups are considered a DSMB: 
•  A group of scientists, physicians, statisticians and others that are not employees of the commercial drug 
company that are appointed to oversee the data and safety of subjects in the study.  
•  A group of scientists, physicians, statisticians and others that are, or are not, employees of UVa, are not 
affiliated with the UVa study team, and are appointed to oversee the data and safety of the subjects in the study. 
 
DSMB Charter Template 
A template for a DSMB charter may be found on the IRB-HSR Website at DSMB Charter Template. 
_____Research Monitor:   Insert Name Answer/Response:  ____________________________ 
Name required for protocols funded by the Department of Defense 
_____Other: Specify   Answer/Response: 

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5.2. What is the composition of the reviewing body and how is it affiliated with the sponsor? 
_____Information may be found in the UVa Cancer Center Institutional DSMP 
___X__ Collaborative Site Analysis Study- see CSAS section of this DSMP  
_____Other- Specify   Answer/Response: 
  
5.3. What items will be included in the aggregate review conducted by the PI?  
_____NA- PI is not the overall person overseeing the safety data for this study.     
__X___All adverse events 
_X___Unanticipated Problems 
_X____Protocol violations/Issues of noncompliance 
_X____Audit results 
_X___Application of dose finding escalation/de-escalation rules  
These should be outlined under 2.4. 
__X___Application of study designed stopping/decision rules 
__X___Early withdrawals 
__X__Whether the study accrual pattern warrants continuation/action 
__X__Endpoint data 
_____Other: Specify   Answer/Response: 
 
5.4 How often will aggregate review occur? 
For additional information on aggregate review see: 
www.virginia.edu/vpr/irb/hsr/continuations.html#aggreview 
_____NA- PI is not the overall person overseeing the safety data for this study.     
_____Per Enrollment/Events 
__X___Annually 
_____Semi-Annually 
_____Quarterly 
_____Monthly 
_____Other: Specify   Answer/Response: 
 
5.5. How often will a report, regarding the outcome of the review by the DSMB/DSMC, be sent to the 
UVa PI?  
_____NA- PI is not the overall person overseeing the safety data for this study.     
_____Per Enrollment/Events 
_____Annually 
_____Semi-Annually 
_____Quarterly 
_____Monthly 
__X___Other: Specify   Answer/Response: N/A no DSMB 

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5.6. How will a report of the information discussed in question 5.4 OR 5.5 be submitted to the IRB?   
 
___X__Part of IRB-HSR continuation status form 
_____Separate report from DSMB/DSMC or UVa PI 
_____Other: Specify   Answer/Response: 
 
Risk/ Benefit Analysis 
1.  What are the potential benefits for the participant as well as benefits which may accrue to society in 
general, as a result of this study? 
Decreased infection rates, decreased re-admission to hospital and repeat surgery, decreased time to union, 
decreased pain and recovery time of patient, decreased morbidity associated with open fractures. The 
benefits to the society are immense.  This avenue of research has the potential to bring down the cost of 
antibiotic treatment, avoid the negative side effects of the antibiotics such as nephrotoxicity and ototoxicity in 
people with kidney disease, and improved delivery of drug to the wound site. 
 
2.  Do the anticipated benefits justify asking subjects to undertake the risks?   
Yes. The risk-benefit analysis is acceptable. 
 
Bibliography 
1. Rathbone CR, Cross JD, Brown KV et al. Effect of various concentrations of antibiotics on osteogenic cell    viability and 
activity. J Orthop Res 2011;29(7):1070-4. 
2. Eckman JB,Jr, Henry SL, Mangino PD et al. Wound and serum levels of  tobramycin with the prophylactic use of  tobramycin-
impregnated polymethylmethacrylate beads in compound fractures. Clin Orthop Relat Res 1988;(237)(237):213-5. 
3. Humphre JS, Mehta S, Seaber AV et al. Pharmacokinetics of a degradable drug delivery system in  bone. Clin Orthop Relat 
Res 1998;349:218-24. 
4. Tsourvakas S. Local Antibiotic Therapy in the Treatment of Bone and Soft Tissue Infections. In: Danilla S, editor. Rijeka, 
Croatia; 2012.  
5. Burdon DW. Principles of antimicrobial prophylaxis. World J Surg 1982;6:262-7. 
6. Lovallo J, Helming J, Jafari SM et al. Intraoperative intra-articular injection of gentamicin: will it decrease  the risk of 
infection in total shoulder arthroplasty? J Shoulder Elbow Surg 2014;23(9):1272-6. 

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7. Yarboro SR, Baum EJ, Dahners LE. Locally administered antibiotics for prophylaxis against surgical  wound infection. An in 
vivo study. J Bone Joint Surg Am 2007;89(5):929-33. 
8. Cavanaugh DL, Berry J, Yarboro SR et al. Better prophylaxis against surgical site infection with local as well as systemic 
antibiotics. An in vivo study. J Bone Joint Surg Am 2009;91(8):1907-12. 
APPENDIX:  Legal/Regulatory 
Recruitment 
The following procedures will be followed: 
• Finders fees will not be paid to an individual as they are not allowed by UVa Policy. 
• All recruitment materials will be approved by the IRB-HSR prior to use.  They will be submitted to 
the IRB after the IRB-HSR has assigned an IRB-HSR # to the protocol. 
• Only those individuals listed as personnel on this protocol will recruit and or conduct the 
consenting process with potential subjects.  
 
Retention Incentives 
Any item used by the sponsor/ study team to provide incentive to a subject to remain in the study, other than 
compensation identified in the Payment section, will be submitted to the IRB for review prior to use.  The IRB-
HSR will provide the study team with a Receipt Acknowledgement for their records.  Retention incentive items 
are such things as water bottles, small tote bags, birthday cards etc.  Cash and gift cards are not allowed as 
retention incentives.  
 
Clinical Privileges 
The following procedures will be followed:  
• Investigators who are members of the clinical staff at the University of Virginia Medical Center must 
have the appropriate credentials and been granted clinical privileges to perform specific clinical 
procedures whether those procedures are experimental or standard.  
• The IRB cannot grant clinical privileges.   
• Performing procedures which are outside the scope of the clinical privileges that have been granted 
may result in denial of insurance coverage should claims of negligence or malpractice arise. 
• Personnel on this protocol will have the appropriate credentials and clinical privileges in place before 
performing any procedures required by this protocol.  
• Contact the Clinical Staff Office- 924-9055 or 924-8778 for further information. 
 
Sharing of Data/Specimens 
Data and specimens collected under an IRB approved protocol are the property of the University of Virginia.  
You must have “permission” to share data/ specimens outside of UVa other than for a grant application and or 
publication.  This “permission” may come in the form of a contract with the sponsor or a material transfer 
agreement (MTA) with others.  A contract/ MTA is needed to share the data outside of UVa even if the data 
includes no HIPAA identifiers and no code that could link the data back to a HIPAA identifier.   

