Secretin Infusion to Prevent Pancreatic Leaks Following Pancreatic Resection
Phase: PHASE2
Conditions: Injury of Body of Pancreas
Sponsor: Dartmouth-Hitchcock Medical Center

 
V.6 November 22 2019 page 0 of 20 
 
 
 
Dartmouth-Hitchcock 
Identifiers: 
NCT02160808   
Unique Protocol ID: D13208 TBG-01 
Brief Title: Secretin Infusion to 
Prevent Pancreatic Leaks Following 
Pancreatic Resection 
 
 
 

 
V.6 November 2019 page 1 of 20 
 
Dartmouth College and Dartmouth-Hitchcock Medical Center 
Committee for the Protection of Human Subjects 
CPHS Study Plan for Full Committee Review 
Template v. 2.24.2011 
Instructions:  
The following information in the format provided below is an application for CPHS review.  Read 
through each section and respond to each item (even if to indicate NA - not applicable). Please also 
review the CHECKLIST for Full Committee Submission.  We have provided some guidance information 
under each question.   
Please define all acronyms at first use and attach a glossary if more than 3 acronyms are used in this 
application. 
When revising a CPHS reviewed Study Plan for further review, please track the changes.  To turn on 
tracking in this document in Microsoft Word:  
1) Display the forms and reviewing toolbars. 
2) Unlock the form by clicking on the lock icon on the forms toolbar.  
3) Turn on change tracking by clicking the icon on the reviewing toolbar.  
4) Lock the form by clicking again on the lock icon on the forms toolbar.   
Attachments:  
Complete and submit Attachment(s) if applicable to the research study. 
Attachments may be downloaded from this webpage:  
http://www.dartmouth.edu/~cphs/tosubmit/forms/StudyPlanAttach 
 Attachment A:  Nonsignificant Risk Devices 
 Attachment B:  Placebo 
 Attachment C:  Genetic Research 
 Attachment D:  Employees and Students 
 Attachment E:  Illiterate Participants 
 Attachment F:  Research Involving Children 
 Attachment G:  Research Involving Individuals With Impaired Decision-Making Capacity  
(formerly referred to as incompetent) 
 Attachment H:  Request for Waiver of Participant Consent  
 Attachment I:  Request for Waiver of Participant Signed Consent Form 
 Attachment J:  Drugs or Biologics 
 Attachment L:  International Research 
 Attachment M:  Pregnant Women, Fetuses and Neonates 
============================================================== 
Local Principal Investigators:  Kerrington D. Smith and Timothy B. Gardner 
Secondary Investigators: Thomas Colacchio MD, Christina Angeles MD and Richard Barth MD 
Department: Departments of Medicine and Surgery 

 
V.6 November 2019 page 2 of 20 
Study Title: Secretin Infusion to Prevent Pancreatic leaks Following Pancreatic Resection 
Funding Source (Sponsor):  ChiRhoClin, Inc, and ChiRhoClin Research Institute.  This is an 
investigator-initiated project.  ChiRhoClin, Inc. will supply the drug, Secretin.  Dr. Gardner will 
also receive a small grant from the ChiRhoClin Research Institute to support the research 
coordinator’s salary. 
1. Abstract.   
Provide an abstract of the proposed research in language that can be understood by a non-scientist.  
The abstract should summarize the objectives of this project and the procedures to be used, with an 
emphasis on what will happen to the subjects. (Maximum 250 words)  
Pancreatic anastomotic leaks complicate pancreatic resection in approximately 20% of cases.  The 
pancreatic anastomosis or repair has been referred to as the Achilles heel of pancreatic surgery.  
Unfortunately, despite recognition of this problem and multiple operative techniques proposed to 
prevent this complication, leaks continue to represent a major cause of morbidity for patients undergoing 
pancreatic surgery.  Treatment of leaks often requires nutritional support with total parenteral nutrition 
to diminish the leak in addition to invasive interventions to contain the leak with drains, stents or in 
severe cases, reoperation.  Experiential data suggest that intra-operative infusions of secretin, a naturally 
occurring hormone that stimulates bicarbonate release from the pancreas, following resection but just 
prior to abdomen closure, may identify a leak if present.  If secretin can demonstrate evidence of leaking 
intra-operatively, the pancreatic duct leak may be able to be fixed prior to abdominal closure.   We aim 
to determine if giving an intra-operative infusion of secretin will allow for identification and treatment 
of leaks after pancreatic reconstruction and prior to abdominal closure, leading to a reduction in the rate 
of pancreatic anastomotic leaks requiring intervention.  We will perform a double-blind, randomized 
pilot study of 176 patients undergoing pancreatic resection (pancreaticoduodenectomy and distal 
pancreatectomy) at Dartmouth-Hitchcock Medical Center.  88 of those patients will receive an 
intraoperative secretin infusion prior to abdominal closure and 88 will receive a saline placebo. Our 
primary outcome of interest will be the rate of pancreas duct leaks in each group as measured by the 
amount of amylase present in the surgical drains on or after post operative day (POD)# 3 following 
surgery. 
2. Objectives & Hypotheses:   
List your research objectives and hypotheses. 
We hypothesize that intra-operative, intravenous secretin administration will decrease the rate of 
pancreatic leaks in patients undergoing pancreatic resection.  Our primary objective is to determine if 
intravenous secretin administration will decrease the amount of pancreatic leaks as defined by  the 2016  
ISGPS definition of postoperative pancreatic fistula, measured by drain fluid amylase on or after 
POD#3days following resection.  Our secondary objectives are to determine if intra-operative 
intravenous secretin administration changes the management of the pancreatic resection margin 
intraoperatively or impacts length of stay (LOS) 
3. Introduction:   
a) Explain the background of this project so that we will understand why it is important to perform this 
research project.  b) Summarize previously published data and pilot studies.  Be sure to include a 
discussion of any data that do not support the study hypothesis.  If a study similar to the one being 

