Intraoperative Sublingual Sufentanil for Acute Pain in the Ambulatory Surgery Center
Phase: PHASE4
Conditions: Pain, Pain, Acute, Anesthesia
Sponsor: University of Minnesota

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Intraoperative Sublingual sufentanil for acute pain in the 
Ambulatory Surgery Center 
VERSION DATE: 0.4 11/20/2020 
 
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Template  Revised On: 09/01/2019 
PROTOCOL COVER PAGE 
 
 
Protocol Title 
Intraoperative Sublingual sufentanil for acute pain in the 
Ambulatory Surgery Center 
Principal 
Investigator/Faculty 
Advisor 
Name: Aaron Berg 
Department: Anesthesiology 
Telephone Number: 612-624-9990 
Email Address: bergx831@umn.edu 
Student 
Investigator 
Name: 
Current Academic Status (Student, Fellow, Resident): 
  
Department: 
Telephone Number: 
Institutional Email Address: 
Scientific 
Assessment 
HRPP facilitated scientific assessment 
IND/IDE # (if 
applicable) 
N/A 
IND/IDE Holder 
N/A 
Investigational Drug 
Services # (if 
applicable) 
N/A 
Version 
Number/Date: 
0.4 11/20/2020 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Intraoperative Sublingual sufentanil for acute pain in the 
Ambulatory Surgery Center 
VERSION DATE: 0.4 11/20/2020 
 
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ANCILLARY REVIEWS 
Which ancillary reviews do I need and when do I need them? 
Refer to HRP-309 for more information about these ancillary reviews. 
Select yes or 
no 
Does your study… 
If yes… 
Impact on 
IRB Review 
☐ Yes 
☒ No 
 
Include Gillette resources, staff 
or locations 
Gillette Scientific review and Gillette 
Research Administration approval is 
required.  Contact: 
research@gillettechildrens.com   
Required 
prior to IRB 
submission 
☒ Yes 
☐ No 
Involve Epic, or Fairview 
patients, staff, locations, or 
resources? 
The Fairview ancillary review will be 
assigned to your study by IRB staff 
Contact: ancillaryreview@Fairview.org 
Approval 
must be 
received 
prior to IRB 
committee/ 
designated 
review.   
 
Consider 
seeking 
approval 
prior to IRB 
submission. 
☐ Yes 
☒ No 
Include evaluation of drugs, 
devices, biologics, tobacco, or 
dietary supplements or data 
subject to FDA inspection? 
The regulatory ancillary review will be 
assigned to your study by IRB staff 
Contact: medreg@umn.edu  
 
See: 
https://policy.umn.edu/research/indide  
☒ Yes 
☐ No 
Require Scientific Review? Not 
sure? See guidance on next 
page. 
 
Documentation of scientific merit must 
be provided.   
Contact: hrpp@umn.edu  
☐ Yes 
☒ No 
Relate to cancer patients, 
cancer treatments, cancer 
screening/prevention, or 
tobacco? 
Complete the CPRC application process.  
Contact: ccprc@umn.edu  
☐ Yes 
☒ No 
Include the use of radiation? 
(x-ray imaging, 
radiopharmaceuticals, external 
beam or brachytherapy) 
Complete the AURPC Human Use 
Application and follow instructions on 
the form for submission to the AURPC 
committee. 
Contact: barmstro@umn.edu  
Approval 
from these 
committees 
must be 
received 
prior to IRB 
approval;  
 
These 
groups 
each have 
their own 
application 
process.  
☐ Yes 
☒ No 
Use the Center for Magnetic 
Resonance Research (CMRR) 
as a study location? 
Complete the CMRR pre-IRB ancillary 
review  
Contact: ande2445@umn.edu  
☐ Yes 
☒ No 
Include the use of 
recombinant or synthetic 
nucleic acids, toxins, or 
infectious agents? 
Complete the IBC application via 
eprotocol.umn.edu 
Contact: 
☐ Yes 
☒ No 
Include the use of human fetal 
tissue, human embryos, or 
embryonic stem cells? 
Contact OBAO for submission 
instructions and guidance 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Intraoperative Sublingual sufentanil for acute pain in the 
Ambulatory Surgery Center 
VERSION DATE: 0.4 11/20/2020 
 
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☒ Yes 
☐ No 
 
Include PHI or are you 
requesting a HIPAA waiver? 
If yes, HIPCO will conduct a review of 
this protocol. 
Contact: privacy@umn.edu  
☐ Yes 
☒ No 
Use data from the Information 
Exchange (IE)? 
The Information Exchange ancillary 
review will be assigned to your study by 
IRB staff 
Contact: ics@umn.edu  
Approval 
must be 
received 
prior to IRB 
approval. 
 
These 
groups do 
not have a 
separate 
application 
process but 
additional 
information 
from the 
study team 
may be 
required. 
 