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• No data will be shared outside of UVa, beyond using data for a grant application and or publication, 
without a signed contract/MTA approved by the SOM Grants and Contracts office/ OSP or written 
confirmation that one is not needed. 
• No specimens will be shared outside of UVa without a signed contract/MTA approved by the SOM 
Grants and Contracts office/ OSP or written confirmation that one is not needed. 
 
Prisoners 
If the original protocol/ IRB application stated that no prisoners would be enrolled in this study and 
subsequently a subject becomes a prisoner, the study team must notify the IRB immediately.  The study team 
and IRB will need to determine if the subject will remain in the study.  If the subject will remain in the study, 
the protocol will have to be re-reviewed with the input of a prisoner advocate.  The prisoner advocate will also 
have to be involved in the review of future continuations, modifications or any other reporting such as 
protocol violations or adverse events.   
 
Prisoner- Individuals are prisoners if they are in any kind of penal institution, such as a prison, jail, or juvenile 
offender facility, and their ability to leave the institution is restricted. Prisoners may be convicted felons, or 
may be untried persons who are detained pending judicial action, for example, arraignment or trial. 
For additional information see the OHRP website at  http://www.hhs.gov/ohrp/policy/populations/index.html 
 
Compensation in Case of Injury  
If a subject requests compensation for an injury, the study team should notify the IRB-HSR (924-
9634/2439847) the UVa Health System Patient Relations Department (924-8315).  As a proactive courtesy, the 
study team may also notify UVa Health System Patient Safety and Risk Management (924-5595). 
 
On request, the study team should provide  the Risk Management Office with the following 
information/documents: 
• Subject Name and Medical Record Number 
• Research medical records 
• Research consent form 
• Adverse event report to IRB 
• Any letter from IRB to OHRP 
 
Subject Complaints  
During a research study, the study team may receive complaints from a subject.  If the study team is uncertain 
how to respond to a complaint, or is unable to resolve it with the subject, the study team may contact the IRB-
HSR (924-9634/243-9847), the UVa Health System Patient Relations Department (924-8315). 
 
Request for Research Records from Search Warrant or Subpoena 
If the study team receives a request for research records from a search warrant or subpoena, they should 
notify UVa Health Information Services at 924-5136. It is important to notify them if information from the 
study is protected by a Certificate of Confidentiality.   

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APPENDIX:  Safeguards for Cognitively Impaired 
1. What additional safeguards that will be employed to protect the cognitively impaired subjects?    
Use of Surrogate decision-maker when permitted by law, i.e. a legally authorized representative via use of 
power of attorney/advance directive for research. 
 
2.  The following steps will be taken to determine the capacity of a potential subject to give consent for 
themselves.  
A.  If there is concern that a potential subject/ subject may be cognitively impaired a determination of 
incompetence will be made after an evaluation by a person with the appropriate expertise to make 
such a determination as delegated by the PI.   If the subject is a patient in the UVa Medical Center, the 
Medical Center Policy No. 0024 will also be followed.  The determination of competency must be 
documented in writing.   
 
B.  The following methods below will be used to determine capacity for consent: 
__X__   Subject is also a patient in the UVa Medical Center and Medical Center Policy No. 0024 
will be followed.  
___X_   Will rely on individual observation of and interaction with the potential subject as well 
as the opinion of the medical provider or caregiver, when available. The prospective 
subject should demonstrate competence in relation to the proposed study in order to be 
judged capable of providing informed consent for that study. In general, an assessment 
an individual's capacity to consent will be based on her/his:  
• Ability to communicate a choice;  
• Ability to understand relevant information;  
• Ability to appreciate the nature of the situation and its likely consequences; 
and,  
• Ability to manipulate information rationally (1)  
 
 
C.  An individual will be considered unable to provide consent if he or she has:  
• An inability to express or communicate a preference or choice (cannot make up his/her mind, 
is comatose, or has severe psychotic thought disorders, etc.);  
• An inability to understand a situation and its potential consequences as well as the impact of 
study participation on those circumstances (does not understand that he/she may be hurt 
or may not be helped or cannot distinguish research from treatment); and/or,  
• An inability to provide a logical rationale for participation/no participation in a study (cannot 
address risk/benefit-related reasons for or against participation in a study.  
 
 
 
 
3.  The following steps will be taken to document the determination of competency to consent. 
___X__   A note to file will be written and filed in the study files and/or medical records to describe the 
consenting process.  The note will include a description of methods used to determine capacity 

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of the subject to consent.  The note should also include the name of the person determining 
competency of the subject.  May use the SOM CTO form Determination of Capacity to 
Consent. 
 
 
4.  When will subjects capacity to consent be assessed? 
__X___ Prior to initial consenting process if there is a concern that the potential subject has a cognitive 
impairment.  Must be checked for all protocols.  
 
___x__   On a periodic basis throughout the study process if there is a concern that the potential 
subject has a cognitive impairment. Must be checked if the study is ongoing and there is the possibility 
that the subject may regain their cognitive ability and be able to consent for themselves. 
 
5.  Will UVa researcher conduct the study outside the state of Virginia?  NO 
 
6. Are you requesting the use of a Legally Authorized Representative?YES 
 
►IF YES, do you confirm that this study includes none of the following which are conditions which limit 
the use of an LAR in Virginia?  
1. non-therapeutic research unless it is determined by the human research committee (IRB) that 
such non-therapeutic research will present no more than a minor increase over minimal risk to 
the human subject. 
2. participation in human research on behalf of a prospective subject if the legally authorized 
representative knows, or upon reasonable inquiry ought to know, that any aspect of the human 
research protocol is contrary to the religious beliefs or basic values of the prospective subject, 
whether expressed orally or in writing. 
3. participation in human research involving non-therapeutic sterilization, abortion, psychosurgery 
or admission for research purposes to a facility or hospital as defined by the Code of Virginia at § 
37.1-1. 
Answer/Response: YES 
 
 
 
APPENDIX:  Drug Information 
1   What is the drug name, manufacturer and IND# if available?    
 Tobramycin injectable 80mg/2ml,  
Hospira at this time, but subject to change. 
 
2.   If IND application has been submitted to the FDA, who is the Principal Investigator on the IND?     
SOM CTO review on file-IND exempt 
 
3.  What is the phase or stage of this study?   Phase 3 

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APPENDIX:  Pharmacy-Investigational Drugs/Biologics  
1.   What is the name of the investigational drug/biologic?    
 tobramycin  
 
2. Where will the subjects be seen for the administration/dispensing of the drug?     
Inpatient Unit:  In the operating room 
 
3.  What dose will be utilized in this study?    
Trobramycin 80mg/40mL 
 
4. What will be the frequency of dosing in this study?    
Once.  The second dose that will be given will be the same randomization treatment as the first injection. 
 
