Toradol to Reduce Ureteroscopic Symptoms Trial
Phase: PHASE2
Conditions: Urinary Lithiasis, Kidney Diseases, Kidney Stone, Pain, Postoperative
Sponsor: Yale University

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YALE UNIVERSITY 
 
                                  HUMAN INVESTIGATION COMMITTEE 
 
                                     Application to Involve Human Subjects in Biomedical Research 
100 FR1 (2015-2)  
 
SECTION I: ADMINISTRATIVE INFORMATION 
 
Title of Research Project:  
Toradol to Reduce Ureteroscopic Symptoms Trial (TRUST) 
Principal Investigator: 
Piruz Motamedinia 
Yale Academic Appointment: 
Assistant Professor of Urology 
Department: 
Campus Address:  
Po Box 208058 New Haven, CT 06520-8058 
Campus Phone: 2037852815 
Fax: 
2037378035 
Pager:  
E-mail: 
Piruz.motamedinia@yale
.edu 
Protocol Correspondent Name & Address (if different than PI): 
  
Campus Phone:  
Fax:  
E-mail:  
Yale Cancer Center 
CTO Protocol 
Correspondent 
Name & Address (if 
applicable): 
 
Campus Phone:  
Fax:  
E-mail:  
Business Manager: Kevin Vest 
Campus Phone :203-
785-4371 
Fax : 
E-mail: Kevin.vest@yale.edu 
 
Investigator Interests: 
Does the principal investigator, or do any research personnel who are responsible for the design, 
conduct or reporting of this project or any of their family members (spouse or dependent child) 
have an incentive or interest, financial or otherwise, that may affect the protection of the human 
subjects involved in this project, the scientific objectivity of the research or its integrity? Note: 
The Principal Investigator (Project Director), upon consideration of the individual’s role and 
Faculty Advisor:(required if PI is a student, 
resident, fellow or other trainee)           
 NA 
 
Yale Academic Appointment: 
 
Campus Address:  
 
Campus Phone:  
Fax:  
Pager:  
E-mail:  

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degree of independence in carrying out the work, will determine who is responsible for the 
design, conduct, or reporting of the research.  
See Disclosures and Management of Personal Interests in Human Research 
http://www.yale.edu/hrpp/policies/index.html#COI  
❏  Yes  
❏x  No 
 
Do you or does anyone on the research team who is determined by you to be responsible for the 
design, conduct or reporting of this research have any patent (sole right to make, use or sell an 
invention) or copyright (exclusive rights to an original work) interests related to this research 
protocol? 
❏  Yes  
❏x  No 
 
 
 
If yes to either question above, list names of the investigator or responsible person: 
 
 
 
The Yale University Principal Investigator, all Yale University co-investigators, and all Yale 
University individuals who are responsible for the design, conduct or reporting of research must 
have a current financial disclosure form on file with the University’s Conflict of Interest Office. 
Yale New Haven Hospital personnel who are listed as co-investigators on a protocol with a Yale 
University Principal Investigator must also have a current financial disclosure form on file with 
the University’s Conflict of Interest Office. If this has not been done, the individual(s) should 
follow this link to the COI Office Website to complete the form:  http://www.yale.edu/coi/   
 
NOTE: The requirement for maintaining a current disclosure form on file with the University’s 
Conflict of Interest Office extends primarily to Yale University and Yale-New Haven Hospital 
personnel.  Whether or not they are required to maintain a disclosure form with the 
University’s Conflict of Interest Office, all investigators and individuals deemed otherwise 
responsible by the PI who are listed on the protocol are required to disclose to the PI any 
interests that are specific to this protocol. 
 
SECTION II: GENERAL INFORMATION 
 
1. Performing Organizations:  Identify the hospital, in-patient or outpatient facility, school or 
other agency that will serve as the location of the research.  Choose all that apply: 
  
a. Internal Location[s] of the Study: 
 Magnetic Resonance Research Center  
 
 Yale University PET Center 
     (MR-TAC)    
 
 
 
 
 YCCI/Church Street Research Unit (CSRU) 
 Yale Cancer Center/Clinical Trials Office (CTO)    
 YCCI/Hospital Research Unit (HRU) 
 Yale Cancer Center/Smilow 
 
 
 YCCI/Keck Laboratories 
 Yale-New Haven Hospital  
 
 
 Yale-New Haven Hospital—Saint Raphael Campus 
 Cancer Data Repository/Tumor Registry 
 Specify Other Yale Location: 
 
 
 
 
 

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b. External Location[s]: 
 APT Foundation, Inc. 
 
 
 
 Haskins Laboratories 
 Connecticut Mental Health Center 
 
 John B. Pierce Laboratory, Inc. 
 Clinical Neuroscience Research Unit (CNRU) 
Veterans Affairs Hospital, West Haven 
 
 Other Locations, Specify:  
 
 
 International Research Site  
(Specify location(s)): 
 
 
c. Additional Required Documents (check all that apply): 
 N/A 
*YCCI-Scientific and Safety Committee (YCCI-SSC)  
Approval Date:  
*Pediatric Protocol Review Committee (PPRC) 
 
Approval Date:  
*YCC Protocol Review Committee (YRC-PRC) 
 
Approval Date: 
 
*Dept. of Veterans Affairs, West Haven VA HSS 
 
Approval Date:  
*Radioactive Drug Research Committee (RDRC) 
 
Approval Date:  
 YNHH-Radiation Safety Committee (YNHH-RSC) 
 
Approval Date:  
 Yale University RSC (YU-RSC) 
 
 
 
Approval Date: 
 Magnetic Resonance Research Center PRC (MRRC-PRC) 
Approval Date: 
 *Nursing Research Committee  
 
 
 
Approval Date: 
 YSM/YNHH Cancer Data Repository (CaDR)  
 
Approval Date:  
 Dept. of Lab Medicine request for services or specimens form 
 Imaging on YNHH Diagnostic Radiology equipment request form (YDRCTO request) found 
at  http://radiology.yale.edu/research/ClinTrials.aspx) 
*Approval from these committees is required before final HIC approval is granted. See instructions 
for documents required for initial submission and approval of the protocol. Allow sufficient time for 
these requests. Check with the oversight body for their time requirements. 
 
2. Probable Duration of Project: State the expected duration of the project, including all 
follow-up and data analysis activities.  
The expected duration of the project including all follow-up and data analysis is 48 months 
from trial initiation. 
 
3. Research Type/Phase: (Check all that apply) 
a. Study Type 
   
 Single Center Study 
   
 Multi-Center Study 
Does the Yale PI serve as the PI of the multi-site study? Yes 
 
No 
 
  
 Coordinating Center/Data Management 
  
 Other:  
 
 
b. Study Phase 
 N/A 
    
 Pilot  
 Phase I 
 Phase II 
 Phase III 
 Phase IV 
    
 Other (Specify)  
 
 

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4. Area of Research: (Check all that apply) Note that these are overlapping definitions and 
more than one category may apply to your research protocol. Definitions for the following 
can be found  in the instructions section 4c: 
 Clinical Research: Patient-Oriented 
   
 
 Clinical Research: Outcomes and  
 Clinical Research: Epidemiologic and Behavioral  
                 Health Services 
 Translational Research #1 (“Bench-to-Bedside”)      
 Interdisciplinary Research 
 Translational Research #2 (“Bedside-to-Community”)  
 Community-Based Research 
 
 
5.   Is this study a clinical trial? Yes 
 
No 
 
NOTE the current ICMJE (International Committee of Medical Journal Editors) definition of a 
clinical trial: “any research study that prospectively assigns human participants or groups of humans 
to one or more health-related interventions to evaluate the effects on health outcomes.” Health-related 
interventions include any intervention used to modify a biomedical or health-related outcome (for 
example, drugs, surgical procedures, devices, behavioral treatments, dietary interventions, and 
process-of-care changes). Health outcomes include any biomedical or health-related measures 
obtained in patients or participants, including pharmacokinetic measures and adverse events” 
  
If yes, where is it registered? 
  