☐ Yes 
☒ No 
Use the Biorepository and 
Laboratory Services to collect 
tissue for research? 
The BLS ancillary review will be 
assigned to your study by IRB staff. 
Contact: cdrifka@umn.edu  
☐ Yes 
☒ No 
Have a PI or study team 
member with a conflict of 
interest? 
The CoI ancillary review will be 
assigned to your study by IRB staff 
Contact: becca002@umn.edu  
☒ Yes 
☐ No 
Need to be registered on 
clinicaltrials.gov? 
If you select “No” in ETHOS, the 
clinicaltrials.gov ancillary review will be 
assigned to your study by IRB staff 
Contact: kmmccorm@umn.edu  
☒ Yes 
☐ No 
Require registration in 
OnCore? 
If you select “No” or “I Don’t Know” in 
ETHOS, the OnCore ancillary review will 
be assigned to your study by IRB staff 
Contact: oncore@umn.edu  
Does not 
affect IRB 
approval. 
 
 
 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Intraoperative Sublingual sufentanil for acute pain in the 
Ambulatory Surgery Center 
VERSION DATE: 0.4 11/20/2020 
 
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REVISION HISTORY 
 
Revision # 
Version Date 
Summary of Changes 
Consent Change? 
1 
0.2 4/22/20 
Scientific Review clarifications 
No 
2 
0.3 6/3/20 
Added enrollment length in 
section 5.3 and pregnancy test 
stipulation to section 5.2 and 
consent changes per 4/29/20 
modifications. Additionally added 
e-consent process to 21.0 
Yes 
3 
0.4 11/20/20 
Added to exclusion criteria  
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Intraoperative Sublingual sufentanil for acute pain in the 
Ambulatory Surgery Center 
VERSION DATE: 0.4 11/20/2020 
 
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Table of Contents  
 
1.0 
Objectives ................................................................................................................ 7 
2.0 
Background .............................................................................................................. 7 
3.0 
Study Endpoints/Events/Outcomes .......................................................................... 7 
4.0 
Study Intervention(s)/Investigational Agent(s)........................................................ 8 
5.0 
Procedures Involved................................................................................................. 8 
6.0 
Data and Specimen Banking .................................................................................. 10 
7.0 
Sharing of Results with Participants ...................................................................... 10 
8.0 
Study Population .................................................................................................... 11 
9.0 
Vulnerable Populations .......................................................................................... 11 
10.0 Local Number of Participants ................................................................................ 13 
11.0 Local Recruitment Methods ................................................................................... 13 
12.0 Withdrawal of Participants .................................................................................... 14 
13.0 Risks to Participants ............................................................................................... 14 
14.0 Potential Benefits to Participants ........................................................................... 16 
15.0 Statistical Considerations ....................................................................................... 16 
16.0 Health Information and Privacy Compliance ........................................................ 16 
17.0 Confidentiality ....................................................................................................... 19 
18.0 Provisions to Monitor the Data to Ensure the Safety of Participants .................... 19 
19.0 Provisions to Protect the Privacy Interests of Participants .................................... 19 
20.0 Compensation for Research-Related Injury ........................................................... 20 
21.0 Consent Process ..................................................................................................... 20 
22.0 Setting .................................................................................................................... 21 
23.0 Multi-Site Research ............................................................................................... 21 
24.0 Coordinating Center Research ............................................................................... 21 
25.0 Resources Available............................................................................................... 21 
26.0 References .............................................................................................................. 22 
 
 
 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Intraoperative Sublingual sufentanil for acute pain in the 
Ambulatory Surgery Center 
VERSION DATE: 0.4 11/20/2020 
 
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ABBREVIATIONS/DEFINITIONS 
 
• ASA class: American Society of Anesthesiologists Classification 
• ASC: Ambulatory surgery center  
• BMI: Body mass index 
• BP: Blood pressure  
• HR: Heart rate 
• NRS: Numerical rating scale 
• OBAS: Overall Benefit of Analgesia Survey 
• PACU: post anesthesia care unit 
• PONV: post-op nausea/vomiting  
• SST: sublingual sufentanil tablet 
 
 
 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Intraoperative Sublingual sufentanil for acute pain in the 
Ambulatory Surgery Center 
VERSION DATE: 0.4 11/20/2020 
 