5.  What will be the duration of dosing in this study?    
Once dose administered over 1 minute  
 
6.  What route of administration will be utilized?    
Injection into a closed wound/subcutaneous tissue  
 
 
 
7.  Will drug need to be prepared by the UVa Investigational Drug Service (IDS)?     
 Investigational pharmacy will store the drug and perform the randomization to drug or placebo, and 
provide the drug to the surgeons on the day of surgery.  The randomization code will be stored by the 
IDS Pharmacy  on a spreadsheet. 
 
8.  Are there any special handling instructions mandated by the study (e.g. weighing hazardous materials)?    
No 
 
9.  Does the protocol provide provisions for dose titration, dose reductions, and or re-challenged (if drug is 
stopped), etc.?   No 
 
10.  How will missed doses be handled?    n/a 
 
11.  Will a comparator (active or placebo) be utilized in the protocol?   Yes 
 
►IF YES, comparator is: Placebo:  0.9% Normal Saline injection of 40mL 
 
12.  Does this study involve research on a drug, biologic, supplement or food additive?    Yes 
►IF YES, is this study investigator initiated?   Yes 

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IF YES, answer questions # 13 and 14               IF NO, answer question # 13 only 
13    Are you using a drug/supplement/ food additive in a manner not approved by the FDA?    Yes 
IF YES, answer questions 13a-13f 
You may reference the non-IRB protocol to answer these questions. 
13a.  Describe pertinent animal data that is available regarding the toxicity/safety of this drug.    
Yarboro SR, Baum EJ, Dahners LE.  Locally administered antibiotics for prophylaxis against surgical wound 
infection.  An in vivo study.  J Bone Joint Surg Am.  2008 Feb;90 (2):384.   
A 2008 study published by the PI in this study used a rat model, in which they inoculated a surgical wound in 
the quadriceps muscle with 8.0 x 10(5) colony-forming units of Staphylococcus aureus and then administered 
one of seven types of treatment: no treatment (control), bacitracin irrigation, calcium sulfate flakes, systemic 
gentamicin, local aqueous gentamicin, local gentamicin-loaded calcium sulfate flakes, and a combination of 
local gentamicin-loaded calcium sulfate and systemic gentamicin. The seven treatment groups consisted of ten 
rats each. To further evaluate a trend, the group treated with systemic gentamicin and the one treated with 
local gentamicin solution were extended to include twenty-five and twenty-seven rats, respectively. At forty-
eight hours postoperatively, specimens from the wounds were obtained for quantitative cultured. They found 
that the control group, the group treated with bacitracin irrigation, and the one treated with plain calcium 
sulfate had very high bacterial counts and high mortality rates while the groups treated with gentamicin had 
low bacterial counts and a 100% survival rate. Local gentamicin was significantly more effective than systemic 
gentamicin in reducing bacterial counts. 
13b. Describe pertinent human data that is available regarding the toxicity/safety of this drug.    
From a patient safety standpoint, this drug has been shown to be appropriate for use locally based on cell 
culture data. The 2mg/ml concentration of aminoglycoside injected into the wounds after closure is high 
enough to decrease replication of osteoblasts, though not to cause cell death, at sustained concentrations in 
vitro (4,5).  In vivo, this concentration decreases quickly as it diffuses. 
 
 
13c. Have there been any human deaths associated with this drug?   No 
13d. In how many humans has this drug been used previously?    
 tobramycin is used routinely in patients across the country through a systemic route of administration.   
 
13e. If this protocol will be used in children describe any previous use of this drug with children of a 
similar age range.   None 

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14.  Do the following criteria apply? Check all that apply 
 
_____  The investigation is intended to be reported to FDA as a well-controlled study in support of a 
new indication for use or intended to be used to support any other significant change in the labeling 
for the drug; 
 
_____  If the drug that is undergoing investigation is lawfully marketed as a prescription drug product, 
the investigation is intended to support a significant change in the advertising for the product; 
 
_____  The investigation does involve a route of administration or dosage level or use in a patient 
population or other factor that significantly increases the risks (or decreases the acceptability of the 
risks) associated with the use of the drug product. 
 
If Not checked- explain why you believe the risk to subjects is not increased:   
 tobramycin has long been used in treatment and prophylactic regimens in humans; the dose used in 
this experiment has been proven on a cellular level in animal models to be non-toxic and effective in 
prophylaxis against infection.   
 
_X___  The investigation will be conducted in compliance with the requirements for institutional 
review set part in part 21CFR56 and with the requirements for informed consent set forth in part 
21CFR50 ; and    
 
_X___ The investigation will be conducted in compliance with the requirements of 21CFR312.7 
(Promotion and charging for investigational drugs) 
  
 
15.  Is this a post-marketing study?      No 
 
APPENDIX:  Recruitment 
 
1. How do you plan to identify potential subjects? 
 
a.__X__ Chart Review/ Clinic Schedule Review/ Database Review from a database established for 
health care operations (departmental clinical database) or an Improvement Project (e.g.  
Performance Improvement, Practice Improvement, Quality Improvement).   
 
If you plan to obtain data from the UVa Enterprise Data Warehouse (EDW) please see option b 
below.   
 
DHHS: Study team requests Waiver of Consent to identify potential subjects.  
 
HIPAA: Allowed under Preparatory to Research if PHI to be accessed.  
 
IMPORTANT 

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Keep in mind that PHI in the medical record may only be accessed by individuals who 
work under the UVa HIPAA covered entity; which means they meet one of the following 
criteria: 
--a UVa student working in the UVa HIPAA Covered Entity*   
--a faculty or staff member in a PAID appointment in  the UVA HIPAA Covered Entity* 
 
b____ Review of a database that was established to keep data to be used for future 
research such as the CDR, departmental research database or use of data from a separate 
current active research protocol.     
If you plan to obtain data from the UVa Enterprise Data Warehouse (EDW) you are required 
to submit your request to the CDR.  The CDR staff will work with the EDW to obtain the data 
you need.   
DHHS: Study team requests Waiver of Consent to identify potential subjects. 
 
HIPAA: Allowed under Preparatory to Research if PHI to be accessed.  
 
IMPORTANT 
Keep in mind that PHI in the medical record may only be accessed by individuals who 
work under the UVa HIPAA covered entity; which means they who meet one of the 
following criteria: 
--a UVa student working in the UVa HIPAA Covered Entity*   
--a faculty  or staff member in a PAID appointment in  the UVA HIPAA Covered Entity* 
 
The information from which you are obtaining potential subjects must also have an IRB 
protocol approval.  If this item is checked, enter the IRB # below.  
 
IRB# ________________ 
If obtaining information from the Clinical Data Repository (CDR) insert IRB # 10797 
 
c. ____ Patients UVa health care provider supplies the UVa study team with the patients 
contact information without patients’ knowledge. 
 
DHHS: Study team requests Waiver of Consent to identify potential subjects.  
 
HIPAA: Allowed under Preparatory to Research if PHI will be shared by the health care 
provider.  
 