 
V.6 November 2019 page 3 of 20 
proposed has already been completed, explain why the proposed study is necessary.  c) For studies 
designed to compare or evaluate therapies, there should be a statement of the relative advantages or 
disadvantages of alternative modes of therapy.  d) If not obvious, explain why human subjects are 
necessary.  Include references for all published data cited.  If a formal protocol for the study exists, 
page references to the protocol are acceptable. 
A) 
Pancreatic duct leaks represent a major complication of pancreatic resection surgery.  With a rate 
of between 20% even at expert, high-volume centers, this dreaded complication causes significant 
morbidity for patients with associated increased hospital costs.  Treatment of pancreatic duct leaks often 
requires pancreatic rest with intravenous nutrition, endoscopic placement of pancreatic duct stents, 
and/or repeat surgical operation to close the leak.  Despite many advancements in terms of leak closure 
techniques (duct to mucosa pancreaticojejunostomy, roux-en-Y reconstruction, devices (automatic 
staplers/ pledgets/stents) pancreatic leaks continue to be a major problem and pancreatic surgeons 
continue to search for methods to prevent or diminish the severity of pancreatic leaks.  
B) 
Currently, there are no pilot studies which have specifically addressed whether secretin therapy 
can help to identify pancreatic duct leaks intra-operatively.  While the drug has been used to identify 
leaks post-operatively using MRI (Gillams AR, Kurzawinski T, Lees WR. Diagnosis of duct disruption 
and assessment of pancreatic leak with dynamic secretin-stimulated MR cholangiopancreatography. 
AJR 2006) no previous studies have been performed.  Secretin is widely available and used to stimulate 
pancreatic secretions from the ductal cells for many indications such as identifying the minor papilla, 
obtaining pancreatic fluid for cytokine analysis, and diagnosing pancreatic cancer. (Levenick JM, 
Andrews CL, Purich, Ed et al. A Phase II Trial of Human Secretin Infusion for Refractory Type B Pain 
in Chronic Pancreatitis. Pancreas 2013)  It is also used to treat autism in select patients and diagnose the 
presence of a gastrinoma.  (Williams K, Wray JA, Wheeler DM. Intravenous Secretin for Autism 
Spectrum Disorders. Cochrane Database Reviews 2012; Imamura M, Komoto I, Ota S. Changing 
treatment strategy for gastrinoma in patients with Zollinger-Ellison syndrome. World J Surg 2006). 
Since 2011, patients at DHMC treated with pancreatic resection have occassionally been given 
intraoperative intravenous secretin to diagnose pancreatic duct leaks.  While this technique has not been 
specifically studied in a prospective fashion, anecdotal expereince demonstrates that secretin infusion 
can identify leaks in the operating room prior to abdominal closure.  Identifying the leaks 
intraoperatively then allows the surgeon to alter the technique of closure or suture placement directed at 
the site of leakage.  Our hypothesis is that secretin-assisted leak identification with localization will 
allow for intraoperative closure and decreased incidence and severity of clinically significant leaks in the 
post-operative period. 
C) 
This would be a randozimed, double-blind, placebo controlled trial.  1/2 of the patients would 
receive intra-operative secretin, the other half would receive saline placebo.  Both the surgeon and 
patient would be blinded to the randomization assignment.  The advantage of giving secretin would be 
that it may allow for the indentification of a leak intra-operatively and subsequently allow for repair if 
the leak was identified prior to abdominal wall closure.  While the safety profile of the drug is excellent, 
receiving the medication could theoretically cause an increased intraductal pressure which may cause a 
leak when one was not already present.  
D) 
Human subjects are needed to evaluate intra-operative, intravenous secretin in patients 
undergoing pancreatic duct resection. 

 
V.6 November 2019 page 4 of 20 
4.  Design, procedures, materials and methods:   
Use a level of detail similar to what would be used when submitting an article for publication in a peer 
reviewed journal.  Explain the study procedures, data collection, and analysis process.  Please define 
terms and explain concepts which might be confusing to reviewers who are not expert in the area of the 
study. If a formal protocol for the study exists, page references to the protocol are acceptable. 
This study design is a prospective, double-blind, randomized-controlled trial.  We will enroll patients in 
our institution undergoing pancreatic resection to receive either 1) one dose weight-based Secretin to be 
given once the closure of the pancreatic resection margin is complete 2) saline placebo. 
Consent and basic demographics will be garnered by the physician in an office visit once the surgery has 
been scheduled and consent for the surgery is being obtained.  The consent will be validated by the 
treating surgeon in the pre-procedure area on the day of the surgery.   
The patient will undergo the scheduled surgery.  Once the pancreatic anastomosis has been deemed 
acceptable by the attending physician, but prior to abdominal closure, the patient will be randomized to 
receive either Secretin (0.2 mcg/kg) or saline placebo.  The attending surgeon will be blinded to this 
assignment.   
10 minutes after receiving the Secretin or placebo, the attending surgeon will examine the anastomosis 
or repaired cut edge of the pancreas to determine if leakage of pancreatic fluid is noted, leak location(s), 
type (side branch/main duct), color of the fluid and whether any further intervention was performed in 
an effort to close the leak.  Specifics of operative intervention will be documented.  The patient will then 
undergo standard surgical closure of the abdomen. 
As is standard of care at DHMC, surgical drains will be placed adjacent to the anastomosis and drain 
amylase output will be checked on POD #1 through POD#5.  Pancreatic leak is defined according to the 
International Study Group of Pancreatic Fistula (ISGPF) definition as a clinically relevant postoperative 
pancreatic fistula is now redefined as a drain output of any measurable volume of fluid with an amylase 
level >3 times the upper limit of institutional normal serum amylase activity, associated with a clinically 
relevant development/condition related directly to the postoperative pancreatic fistula. Randomization 
assignments will be revealed once the patient has been discharged from the hospital following their 
initial surgical intervention.  A follow-up visit with the patient two weeks following discharge, will 
evaluate for any evidence of ongoing pancreatic duct leak. 
The patient will also be followed for thirty (30) days after secretin/placebo administration by the research 
team to assess for a pancreatic leak and sequelae of a leak, - intra abdominal deep soft tissue infection, 
surgical site infection, hemorrhage, IR (interventional radiology) drain placement, or reoperation. This will 
be accomplished by telephone and/or by chart review Patients discharge date will be followed for the study. 
If no secretin/placebo is administered, the patient will not be followed on the study. 
If any of the above are noted during the 30 days following secretin/placebo administration the following will 
be used to assess causality: 
Causality 
The following 4-point scale will be used for rating the causal relationship of the AE to the 
investigational product: 
Unrelated:      Clearly and incontrovertibly due to extraneous causes, and does not meet criteria listed  
under unlikely, possible, or probable. 