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1.0 
Objectives 
1.1 Purpose: The purpose of this study is to determine if a single dose of 
sublingual sufentanil given 15-30 minutes prior to wake up is efficacious at 
reducing initial PACU pain scores. 
2.0 
Background 
2.1 Significance of Research Question/Purpose: This study will help to 
determine the appropriate timing for the use of sublingual sufentanil in an 
ambulatory surgery practice. 
2.2 Preliminary Data: N/A 
2.3 Existing Literature: This is a follow up study to a prospective randomized 
trial giving sublingual sufentanil immediately upon a pain score of 4 in the 
recovery room, which showed that when used as an immediate rescue SST 
performed similar to IV fentanyl (STUDY00007956). SST is an opioid 
medication with unique properties as the route of administration differs 
from traditional opioids used in the peri-operative setting. Of note, 
sublingual medications are frequently given in this setting without 
complications however. The half-life of SST is 164 minutes with an 
estimated onset of 15-30 minutes. These qualities are consistent with 
standard of care as opioid medications used intraoperatively have shorter 
and longer half-lives. Intraoperative dosing of opioids is dynamic and the 
dose of this sublingual sufentanil tablet does not diverge from standard 
dosages. This study intends to further help determine its perioperative 
place. Previous studies have demonstrated the superiority of SST to placebo 
when used for abdominal surgery. Additional open label studies have 
demonstrated that SST has no change in mental status when given in an 
emergency room setting and has a safe adverse event profile when used in 
various inpatient surgical procedures. 
3.0 
Study Endpoints/Events/Outcomes 
3.1 Primary Endpoint/Event/Outcome:  
Initial NRS pain score upon arrival to PACU (11 point 0-10 scale; 0 being no 
pain, 10 being maximum imaginable pain).  
Superiority 
H0: no significant difference in initial NRS pain score 
HA: decreased mean initial NRS pain score of 2 points or greater for 
Group 1 (≥2 chosen as evidence suggests this is a clinically 
significant decrease) 
 
Secondary Endpoint(s)/Event(s)/Outcome(s):  

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Intraoperative Sublingual sufentanil for acute pain in the 
Ambulatory Surgery Center 
VERSION DATE: 0.4 11/20/2020 
 
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Length of time in PACU (recording both Phase 1, Phase 2, and total duration 
measured in minutes; as is standardly recorded for every case). 
Superiority 
H0: no significant difference in recovery room duration 
HA: decreased recovery room duration for the SST group 
 
Additional outcomes: Opioid use in recovery room (medication type and 
dose, these will also be converted to milligram morphine equivalents for 
overall summation and comparison), NRS pain score upon discharge from 
PACU, reduction in pain from initial to discharge pain scores, PONV (defined 
as treated) and any other adverse events, OBAS score, and anesthesia 
wake-up time (duration in minutes from procedure closure to removal of 
endotracheal tube or laryngeal mask airway). 
4.0 
Study Intervention(s)/Investigational Agent(s) 
4.1 Description: 15-30 minutes prior to planned emergence from anesthesia 
patients will either receive 30 mcg of sublingual sufentanil or nothing 
dispensed by the anesthesia provider who will be the only person who is 
unblinded. Envelopes will be used for them to discover the randomization 
group and distributed in order according to a randomization scheme 
provided by the biostatistician. Upon arrival in the ASC PACU, patient’s pain 
will be assessed. There the patient will receive IV fentanyl for a pain score 
of 4 or greater (25-50 mcg doses of Fentanyl, up to 100mcg if needed). If 
100 mcg of fentanyl is given and pain remains above a 7 then IV 
hydromorphone will be used (max dose of 1 mg and given in increments of 
0.3 mg q 10 minutes prn severe pain). Once the patient is able to tolerate 
oral medications a dose of 5 mg of oral oxycodone (or 2 mg of oral 
hydromorphone if allergic to oxycodone) will be given if their pain score is 4 
or greater (on the Numerical Rating Scale). This PACU process is all similar 
to the standard process and medications that would be used in standard 
care, standardized for study purposes. OBAS and final pain score will be 
assessed just prior to discharge from the PACU by the PACU nurse doing the 
discharge. If they request assistance a research coordinator will help ask 
and record this. 
4.2 Drug/Device Handling: Sublingual sufentanil will be stored in the OR 
anesthesia pyxis like other controlled substances. 
4.3 Biosafety: N/A 
4.4 Stem Cells: N/A 
4.5 Fetal tissue: N/A 
5.0 
Procedures Involved 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Intraoperative Sublingual sufentanil for acute pain in the 
Ambulatory Surgery Center 
VERSION DATE: 0.4 11/20/2020 
 