IMPORTANT 
Keep in mind that PHI may only be given to individuals who work under the UVa HIPAA covered 
entity; which means they meet one of the following criteria: 
--a UVa student working in the UVa HIPAA Covered Entity*   
--a faculty or staff member in a PAID appointment in the UVA HIPAA Covered Entity* 

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d. ____ Patient obtains information about the study from their health care provider.  The 
patient contacts the study team if interested in participating. (Health care provider may 
or may not also be the a member of the study team) 
DHHS:  NA 
HIPAA:  Allowed under Health Care Operations 
 
If this choice is checked, check 3d-INDIRECT CONTACT below.  
 
e. ____ Potential subjects will not be directly identified. They will respond to an 
advertisement such as a flyer, brochure etc.   
If this choice is checked, check 3d- INDIRECT CONTACT below.  
DHHS & HIPAA:  NA 
 
f. _____ Potential subjects have previously signed a consent to have their name in a 
registry/database to be contacted for future studies of this type.   
IRB#  of registry/ database:  ________________ 
DHHS & HIPAA:  NA 
 
 
If item # a, b or c is checked above and if this protocol involves the use of protected health 
information do you confirm the following to be true? yes 
• The use or disclosure is sought solely to review protected health information as 
necessary to prepare the research protocol or other similar preparatory purposes. 
• No PHI will be removed from the UVa covered entity. 
• The PHI that the researcher seeks to use or access is necessary for the research 
purposes. 
 
2. How will potential subjects be contacted? 
To "contact" a potential subjects refers to the initial contact you plan to take to reach a potential 
subject to determine if they would be interested in participating in your study.  This may include 
direct contact by such methods as by letter, phone, email or in-person or indirect contact such as 
the use of flyers, radio ads etc.  
 
If your study involves more than one group of subjects (e.g. controls and cases or subjects and 
caregivers) note below which groups are being contacted by the given method.    
 
Check the methods below you plan to utilize: 
a.____Direct contact of potential subjects by the study team via letter, phone, direct e-
mail. Members of study team ARE NOT health care providers of patients.  Information 
will not be collected from psychotherapy notes.  
Note:  Letter, phone, direct email scripts must be approved by IRB prior to use.  
See IRB-HSR Website for templates. 

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DHHS/HIPAA: Study team requests a Waiver of Consent and Waiver of HIPAA 
Authorization to contact potential subjects.  
 
IMPORTANT:   
Keep in mind that if PHI was collected during the identification phase that contact with 
potential subjects may only be performed by individuals who work under the UVa HIPAA 
covered entity; which means they meet one of the following criteria: 
 
a UVa student working in the UVa HIPAA Covered Entity*   
 
a faculty  or staff member in a PAID appointment in  the UVA HIPAA Covered Entity* 
 
b.____Potential subjects will be approached while at UVa Hospital or Health Clinic by a 
person who is NOT a member of their health care team.  Information will not be 
collected from psychotherapy notes.  
DHHS & HIPAA: Study team requests a Waiver of Consent and a Waiver of HIPAA 
Authorization to contact potential subjects.  
 
IMPORTANT:   
Keep in mind that contacting individuals in a clinical setting may only be performed by 
individuals who work under the UVa HIPAA covered entity; which means they  meet one of the 
following criteria: 
a UVa student working in the UVa HIPAA Covered Entity*   
a faculty  or staff member in a PAID appointment in  the UVA HIPAA Covered Entity* 
 
You should share the following information with the potential subject:  
• Your name 
• Who you are:  physician, nurse etc. at the University of Virginia.    
• Why you want to speak with them 
• Ask if you have their permission to explain the study to them 
• If asked about how you obtained their information use one of the following as an 
option for response.     
o DO NOT USE THIS RESPONSE UNLESS YOU HAVE OBTAINED PERMISSION 
FROM THEIR UVa PHYSICIAN:  Your doctor, Dr. insert name wanted you 
to be aware of this research study and gave us permission to contact you.    
o We obtained your information from your medical records at UVa.   
o Federal regulations allow the UVa Health System to release your 
information to researchers at UVa, so that we may contact you regarding 
studies you may be interested in participating.  We want to assure you 
that we will keep your information confidential.  

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• IF THE PERSON SEEMS ANGRY, HESITANT OR UPSET, THANK THEM FOR THEIR 
TIME AND DO NOT ENROLL THEM IN THE STUDY.  YOU MAY ALSO REFER THEM 
TO THE IRB-HSR AT 924-9634. 
 
c.__X__Direct contact of potential subjects by the study team by approaching in person 
at UVa or via letter, phone, direct e-mail. Members of study team contacting potential 
subjects ARE health care providers of patients.  
If you are not approaching them in person but using a letter, phone call or direct email 
please note that the letter, phone, direct email scripts must be approved by IRB prior to 
use.   
See IRB-HSR Website for templates. 
 
DHHS:  Study team requests a Waiver of Consent to contact potential subjects 
HIPAA:  Allowed under Health Care Operations.  
 
d.____ Indirect contact (flyer, brochure, TV, broadcast emails, patient provided info 
about the study from their health care provider and either the patient contacts study 
team or gives their healthcare provider permission for the study team to contact them.) 
The indirect method used (flyer, brochure, TV, broadcast emails) must be approved by 
the IRB prior to use.    The IRB does not need to review any type of script to use when 
the potential subject responds to the indirect method.   
 
DHHS & HIPAA:  NA 
 
 
e. ____  Potential subjects are not patients.  The study does not include obtaining 
subjects health information.   Subjects will be contacted directly via email, phone, 
letter or presentation in group setting with consent then obtained individually in a 
private setting.  
If you are not approaching them in person but using a letter, phone call or direct 
email please note that the letter, phone, direct email scripts must be approved by 
IRB prior to use.   
See IRB-HSR Website for templates. 
 
DHHS: Study team requests a Waiver of Consent to contact potential subjects.  
HIPPA:  NA 
 
3. Will any additional information be obtained from a potential subject during "prescreening"?   
NO 
 
4. Do you plan to ask the subjects to do anything, other than answering questions, for the study 
prior to signing a consent? NO 
 

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5. How will the consenting process take place with either the prospective subject, the subject’s 
legally authorized representative or parent/legal guardian of a minor ( if applicable)?    
HIPPA:  
If the individual, obtaining consent, works under the HIPAA Covered Entity consenting is 
covered under Health Care Operations. 
 
If the individual obtaining consent does not work under the HIPAA covered entity, HIPAA does 
not apply.  
 
Subjects who are being treated for open fractures at University of Virginia, who agree to participate in the 
study will be asked to sign an informed consent at the hospital.  Subjects will be given ample time to go over 
the informed consent, and an opportunity will be provided to ask questions.  Subjects are also allowed to 
discuss with family and relatives before they sign the consent. Anywhere, from one hour to one week may 
pass between written consent and initiation of study procedures.  
 