 
Clinical Trials.gov registry 
 
  
 
Other (Specify)  
 
Registration of clinical trials at their initiation is required by the FDA, NIH and by the ICMJE. 
 
If this study is registered on clinicaltrials.gov, there is new language in the consent form and compound 
authorization that should be used. 
For more information on registering clinical trials, including whether your trial must be 
registered, see the YCCI webpage, http://ycci.yale.edu/researchers/ors/registerstudy.aspx 
or  contact YCCI at 203.785.3482) 
 
6. Does the Clinical Trials Agreement (CTA) require compliance with ICH GCP (E6)?  
Yes 
 No
 
 
 
7. Will this study have a billable service? A billable service is defined as any service rendered to 
a study subject that, if he/she was not on a study, would normally generate a bill from either 
Yale-New Haven Hospital or Yale Medical Group to the patient or the patient’s insurer. The 
service may or may not be performed by the research staff on your study, but may be provided by 
professionals within either Yale-New Haven Hospital or Yale Medical Group (examples include 
x-rays, MRIs, CT scans, specimens sent to central labs, or specimens sent to pathology). Notes: 
1. There is no distinction made whether the service is paid for by the subject or their insurance 
(Standard of Care) or by the study’s funding mechanism (Research Sponsored). 2. This generally 
includes new services or orders placed in EPIC for research subjects.  
 
Yes 
 No
 

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 If answered, “yes”, this study will need to be set up in OnCore, Yale’s clinical research 
management system, for Epic to appropriately route research related charges. Please contact 
oncore.support@yale.edu 
8.. Are there any procedures involved in this protocol that will be performed at YNHH or one of 
its affiliated entities?  Yes _x__ No ___  If Yes, please answer questions a through c and note 
instructions below.  If No, proceed to Section III. 
a. Does your YNHH privilege delineation currently include the specific procedure that you will 
perform? Yes 
 
b. Will you be using any new equipment or equipment that you have not used in the past for 
this procedure? No 
  
c. Will a novel approach using existing equipment be applied? No 
  
If you answered “no” to question 8a, or "yes" to question 8b or c, please contact the YNHH 
Department of Physician Services (688-2615) for prior approval before commencing with your 
research protocol. 
 
Please note that if this protocol includes Yale-New Haven Hospital patients, including patients at 
the HRU, the Principal Investigator and any co-investigators who are physicians or  mid-level 
practitioners (includes PAs, APRNs, psychologists and speech pathologists) who may have direct 
patient contact with patients on YNHH premises must have medical staff appointment and 
appropriate clinical privileges at YNHH. If you are uncertain whether the study personnel meet 
the criteria, please telephone the Physician Services Department at 203-688-2615. By signing 
this protocol as a PI, you attest that you and any co-investigator who may have patient contact 
has a medical staff appointment and appropriate clinical privileges at YNHH. 
 
 
SECTION III: FUNDING, RESEARCH TEAM AND TRAINING 
 
1. Funding Source: Indicate all of the funding source(s) for this study. Check all boxes that apply. 
Provide information regarding the external funding source.  This information should include 
identification of the agency/sponsor, the funding mechanism (grant or contract), and whether 
the award is pending or has been awarded. Provide the M/C# and Agency name (if grant-
funded).  If the funding source associated with a protocol is “pending” at the time of the 
protocol submission to the HIC (as is the case for most NIH submissions), the PI should note 
“Pending” in the appropriate section of the protocol application, provide the M/C# and 
Agency name (if grant-funded) and further note that University (departmental) funds support 
the research (until such time that an award is made).   
 
 
PI  
Title of Grant 
Name of Funding Source  
Funding 
Funding Mechanism 

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Piruz 
Motamedinia, 
M.D. 
Toradol to Reduce 
Ureteroscopic 
Symptoms Trial 
(TRUST) 
Yale Department of Urology 
  Federal 
  State 
  Non Profit 
  Industry 
  Other For 
Profit  
  Other 
 
Grant-M#            
Contract#  
Contract Pending 
  Investigator/Department 
Initiated 
  Sponsor Initiated 
  Other, Specify: 
 
 
 
 
 
  Federal 
  State 
  Non Profit 
  Industry 
  Other For 
Profit  
  Other 
 
Grant-M#            
Contract#  
Contract Pending 
  Investigator/Department 
Initiated 
  Sponsor Initiated 
  Other, Specify: 
 
 
 
 
 
  Federal 
  State 
  Non Profit 
  Industry 
  Other For 
Profit  
  Other 
 
Grant-M#            
Contract#  
Contract Pending 
  Investigator/Department 
Initiated 
  Sponsor Initiated 
  Other, Specify:  
 
 
IRB Review fees are charged for projects funded by Industry or Other For-Profit Sponsors.  
Provide the Name and Address of the Sponsor Representative to whom the invoice should be 
sent.  Note: the PI’s home department will be billed if this information is not provided. 
 
Send IRB Review Fee Invoice To: 
 
Name: 
 
Company: 
Address: 
  
2. Research Team:  List all members of the research team. Indicate under the affiliation column whether 
the investigators or study personnel are part of the Yale faculty or staff, or part of the faculty or staff 
from a collaborating institution, or are not formally affiliated with any institution. ALL members of 
the research team MUST complete Human Subject Protection Training (HSPT) and Health 
Insurance Portability and Accountability Act (HIPAA) Training before they may be listed on the 
protocol.  See NOTE below. 
 
Name 
Affiliation: Yale/Other 
Institution (Identify) 
 
NetID 
Principal Investigator  
Piruz Motamedinia MD 
Yale University Urology Pm639 

Page 7 of 28 
 
 
NOTE: The HIC will remove from the protocol any personnel who have not completed required training. 
A personnel protocol amendment will need to be submitted when training is completed. 
 
SECTION IV: 
 PRINCIPAL INVESTIGATOR/FACULTY ADVISOR/ DEPARTMENT CHAIR AGREEMENT 
 
 
 
 
 
 
 
 
 
 
 
Role: Data Analysis, Data 
Collection, Manuscript 
Preparation 
Jamil Syed  
Yale University Urology Js3569 
 
 
 
 
 
Role: 
 
 
 
Role: 
 
 
 
 
 
 
 
 
 
 
 
 
As the principal investigator of this research project, I certify that: 
§ 
The information provided in this application is complete and accurate. 
§ 
I assume full responsibility for the protection of human subjects and the proper conduct of the 
      research. 
§ 
Subject safety will be of paramount concern, and every effort will be made to protect subjects’ 
      rights and welfare. 
§ 
The research will be performed according to ethical principles and in compliance with all federal, 
      state and local laws, as well as institutional regulations and policies regarding the protection of   
      human subjects. 
§ 
All members of the research team will be kept apprised of research goals. 
§ 
I will obtain approval for this research study and any subsequent revisions prior to my initiating the 
      study or any change and I will obtain continuing approval of this study prior to the expiration date      
      of any approval period. 
§ 
I will report to the HIC any serious injuries and/or other unanticipated problems involving risk to 
      participants. 
§ 
I am in compliance with the requirements set by the University and qualify to serve as the 
      principal investigator of this project or have acquired the appropriate approval from the  
      Dean’s Office or Office of the Provost, or the Human Subject Protection Administrator at 
      Yale-New Haven Hospital, or have a faculty advisor. 
§ 
I will identify a qualified successor should I cease my role as principal investigator and facilitate a 
smooth transfer of investigator responsibilities. 
 