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5.1 Study Design: This is a level I randomized prospective outcomes study 
comparing two groups of patients.  Within 15-30 minutes of planned wake-
up Group 1 will receive 30 mcg of sublingual sufentanil and group 2 will not 
receive sublingual sufentanil. 
5.2 Study Procedures: Patients will be approached on the day of surgery about 
participating in the trial after being screened for eligibility (inclusion per 
negative pregnancy test for women of child-bearing age). This will be done 
as soon as they arrive at the ASC to allow adequate time for them to review 
the study procedures and consent forms.  All questions will be answered 
and patients will be ensured that they have adequate time to review and 
understand all study procedures.  Patients undergoing orthopedic surgical 
procedures with general anesthesia will be eligible to participate.  
All patients will have standardized opioid sparing total IV anesthetic with 
propofol.  No opioids will be used on induction and patients will only receive 
intraoperative opioids if their HR or BP is increased by 20% above baseline.  
Within 15-30 minutes of wakeup patients will be randomized to receive 
either 30 mcg of sublingual sufentanil or nothing. There is no need for a 
placebo as the patient will be under anesthesia. No additional 
intraoperative opioids will be given after that.  
Once in the PACU patients initial pain will be assessed and recorded. There 
the patient will receive IV fentanyl for a pain score of 4 or greater (25-50 
mcg doses of Fentanyl, up to 100 mcg if needed). If 100 mcg of fentanyl is 
given and pain remains above a 7 then IV hydromorphone will be used (max 
dose of 1 mg and given in increments of 0.3 mg q 10 minutes prn severe 
pain). Once the patient is able to tolerate oral medications a dose of 5 mg 
of oral oxycodone (or 2 mg of oral hydromorphone if allergic to oxycodone) 
will be given if their pain score is 4 or greater (on the Numerical Rating 
Scale). This PACU process is all similar to the standard process and 
medications that would be used in standard care, standardized for study 
purposes. OBAS and final pain score will be assessed just prior to discharge 
from the PACU by the PACU nurse doing the discharge. OBAS is a standard 
survey asking seven questions regarding grade of distress from several 
possible symptoms and can be done very quickly. This will be recorded on 
the instruction sheet.  
Time until readiness to discharge, opioid use, pain scores and baseline 
demographics such as surgical procedure, intraoperative opioids, surgical 
procedure length, ASA class, BMI, weight, age, and sex will be recorded. 
Table of Events (research activities, operative day) 
Informed Consent 
Research team, pre-op  
Randomization envelope 
Research team, pre-op 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Intraoperative Sublingual sufentanil for acute pain in the 
Ambulatory Surgery Center 
VERSION DATE: 0.4 11/20/2020 
 
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Group 1/(2) (in)action 
Anesthesia provider, intra-op 
PACU care/Pain scores 
PACU nurse, post-op 
OBAS survey 
PACU nurse or research assistant, post-op 
 
5.3 Study Duration: Once ready to discharge from PACU the patient will end 
study participation after answering questions for the OBAS survey. 
Participants will be informed that study participation is for their 
perioperative course until they leave the ambulatory surgery center, an 
estimated average duration of six hours. It should take 2 months to enroll 
all patients and another 2 months for full data analysis. 
5.4 Individually Identifiable Health Information: See attached combined 
consent/HIPAA form. 
5.5 Use of radiation: N/A 
5.6 Use of Center for Magnetic Resonance Research: N/A 
6.0 
Data and Specimen Banking 
6.1 Storage and Access: All study data will be stored on excel spreadsheets in 
Box. Only the PI and members of the research team will have access to the 
data. 
6.2 Data: The data from this study will be collected both from Epic and directly 
from the patient. The data collected includes: demographic data, age, sex, 
weight, BMI, ASA class, duration of surgery, length of stay in recovery room 
both phase 1 and 2, amount of opioids given intraoperatively and post-
operatively, non-opioid pain medication, pain score (0-10 at arrival in PACU, 
30 minutes after arrival, and upon discharge), OBAS score at time to ready 
to discharge, and any adverse events. 
6.3 Release/Sharing: De-identified study data will be shared with our 
biostatistician for assistance with analysis and may be shared with a peer-
reviewed journal. 
7.0 
Sharing of Results with Participants 
7.1 Sharing Results: If participants ask, they will be informed that we plan to 
publish the study and informed of a potential method for how to search for 
it, such as searching for the investigator’s name, in a number of months.  
7.2 Sharing Genetic Results: N/A 
7.2.1 Disclosure of Results: N/A 
7.2.2 Returning Results to Participants: N/A 
7.2.3 Future analysis of genotypes: N/A 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Intraoperative Sublingual sufentanil for acute pain in the 
Ambulatory Surgery Center 
VERSION DATE: 0.4 11/20/2020 
 
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8.0 
Study Population 
8.1 Inclusion Criteria: Adult patients aged 18-80 undergoing outpatient 
ambulatory surgery undergoing general anesthesia for orthopedic surgery.  
Those not able to read will be allowed to participate and the consent 
process will be followed, including witness signature. Military personnel will 
be allowed to participate and not be identified and information will not be 
collected as to a patient’s military status. Undervalued and disadvantaged 
groups will also have the option of participating. This research does not add 
risk to these groups.  
8.2 Exclusion Criteria: Patients under the age of 18, and over 80. Patients who 
have allergy or intolerance to the study drugs or derivatives. Patients with 
chronic pain or a three week or greater history of daily opioid use. Patients 
undergoing procedures in the prone position. 
Due to cultural concerns over pain tolerance and interpretation observed by 
the academic pain research community, non-English speaking patients will 
be excluded. Pregnancy, those with lacking/diminished ability to consent, 
employees and students of researcher, those in a stressful situation (for 
example a non-elective procedure), serious health condition for which there 
are no satisfactory standard treatments, prisoners, those with possible fear 
of negative consequences for not participating in the research like 
deportation, and any other dynamic that deemed to increase vulnerability 
to coercion or exploitation. 
8.3 Screening: Due to dynamic surgical schedules, patients will be screened by 
looking at the surgical schedule. They arrive several hours before the 
procedure and will be approached by a member of the clinical care team as 
they are roomed in the pre-operative area and informed of a potential 
study they could elect to participate in. If they indicate they are open to 
hearing more about it they will be asked if a member of the research team 
can discuss it with them. They will be ensured that they have time to read 
the consent, discuss and evaluate the study, all questions will be answered 
and they will be informed that they can decide not to participate for any 
reason without any consequence.  
9.0 
Vulnerable Populations 
9.1 Vulnerable Populations:  
Population / Group 
Identify whether any of the 
following populations will be 
targeted, included (not necessarily 
targeted) or excluded from 