If subject is unresponsive or intubated, and cannot adequately answer the questions and if it is determined 
that the patient’s level  of cognition is not likely to change before surgery, a legally authorized representative 
(LAR) will be approached for proxy consent.  Guidance will be provided to assist the LAR in making consent 
decision. They will be advised to base the decision on the patient’s expressed wishes, or, what they believe the  
patient would have desired under the circumstances of the injury. His or her beliefs and values. When 
participant regains capacity to consent during the study period, the participant will be re-consented using 
standard consenting procedures as described below. 
 
6. Will subjects sign a consent form for any part of the study? NO 
 
7.  Will the study procedures be started the same day the subject is recruited for the study?  
This will depend on the patient’s clearance status for the OR.  Often, some patients will have to 
be resuscitated in an ICU setting prior to going to the OR for definitive treatment and wound 
closure.  Also, some wounds cannot be closed during the index procedure and they will have to 
be taken back to the OR for further treatment and wound closure. 
 
►IF YES, explain in detail why the subject cannot be given more time to make a decision to 
consent.  
Open fractures are surgical emergencies that need to be irrigated/debrided and stabilized and 
possibly closed as quickly as possible. 
 
►IF YES, explain in detail what will be done to assure the potential subject has enough time 
to make an informed decision. 
The study will be explained to the patient before the patient is brought back to the OR and the 
patient will have adequate time to ask questions and discuss his or her eligibility in the study 
with family and friends in the preoperative holding area or in the respective room. 
 

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8.  Is there the potential to recruit economically or educationally disadvantaged subjects, or other 
vulnerable subjects such as students or employees?YES 
 
IF YES, what protections are in place to protect the rights and welfare of these subjects so 
that any possible coercion or undue influence is eliminated?   
Subjects will be told that their participation is totally voluntary.  If they are employees of 
UVA, they will be assured that their decision to participate or not will not affect their 
job. If they are students, they will be assured that their decision will not in any way 
affect their grades.   
 
9. Do you need to perform a “dry run” of any procedure outlined in this protocol?   NO 
 
 
APPENDIX:  Privacy Plan for Studies With Consent/HIPAA Authorization 
 
1. Answer the questions below (1A-1G) to describe the plan to protect the data from improper use and disclosure.   
 
1A.  Will any HIPPA identifiers be collected by the UVa study team ?       YES 
INSTRUCTIONS:   
Answer YES to any item below that will be written down/kept/recorded in any way.  
If you answer NO to all items it means you would never be able to go back and obtain any additional data 
about an individual.   

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YES 
NO 
HIPAA Identifier 
 
X 
1.  Name 
 
X 
2.  Postal address information, other than town or city, state, and zip code 
 
X 
3.  Age or Date of Birth if over the age of 89 
 
X 
4.  Telephone numbers 
 
X 
5.  Fax numbers 
 
X 
6.  Electronic mail addresses 
 
X 
7.  Social Security number 
X 
 
8.  Medical Record number 
 
X 
9.  Health plan beneficiary numbers 
 
X 
10.  Account numbers 
 
X 
11.  Certificate/license numbers 
 
X 
12.  Vehicle identifiers and serial numbers, including license plate numbers 
 
X 
13.  Device identifiers and serial numbers 
 
X 
14.  Web Universal Resource Locators (URLs) 
 
X 
15.  Internet Protocol (IP) address numbers 
 
X 
16.  Biometric identifiers, including finger and voice prints 
 
X 
17.  Full face photographic images and any comparable images 
 
X 
18.  Any other unique identifying number, characteristic, code that is derived from or related to information about 
the individual (e.g. initials, last 4 digits of Social Security #, mother’s maiden name, first 3 letters of last name.) 
 
X 
19.  Any other information that could be used alone or in combination with other information to identify an 
individual. 
(e.g. rare disease, study team or company has access to the health information and a HIPAA identifier or the key to 
the code) 
1A(1)►If you checked any item above, list the HIPAA identifiers that will be kept with the data in the same 
location (e.g. on the same electronic drive (e.g. F or O drive)  or in the same paper file with the data). 
INSTRUCTIONS : If you checked # 19 above: If the key to the code ( subject # 1= John Smith) will be 
kept in the same location as the data, list item # 19 below.  
Medical Record Number 
  
INSTRUCTIONS: 
If you did not list any HIPAA Identifier under 1A(1) skip to 1G.  
 
1B.  How will data be collected?  
 
1B(1)._____ Collection of data ONTO* an individual-use device (e.g. desktop computer, smart phone app, tablet, 
laptop) 
INSTRUCTIONS:  *ONTO means the data will reside on the device.   
Do not check this box if the device will simply be used to access a server.  
  
If checked answer the following questions: 
• What kind of device is it (e.g. laptop, tablet, desktop computer)? _____   
 
• Who manages / supports the device (e.g., Health Systems Computing Services (HS/CS), Information 
Technology Services (ITS), self)? __  

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INSTRUCTIONS: If the device is managed/support by self you must follow both the setup and 
maintenance security standards described on the UVa Office of Information Security, Policy & Records 
Office (ISPRO) webpage: http://www.virginia.edu/informationsecurity/device-requirements.html 
 
• How long with the data remain on the device before it is downloaded to a server _____   
 
• Will anyone other than study team members have access to the data on the device? ___ __   
 
• Will data be downloaded to UVa in an encrypted secure manner such as the use of SFTP or HTTPS? _____   
 
• Are any backups made of the information on the device? _____   
 
• After information is downloaded will you securely delete all UVa subject data from the device? _____   
INSTRUCTIONS: For computers not using Windows 8 or newer, download and use the Secure Delete 
Program from ITS.  If using Windows 8 or newer, click on Secure Delete when deleting a file. For 
Macintosh computers, select "Secure Empty Trash" from the Finder menu. 
 
 
• Does the owner of the device (e.g. phone service provider/ app developer) have any rights to use or access 
the data either individually or in aggregate?  _____   
 
1B(2.)_____ Collection of data via web-based format (e.g. online consent, online surveys) via a non-UVa secure 
server (e.g. NOT HS/CS, ITS or SON SECUREnet) 
 
 
See 1B(6) below for an exception.  
 
If checked answer the following questions: 
• 
Provide the web address (URL): _____   
INSTRUCTIONS :  (e.g., https://name1.name2.org/mystudy/login.html)  
You may locate this URL by taking the following step: 
In Windows under Computer, right click on the Drive. Then click on Properties.  The URL name 
will appear at the very top of the box.   
If you need additional assistance contact your department computer support or system 
administrator for assistance in answering this question.  
 
• How long will the data remain on the non-UVa secure server before it is downloaded to a server 
managed by HS/CS, ITS or SON SECUREnet? _____   
 
• 
Will anyone other than study team members have access to the data on the non-UVa secure 
server? _____   
 

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• 
Will data be downloaded to a UVa secure server in an encrypted secure manner such as the use 
of SFTP or HTTPS? _____   
 If checked please provide the web address (URL): _____  
INSTRUCTIONS :  (e.g., https://name.hsc.virginia.edu) 
You may locate this URL by taking the following step: 
In Windows under Computer, right click on the Drive. Then click on Properties.  The URL name 
will appear at the very top of the box.   
If you need additional assistance contact your department computer support or system 
administrator for assistance in answering this question.  
  