_____ 
 
 
 
 
 
 
 
 
 
 
 
 
  
PI Name (PRINT) and Signature 
 
 
 
 
Date 
As the faculty advisor of this research project, I certify that: 
§ 
The information provided in this application is complete and accurate. 
§ 
This project has scientific value and merit and that the student or trainee investigator has the 
necessary resources to complete the project and achieve the aims. 
§ 
I will train the student investigator in matters of appropriate research compliance, protection 
of human subjects and proper conduct of research. 
§ 
The research will be performed according to ethical principles and in compliance with all 
federal, state and local laws, as well as institutional regulations and policies regarding the 
protection of human subjects. 
§ 
The student investigator will obtain approval for this research study and any subsequent 
revisions prior to initiating the study or revision and will obtain continuing approval prior to 
the expiration of any approval period. 
§
The student investigator will report to the HIC any serious injuries and/or other unanticipated

Page 8 of 28 
 
 
 
 
 
 
 
 
 
 
 
 
 
Department Chair’s Assurance Statement 
Do you know of any real or apparent institutional conflict of interest (e.g., Yale ownership of a 
sponsoring company, patents, licensure) associated with this research project? 
 Yes (provide a description of that interest in a separate letter addressed to the HIC.) 
 No 
 
As Chair, do you have any real or apparent protocol-specific conflict of interest between yourself and 
the sponsor of the research project, or its competitor or any interest in any intervention and/or method 
tested in the project that might compromise this research project? 
Yes (provide a description of that interest in a separate letter addressed to the HIC) 
No 
 
I assure the HIC that the principal investigator and all members of the research team are qualified by 
education, training, licensure and/or experience to assume participation in the conduct of this research 
trial. I also assure that the principal investigator has departmental support and sufficient resources to 
conduct this trial appropriately. 
 
   ____________________________  
 
 
 
 
 
 
   Chair Name (PRINT) and Signature   
     
 
 
 Date 
 
   _________________________________ 
   Department 
 
 
YNHH Human Subjects Protection Administrator Assurance Statement 
Required when the study is conducted solely at YNHH by YNHH health care providers. 
 
As Human Subject Protection Administrator (HSPA) for YNHH, I certify that: 
§ I have read a copy of the protocol and approve it being conducted at YNHH. 
§ I agree to notify the IRB if I am aware of any real or apparent institutional conflict of interest. 
§ The principal investigator of this study is qualified to serve as P.I. and has the support of the hospital 
for this research project. 
 
  ______________________________________ 
 
 
 
 
 
 
 
 

Page 9 of 28 
 
    YNHH HSPA Name (PRINT) and Signature         
 
 
Date 
 
 
 
 
 
 
 
 
SECTION V: RESEARCH PLAN 
 
1. Statement of Purpose: State the scientific aim(s) of the study, or the hypotheses to be tested.  
 
The objective of this study is to evaluate the effect of a single intraoperative ketorolac injection 
on intra-operative narcotic use, postoperative pain and narcotic use, and hospital readmission 
rates in patients who undergo retrograde ureteroscopy for kidney and/or ureteral stone 
management.  
 
2. Background: Describe the background information that led to the plan for this project. 
Provide references to support the expectation of obtaining useful scientific data. 
 
The incidence and prevalence of urolithiasis in the United States has risen considerably over 
the past few decades.(1) Treatment for ureteral stones can include expectant therapy for 
asymptomatic and small stones,, shock wave lithotripsy (SWL) or ureteroscopy (URS) with 
lithotripsy for obstructing or symptomatic stones up to 15-20mm, and percutaneous 
nephrolithotomy for larger more complex stones. 
 
Historically, SWL offered a non-invasive and effective intervention for the treatment of most 
symptomatic stones and was the preferred therapy. However, with advancement in 
ureteroscopic digital optics, miniaturization of scope caliber, improved flexibility and 
durability, and recognized better stone free rates, utilization of URS has steadily grown and 
is overtaking SWL as the preferred treatment modality for kidney stones. URS is accepted as 
the treatment of choice for lower ureteral stones and is associated with stone free rates of up 
to 100% by post-operative day 2.(2)  
 
One limitation of URS is that post-operative pain due to intra-operative instrumentation and 
the common utilization of temporary ureteral stents can be challenging to manage. The 
complication rate for URS requiring postoperative hospital admission has been reported at 
up to 14%, with pain being the predominant complication.(4)  This temporary post-operative 
pain and stent related colic is perhaps the greatest barrier, aside from surgeon skill, to the 
wider utilization of this URS over SWL, which has less efficacy but can be better tolerated.  
In addition to improving URS as a technology, we as physicians must improve the tolerance 
of URS for the patients.  
 
Ketorolac is a non-steroidal anti-inflammatory drug (NSAID) available in oral or parenteral 
formulations. It is a highly effective analgesic with comparable potency to narcotics, non-

Page 10 of 28 
 
habit forming, and without the gastro-intestinal (e.g. nausea, ileus, constipation) or 
neurologic side effects seen with narcotics. Ketorolac use is generally safe for short 
durations limited to less than 5 days. Contraindications including NSAID allergy, renal 
insufficiency, NSAID induced asthma, peptic ulcer disease, bleeding diathesis, 
pregnancy/breast feeding, or advanced age. The peri-operative use of ketorolac had been 
limited due to bleeding concerns. However, surgical studies have shown that its use in 
appropriately selected patients does not result in increased clinically significant bleeding but 
does improve pain control over placebo with reduced narcotic use. (6)  
  
 
It has been previously shown that in-patients who undergo ureteral stent placement following 
SWL, the use of ketorolac as an intravesical agent significantly decreased discomfort 1hour 
after treatment in comparison to patients who did not receive the treatment.(5) The safety of 
this was also confirmed as there were no postoperative side effects from the instillation.(5)  
 
Currently,  there is currently no consensus on standard of care regarding intraoperative 
analgesia for ureteroscopy. A ureteral stent is utilized in about 90% of patient. Patients are 
discharged with a prescription for oral narcotics and stents are usually removed on post-
operative day 5-7.  
 
To the best of our knowledge there have not been any prospective studies that have evaluated 
the use of intraoperative ketorolac in patients who undergo URS, regardless of stent 
placement, to minimize postoperative pain.  We hypothesize that patients who receive 
intraoperative ketorolac during URS will have improved outcomes with regards to 
postoperative pain assessment as well as decreased pain related hospital admissions in 
comparison to patients with no treatment.  
 
3. Research Plan: Summarize the study design and research procedures using non-technical 
language that can be readily understood by someone outside the discipline. Be sure to 
distinguish between standard of care vs. research procedures when applicable, and 
include any flowcharts of visits specifying their individual times and lengths. Describe 
the setting in which the research will take place. 
 
This is an investigator-initiated, single-center, prospective randomized clinical trial evaluating 
the efficacy of intraoperative Ketorolac on post-operative pain in patients undergoing 
ureteroscopy at Yale-New Haven Hospital. 
 
The study population will include anyone between the age of 18-80 who is  undergoing elective 
ureteroscopy for management of stone disease without contraindication to ketorolac. 
 
Patients who are being consented to undergo a ureteroscopy with Dr. Motamedinia will be asked 
to participate in this study. There is currently no consensus on standard of care regarding 
intraoperative analgesia for ureteroscopy. There is wide variability in practice, some clinicians 
choose to administer intraoperative analgesia while others rely only on the sedation effects of 
general anesthesia. This study is being carried out to see if administration of Ketorolac during 
ureteroscopy provides a post-operative benefit in pain scores when compared to no treatment.  