 
V.6 November 2019 page 5 of 20 
Unlikely:         Does not follow a reasonable temporal sequence from administration.  May have been  
produced by the patient’s clinical state or by environmental factors or other therapies 
administered. 
Possible:         Follows as reasonable temporal sequence from administration.  May have been produced  
by the patient’s clinical state or by environmental factors or other therapies administered. 
Probable:       Clear-cut temporal association with improvement or cessation of test drug or reduction in  
dose.  Reappears upon re-challenge.  Follows a known pattern or response to test drug. 
The primary outcome of interest will be the presence of pancreatic leaks based on the amount of drain 
amylase on or after POD#3.  Secondary outcomes will include: 1) technical interventions 
intraoperatively directed to leak closure or manipulation of the anastomosis following Secretin or 
placebo stimulation 2) length of stay as a surrogate to complication severity after pancreatic surgery. 
Patient demographics, risk factors, operative technique, randomization assignment and outcome data 
will be recorded on standard case report forms – See Case Report Forms in Appendix.  Data will be 
stored in an encrypted hard-drive by a single agent (Gardner) who is the only researcher who has access 
to the randomization data.  
5. Inclusion/Exclusion Criteria:   
Please provide detailed description of inclusion and exclusion criteria. If a formal protocol for the study 
exists, page references to the protocol are acceptable. 
Inclusion criteria:  
1. Scheduled for pancreatic surgery requiring pancreatic resection at DHMC 
2. Age greater than 18 years old 
3. Ability to provide written informed consent 
Exclusion criteria:  
1. Inability to provide written informed consent 
2. Current ongoing acute pancreatitis 
3. Pregnant or nursing mothers 
4. Any medical condition which in the judgment of the Investigator renders participation in this 
study medically inadvisable. 
5. Participation in an investigational clinical study for a drug or medical device within 30 days 
prior to Visit 1. 
6. Any known allergy to methylene blue.  
6. Financial Considerations:  
Disclosure of financial impact on the participant is critical to informed consent.  Insurance cannot be 
billed for research-related services outside the standard of care or paid for by the funding agency for 

 
V.6 November 2019 page 6 of 20 
the study.  The department, the study or the participant may be responsible for payment for 
researchrelated services.  Participants should know which tests, visits, or procedures will be billed to 
them or their insurance and which ones will be paid by the funding agency for the study or the 
department.  
a) 
List tests, visits, and procedures performed for only research purposes.  These services are 
outside the standard of care.  They would not be performed if the individual were not a research 
participant, and may not be billed to a health insurance plan.  
Note:  6a information must also be in "How is this different . . ." section of the consent form. 
The administration of Secretin or placebo is for research purposes only and will not be billed to the 
patient. Drain placement, drain amylase measurement and the two week follow-up visit are per standard 
of care and will be billed directly to the patient.   
b) 
List the tests, visits, and procedures that may be standard care, but for which the funding agency 
for the study is paying.   
None 
c) 
Will the funding agency for the study be responsible for the above costs? 
 Yes   
 No      
If  No,  describe who will be responsible (i.e., department or participant). 
Secretin will be supplied by ChiRhoClin, Inc and saline placebo will be supplied by the Section of 
Gastroenterology and Hepatology out of research funds maintained by the primary investigators. No 
additional tests, visits, or procedures will be performed for research purposes only.  
PLEASE ENCLOSE THE DHMC BILLING GRID/PLAN. Also enclose the schedule of events or 
table listing all procedures from the sponsor protocol.   
7.  Statistical Methods and Review Statement:   
a) Specify the primary endpoint, as well as other endpoint(s). 
Primary Objective: 
1. Pancreatic leak as defined by the ISGPF definition of post-operative pancreatic leaks 
Secondary Objective: 
1. Assess whether intervention is performed intra-operatively on the pancreatic anastomosis 
following Secretin or placebo injection. 
2. Assess degree to which leakage severity, as a complication, increases length of stay. 
b) State the statistical analysis plan, including all hypothesis tests (e.g., t-test, chi-square), and 
estimation methods related to the primary endpoint. If a formal protocol for the study exists, page 
references to the protocol are acceptable. 
For the analysis of the primary endpoint, a categorical variable, we will use a two-tailed Fisher’s Exact 
test to determine a p-value. We will then be able to calculate an absolute and relative risk reduction.  We 
will also evaluate this variable using a student’s t-test for means of amylase levels in the drain fluid.  We 
will plan on performing univariate analysis of all of the potentially contributing variables outlined in the 