 
• 
Are any backups made of the information on the non-UVa secure server? _____   
 
• 
After information is downloaded will you securely delete all UVa subject data from the 
Non-UVa secure server? _____   
 
• 
Do the owners of the non-UVa secure server have any rights to use or access the data either 
individually or in aggregate?  _____   
 
• 
Is there a Business Associates Agreement (BAA) with the provider of the Non- UVa secure 
server? _____  
 
1B(3)._____  Directly to a server managed by the principal investigator’s department or school  
If checked, please provide the name of the server: _____  
INSTRUCTIONS :  (e.g. name.virginia.edu)  
You may locate this URL by taking the following step: 
In Windows under Computer, right click on the Drive. Then click on Properties.  The URL name 
will appear at the very top of the box.   
If you need additional assistance contact your department computer support or system 
administrator for assistance in answering this question.  
   
• What kind of individual-use device will be used to connect to this server?  
 (e.g. laptop, tablet, desktop computer)? __ ___   
 
• Who manages / supports this individual-use device (e.g., Health Systems Computing Services 
(HS/CS), Information Technology Services (ITS), self)? _____   
INSTRUCTIONS: If the device is managed/support by self you must follow both the setup and 
maintenance security standards described on the UVa Office of Information Security, Policy & Records 
Office (ISPRO) webpage: http://www.virginia.edu/informationsecurity/device-requirements.html 
 
1B(4)._____  Directly to an Information Technology Services (ITS) managed server. 

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If checked, please provide the name of the server: _____ 
INSTRUCTIONS :  (e.g., name.its.virginia.edu)  
You may locate this URL by taking the following step: 
In Windows under Computer, right click on the Drive. Then click on Properties.  The URL name 
will appear at the very top of the box.   
If you need additional assistance contact your department computer support or system 
administrator for assistance in answering this question.  
  
• What kind of individual-use device will be used to connect to this server?  (e.g. laptop, tablet, 
desktop computer)? _____   
 
• Who manages / supports this individual-use device (e.g., Health Systems Computing Services 
(HS/CS), Information Technology Services (ITS), self)? _____   
 
INSTRUCTIONS: If the device is managed/support by self you must follow both the setup and 
maintenance security standards described on the UVa Office of Information Security, Policy & Records 
Office (ISPRO) webpage: http://www.virginia.edu/informationsecurity/device-requirements.html 
 
1B(5).__X__  Directly to a Health Systems Computing Services (HS/CS), or School of Nursing SECUREnet with I 
Key managed server that is configured to store data regulated by HIPAA. 
If checked, please provide the name of the server: _central(//hscs-SS10)(F:)___and / or 
central(\\hscs-share1)(O:)  
INSTRUCTIONS :  (e.g., \\hscs\name.virginia.edu)  
You may locate this URL by taking the following step: 
In Windows under Computer, right click on the Drive. Then click on Properties.  The URL name 
will appear at the very top of the box.   
If you need additional assistance contact your department computer support or system 
administrator for assistance in answering this question.  
 
• What kind of individual-use device will be used to connect to this server?  (e.g. laptop, tablet, 
desktop computer)? _Desk top Computer_ 
___   
 
• Who manages / supports this individual-use device (e.g., Health Systems Computing Services 
(HS/CS), Information Technology Services (ITS), self)? __HS/CS___   
INSTRUCTIONS: If the device is managed/support by self you must follow both the setup and maintenance 
security standards described on the UVa Office of Information Security, Policy & Records Office (ISPRO) 
webpage: http://www.virginia.edu/informationsecurity/device-requirements.html 
 
 

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1B(6)._____  Directly to a server managed by the sponsor or CRO in which the data will be sent and stored in 
an encrypted fashion (e.g. must be shared and stored via Secure FX, Secure FTP, HTTPS, PGP) 
and the server is configured to store data regulated by HIPAA. 
 
• What kind of individual-use device will be used to connect to this server?  
 (e.g. laptop, tablet, desktop computer)? __ ___   
 
• Who manages / supports this individual-use device (e.g., Health Systems Computing Services 
(HS/CS), Information Technology Services (ITS), self)? _____   
INSTRUCTIONS: If the device is managed/support by self you must follow both the setup and maintenance 
security standards described on the UVa Office of Information Security, Policy & Records Office (ISPRO) 
webpage: http://www.virginia.edu/informationsecurity/device-requirements.html 
 
1.B(7).__x___ Paper   
►IMPORTANT: If you checked any of the items 1B(1) through 1B(4) submit ISPRO approval with new protocol 
submission. 
You should consult with ISPRO during the development phase of this protocol if your protocol will involve highly 
technical issues such as the creation of a website to collect data, software application development, the use of a 
smart phone app, or if you plan to store identifiable data ONTO a tablet/laptop.  
 
Otherwise submit the protocol to ISPRO for review when it is submitted to the IRB-HSR for  
pre-review.   
 
ISPRO CONTACT INFORMATION: 
UVa Office of Information Security, Policy & Records Office (ISPRO)  
www.virginia.edu/ispro    
Email: IT-Security@Virginia.edu 
 
1C. How will data be stored by the UVa study team? 
___X__   Data, which may include health information or other highly sensitive data, will be stored with HIPAA 
identifiers.  

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1D.  Will any of the data be stored electronically by the UVa study team?YES 
 
1D(1)►IF YES, will it include storage of any health information or other sensitive data?  YES 
 
1D(2)►IF YES, will you store/keep any of the HIPAA identifiers listed below in electronic format?   
ANSWER QUESTION IN TABLE BELOW  
YES 
NO 
HIPAA Identifier  
 
X 
1.  Name 
 
X 
2.  Postal address information, other than town or city, state, and zip code 
 
X 
3.  Age or Date of Birth if over the age of 89 
 
X 
4.  Telephone numbers 
 
X 
5.  Fax numbers 
 
X 
6.  Electronic mail addresses 
 
X 
7.  Social Security number 
X 
 
8.  Medical Record number 
 
X 
9.  Health plan beneficiary numbers 
 
X 
10.  Account numbers 
 
X 
11.  Certificate/license numbers 
 
X 
12.  Vehicle identifiers and serial numbers, including license plate numbers 
 
X 
13.  Device identifiers and serial numbers 
 
X 
14.  Web Universal Resource Locators (URLs) 
 
X 
15.  Internet Protocol (IP) address numbers 
 
X 
16.  Biometric identifiers, including finger and voice prints 
 
X 
17.  Full face photographic images and any comparable images  
 
X 
18.  Any other unique identifying number, characteristic, code that is derived from or related to 
information about the individual (e.g. initials, last 4 digits of Social Security #, mother’s maiden 
name, first 3 letters of last name.) 
 