Page 11 of 28 
 
 The intervention group in this study will receive a one time dose of Ketorolac 30mg 
intravenously after undergoing general anesthesia. Because they will be under general 
anesthesia, they will not know if they received the medication. Following the procedure, the 
intervention group may continue to use Ketorolac as needed to manage pain. The only difference 
between the intervention group and the non-intervention group is the one time dose of 
intraoperative ketorolac.  
 
The FDA approves Ketorolac as a nonsteroidal anti-inflammatory drug (NSAID), indicated for 
the short-term (up to 5 days in adults) management of moderately severe acute pain that requires 
analgesia at the opioid level. 
 
Following assessment of eligibility and documentation of consent to participate in the study, 
patients will be randomized to receive intraoperative Ketorolac Tromethamine (Toradol®) or 
not. In the no-treatment group, participants will not receive a dose of intra-operative Ketorolac. 
Pain will be managed in the standard way with post-operative Ketorolac as needed. In the 
treatment group, participants will receive one dose of Ketorolac IV 30mg during the procedure. 
Randomization will occur by the attending anesthesiologist.  
 
For this trial the investigators, surgical team, and patients will be blinded to the administration 
of the agent,  which is given as an IV Push of 30mg. For patients who are older than 65 years or 
weight less than 50kg the dose will be adjusted to 15mg to minimize the risk of bleeding. The 
anesthesiologist will not be blinded as he/she will deliver the agent and because the use of 
ketorolac may alter their usage of other intra-operative agents and post-operative agents. The 
surgical team will be un-blinded post-operatively. 
 
Following the procedure, patients will rate their pain using a visual pain assessment scale at 1 
hour postoperatively and at the time of discharge from the recovery room. Once the patient is at 
home, they will fill out a validated survey that has questions related to pain. This will be filled out 
once a day for a total of 7 days following the procedure. In addition, we will provide a medication 
utilization diary sheet for the patient to record daily use of prescribed narcotic and other as needed 
over the counter medications such as acetaminophen and ibuprofen.This will also be done daily 
for a total of 7 days. The patient will be surveyed at their one-week postoperative visit using the 
same assessment. All adverse drug reactions will be recorded from time of administration to initial 
follow-up. The following is the study schedule: 
 
Study Schedule 
 Preop Intraop 1hr post op 2 hr post op 1 week  
 
 
 
 
 
 
 
Assessments 
  
 
 
 
 
Consent 
 
x 
 
 
 
 
History and Physical 
 
x 
 
 
 
 
Urine Culture 
  
 
 
 
 
Post URS medication record   
 
x 
x 
 
Pain Questionnaire 
 
x 
 
x 
x 
x 
Adverse Events 
  
x 
x 
x 
x 
 

Page 12 of 28 
 
 
4. Genetic Testing    N/A 
 
A. Describe 
i. the types of future research to be conducted using the materials, specifying if 
immortalization of cell lines, whole exome or genome sequencing, genome wide 
association studies, or animal studies are planned 
ii. the plan for the collection of material or the conditions under which material will 
be received 
iii. the types of information about the donor/individual contributors that will be 
entered into a database 
iv. the methods to uphold confidentiality 
 
B. What are the conditions or procedures for sharing of materials and/or distributing for 
future research projects? 
C. Is widespread sharing of materials planned? 
D. When and under what conditions will materials be stripped of all identifiers? 
E. Can donor-subjects withdraw their materials at any time, and/or withdraw the identifiers 
that connect them to their materials? 
i. How will requests to withdraw materials be handled (e.g., material no longer 
identified: that is, anonymized) or material destroyed)? 
 
F. Describe the provisions for protection of participant privacy 
G. Describe the methods for the security of storage and sharing of materials  
 
 
5. Subject Population: Provide a detailed description of the types of human subjects who will 
be recruited into this study. 
 
Only patients with the following indications for URS will be included: All patients who are 
undergoing elective ureteroscopy for management of stone disease without contraindication to 
ketorolac.   
 
6. Subject classification: Check off all classifications of subjects that will be specifically 
recruited for enrollment in the research project. Will subjects who may require additional 
safeguards or other considerations be enrolled in the study? If so, identify the population of 
subjects requiring special safeguards and provide a justification for their involvement. 
 
 
 
 Children 
 
 
 Healthy  
 
Fetal material, placenta, or dead fetus 
 Non-English Speaking 
 Prisoners  
 Economically disadvantaged persons 
 Decisionally Impaired 
 Employees  
 Pregnant women and/or fetuses 
 Yale Students  
 
Females of childbearing potential 
 

Page 13 of 28 
 
NOTE: Is this research proposal designed to enroll children who are wards of the state as 
potential subjects? 
 Yes  
 No (If yes, see Instructions section VII #4 for further 
requirements) 
 
 
7. Inclusion/Exclusion Criteria: What are the criteria used to determine subject inclusion or    
exclusion? 
Inclusion criteria 
 
Kidney Stones requiring surgery 
 
Ureteral stones requiring surgery 
 
Able to undergo general anesthetic 
 
Willing and able to consent to treatment 
 
Willing and able to complete all questionnaires  
 
18 years of age and older 
Exclusion criteria 
Solitary Kidney 
Anatomic Bladder or ureteral abnormality 
Previous urinary diversion 
Interstitial cystitis 
Pregnancy 
Ectopic kidney 
Renal failure 
Coagulopathy 
Neurogenic bladder 
Transplanted kidney 
Indwelling foley catheter or suprapubic tube 
Chronic narcotic use 
Known contraindications to agent (NSAID allergy, renal insufficiency, NSAID induced 
asthma, peptic ulcer disease, bleeding diathesis, pregnancy/breast feeding, or advanced age) 
 
 
 
8. How will eligibility be determined, and by whom?  
 
Eligibility will be determined based on URS indications and inclusion and exclusion 
criteria. All patients will be determined eligible by Dr. Motamedinia 
 
9. Risks: Describe the reasonably foreseeable risks, including risks to subject privacy, 
discomforts, or inconveniences associated with subjects participating in the research.  
 
Additional risks from participating in this trial include those associated with the use of 
ketorolac. This includes but is not limited to bruising at place of injection, indigestion, 
allergic reactions including anaphylactic shock, abdominal pain, abnormal bleeding, 
vomiting, diarrhea, constipation, gas, bloating, dizziness, drowsiness, sweating, nausea, 
ringing in the ears, & headaches. 
 

Page 14 of 28 
 
The delivery of pain medications during ureteroscopy require the use of an intravenous 
(IV) line. This is a safe procedure used in every surgery requiring general anesthesia.  There is a 
slight chance that multiple needle-sticks will be needed to make sure the IV is placed correctly.  
The subject might feel a small amount of pain when the IV is placed but it does not last very 
long.  A bruise or a minor infection might develop where the IV is placed.  A bruise will go away 
by itself and it might help if you wrap a warm towel around your arm.  Infections can also be 
treated if necessary.      
 
 
10. Minimizing Risks: Describe the manner in which the above-mentioned risks will be 
minimized. 
 
The above mentioned risks will be minimized as a thorough medication history for each 
patient will be assessed. Those who are previously known to have adverse events with 
NSAIDS or specifically ketorolac will be excluded. In addition, medication dosing will be in 
compliance with federal drug administration recommendation. For severe allergic reactions 
such as anaphylaxis, all patients will be under monitored anesthesia care during the 
procedure and immediately postoperatively and as such under the care of indivdiduals trained 
to recognize and treat this. Patients who are older than 65 may be more sensitive to the effects 
of ketorolac and clear the drug more slowly, so for this population we will dose reduce to 
15mg. In addition, abdominal pain, nausea, vomit- ing, hyperventilation, peptic ulcers and/or 
erosive gastritis and renal dysfunction which have been associated with single dose ketorolac 
have resolved with medication discontinuation and for the purposes of this study, participants 
will only receive one dose and subsequently be discontinued on it.  
  