MEDICAL PROTOCOL (HRP-590) 
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Ambulatory Surgery Center 
VERSION DATE: 0.4 11/20/2020 
 
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participation in the study.  
Children 
Excluded from Participation 
Pregnant women/fetuses/neonates 
Excluded from Participation 
Prisoners 
Excluded from Participation 
Adults lacking capacity to consent 
and/or adults with diminished 
capacity to consent, including, but 
not limited to, those with acute 
medical conditions, psychiatric 
disorders, neurologic disorders, 
developmental disorders, and 
behavioral disorders 
Excluded from Participation 
Non-English speakers 
Excluded from Participation 
Those unable to read (illiterate) 
Included/Allowed to Participate 
Employees of the researcher 
Excluded from Participation 
Students of the researcher 
Excluded from Participation 
Undervalued or disenfranchised 
social group 
Included/Allowed to Participate 
Active members of the military 
(service members), DoD personnel 
(including civilian employees) 
Included/Allowed to Participate 
Individual or group that is 
approached for participation in 
research during a stressful situation 
such as emergency room setting, 
childbirth (labor), etc. 
Excluded from Participation 
Individual or group that is 
disadvantaged in the distribution of 
social goods and services such as 
income, housing, or healthcare. 
Included/Allowed to Participate 

MEDICAL PROTOCOL (HRP-590) 
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Ambulatory Surgery Center 
VERSION DATE: 0.4 11/20/2020 
 
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Individual or group with a serious 
health condition for which there are 
no satisfactory standard treatments. 
Excluded from Participation 
Individual or group with a fear of 
negative consequences for not 
participating in the research (e.g. 
institutionalization, deportation, 
disclosure of stigmatizing behavior). 
Excluded from Participation 
Any other circumstance/dynamic 
that could increase vulnerability to 
coercion or exploitation that might 
influence consent to research or 
decision to continue in research. 
Excluded from Participation 
 
9.2 Additional Safeguards: N/A 
10.0 Local Number of Participants 
10.1 Local Number of Participants to be Consented: Minimum of 50 and 
maximum of 65 
11.0 Local Recruitment Methods 
11.1 Recruitment Process: Patients will be recruited from the group of adult 
patients undergoing orthopedic surgery at the University of Minnesota 
Ambulatory Surgery Center. On the day of surgery as soon as they are 
checked in, patients will be informed of a research opportunity by a 
member of the clinical care staff, including the check-in staff, nursing staff, 
or member of the anesthesiology team, and asked if they are interested in 
talking with a member of the research team. A research team member will 
then explain the study and present the consent form.  All patients will have 
sufficient time to review this, ask questions and go over the potential risks 
of the study with the research team as they arrive several hours prior to the 
procedure.  If they decide to participate they will be consented and 
provided a copy of the consent form. 
11.2 Identification of Potential Participants: Patients will be identified by 
members of the research team by evaluating the surgical schedule.  
Patients who have opted out of research will not be approached.  Patients 
who agree to participate will sign the combined consent and HIPAA 
authorization form. 
11.3 Recruitment Materials: N/A 

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11.4 Payment: No payment will be provided. 
12.0 Withdrawal of Participants 
12.1 Withdrawal Circumstances: Subjects who have consented and later choose 
not to participate for any reason will be withdrawn and a notation will be 
made in the study records. The surgeon may choose to withdraw the 
patient from the study prior to surgery for any medical reason or if they 
suffer a major life-threatening adverse event. 
12.2 Withdrawal Procedures: If the patient is withdrawn from study prior to the 
procedure, for example if they change their mind before induction of 
anesthesia in the operating room, they will be noted in study records as 
screen failures. If they undergo the procedure and they decide for any 
reason they no longer want to be included in the study or are withdrawn by 
the physician, they will be withdrawn and no further data will be collected.  
This will also be noted in the study documentation. 
12.3 Termination Procedures: If the study is terminated for any reason, or there 
are more than 5% major adverse events the data that is already collected 
will be stored in a secure location only accessible to research personnel on 
this study.  No further data will be collected if the study is terminated. 
Existing data may still be sent to the biostatistician in the manner as 
described in the protocol to help determine if it is sufficient for any 
conclusions.  
13.0 Risks to Participants 
13.1 Foreseeable Risks:  
Medication risks include: 
• Life threatening respiratory depression 
• Addiction, abuse, and misuse 
• Adrenal insufficiency 
• Severe hypotension 
• Gastrointestinal adverse reactions 
• Seizures 
These risks are the standard risks of using opioids, the standard of care for 
treating surgical pain. Sublingual sufentanil is already used as an analgesic 
option at University of MN ASC. 
The Department of Anesthesiology has an adverse event and serious 
adverse event reporting standard operating procedure in place to define, 
record, report and evaluate adverse events based on the International 
Conference on Harmonization guidelines.  