 
V.6 November 2019 page 7 of 20 
CRF, and then building a multivariable logistic regression model using the categorical variable of drain 
amylase >3x the upper limit of normal.  The data from the multivariate regression will be reported as 
Odds Ratios. 
The secondary outcomes are both categorical and continuous variables and thus we will use the Fisher’s 
Exact test as well as the two-tailed student’s t-test.  A multivariable analysis is not planned for 
evaluating the secondary variable. 
Randomization will occur in a block format of 5 and will be generated by the primary investigators. 
c) Justify the sample size, using the concepts of power, type I error, and effect size if applicable. If a 
formal protocol for the study exists, page references to the protocol are acceptable. 
A clinically significant absolute decrease of 15% (20% to 5%) in the pancreatic duct leak rate. Based on 
these estimates and a two-tailed test comparing proportions using the statistical calculator 
(http://homepage.stat.uiowa.edu/~rlenth/Power), we project an estimated sample size of 176 
participants (88 per arm) to demonstrate an absolute 15% reduction in the leak rate with 80% power at 
a two-sided alpha level of 0.05.   
8.  Data and Safety Monitoring:  
Describe plans for data and safety monitoring to ensure the safety of subjects and the quality of the 
data. As described in federal guidance “… a variety of types of monitoring may be anticipated 
depending on the nature, size, and complexity of the trial.  In many cases, the principal investigator 
would be expected to perform the monitoring function.” This plan should include monitoring to 
determine: 
The progress of the trial, including periodic assessments of data quality and timeliness, participant 
recruitment, accrual and retention, participant risk versus benefit, and other factors that can affect 
study outcome.  Monitoring should also consider factors external to the study when interpreting the 
data, such as scientific or therapeutic developments that may have an impact on the safety of the 
participants or the ethics of the study. 
Note:  This section does not request information related to sponsor study monitor visits.  This section 
requires a description of an adequate data and safety monitoring plan.  
Interim analysis will be performed once 50% (88) patients have been enrolled.  If more than 66% of 
cases of duct leak are in a particular study group, a formal comparison between groups will be 
performed with the use of a two-sided stopping boundary of 0.005%. 
The co-heads of the DSMB will be Dr. Theodore Trus and Dr. Stuart Gordon, in the Section of General 
Surgery and Gastroenterology and Hepatology.  Drs. Trus and Gordon will not be participating in the 
trial. 
9. Genetics:   
Does any part of the study involve genetic analysis of biological specimens? 
 
Yes   x
 No 
If yes, respond to Genetics Attachment C    
  

 
V.6 November 2019 page 8 of 20 
10. Instruments:  
Describe each instrument, if any, used to collect data in this study. 
Please see the CRF included in the appendix. 
11. Deception.   
Will deception of participants, including withheld information, be used in this research? 
 
Yes   
 No  
If yes, complete a-d. 
12. Enrollment: 
a) Estimated number of participants for duration of entire study: 
      
At Dartmouth or associated sites: Female: 88    Male: 88       
 
If Multi-center study: Estimated total number at all sites: 0  
b) Estimated age range of participants: Age >18 
13. Timetables:   
a) Indicate length of participant involvement in the study:  
      Participation will involve enrollment at the time of surgery and discharge following surgery.  
Patients will then be seen in the clinic two weeks following the procedure. 
b) Estimate how long it will take to enroll enough participants to complete this study:  At DHMC, 
approximately 120 major pancreas surgeries are performed annually.  If 80% of patients agree to 
participate in the study, the enrollment should be complete after 24 months.  
14.  Risks:   
The purpose of this section is to determine if subjects will be placed "at risk," which in general means 
exposed to the possibility of physical, psychological, social, economic, legal, dignitary or other harm as 
a consequence of any activity proposed in the research project.  
a) What is the overall risk classification of the research? 
 Minimal 
 Greater than minimal 
 Significant 
 Unknown  
Note: In the federal regulations on human subjects protection minimal risk means "The probability and magnitude of harm or 
discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or 
during the performance of routine physical or psychological examinations or tests." 
b) Describe any potential risks (physical, psychological, social, legal, economic, or other) and assess 
their likelihood and seriousness.  Describe the procedures for protecting against or minimizing these 
risks, including risks to confidentiality, and assess their likely effectiveness. Please list risks from 
most severe/likely to least severe/unlikely. 

 
V.6 November 2019 page 9 of 20 
Synthetic secretin is FDA approved to diagnose exocrine pancreas dysfunction by the functional secretin 
stimulated pancreas function test and to facilitate pancreatic duct cannulation during ERCP.  It is 
identical in amino acid sequence to native human secretin.   
There has not been any reported adverse drug reaction to human secretin stimulation.  Rarely, in over 
1000 patients who have undergone Secretin-enhanced pancreatic function tests, there is transient 
vasodilatory effect resulting in flushing of the face and lips with stable vital signs.  Therefore, the risks 
of administrating intravenous secretin are modest as described in the package label. 
In doses (800cu SQ bid x 7 days) given in clinical studies greater than those offered in the current study, 
there were no adverse events reported 
Secretin is not known to increase the risk of acute pancreatitis episodes in patients with chronic 
pancreatitis not presently having an acute pancreatitis attack.  No allergic reactions have been reported 
with secretin in commercial use although the administration of a test dose 0.2 mcg IV is still 
recommended.  No significant hemodynamic effects have been observed following administration of 
secretin.  Otherwise, the risks of administering secretin are modest as described in the package label.  
The risk of confidentiality should be low given the case report form will be only available to Dr.  
Gardner and will be kept in a locked cabinet.  All data will be entered on a password-protected 
Microsoft Excel spreadsheet. Any statistical analysis will be done with patient study numbers and 
initials for identification of patient.   
15. Risk/Benefit analysis:   
Describe why the risks to subjects are reasonable in relation to the anticipated benefits to participants 
and in relation to the importance of the knowledge that may reasonably be expected to result from the 
study. 
     A potential risk reduction of up to 15% for pancreatic duct leaks outweighs the given theoretical risks 
of one time Secretin administration.   
16. Research Setting  
a) Is this a multi-center study?   
 Yes   
 No 
If yes:  Are you the lead investigator? 
 Yes   
 No If 
you are NOT the lead investigator: 
Name of lead investigator:         
Institution where the lead investigator is located:         
b) List all sites where research will take place and the CPHS at Dartmouth College is the reviewing IRB 
(e.g. DHMC Alliance Hospitals, DHMC Clinics, WRJ VAMC): 
Dartmouth-Hitchcock Medical Center 
c) If you are the lead investigator of a multi-center study, list all sites where research will take place 
and the CPHS at Dartmouth College is NOT the reviewing IRB: or check 
N/A 