X 
19.  Any other information that could be used alone or in combination with other information to 
identify an individual. 
    (e.g. rare disease, study team or company has access to the health information and a HIPAA 
identifier or the key to the code) 
1D(3)►If you checked any item above, list the HIPAA identifiers that will be kept with the data in the same 
location (e.g. on the same electronic drive (e.g. F or O drive)  or in the same paper file with the data). 
Medical Record Number 
 
1D(4) Check all locations where the data with these HIPAA identifiers will be kept : 
 
 
__X___  in an electronic file- If checked list HIPAA identifiers:_MRN____ 
 
 
 
1E.  If you listed any HIPAA identifier under 1D(3), where will the data be stored?  
1E(1)_____   a server managed by the principal investigator’s department or school that is configured to store 
data regulated by HIPAA or highly sensitive data.   
• If checked, please provide the name of the server: _____   
 
• 
Contact information for the person(s) who manages / supports this server. _____   

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SKIP the following two questions if you checked 1B(3) 
• What kind of individual-use device will be used to connect to this server?  (e.g. laptop, tablet, 
desktop computer)? _____   
 
• Who manages / supports this individual-use device (e.g., Health Systems Computing Services 
(HS/CS), Information Technology Services (ITS), self)? _____   
 
1E(2)_____   a Information Technology Services (ITS) managed server that is configured to store data regulated 
by HIPAA 
• If checked, please provide the name of the server: _____    
INSTRUCTIONS :  (e.g., name.its.virginia.edu)  
You may locate this URL by taking the following step: 
In Windows under Computer, right click on the Drive. Then click on Properties.  The URL name will 
appear at the very top of the box.   
If you need additional assistance contact your department computer support or system 
administrator for assistance in answering this question.  
 
SKIP the following two questions if you checked 1B(4) 
• What kind of individual-use device will be used to connect to this server?  (e.g. laptop, tablet, 
desktop computer)? _____   
 
• Who manages / supports this individual-use device (e.g., Health Systems Computing Services 
(HS/CS), Information Technology Services (ITS), self)? _____   
INSTRUCTIONS: If the device is managed/support by self you must follow both the setup and maintenance 
security standards described on the UVa Office of Information Security, Policy & Records Office (ISPRO) 
webpage: http://www.virginia.edu/informationsecurity/device-requirements.html 
•  
 
1E(3)__X___   a Health Systems Computing Services (HS/CS) managed server that is configured to store data 
regulated by HIPAA.   
• If checked, please provide the name of the server: _ central(//hscs-SS10)(F:) and / or central(\\hscs-
share1)(O:)___ ____   
 
1E(4)_____   a server managed by the sponsor or CRO in which the data will be sent and stored in an encrypted 
fashion (e.g. must be shared and stored via Secure FX, Secure FTP, HTTPS, PGP)  onto a server that is 
configured to store data regulated by HIPAA.   
INSTRUCTIONS:  The study team should confirm the security of the site with the sponsor, CRO or other 
outside group. 
NOT ALLOWED if you have answered YES to any HIPAA identifier above and data will not be sent/stored 
in an encrypted manner.  

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►IMPORTANT: If you checked any of the items 1E(1) or 1E(2) submit ISPRO approval with new protocol 
submission. N/A 
You should consult with ISPRO during the development phase of this protocol if your protocol will involve highly 
technical issues such as the creation of a website to collect data, software application development, the use of a 
smart phone app, or if you plan to store identifiable data ONTO a tablet/laptop.  
 
Otherwise submit the protocol to ISPRO for review when it is submitted to the IRB-HSR for  
pre-review.   
 
ISPRO CONTACT INFORMATION: 
UVa Office of Information Security, Policy & Records Office (ISPRO)  
www.virginia.edu/ispro    
Email: IT-Security@Virginia.edu 
 
1F. Will any of the data be collected or stored in hard copy format by the UVa study team (e.g. on paper)?  NO 
 
 
1G.  The following procedures must also be followed.  
• Only investigators for this study and clinicians caring for the patient will have access to the data.  They will 
each use a unique login ID and password that will keep confidential.   The password should meet or exceed 
the standards described on the Information Technology Services (ITS) webpage about The Importance of 
Choosing Strong Passwords. 
• Each investigator will sign the University’s Electronic Access Agreement forward the signed agreement to the 
appropriate department as instructed on the form. 
If you currently have access to clinical data it is likely that you have already signed this form.  You are not 
required to sign it again.  
• UVa University  Data Protection Standards will be followed 
http://www.virginia.edu/informationsecurity/dataprotection.   
• If identifiable data is transferred to any other location such as a desktop, laptop, memory stick, CD etc. the 
researcher must follow the University’s  “Electronic Storage of Highly Sensitive Data Policy”. Additional 
requirements may be found in the Universities Requirements for Securing Electronic Devices.  
• If identifiable health information is taken away from the UVa Health System, Medical Center Policy # 0218 
will be followed.  
• The data will be securely removed from the server, additional computer(s), and electronic media according 
to the University's Electronic Data Removal Policy.  
• The data will be encrypted or removed if the electronic device is sent outside of UVa for repair according 
to the University's Electronic Data Removal Policy. 
• If PHI will be faxed, researchers will follow the Health System Policy # 0194.     
• If PHI will be emailed, researchers will follow the Health System Policy # 0193 and University Data 
Protection Standards . 
• The data may not be analyzed for any other study without additional IRB approval.  
• If you are using patient information you must follow Health System Policy  # 0021. 

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• Both data on paper and stored electronically will follow the University's Record Management policy and 
the Commonwealth statute regarding the Destruction of Public Records. 
 
Summary of Requirements to Comply with UVa Health System, Medical Center and University Policies and 
Guidance as noted above: 
Highly Sensitive Data is: 
-personal information that can lead to identity theft if exposed or 
-health information that reveals an individual’s health condition and/or history of health services use.  
Protected Health Information (PHI) a type of Highly Sensitive Data, is health information combined with a 
HIPAA identifier  
Identifiable Health Information under HIPAA regulations is considered to be Highly Sensitive Data at UVa. 
A Limited Data Set (LDS) under HIPAA regulations is considered to be Moderately Sensitive Data at UVa. The 
only HIPAA identifiers associated with data: dates and or postal address information limited to town or city, 
state, and zip code.  See Table A below for details. 

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Highly Sensitive Data 
(Identifiable Health Info per HIPAA )  
Moderately Sensitive Data  
(Limited Data Set and De-identified data per 
HIPAA) 
General Issues  
General Issues 
Discussions in private 
Do not share with those not on the study team or 
those who do not have a need to know. 
 
Do not share with those not on the study team or 
those who do not have a need to know 
Password protect  
Password protect 
Physically secure (lock) hard copies at all times if not 
directly supervised.  
If not supervised hard copies must have double 
protection (e.g. lock on room OR cabinet AND in 
building requiring swipe card for entrance).    
 
Physically secure (lock) hard copies at all times if 
not directly supervised.   
For electronic documents turn off File Sharing; turn 
on firewalls; use up to date antivirus and 
antispyware; delete data securely. 
 