  
A bruise from the IV will go away by itself and it might help to wrap a warm towel 
around the arm.  Infections can also be treated with antibiotics if necessary.      
 
 
11. Data and Safety Monitoring Plan: Include an appropriate Data and Safety Monitoring Plan 
(DSMP) based on the investigator’s risk assessment stated below. (Note: the HIC will make 
the final determination of the risk to subjects.) For more information, see the Instructions, 
page 24. 
a.  
What is the investigator’s assessment of the overall risk level for subjects participating in this 
study? Greater than Minimal risk 
b. 
If children are involved, what is the investigator’s assessment of the overall risk level for 
the children participating in this study? n/a 
c. 
Include an appropriate Data and Safety Monitoring Plan. Examples of DSMPs are   
available here http://your.yale.edu/policies-procedures/forms/420-fr-01-data-and-
safety-monitoring-plans-templates for 
i. Minimal risk 
ii. Greater than minimal 
 
 
1. Personnel responsible for the safety review and its frequency: 
 

Page 15 of 28 
 
The principal investigator will be responsible for monitoring the data, assuring protocol 
compliance, and conducting the safety reviews at the specified frequency, which must be 
conducted at a minimum of every 6 months (including when reapproval of the protocol is 
sought).  During the review process, the principal investigator will evaluate whether the study 
should continue unchanged, require modification/amendment, or close to enrollment. Either the 
principal investigator, or the IRB have the authority to stop or suspend the study or require 
modifications. 
 
2. The risks associated with the current study are deemed greater than minimal for the 
following reasons: (choose those that apply) 
 
1. We do not view the risks associated with the _use of Ketorolac as minimal risks. 
 
Although we have assessed the proposed study as one of greater than minimal risk, the potential 
exists for anticipated and/or unanticipated adverse events, serious or otherwise, to occur since it 
is not possible to predict with certainty the absolute risk in any given individual or in advance of 
first-hand experience with the proposed study methods. Therefore, we provide a plan for 
monitoring the data and safety of the proposed study as follows: 
 
3. Attribution of Adverse Events: 
Adverse events will be monitored for each subject participating in the study and attributed to the 
study procedures / design by the principal investigator Piruz Motamedinia according to the 
following categories: 
 
Possible: bruising at place of injection, indigestion, allergic reaction, abdominal pain, abnormal 
bleeding, vomiting, diarrhea, constipation, gas, bloating, dizziness, drowsiness, sweating, 
nausea, ringing in the ears, & headachesmay be related to intraoperative Toradol use. 
 
4. Plan for Grading Adverse Events: 
 
The following scale will be used in grading the severity of adverse events noted during the study: 
 
1. Mild adverse event- Abdominal pain (mild), headache, gas, bloating, indigestion, nausea 
2. Moderate adverse event- Abdominal pain (mild), bruising at place of injection, sweating, 
diarrhea, dizziness, drowsiness, ringing in the ears 
3. Severe- allergic reaction leading to anaphylaxis, abnormal bleeding 
 
5. Plan for Determining Seriousness of Adverse Events: 
 
Serious Adverse Events: 
In addition to grading the adverse event, the PI will determine whether the adverse event meets 
the criteria for a Serious Adverse Event (SAE).  An adverse event is considered serious if it 
results in any of the following outcomes: 
 
1. Death; 

Page 16 of 28 
 
2. A life-threatening experience in-patient hospitalization or prolongation of existing 
hospitalization;  
3. A persistent or significant disability or incapacity;  
4. A congenital anomaly or birth defect; OR 
5. Any other adverse event that, based upon appropriate medical judgment, may jeopardize 
the subject’s health and may require medical or surgical intervention to prevent one of 
the other outcomes listed in this definition.  
 
An adverse event may be graded as severe but still not meet the criteria for a Serious Adverse 
Event.  Similarly, an adverse event may be graded as moderate but still meet the criteria for an 
SAE.   
 
6. Plan for reporting UPIRSOs (including Adverse Events) to the IRB 
 
 
The principal investigator will report the following types of events to the IRB:  
Any incident, experience or outcome that meets ALL 3 of the following criteria: 
1. Is unexpected (in terms of nature, specificity, severity, or frequency) given (a) the 
research procedures described in the protocol-related documents, such as the IRB-
approved protocol and informed consent document and (b) the characteristics of the 
subject population being studied; AND  
2. Is related or possibly related to participation in the research (possibly related means 
there is a reasonable possibility that the incident, experience, or outcome may have 
been caused by the procedures involved in the research); AND 
3. Suggests that the research places subjects or others at greater risk of harm (including 
physical, psychological, economic, legal, or social harm) than was previously known 
or recognized. 
Unanticipated Problems Involving Risks to Subjects or Others (UPIRSOs) may be medical or 
non-medical in nature, and include – but are not limited to – serious, unexpected, and related 
adverse events and unanticipated adverse device effects.  Please note that adverse events are 
reportable to the IRB as UPIRSOs only if they meet all 3 criteria listed above. 
 
These UPIRSOs/SAEs will be reported to the IRB in accordance with IRB Policy 710, using the 
appropriate forms found on the website. All related events involving risk but not meeting the 
prompt reporting requirements described in IRB Policy 710 should be reported to the IRB in 
summary form at the time of continuing review. If appropriate, such summary may be a simple 
brief statement that events have occurred at the expected frequency and level of severity as 
previously documented.  In lieu of a summary of external events, a current DSMB report can be 
submitted for research studies that are subject to oversight by a DSMB (or other monitoring 
entity that is monitoring the study on behalf of an industry sponsor). 
 
7. Plan for reporting adverse events to co-investigators on the study, as appropriate the 
protocol’s research monitor(s), e.g., industrial sponsor, Yale Cancer Center Data and 
Safety Monitoring Committee (DSMC), Protocol Review Committee (PRC), DSMBs, study 
sponsors, funding and regulatory agencies, and regulatory and decision-making bodies. 

Page 17 of 28 
 
 
For the current study, the following individuals, funding, and/or regulatory agencies will be 
notified (choose those that apply): 
 
□x All Co-Investigators listed on the protocol. 
□ Yale Cancer Center Data and Safety Monitoring Committee (DSMC) 
□ National Institutes of Health 
□ Food and Drug Administration (Physician-Sponsored IND #_______) 
□ Medical Research Foundation (Grant______) 
□ Study Sponsor 
□x Other Data Safety Monitoring Board (DSMB) or Committee (DSMC) 
 
The principal investigator Piruz Motamedinia will conduct a review of all adverse events upon 
completion of every study subject. The principal investigator will evaluate the frequency and 
severity of the adverse events and determine if modifications to the protocol or consent form are 
required. 
 
 
 
d. For multi-site studies for which the Yale PI serves as the lead investigator: This is a 
single site study 
i. How will adverse events and unanticipated problems involving risks to subjects or 
others be reported, reviewed and managed? 
ii. What provisions are in place for management of interim results? 
iii. What will the multi-site process be for protocol modifications? 
 
12. Statistical Considerations: Describe the statistical analyses that support the study design.  
 
All data will be collected prospectively. Preoperative data will include patient demographics, 
number of previous URS, baseline medications including analgesics, urine culture, stone size 
and location, and pain questionnaire scores. Mean scores will be calculated and compared 
between groups stratified by follow-up time. The number of adverse events and hospital 
admissions related to pain will recorded and described as counts and percentages.  
The primary outcome that will be used to estimate effect size is mean post-operative pain.  
 