 
V.6 November 2019 page 10 of 20 
NA 
d) Does the study involve sites outside of the United States and Canada?   Yes    No  
If yes, are arrangements for the international site(s) being made by a multinational pharmaceutical 
or device sponsor or a cooperative oncology working group?   Yes    No  
If no, please complete Attachment L. 
17. Adequacy of Resources to Protect Subjects: 
a) Investigator (including co-investigators) has sufficient time to conduct and complete the research.  
 Yes   
 No 
b) Adequately qualified (including experience, training, supervision, and familiarity with the protocol) 
staff are available for this research. 
 Yes   
 No. 
c) Describe availability of psychological, social, or medical services, which include counseling or 
social support services, that may be required as a consequence of research participation.  
Dartmouth-Hitchcock Medical Center provides adequate access to mental health services, including 
social and behavioral counseling.  Secretin is already being used on patients at high risk for pancreatic 
duct leaks, and we have in place the medical ability to treat a complication of this therapy in the rare 
event that one would occur. 
d) Describe psychological, social, or medical monitoring, ancillary care, equipment needed to protect 
participants (e.g. close proximity to resuscitation equipment or a plan for monitoring of emotional 
state during study procedures).  
None 
e) Describe other resources needed for the protection of subjects in the conduct of this research (e.g.  
language translation services). 
None 
f) Explain how the investigator has access to a population that would allow recruitment of the required 
number of subjects. 
DHMC performs about 120 major pancreatic surgeries annually. 
18.  Participant Population:   
Certain populations are considered vulnerable to coercion and undue influence.  These populations are 
provided with additional protections when participating in a research study. The populations include: 
• 
prisoners 
• 
human embryos 
• 
fetuses 
• 
elderly people 
• 
people with an cognitive disability (also see #24 below) 
• 
people with a disabling psychiatric illness 
• 
people who are economically disadvantaged persons 

 
V.6 November 2019 page 11 of 20 
• 
people who are illiterate 
Refer to:  
Students, Employees  Attachment D  
Illiterate Subjects 
Attachment E 
a) List vulnerable groups:  or check  None 
b) Describe additional protections:  or check  N/A  
19. Gender and Racial/Ethnic distribution:   
NIH guidelines state that research involving human participation should include minorities and both 
genders.  
Note:  If one gender or minorities are excluded or are inadequately represented in this research, particularly in proposed 
population-based studies, a clear and compelling rationale for exclusion or inadequate representation should be provided.  
Will eligibility for the study be based on gender, race, or ethnicity? 
 Yes   
 No If 
yes, explain: 
20. Pregnant Women:    
Are pregnant women eligible for enrollment into this study?  
 Yes   
 No 
If yes, respond to Research Involving Pregnant Women, Fetuses and Neonates:  Attachment M If no, 
explain and include a process to determine pregnancy status. If a pregnancy test is required, note who 
will pay: 
     They will not be included as pancreatic surgery is contraindicated, with very rare exceptions, in 
pregnancy. 
21. Fetuses and Neonates:   
Are fetuses and neonates participants in the research?    
 Yes   
 No  
If yes, respond to Research Involving Pregnant Women, Fetuses and Neonates:  Attachment M   
22. Children:   
Are children eligible for enrollment into this study? Under state law, a child is a person less than 18 
years old. 
 Yes   
 No  
If yes, respond to Children:  Attachment F 
If no, present an acceptable justification for the exclusion: 
Note:  NIH guidelines state that research involving human participation should include children unless there is appropriate 
justification for their exclusion.  The investigator should address the rationale for selecting or excluding a specific age range 
of children, or an explanation of the reasons for excluding children as participants in the research.  When children are 
included, the plan should also include a description of the expertise of the investigative team for dealing with children at the 
ages included, of the available facilities to accommodate the children, and a sufficient number of children to contribute 
meaningfully to the study analysis.  

 
V.6 November 2019 page 12 of 20 
23. Women of Child-Bearing Capability  
Are women of child-bearing capability eligible for enrollment into this study?  
 
Yes   
 No 
If yes, describe potential harm to an unborn fetus from study activities and the process for determining 
pregnancy status if necessary. If a pregnancy test is required, note who will pay.  If there is potential 
harm to an unborn fetus, the investigator should review with each individual a plan to avoid pregnancy.  
If the investigator regards these contraceptive plans as inadequate, the individual should be advised on 
how to achieve adequate contraception or should be excluded from the study. 
     Since the standard of care when performing surgery in patients with potential child-bearing capability 
is to perform pregnancy tests, we will require them for this study. 
24. Individuals With Impaired Decision-Making Capacity:   
a) 
Will participants potentially lacking capacity to provide informed consent be eligible to enroll in 
this study?  
 Yes   
 No 
b) 
Is it likely study participants may lose their capacity to provide informed consent during the 
conduct of the study? 
 Yes   
 No 
If yes to a or b, respond to Research Involving Individuals with Impaired Decision-Making Capacity:   
Attachment G    
25.  Recruitment:   
Describe how subjects will be recruited for participation in this study:   
Eligible participants may be identified from medical record information as a “preparatory to research” 
activity under the HIPAA Privacy Rule.  Protected health information obtained as a preparatory to 
research activity may not be removed by a researcher from DHMC, including on mobile electronic 
storage devices.  Contact with the identified participants, however, may not occur without prior CPHS 
approval of the recruitment plan for the study.  This plan should describe how initial contact with 
participants will be made and by whom.  Please note in general, individuals should not be contacted for 
recruitment into a research study by someone unknown to the individual. 
a) Will subjects be recruited by searching records 
(e.g., school records, medical records)?  Yes   
 
 No    
If yes, will this search include paper files?  
 