For electronic documents turn off File Sharing; turn 
on firewalls; use up to date antivirus and 
antispyware; delete data securely. 
 
Encrypt 
See Encryption Solutions Guidance  
Files on Health System Network drives are 
automatically encrypted.  If not stored there it is study 
teams responsibility to make sure data are encrypted. 
 
If device sent out for service or repair, encrypt or 
remove data AND contract for repair using a UVa 
Purchase order. 
If device sent out for service or repair, encrypt or 
remove data AND contract for repair using a UVa 
Purchase order. 
Store files on a network drive specifically designated 
for storing this type of data, e.g. high-level security 
servers managed by Information Technology 
Services or the “F” and “O” managed by Heath 
Systems Computing Services.  You may access it via a 
shortcut icon on your desktop, but you are not 
allowed to take it off line to a local drive such as the 
desktop of your computer (e.g. C drive) or to an 
individual  Use Device*.  May access via VPN 
 
Do not share with sponsor or other outside group 
before consent is obtained or the IRB has granted 
appropriate approvals and contract/ MTA is in place  
Do not share with sponsor or other outside group 
before consent is obtained or the IRB has granted 
appropriate approvals and contract/ MTA is in 
place 
If collected without consent/ HIPAA authorization 
will NOT be allowed to leave UVa HIPAA covered 
entity unless disclosure is approved by the IRB and 
the disclosure is tracked in EPIC  
If collected without consent/ HIPAA authorization 
will NOT be allowed to leave UVa HIPAA covered 
entity unless disclosure is approved by the IRB and 
an MTA is in place prior to sharing of data 

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Highly Sensitive Data 
(Identifiable Health Info per HIPAA )  
Moderately Sensitive Data  
(Limited Data Set and De-identified data per HIPAA) 
Individual-Use Device  
Individual-Use Device 
Do not save to individual-use device* without 
written approval of your Department AND VP 
or Dean.   
If approval obtained, data must be password 
protected and encrypted. 
 
Do not save an email attachment containing 
HSD to an individual use device ( e.g. smart 
phone)  
 
E Mail 
E Mail 
Do not share via email with Outlook Web/ or 
forward email using other email vendors like 
Gmail/ Yahoo  
 
Do not send via email on smart phone unless 
phone is set up by Health System  
 
Email may include name, medical record 
number or Social Security number only if 
sending email to or from a person with * HS in 
their email address. 
NOTE: VPR & IRB staff do not meet this 
criteria!  
In addition to sharing LDS, may include initials if 
persons sending and receiving email work within the 
UVa HIPAA covered entity.** 
FAX 
FAX 
Verify FAX number before faxing 
Verify FAX number before faxing 
Use Fax Cover Sheet with Confidentiality 
Statement 
Use Fax Cover Sheet with Confidentiality Statement 
Verify receiving fax machine is in a restricted 
access area 
Verify receiving fax machine is in a restricted access 
area 
Verify intended recipient is clearly indicated 
Verify intended recipient is clearly indicated 
Recipient is alerted to the pending 
transmission and is available to pick it up 
immediately 
Recipient is alerted to the pending transmission and 
is available to pick it up immediately 

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*  Individual Use Device – examples include smart phone, CD, flash (thumb) drive, laptop, C drive of your 
computer.  
**The UVa HIPAA covered entity is composed of the UVa VP Office of Research, the Health System, School of 
Medicine, School of Nursing, Nutrition Services (Morrison’s), the Sheila C. Johnson Center, the Exercise and 
Sports Injury Laboratory and the Exercise Physiology Laboratory.   
 
2. Will specimens be stored at UVa by the UVa study team?NO 
 
3.  Do you confirm that you will not reuse the identifiable data (HIPAA identifiers or health information) or 
disclose any of this information to any other person or entity except as outlined in this protocol, except as 
required by law, for authorized oversight of the research study, or use it for other research unless approved 
by the IRB-HSR?  Yes 
This means that after the study is closed at UVa: 
 
• You cannot contact the subject by any method (you cannot call them, send a letter, talk to them in person 
about the study, etc) without additional IRB approval 
• You cannot use the data for any research that is not already described in your IRB protocol without 
additional IRB approval (if you change your hypothesis you must modify your protocol)  
• You cannot share your research data with another researcher outside of your study team without 
additional IRB approval 
• Any health information with HIPAA identifiers will be shredded or discarded by using recycling bins for 
confidential material found in clinic settings.  For large item disposal of confidential material contact 
Environmental Services at 2-4976 or University Recycling at 2-5050.  
Highly Sensitive Data 
(Identifiable Health Info per HIPAA )  
Moderately Sensitive Data  
(Limited Data Set and De-identified data per HIPAA) 
Electronic Data Collection & Sharing 
Electronic Data Collection & Sharing 
(e.g. smart phone app, electronic consent 
using tablet etc.) 
MUST consult with ISPRO or Health System 
Web Development Office: 434-243-6702 
University Side:    IT-Security@virginia.edu  
Health System: Web Development Center:   
Contract must include required security 
measures.  
 
May NOT be stored in places like UVaBox, 
UVaCollab, QuestionPro.  
May also NOT be stored in non-UVa licensed 
cloud providers, such as Dropbox, Google 
Drive, SkyDrive, Survey Monkey, etc.  
May be stored in places like UVaBox, UVaCollab, 
QuestionPro.   
May NOT be stored in non-UVa licensed cloud 
providers, such as Dropbox, Google Drive, SkyDrive, 
Survey Monkey, etc.  
LOST OR STOLEN:  
LOST OR STOLEN: 
Must report in accordance with protocol/ in 
accordance with the Information Security 
Incident Reporting Policy 
 
Must report in accordance with protocol/ in 
accordance with the Information Security Incident 
Reporting Policy 
 

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TABLE A:  HIPAA Identifiers (Limited Data Set)  
1.  Name 
2.  Postal address information, other than town or city, state, and zip code 
3.  Telephone numbers 
4  Fax numbers 
5.  Electronic mail addresses 
6.  Social Security number 
7.  Medical Record number 
8.  Health plan beneficiary numbers 
9.  Account numbers 
10.  Certificate/license numbers 
11.  Vehicle identifiers and serial numbers, including license plate numbers 
12.  Device identifiers and serial numbers 
13.  Web Universal Resource Locators (URLs) 
14.  Internet Protocol (IP) address numbers 
15.  Biometric identifiers, including finger and voice prints 
16.  Full face photographic images and any comparable images  
17.  Any other unique identifying number, characteristic, code that is derived 
from or related to information about the individual (e.g. initials, last 4 digits of 
Social Security #, mother’s maiden name, first 3 letters of last name.) 
 
The Pharmacy department is assisting us with this project, they will be storing the data of which patient’s 
receive the experimental or control treatment.  They will be storing the data on a Health Systems Computing 
Services managed server (hospital based) that is configured to store data regulated by HIPAA.  Once we have 
gathered enough patient’s to they will release the data to us to analyze.