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Adverse event means any untoward medical occurrence associated with 
the use of an intervention in humans, whether or not considered 
intervention-related (21 CFR 312.32 (a)); An adverse event (AE) or 
suspected adverse reaction is considered "serious" if, in the view of either 
the investigator or sponsor, it results in any of the following outcomes: 
death, a life-threatening adverse event, inpatient hospitalization or 
prolongation of existing hospitalization. 
RATING: Mild – Events require minimal or no treatment and do not 
interfere with the participant’s daily activities. Moderate – Events result in a 
low level of inconvenience or concern with the therapeutic measures. 
Moderate events may cause some interference with functioning. Severe – 
Events interrupt a participant’s usual daily activity and may require 
systemic drug therapy or other treatment. Severe events are usually 
potentially life-threatening or incapacitating. Of note, the term “severe” 
does not necessarily equate to “serious”.] 
RELATED: Related – The AE is known to occur with the study intervention, 
there is a reasonable possibility that the study intervention caused the AE, 
or there is a temporal relationship between the study intervention and 
event. Reasonable possibility means that there is evidence to suggest a 
causal relationship between the study intervention and the AE. Not Related 
– There is not a reasonable possibility that the administration of the study 
intervention caused the event, there is no temporal relationship between 
the study intervention and event onset, or an alternate etiology has been 
established. (The Principal Investigator will be responsible for determining 
whether an adverse event (AE) is expected or unexpected. An AE will be 
considered unexpected if the nature, severity, or frequency of the event is 
not consistent with the risk information previously described for the study 
intervention.) 
 
Confidentiality risks: 
Participation in research may involve a loss of privacy due to the nature of 
the questions that are asked during assessment visits and/or data collected. 
However, records will be handled as confidentially as possible. All 
participants will be assigned a unique study identifier that will be used to 
label all of their records only be accessible to specific study staff listed in the 
Delegation of Authority log. This link will connect the participant’s 
identifying information, such as name, etc., to their assigned ID number. No 
identifying information will be used in any report or publications that may 
result from this study. All study records will be kept in a secure database. 
Paper records will be kept in locked cabinets in locked rooms.  
 
13.2 Reproduction Risks: N/A 

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13.3 Risks to Others: N/A 
14.0 Potential Benefits to Participants 
Potential Benefits: There may be no direct benefit to participants. However, 
potential benefits include reduced pain and shortened recovery room stay. 
15.0 Statistical Considerations 
15.1 Data Analysis Plan: We plan to collect our data using excel which will be 
maintained in the box.  When the study is completed and ready for 
statistical analysis the data will be shared with our staff statistician. 
15.2 Power Analysis: We based our power analysis off a previous prospective 
randomized controlled trial which showed average initial pain scores of 
patients who had orthopedic surgery to be 6.63 (SD=2.13). In order to 
detect a mean difference of 2 in the pain scores between groups with a 
two-sample t-test assuming equal variances, we need 50 total participants 
(25 per group) to achieve 90% power. 
15.3 Statistical Analysis: This study data will be de-identified and shared with our 
staff biostatistician to be analyzed. The statistician will be provided the 
protocol so they are able to analyze for primary and secondary objectives.  
Continuous data will be summarized with mean (standard deviation) or 
median (interquartile range) and categorical data will be summarize by 
count (percent). Normality will be evaluated with both the Shapiro-Wilk test 
and graphical evaluation. Univariate comparisons between groups will use 
t-tests or Mann-Whitney U-tests, as appropriate for normality, to compare 
continuous variables and chi-squared or Fisher’s exact tests to compare 
categorical variables between groups. Linear regression models will be 
explored to adjust for variables that are imbalanced after randomization or 
other covariates that may be clinically relevant. 
15.4 Data Integrity: All patients will be assigned a unique patient identifier.  
Research assistants will have experience with similar trials and data 
collection. 
16.0 Health Information and Privacy Compliance 
16.1 
Select which of the following is applicable to your research: 
☐ My research does not require access to individual health 
information.   
☒ I am requesting that all research participants sign a HIPCO approved 
HIPAA Disclosure Authorization to participate in the research (either 
the standalone form or the combined consent and HIPAA 
Authorization). 
☐ I am requesting the IRB to approve a Waiver or an alteration of 
research participant authorization to participate in the research. 