 Yes    
 No 
If yes, where will these paper files be located?         
If yes, will this search include electronic files?  
 Yes   
 No 
If yes, who maintains these electronic files?           
b) Will databases be utilized? 
 Yes   
 No 
If yes, please specify types and locations of databases:       
c) Will fliers or brochures be posted, mailed or 
otherwise distributed?  Yes    No 

 
V.6 November 2019 page 13 of 20 
d) Will letters be sent to potential participants?  
Yes    No   
If yes, please provide the letter(s) for CPHS review. 
e) Will referral be utilized for recruitment?  
 Yes   
 No    
If yes, please be aware patients should first be informed about the study and agree to the contact before 
any referral.  
f) Will any other method be employed? 
 Yes   
 
No  
If yes, please specify, in detail, what those methods will be:  
      Patients will be identified as study subjects when they present to DHMC for consideration of 
pancreas surgery. 
. 
g) Does the research plan include “finder fees” or 
incentives (bonus payment, gift certificates) 
offered to study personnel for enrollment of 
participants?  
 Yes   
 No    
Note:  As a rule, finder fees or incentives are not acceptable.  Please justify any offered incentives.  If incentives become 
available during the course of the study, please notify the CPHS. 
Attach copies of any proposed flyers, posters, pamphlets, print advertisements, and scripts for on-air 
advertisements or telephone calls.  All recruitment materials should be approved by CPHS prior to use. 
  
Note:  Advertising should not use terms such as “new treatment,” “new medication,” or “new drug” without explaining that 
the test article is investigational.  A phrase such as “receive new treatments” implies that research participants will be 
receiving newly marketed products of proven worth. Advertisements should not promise “free medical treatment,” when the 
intent is only to say participants will not be charged for taking part in the investigation.  The CPHS will determine if the 
promise of treatment without charge is an inappropriate inducement for study participation.  Advertisements may state that 
participants will be paid, but should not emphasize the payment or the amount to be paid.  The advertisement should include:  
the name and address of clinical investigator and research facility; the condition under study or the purpose of the research;  
in summary form, the criteria that will be used to determine eligibility for the study; a brief list of participation benefits, if 
any (e.g., a no-cost health examination); the time or other commitment required of the participants; and the location of the 
research activities; and the person or office from whom to obtain further information. 
26.  Consent Process:   
a) Informed Consent: 
The Principal Investigator (PI) is responsible for ensuring all participants have provided informed 
consent to participate in this study unless the consent process is waived or altered by the CPHS.  The PI 
may authorize other appropriately trained individuals to obtain consent from participants. 
Please file the consent form in the medical record of each research participant if study participation 
may affect other medical treatment. 
Explain how informed consent to research participation will be obtained.  Please describe the consent 
process, including information about:  
• Who has been authorized by the PI to obtain consent 

 
V.6 November 2019 page 14 of 20 
• The time interval between providing information potential participants about a study and having 
the consent form signed 
• Any precautions taken to minimize the possibility of coercion or undue influence 
• Plans for responding to a potential participant or a legally authorized representative who does 
not speak English, such as the use of a translator or a translated consent form 
• Any aids used to simplify scientific or technical information, like a diagram 
• Plans to accommodate the probable literacy level of potential participants 
      Informed consent will be obtained by primary investigator in the clinic at the time of consent for 
surgery.  Consent will be re-evaluated on day of surgery.  We will use a translator for non English 
speakers and since the study is very simple, we will not use any aids.  Literacy levels can be 
accommodated by having the consenting nurse or physician able to read the consent to the trial 
participants if necessary. 
 I intend to obtain consent for research participation but I am requesting a waiver for the use of a 
signed and dated consent form.  Please respond to the criteria listed in Attachment I and include an 
information sheet based on the CPHS template. 
 I am requesting an alteration of the consent process to exclude certain information that is ordinarily 
required.  A list of the essential elements of consent to research participation is available on the CPHS 
website: http://www.dartmouth.edu/~cphs/tosubmit/ConsentElements.html. Please respond to 
Attachment H. 
 I am requesting a waiver of the entire consent process and use of a consent form.  Please respond to 
Attachment H. 
Explain why any alteration or waiver to the consent process or form is necessary.   
b) Authorization:  Explain how an authorization for research use of protected health information (PHI) 
will be obtained.  PHI is individually identifiable health information obtained from a health care 
provider or insurance plan.  In general, the HIPAA Privacy Rule permits the use or disclosure of PHI 
for research purposes only with an authorization from each participant whose PHI will be involved.  
Only when certain criteria are satisfied can the CPHS grant a waiver of authorization or of the use of a 
signed and dated authorization form.  A waiver of authorization is necessary for recruitment procedures 
when patient information is used to identify and contact potentially eligible research participants.  A 
single form may combine the essential information for both consent and an authorization.  The CPHS 
consent template contains this combination and is available on the CPHS website at 
www.dartmouth.edu/~cphs.  
Check all that apply: 
 This study does not involve PHI. 
 A single form combining an authorization with the consent form and based on the CPHS template is 
included with this application. 
 A separate authorization form is included with this application. 
 I am requesting a waiver of authorization for only the recruitment procedure.  Please respond to 
Attachment H. 
 I am requesting a waiver of signed and dated authorization.  Please respond to Attachment I. 
 I am requesting a waiver of authorization for the use or disclosure of PHI in this entire study.  
Please respond to Attachment H. 