Our study is set up as two independent groups with a continuous outcome (Pain measured on a 
1-10 scale) and an enrollment ratio of 1. We anticipate mean post-operative pain in the non-
intervention group to be 7 with a standard deviation of 2. We aim to detect a 10% difference in 
pain, in the intervention arm. With an alpha of 0.05 and a power of 80% we will need to enroll 
63 patients in each arm. 

Page 18 of 28 
 
 
 
SECTION VI: RESEARCH INVOLVING DRUGS, BIOLOGICS, RADIOTRACERS, PLACEBOS AND 
DEVICES 
 
 
If this section (or one of its parts, A or B) is not applicable, state N/A and delete the rest of the 
section. 
 
A.  DRUGS, BIOLOGICS and RADIOTRACERS 
 
1. Identification of Drug, Biologic or Radiotracer: What is (are) the name(s) of the drug(s)  
biologic(s)  or radiotracer(s) being used? Identify whether FDA approval has been granted and for 
what indication(s).  
 
Name of Drug: Ketorolac Tromethamine.  
It has FDA approval as a nonsteroidal anti-inflammatory drug (NSAID), indicated for the short-
term (up to 5 days in adults), management of moderately severe acute pain that requires 
analgesia at the opioid level.  
 
 
 
 
2.  Background Information: Provide a description of previous human use, known risks, and data 
addressing dosage(s), interval(s), route(s) of administration, and any other factors that might 
influence risks. If this is the first time this drug is being administered to humans, include relevant 
data on animal models.  
 
 
Ketorolac has been used for roughly the past 20 years as an alternative to opiates for parenteral 
pain management. Limiting the duration of use to 5 days or less has been shown to reduce the 
adverse effects associated with long-term use (8). The adverse effects of ketorolac are similar to 
other NSAIDs, including gastrointestinal bleeding, peptic ulcers, renal failure in patients with 
chronic kidney disease, and bleeding due to platelet enzyme inhibition (9). To minimize the risk of 
bleeding, it is recommended not to administer ketorolac along with warfarin, heparin, or other 
NSAIDs (7).    
 
The effects of analgesia with IV and IM administration of ketorolac is generally observed within 
10 minutes, with peak pain control at 75-150 minutes. Current dosing recommendations for 
patients is 30 mg for a single dose, with totally daily dosages totaling less than 60 mg. Age related 
dosing for patients >65 years is generally accepted to be half of the dosage used for patients <65 
years (7, 10).  
 
 
Studies assessing the use of pre-operative IV administration of ketorolac demonstrated that 15-30 
mg of ketorolac did not increase operative times or estimated blood loss, and also did not 

Page 19 of 28 
 
significantly affect renal function. Ketorolac also decreased the use of morphine in the 
experimental group (11).  
 
Other studies assessing the risk of bleeding in patients with concomitant use of ketorolac and 
anticoagulants failed to demonstrate any enhanced risk of operative site bleeding (8). There was a 
small risk of gastrointestinal bleeding noted in elderly patients who had used ketorolac more than 5 
days with dosages exceeding 105 mg/day; however, use in patients younger than 65 years with 
dosages less than 105 mg/day, and usage for 5 days or less failed to show any increased risk of GI 
bleeding (12).  
 
 
Bleeding risk with ketorolac has been established in spinal surgeries, where a single IV intra-
operative dose of 30 mg failed to induce any significant changes in gross or surgical site bleeding 
(13).  
 
 
3.  Source:  a) Identify the source of the drug or biologic to be used.  
 
  
 
 
  
b) Is the drug provided free of charge to subjects? 
 Yes  
 No 
 
  
    If yes, by whom?  This drug is routinely covered as a cost by insurance as part of pain 
management for outpatient procedures.  
 
4.  Storage, Preparation and Use: Describe the method of storage, preparation, stability information, 
and for parenteral products, method of sterilization and method of testing sterility and 
pyrogenicity. This drug is routinely utilized by Yale-New Haven hospital and is subjected to the 
same standards of storage and handling as other commonly utilized post-operative pain 
medication. 
 
Check applicable Investigational Drug Service utilized: 
     
   YNHH IDS                                                                      
   Yale Cancer Center  
     
   CMHC Pharmacy                                                          
  West Haven VA 
     
   PET Center                                                       
    None       
     
    Other:  
Note: If the YNHH IDS (or comparable service at CMHC or WHVA) will not be utilized, explain in 
detail how the PI will oversee these aspects of drug accountability, storage, and preparation.   
   
 
5.  Use of Placebo: 
 Not applicable to this research project 
 
If use of a placebo is planned, provide a justification which addresses the following: 
1.  
Describe the safety and efficacy of other available therapies. If there are no other 
available therapies, state this. 
 
b.   State the maximum total length of time a participant may receive placebo while on the study.  
 
c.   Address the greatest potential harm that may come to a participant as a result of  receiving     
       placebo.  
 
d.   Describe the procedures that are in place to safeguard participants receiving placebo.  
 
6. Use of Controlled Substances: 
 
Will this research project involve the use of controlled substances in human subjects? 

Page 20 of 28 
 
 
 Yes  
 No  See HIC Application Instructions to view controlled substance listings.  
 
 
If yes, is the use of the controlled substance considered: 
 
 Therapeutic: The use of the controlled substance, within the context of the research, has the 
potential to benefit the research participant. 
 
 Non-Therapeutic: Note, the use of a controlled substance in a non-therapeutic research study 
involving human subjects may require that the investigator obtain a Laboratory Research License. 
Examples include controlled substances used for basic imaging, observation or biochemical 
studies or other non-therapeutic purposes. See Instructions for further information. 
 
7. Continuation of Drug Therapy After Study Closure   
 Not applicable to this project 
 
Are subjects provided the opportunity to continue to receive the study drug(s) after the study has 
ended? 
 
 Yes   If yes, describe the conditions under which continued access to study drug(s) may apply 
as well as conditions for termination of such access.  
 
 
 
 No    If no, explain why this is acceptable. 
 
 B.  DEVICES 
 
1.      Are there any investigational devices used or investigational procedures performed at Yale-
New Haven Hospital (YNHH) (e.g., in the YNHH Operating Room or YNHH Heart and 
Vascular Center)?  ☐Yes   ☒No    If Yes, please be aware of the following requirements: 
 
SECTION VII: RECRUITMENT/CONSENT AND ASSENT PROCEDURES  
1. Targeted Enrollment: Give the number of subjects: 
a.   targeted for enrollment at Yale for this protocol_126__ 
b.    If this is a multi-site study, give the total number of subjects targeted across all 
sites_N/A__  
 
2. Indicate recruitment methods below.  Attach copies of any recruitment materials that will be used. 
 
 Flyers 
 
 
 
 
 Internet/Web Postings 
 
 
 Radio 
 Posters  
 
 
 
 Mass E-mail Solicitation  
 
 Telephone 
 Letter 
 
 
 
  
 Departmental/Center Website 
 
 Television 
 Medical Record Review  
 
 Departmental/Center Research Boards 
 Newspaper 
 Departmental/Center Newsletters 
 Web-Based Clinical Trial Registries 
 
  YCCI Recruitment database 
 
 Clinicaltrials.gov Registry (do not send materials to HIC) 
 Other (describe): Patients will be recruited at time of consultation for URS 
 
3.  Recruitment Procedures:  
a. Describe how potential subjects will be identified. 
Subjects will be identified at time of consultation for URS  
b. Describe how potential subjects are contacted.  
Subjects are contacted in person at consultation  
c. Who is recruiting potential subjects?  