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Appropriate Use for Research:  
 
 
16.2 
Identify the source of Private Health Information you will be using for 
your research (Check all that apply)   
☐ I will use the Informatics Consulting Services (ICS) available through 
CTSI (also referred to as the University's Information Exchange (IE) or 
data shelter) to pull records for me 
☒ I will collect information directly from research participants. 
☐ I will use University services to access and retrieve records from 
the Bone Marrow Transplant (BMPT) database, also known as the 
HSCT (Hematopoietic Stem Cell Transplant) database. 
☒ I will pull records directly from EPIC. 
☐ I will retrieve record directly from axiUm / MiPACS 
☐ I will receive data from the Center for Medicare/Medicaid Services  
☐ I will receive a limited data set from another institution  
☐ Other.  Describe:  
16.3 
Explain how you will ensure that only records of patients who have 
agreed to have their information used for research will be reviewed: Only 
records from patients that have signed a combined consent and HIPAA 
Authorization form will be reviewed. Patients who have research opt-out 
indicated in chart will not be approached.  
16.4 
Approximate number of records required for review: 65 
16.5 
Please describe how you will communicate with research participants 
during the course of this research.  Check all applicable boxes 
☐ This research involves record review only. There will be no 
communication with research participants. 
☒ Communication with research participants will take place in the 
course of treatment, through MyChart, or other similar forms of 
communication used with patients receiving treatment.  
☐ Communication with research participants will take place outside of 
treatment settings. If this box is selected, please describe the type of 
communication and how it will be received by participants.  
16.6 
Explain how the research team has legitimate access to 
patients/potential participants: Team consists of those providing 
anesthetic care to the patients and department of anesthesiology 
research assistants.  
16.7 
Location(s) of storage, sharing and analysis of research data, including 
any links to research data (check all that apply).   

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☐ In the data shelter of the Information Exchange (IE)  
 
☐ Store 
☐ Analyze 
☐ Share 
☐ In the Bone Marrow Transplant (BMT) database, also known as the 
HSCT (Hematopoietic Stem Cell Transplant) Database  
 
☐ Store 
☐ Analyze 
☐ Share 
☐ In REDCap (recap.ahc.umn.edu)  
 
☐ Store 
☐ Analyze 
☐ Share 
☐ In Qualtrics (qualtrics.umn.edu) 
 
☐ Store 
☐ Analyze 
☐ Share 
☒ In OnCore (oncore.umn.edu)  
 
☒ Store 
☐ Analyze 
☐ Share 
☒ In the University’s Box Secure Storage (box.umn.edu) 
 
☒ Store 
☒ Analyze 
☒ Share 
☐ In an AHC-IS supported server. Provide folder path, location of 
server and IT Support Contact: 
 
☐ Store 
☐ Analyze 
☐ Share 
☐ In an AHC-IS supported desktop or laptop.  
Provide UMN device numbers of all devices: 
 
☐ Store 
☐ Analyze 
☐ Share 
☐ Other: 
Indicate if  data will be collected, downloaded, accessed, shared or stored 
using a server, desktop, laptop, external drive or mobile device (including 
a tablet computer such as an iPad or a smartform (iPhone or Android 
devices) that you have not already identified in the preceding questions 
☐I will use a server not previously listed to collect/download research 
data 
☐I will use a desktop or laptop not previously listed 
☐I will use an external hard drive or USB drive (“flash” or “thumb” 
drives) not previously listed  
☐I will use a mobile device such as an tablet or smartphone not 
previously listed 
16.8 
Consultants. Vendors. Third Parties: N/A 
16.9 
Links to identifiable data: All data will be identified with an identification 
code unique to the participant. Study staff will keep the mapping of 
identification code to the identity of the participant on an Xcel 
spreadsheet in Box, protected by two-levels of password protection stored 
separately from the data. Any internal data reports will use only these 
codes and will not use any identifiable information. Any external data 
reports, abstracts, publications, presentations, etc. will present de-

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identified, grouped, and/or aggregate data. Any reports to the University 
of Minnesota IRB (such as Adverse Event reporting and annual renewal 
reports) will be kept confidential; they will not include participant- 
identifiable information; only the participant’s identification code will be 
used. 
16.10 Sharing of Data with Research Team Members: Only IRB-approved 
members of the study team will have access to the data. Data will be 
shared through UMN Box. 
16.11 Storage and Disposal of Paper Documents: All paper documents and 
consent forms will be stored in a locked cabinet in the anesthesia research 
office in B573 Mayo. All paper documents will be destroyed after 
completion of the study in accordance with U of M policy. 
17.0 Confidentiality 
17.1 Data Security: All study data will be stored electronically in Box and only the 
PI and members of the research team will have access to the data. 
18.0 Provisions to Monitor the Data to Ensure the Safety of Participants 
18.1 Data Integrity Monitoring: The PI, co-investigators, research supervisor and 
research assistants will all have access to the study data stored in the 
University’s Box storage system. All the research assistants have experience 
collecting pain scores and other relevant study information. The PI of the 
study will periodically review the study data to ensure accuracy and 
completeness of study data.  
18.2 Data Safety Monitoring: The Department of Anesthesiology has a Data and 
Safety Monitoring Committee consisting of several staff anesthesiologists 
which include persons who are board certified as pain specialists. If there 
are patterns of adverse events, the board will meet as needed and provide 
recommendations. The data will be reviewed on a regular basis (weekly) by 
the PI and research staff. Chi-square or Fisher’s exact tests (performed in R 
or SAS) will be used to test for differences in adverse event rates between 
treatment and control groups for Data Safety monitoring reports. 
19.0 Provisions to Protect the Privacy Interests of Participants 
19.1 Protecting Privacy: Patients will be able to decline research involvement 
when member of care team mentions it. The study consent form will 
describe in detail any intrusive, uncomfortable, or unfamiliar questions, 
procedures, or interactions with researchers or study personnel that the 
participant will be asked to complete. Furthermore, the study consent form 
will communicate that it is the participant’s right to opt-out of any study 
procedures or the study as a whole or withdraw from the study at any time 
and this information will be reiterated and revisited periodically throughout 