 
V.6 November 2019 page 15 of 20 
In your explanation of the consent process above, please include information about obtaining 
authorization for the research use of PHI. 
27.  Privacy and Confidentiality:   
Describe the plans to protect the privacy of subjects and maintain the confidentiality of the data.  
Note:  Under certain circumstances, an invasion of privacy or breach of confidentiality may present a risk of serious harm to 
subjects (e.g., as when the research obtains information about subjects that would, if disclosed by the researcher, jeopardize 
jobs or lead to prosecution for criminal behavior).  Under other circumstances, an invasion of privacy or breach of 
confidentiality can be a moral wrong  
a) 
Will any study activities involve an interaction or reveal information for which protection of 
participant privacy is necessary? 
 Yes   
 No  
If yes, please identify the activities and describe the plan to protect the privacy of participants.  For 
example, a plan for protection of privacy might consist of conducting the assent process for an 
adolescent minor in a private setting, rather than in the presence of the minor’s parent. 
b) 
Will the data collected in the course of the study be considered sensitive, e.g., include 
information about a mental health disorder, HIV status, or SS#?  
 Yes   
 No  
If yes, provide the rationale for why these data are needed: 
If yes, could any of these data, if disclosed, damage financial standing, employability, insurability, or 
reputation? 
No   
If yes, will a Certificate of Confidentiality be 
obtained?  Yes   
 No 
Any person engaged in research collecting information about illegal conduct from human research subjects may apply for a 
Certificate of Confidentiality.  NIH provides detailed instructions for investigators wishing to make an application at 
http://grants.nih.gov/grants/policy/coc/index.htm.   
c) 
Describe specific physical, administrative, and technical safeguards employed to secure data, 
e.g., limitation of access to data, use of locked file cabinets, protection of computer-based data 
systems.       Data will be kept by one investigator (Dr. Gardner) on a password-protected hard drive 
that only he has access to.  No other investigators will have access to this data. 
d) 
Will data that identify individual subjects be published or in any way be disclosed to third 
parties other than project personnel?   
 Yes   
 No   
If yes, please explain here and incorporate the information in consent form:  
28.  Responsibility for costs of injury or illness related to research: 
Will the sponsor or other funding agency be responsible for costs of injury or illness related to the 
research?    
 Yes   
 No 
If applicable, describe whether or not the sponsor will be responsible for investigational device removal 
if required: 
Yes    

 
V.6 November 2019 page 16 of 20 
If the sponsor or other funding agency will not be responsible for costs of injury or illness related to 
research, please complete: 
a) 
The reasons why the sponsor or funding agency is not accepting responsibility for research-
related injury. 
     All procedures for Secretin stimulation are standard of care  
b) 
Summary of risks as related to potential costs that could be incurred as a result of research-
related injury or illness.   
      The risk of using one dose of Secretin are extremely rare.  Please see above. 
c) 
Describe reasons for requesting that DHMC or Dartmouth College provide coverage for 
research-related injury or illness, which is not standard policy.   
      NA 
29. Participant Remuneration: 
Will participants be paid for their time, reimbursed for travel or meal expenses, or receive any sort of 
"gift" for participating in this study?  
 Yes   
 No 
If yes, please describe in detail: 
Note: Participant remuneration is not considered a benefit of being in a research study.  CPHS will consider the amount of 
payment in relation to the time needed and any inconvenience to participants.  Payment, reimbursement, or gifts should not 
be  in an amount that would be coercive to the participant population. 
If study is to be done at the VA, specific questions need to be answered if a participant is being paid "in excess of 
reimbursement for travel."  Please contact the CPHS office if you need more information. 
30. Use of Drug or Biological Agent:   
Respond to items below or check x No drug or biological agent involved.  
List the drugs and biologic agents to be used in this study: Secretin (0.2 mcg/kg) in a single dose 
Is each drug or biological agent approved by the FDA for the specific indication for which it is used in 
this study?   
Drug or Biologic Agent: Secretin 
 Yes     No  This drug is an FDA designated orphan 
drug "for use in conjunction with diagnostic procedures (excluding ERCP) for pancreatic 
disorders to increase pancreatic fluid secretions."  In this study, secretin is being used 
under an IND granted to ChiRhoClin. 
 
Drug or Biologic Agent:       
 Yes    
 No 
If no, respond to a and b for each drug or biologic agent used for an unapproved indication:  
a) Briefly discuss the plan for the storage, dispensing, handling, and disposal of investigational and 
FDA-approved drugs, devices, and biologics. When these activities are being done by the 
investigator, include a description of the procedures for inventory control and documentation. 
DHMC Investigational Pharmacy is managing all study drugs.   
Yes   
 No 
If No please describe management plan below. 

 
V.6 November 2019 page 17 of 20 
b) Check and respond to one of the following statements for each drug or biologic agent:  
 If this study is being done under an Investigational New Drug (IND) application to the FDA please 
provide:  IND # (Investigational New Drug):  # 56821  and specify who holds the IND#: ChiRhoClin, 
Inc. 
OR 
 If a drug or biologic agent or the combination of drugs or agents is not FDA approved for the 
indication for which it is used in this study, but an IND # has not been obtained, please complete 
Attachment J 
31. Placebo vs. Standard Care:   
Does any part of the study involve use of a placebo or procedures that are inconsistent with the 
standard of care at DHMC?   
 Yes   
 No 
If yes, respond to Placebo:  Attachment B 
32. Medical Device:  
Respond to items below or check x No devices involved. 
List the devices to be used in this study: NA 
Is each device approved by the FDA for this indication?    
 
Device:       
 Yes    
 No 
 
Device:       
 Yes    
 No 
If no or if FDA approval is pending, respond to a, b, and c for each device used for an unapproved 
indication. 
a) Is the device provided free of charge by the sponsor?   
 Yes   
 No 
b) Where are the devices used in the study stored?  Who controls their use? 
 