Page 21 of 28 
 
The principle investigator 
 
 
4. Screening Procedures 
a. Will email or telephone correspondence be used to screen potential subjects for 
eligibility prior to the potential subject coming to the research office? 
 Yes  
 No 
b.  If yes, identify below all health information to be collected as part of screening and 
check off any of the following HIPAA identifiers to be collected and retained by the 
research team during this screening process.  
 
HEALTH INFORMATION TO BE COLLECTED: 
 
 
 
  
HIPAA identifiers:  
 Names  
 All geographic subdivisions smaller than a State, including: street address, city, county, precinct, zip codes and their 
equivalent geocodes, except for the initial three digits of a zip code if, according to the current publicly-available data from 
the Bureau of the Census: (1) the geographic unit formed by combining all zip codes with the same three initial digits contains 
more than 20,000 people, and (2) the initial three digits of a zip code for all such geographic units containing 20,000 or fewer 
people is changed to 000.  
  Telephone numbers 
 Fax numbers  
 E-mail addresses 
 Social Security numbers  
 Medical record numbers 
 Health plan beneficiary numbers  
 Account numbers  
  All elements of dates (except year) for dates related to an individual, including: birth date, admission date, discharge 
date, date of death, all ages over 89 and all elements of dates (including year) indicative of such age, except that such ages 
and elements may be aggregated into a single category of age 90 or older  
 Certificate/license numbers  
 Vehicle identifiers and serial numbers, including license plate numbers  
 Device identifiers and serial numbers  
 Web Universal Resource Locators (URLs)  
 Internet Protocol (IP) address numbers  
 Biometric identifiers, including finger and voice prints  
 Full face photographic images and any comparable images  
 Any other unique identifying numbers, characteristics, or codes  
 
 
5. Assessment of Current Health Provider Relationship for HIPAA Consideration: 
Does the Investigator or any member of the research team have a direct existing clinical 
relationship with any potential subject?  
 Yes, all subjects 
 Yes, some of the subjects 
 No 
 
If yes, describe the nature of this relationship. 

Page 22 of 28 
 
All patients that are recruited into the study will be patients of the Principle Investigator (Piruz 
Motamedinia) and have a direct clinical relationship with him. Recruitment and data collection 
will be done through clinical visits.  
 
6. Request for waiver of HIPAA authorization: (When requesting a waiver of HIPAA Authorization 
for either the entire study, or for recruitment purposes only.  Note: if you are collecting PHI as part of 
a phone or email screen, you must request a HIPAA waiver for recruitment purposes.) 
 
Choose one:  
☐ For entire study  
☐ For recruitment purposes only  
☐ For inclusion of non-English speaking subject if short form is being used 
 
i. Describe why it would be impracticable to obtain the subject’s authorization for 
use/disclosure of this data; 
ii. If requesting a waiver of signed authorization, describe why it would be 
impracticable to obtain the subject’s signed authorization for use/disclosure of this 
data; 
 
By signing this protocol application, the investigator assures that the protected 
health information for which a Waiver of Authorization has been requested will not 
be reused or disclosed to any person or entity other than those listed in this 
application, except as required by law, for authorized oversight of this research 
study, or as specifically approved for use in another study by an IRB. 
 
Researchers are reminded that unauthorized disclosures of PHI to individuals outside of the Yale 
HIPAA-Covered entity must be accounted for in the “accounting for disclosures log”, by subject 
name, purpose, date, recipients, and a description of information provided.  Logs are to be 
forwarded to the Deputy HIPAA Privacy Officer. 
 
7. Required HIPAA Authorization: If the research involves the creation, use or disclosure of 
protected health information (PHI), separate subject authorization is required under the 
HIPAA Privacy Rule. Indicate which of the following forms are being provided: 
 
  
 Compound Consent and Authorization form 
 
  
 HIPAA Research Authorization Form 
 
 
8. Consent Personnel: List the names of all members of the research team who will be obtaining 
consent/assent.  
Dr. Piruz Motamedinia will be obtaining consent/assent 
 
 
9. Process of Consent/Assent: Describe the setting and conditions under which consent/assent will 
be obtained, including parental permission or surrogate permission and the steps taken to ensure 
subjects’ independent decision-making.  
 

Page 23 of 28 
 
The PI routinely consults with patients regarding urinary stones. During the initial outpatient 
consultation with the PI, patients who are candidates for ureterscopic management and are in 
agreement to this surgical method will be recruited to participate in the study. These are all 
patients being seen in the outpatient clinic prior to surgery and are not under any acute 
distress/pain.  
The investigator will explain the research study to the participant and answer any questions that 
may arise.  The participants will sign the informed consent document prior to any procedures 
being done specifically for the study.  The participants will have sufficient opportunity to discuss 
the study and process the information in the consent process prior to agreeing to participate.  A 
copy of the informed consent document will be given to the participants for their records.  The 
rights and welfare of the participants will be protected by emphasizing to them that the quality of 
their medical care will not be adversely affected if they decline to participate in this study. 
The acquisition of informed consent will be documented in the participant’s medical records.  The 
informed consent form will be signed and personally dated by the participant and the person who 
conducted the informed consent discussion. The original signed informed consent form will be 
retained in the medical chart and a copy will be provided to the participant 
 
 
 
10. Evaluation of Subject(s) Capacity to Provide Informed Consent/Assent: Indicate how the 
personnel obtaining consent will assess the potential subject’s ability and capacity to consent to the 
research being proposed.  
 
The PI performs a mental status exam as part of every physical exam during clinic visit. This exam 
assesses the subjects thought process, cognition, insight, and judgement. In addition to using this 
routine exam, the PI will assess the subject’s ability and capacity to consent by asking questions 
during the consent process to gauge whether they have an understanding of the study.  If the 
subject does not fully understand the study as it is described, he/she will not be enrolled. 
 
 
11. Documentation of Consent/Assent: Consent form and pain assessment questionnaire will be used 
during the consent/assent process. Copies are attached 
 
 
12. Non-English Speaking Subjects: Explain provisions in place to ensure comprehension for 
research involving non-English speaking subjects. If enrollment of these subjects is anticipated, 
translated copies of all consent materials must be submitted for approval prior to use.  
 
We will not be recruiting non-English speaking patients in this trial. 
 
12(a) As a limited alternative to the above requirement, will you use the short form* for 
consenting process if you unexpectedly encounter a non-English speaking individual interested 
in study participation and the translation of the long form is not possible prior to intended 
enrollment?  
YES ☐  NO ☐ 
 

Page 24 of 28 
 
Note* If more than 2 study participants are enrolled using a short form translated into the same 
language, then the full consent form should be translated into that language for use the next time 
a subject speaking that language is to be enrolled. 
 
Several translated short form templates are found on our website 
at:  http://www.yale.edu/hrpp/forms-templates/biomedical.html. If the translation of the short 
form is not available on our website, then the translated short form needs to be submitted to the 
IRB office for approval via amendment prior to enrolling the subject. Please review the 
guidance and presentation on use of the short form available on the HRPP website. 
 
If using a short form without a translated HIPAA Research Authorization Form, please 
request a HIPAA waiver in the section above.  
 
 
13. Consent Waiver: In certain circumstances, the HIC may grant a waiver of signed consent, or 
a full waiver of consent, depending on the study. If you will request either a waiver of consent, 
or a waiver of signed consent for this study, complete the appropriate section below.   
 