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the study in advance of intrusive, uncomfortable, or unfamiliar questions 
procedures or interactions. Participants will not be compelled or pressured 
to provide information or specimens or study data that they do not wish to 
provide. 
19.2 Access to Participants: They will have signed the consent and HIPAA form 
during consent process giving permission. Participants have been fully 
informed of the ways in which their data will/may be used during the 
informed consent process. The research team has been trained in 
conducting these conversations and the participants are also assessed for 
their understanding of consent prior to signing the consent form or 
initiating any study procedures. 
20.0 Compensation for Research-Related Injury 
20.1 Compensation for Research-Related Injury: In the event that this research 
activity results in an injury, treatment will be available, including first aid, 
emergency treatment, and follow-up care as needed.  Care for such injuries 
will be billed in the ordinary manner, to the patient and/or insurance 
company. 
20.2 Contract Language: N/A 
21.0 Consent Process 
21.1 Consent Process (when consent will be obtained): Patients will be identified 
in the pre-operative time period by the research team on the day of surgery. 
As soon as they enter the pre-operative room, an anesthesiologist will 
mention the study and ask permission for them or a research staff member 
to discuss it further if they are interested. If an anesthesiologist is not 
available when they are roomed, check-in or nursing staff will mention the 
study and ask the patient if a research member can discuss it with them 
further. If they are interested they will meet a research staff member and 
be presented with a combined Health and Insurance Portability and 
Accountability Act (HIPAA) and study consent form, with the REDCap e-
consent process being preferentially used. The patient will review the form 
with a member of the research team. They will be reminded that 
participation is completely voluntary, and that they may stop participation 
at any time without question or penalty. The research team will answer any 
questions that they may have about the study, and the teach-back method 
will be utilized to ensure comprehension. If the patient decides to 
participate, they will be asked to sign the consent and HIPAA form.  One 
copy will be saved for study records, and the subject will be provided with a 
copy of the forms. 

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21.2 Waiver or Alteration of Consent Process (when consent will not be 
obtained): N/A 
21.3 Waiver of Written/Signed Documentation of Consent (when written/signed 
consent will not be obtained): N/A 
21.4 Non-English Speaking Participants: N/A 
21.5 Participants Who Are Not Yet Adults (infants, children, teenagers under 18 
years of age): N/A 
21.6 Cognitively Impaired Adults, or adults with fluctuating or diminished 
capacity to consent: N/A 
21.7 Adults Unable to Consent: 
• 
Permission: N/A 
• 
Assent: N/A 
• 
Dissent: N/A 
22.0 Setting 
22.1 Research Sites: M Health Fairview ASC. 
22.2 International Research: N/A 
23.0 Multi-Site Research 
23.1 Study-Wide Number of Participants: N/A 
23.2 Study-Wide Recruitment Methods: N/A 
23.3 Study-Wide Recruitment Materials: N/A 
23.4 Communication Among Sites: N/A 
23.5 Communication to Sites: N/A 
24.0 Coordinating Center Research 
24.1 Role: N/A 
24.2 Responsibilities: N/A 
24.3 Oversight: N/A 
24.4 Collection and Management of Data: N/A 
25.0 Resources Available 
25.1 Resources Available: A research supervisor and research assistants are 
available to aid in consent and data acquisition. All research team members 
will be familiar with the study protocol and have experience working with 
similar studies as well as CITI and HIPAA training completed and up-to-date. 
All procedures will be performed in the clinical facilities at the M Health 
Fairview Clinics and Surgery Center. We do not anticipate this issue, but if 
research activity may disrupt normal work flow, the patient will not be 
approached. A delegation of authority log will also be maintained to track 
which personnel are responsible for specific duties. 
This center performs approximately 40 orthopedic surgical procedures 
under general anesthesia weekly.  We plan to conduct this study over 2 

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months.  Enrollment and data collection will be completed at this time.  
Statistical Analysis will take approximately two months to complete.  
 
26.0 References 
1. Hutchins JL et al. An Open-Label study of sufentanil sublingual tablet 30 mcg 
in patients with postoperative pain. Pain Med 2017 
2. Minkowitz HS et al. Sufentanil sublingual tablet 30 mcg for the management 
of pain following abdominal surgery: A randomized, placebo-controlled phase-
3 study. Pain Pract. 2017;17:848-858. 
3.  Kendrick DB et al. The minimum clinically significant difference in patient-
assigned numeric scores for pain, Am. J. Emerg. Med. 2005;828-832.