      
 
c) Respond to (1), (2), (3), or (4) 
(1) 
If this study is being done under an Investigational Device Exemption (IDE) from the 
FDA please provide:  IDE#: #      or check here if the IDE is pending: 
 
Also check the FDA Device HCFA Reimbursement Category: 
 
      
 A      
 B2     
 B3 
Please note: CPHS will not approve a study before an IDE # has been received. 
OR 

 
V.6 November 2019 page 18 of 20 
(2) 
If 510(k) notification for a device has been sent to FDA check here 
 and either: provide 
a copy of the documentation verifying 510(k) clearance, or check here if 510(k) clearance is 
pending 
. 
OR 
(3) 
If a device is exempt from IDE requirements, check here 
 and provide a copy of a letter 
from the FDA or sponsor stating that the device is exempt from IDE requirements under 
812.2(c). 
OR  
(4) 
If you are requesting a nonsignificant risk determination for a device from CPHS, please 
check here 
 and complete Attachment A. 
Please note: The CPHS may approve, disapprove, or require modifications in a protocol that has been 
approved or cleared by the FDA.  
33.  Conflict of Interest Review: 
Dartmouth College, Dartmouth-Hitchcock Clinic, and Mary Hitchcock Memorial Hospital have 
adopted a policy on Conflict of Interest in Human Subject Research.  Copies of the policy are available 
on the Dartmouth College, Office of Sponsored Projects web site at 
http://www.dartmouth.edu/~osp/policies.html. 
Definitions: 
“Conflict of interest” occurs when an independent observer may reasonably question whether an 
individual's professional actions or decisions are influenced by considerations of the individual’s 
private interests, financial or otherwise. 
Conflicting financial interests do not include: 
• 
salary and benefits from Dartmouth College, Dartmouth-Hitchcock Clinic, and Mary 
Hitchcock Memorial Hospital; 
• 
income from seminars, lectures, teaching engagements, or publishing sponsored by 
federal, state, or local entities, or from non-profit academic institutions, when the funds do 
not originate from corporate sources; 
• 
income from service on advisory committees or review panels for governmental or 
nonprofit entities; 
• 
investments in publicly-traded mutual funds;  
• 
gifts and promotional items of nominal value; and 
• 
meals and lodging for participation in professional meetings. 
“Principal investigator or other key personnel” means the principal investigator and any other person, 
including students, who is responsible for the design, conduct, analysis, or reporting of research 
involving human subjects. 
Instructions: 
To assist institutional review of the proposed research for conflicts of interest, please respond to the 
question below. 
With regard to this proposed research study, does the principal investigator or other key personnel, or 
any of their spouses, domestic partners, or dependent children, hold a financial interest that would 

 
V.6 November 2019 page 19 of 20 
reasonably appear to affect or be affected by the proposed study, including but not limited to the 
following interests? 
a. compensation for services (e.g., consulting fees or honoraria), or in-kind payments, other than 
from the researcher's primary employer, in the prior calendar year or projected over the next 
twelve months; 
b. royalty income or the right to receive future royalties under a patent license or copyright, 
when the proposed research is directly related to the licensed technology or work; 
c. equity interests (e.g., stocks, stock options or other ownership interests), including equity 
holdings where the value cannot readily be determined by reference to public prices;  
d. intellectual property rights (e.g., patents and copyrights), and royalties from such rights;  
e. gifts or funds available to the researcher from the sponsor of this study beyond the current 
project; 
f. funding expected to significantly exceed the projected costs of conducting this study; or 
g. another financial or private interest that may present a conflict of interest. 
No:  The Principal Investigator or other key personnel do not have any financial interests listed in a. -g. 
above. 
x  Yes:  The Principal Investigator or other key personnel do have financial interests listed in items a. - 
g. above. 
Only if you have answered yes to the question above about study-specific financial interests for a 
member of the research team, please provide the following additional information. 
Name of each individual with a listed financial interest:  Timothy Gardner 
Each individual on the above list should complete a Conflict of Interest Disclosure Form for Human 
Subject Research.  The disclosure should include only those financial interests that are specifically 
relevant to this research study. 
The Conflict of Interest Disclosure Form for Human Subject Research is available on the CPHS website 
at the following url: 
http://www.dartmouth.edu/~cphs/tosubmit/forms/ 
Please complete and sign the Conflict of Interest Disclosure Form for Human Subject Research form.  In 
an envelope marked "Confidential", send the form to the Director of the Office of Sponsored Projects, 
using the following address: 
CPHS/COI-HS, Hinman Box 6254. 
 

 
V.6 November 2019 page 20 of 20 
Attachment B 
Placebo or Procedures that are Inconsistent with the Standard of Care  
Consider the ethical implications of using a placebo or procedures that are inconsistent with the 
standard of care in this study.  Specifically, explain what "standard of care" therapy is for this 
participant population and how the use of placebo therapy may affect risks for participants. Also 
discuss: 
a) the safety and efficacy of other available therapies (if any), 
b) the maximum total length of time a participant may receive placebo on study, 
c) the greatest potential harm that may come to a participant as a result of not receiving effective 
therapy  (immediate or delayed onset), and 
d) safeguards for the participants receiving placebo. 
Required comment from the local research team specifically addressing a-d above and in addition to 
any justification included in the study protocol.  Information copied directly from the protocol is not 
acceptable in this section: 
 
At this time, in average risk patients, we are unclear of giving Secretin intra-operatively will allow better 
identification and repair of pancreatic duct leaks.  The dug is used occasionally in high risk patients to 
evaluate for duct leaks and we would like to see if this drug is universally useful in all patients 
undergoing pancreatic surgery.  The patient will only be included in the study from the time of their 
surgery to initial hospital discharge.  The risk of not receiving therapy is that they may have a higher risk 
of duct leak (we will know better after the study).  Patients receiving placebo will receive the same 
standard of care post-operatively than those receiving Secretin stimulation.