 Not Requesting a consent waiver  
 
 Requesting a waiver of signed consent 
       
 Requesting a full waiver of consent 
    
 
A. Waiver of signed consent: (Verbal consent from subjects will be obtained. If PHI is 
collected, information in this section must match Section VII, Question 6) 
 Requesting a waiver of signed consent for Recruitment/Screening only  
If requesting a waiver of signed consent, please address the following: 
a. Would the signed consent form be the only record linking the subject and the research? 
 Yes  
 No 
b. Does a breach of confidentiality constitute the principal risk to subjects?  
 Yes  
 No 
 
 
 
 
 
OR 
 
c. Does the research activity pose greater than minimal risk?  
 Yes If you answered yes, stop. A waiver cannot be granted.  Please note: 
Recruitment/screening is generally a minimal risk research activity   
 No  
AND 
d. Does the research include any activities that would require signed consent in a non-
research context? 
 Yes  
 No 
 
 Requesting a waiver of signed consent for the Entire Study (Note that an information 
sheet may be required.) 
 
  
If requesting a waiver of signed consent, please address the following: 
a. Would the signed consent form be the only record linking the subject and the research? 
 Yes  
 No 

Page 25 of 28 
 
b. Does a breach of confidentiality constitute the principal risk to subjects?  
 Yes  
 No 
 
 
 
 
 
OR 
 
c. Does the research pose greater than minimal risk? 
 Yes If you answered yes, stop. A 
waiver cannot be granted.    
 No  
AND 
d. Does the research include any activities that would require signed consent in a non-
research context? 
 Yes  
 No 
 
  
 B. Full waiver of consent: (No consent from subjects will be obtained for the activity.)  
 Requesting a waiver of consent for Recruitment/Screening only  
a. Does the research activity pose greater than minimal risk to subjects?   
 Yes  If you answered yes, stop. A waiver cannot be granted. Please note: 
Recruitment/screening is generally a minimal risk research activity  
 No 
 
  
b. Will the waiver adversely affect subjects’ rights and welfare? 
 Yes  
 No 
 
  
c. Why would the research be impracticable to conduct without the waiver?  
 
d. Where appropriate, how will pertinent information be returned to, or shared with 
subjects at a later date?  
 
 
 Requesting a full waiver of consent for the Entire Study (Note: If PHI is 
collected, information here must match Section VII, question 6.) 
 
  
 
If requesting a full waiver of consent, please address the following: 
 
 
  
a. Does the research pose greater than minimal risk to subjects?   
 Yes  If you answered yes, stop. A waiver cannot be granted.   
 No 
 
  
b. Will the waiver adversely affect subjects’ rights and welfare? 
 Yes  
 No 
 
  
c. Why would the research be impracticable to conduct without the waiver?  
 
d. Where appropriate, how will pertinent information be returned to, or shared with 
subjects at a later date?  
 
SECTION VIII: PROTECTION OF RESEARCH SUBJECTS 
 
    Confidentiality & Security of Data: 
What protected health information (medical information along with the HIPAA identifiers) about 
subjects will be collected and used for the research?   
        
Patient name, age and medical record number will be collected. 
 
b. How will the research data be collected, recorded and stored?  

Page 26 of 28 
 
Participants’ signed consent forms will be contained in a secure location separate from the 
questionnaires – within a locked file cabinet in the principle investigators office.  The 
questionnaires will not have any identifying information on them.  All data will be accessible 
only to the researcher(s) and the research advisor. 
 
 
c.    How will the digital data be stored? 
 CD  
 DVD  
 Flash Drive  
 Portable Hard    
       Drive  
 Secured Server  
 Laptop Computer  
 Desktop Computer  
 Other 
 
d.    What methods and procedures will be used to safeguard the confidentiality and security of     
the identifiable study data and the storage media indicated above during and after the subject’s 
participation in the study?    
 
The investigators will ensure that the subject’s anonymity is maintained.  Subjects will not 
be identified in any publicly released reports of this study.  All records will be kept 
confidential to the extent provided by federal, state and local law.   The study monitors may 
inspect all documents and records required to be maintained by the Investigator, including 
but not limited to, medical records.  The investigator will inform the subjects that the 
above-named representatives will review their study-related records without violating the 
confidentiality of the subjects. All laboratory specimens, evaluation forms, reports, and 
other records that leave the site will be identified only by a coded number in order to 
maintain subject confidentiality.  All records will be kept in a password protected 
computer.  Clinical information will not be released without written permission of the 
subject, except as necessary for monitoring by IRB. 
 
Do all portable devices contain encryption software? 
 Yes   
 No 
         If no, see http://hipaa.yale.edu/guidance/policy.html 
  
c. What will be done with the data when the research is completed? Are there plans to destroy     
the identifiable data? If yes, describe how, by whom and when identifiers will be destroyed. If 
no, describe how the data and/or identifiers will be secured. Anonymized data will be kept 
through the course of the study and upon completion of manuscript after which it will be 
destroyed.  
 
d. Who will have access to the protected health information (such as the research sponsor, the  
investigator, the research staff, all research monitors, FDA, Yale Cancer Center Data and 
Safety Monitoring Committee (DSMC), SSC, etc.)? (please distinguish between PHI and de-
identified data)  
 
Only the specified research team will have access to the PHI.  
 
 
g.   If appropriate, has a Certificate of Confidentiality been obtained? 
h.   Are any of the study procedures likely to yield information subject to mandatory reporting   
requirements? (e.g. HIV testing – reporting of communicable diseases; parent interview -incidents 
of child abuse, elderly abuse, etc.). Please verify to whom such instances will need to be reported.  

Page 27 of 28 
 
 
We do not anticipate that any of the study procedures will yield information subject to mandatory 
reporting requirements 
 
 
SECTION IX: POTENTIAL BENEFITS 
 
 
Potential Benefits: Identify any benefits that may be reasonably expected to result from the 
research, either to the subject(s) or to society at large. (Payment of subjects is not considered a 
benefit in this context of the risk benefit assessment.)  
 
The treatment group may experience decreased postoperative pain and decreased risk of needing 
hospital readmission. The results of this study may be useful for guiding treatment strategies for 
other institutions involved in URS procedures.  In the event that no-benefit is noted (negative 
study) these findings would discourage the ineffective use of a medication which is cost saving 
and limit potential drug related side effects.   
         SECTION X: RESEARCH ALTERNATIVES AND ECONOMIC CONSIDERATIONS 
 
1.     Alternatives: What other alternatives are available to the study subjects outside of the research? 
Alternatives include no additional pain medication intraoperatively. 
 
2. Payments for Participation (Economic Considerations): Describe any payments that 
will be made to subjects, the amount and schedule of payments, and the conditions for 
receiving this compensation. 
  
There will be no payments made to subjects of this trial. 
 
3. Costs for Participation (Economic Considerations): Clearly describe the subject’s costs 
associated with participation in the research, and the interventions or procedures of the 
study that will be provided at no cost to subjects.  
Ketorolac is commonly used in the peri-operative setting. Costs of the drug are bundled 
into the billed amount for the specific procedure performed.   
 
4. 
In Case of Injury: This section is required for any research involving more than minimal risk. 
 
a.     Will medical treatment be available if research-related injury occurs? Yes medical treatment 
will be available for research-related injury, this will be coordinated by the PI. 
 
b.     Where and from whom may treatment be obtained? The surgical team will routinely 
evaluate the patient during their operative stay and consult the appropriate specialty service 
should an injury occur. 
 
c.     Are there any limits to the treatment being provided? No 
 
d.     Who will pay for this treatment?  This will be under the same coverage of the patients 
insurance for the procedure. 
 
e.     How will the medical treatment be accessed by subjects? Patients may present to Yale-New 
Haven Hospital for medical assistance that is required as part of this research project. 
 
 

Page 28 of 28 
 
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