Clinical trial NCT02895035
Conditions: Cataract
Sponsor: Milton S. Hershey Medical Center
Start date: 2016-09-01; Completion date: 2018-12-31
Enrollment: 59 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The objective of this study is to compare the maintenance of intraoperative mydriasis during cataract surgery between two drugs: epinephrine, which has routinely been used for decades, and Omidria, a newly FDA approved combination drug of phenylephrine and ketorolac. Patients undergoing cataract surgery that are enrolled in the trial will randomly receive one of the drugs in one eye, and the other eye will receive the drug during the subsequent cataract surgery.

Detailed description:
Cataract remains a leading cause of correctable blindness worldwide. Over 3.5 million cataract surgeries in the United States and 20 million cataract surgeries worldwide are performed every year. Cataract surgery is performed by making a small incision, removing the cataractous lens, most often through the process of phacoemulsification, and replacement with an intraocular lens. Like all surgeries, adequate exposure and field of view is vital for a safe and effective surgery. In cataract surgery, the field of view is limited by the diameter of the pupil. Several different drugs, such as cyclopentolate, tropicamide, phenylephrine, and epinephrine are utilized to maintain dilation (mydriasis) of the pupil during surgery.

There are currently two prospective randomized controlled trials comparing phenylephrine/ketorolac to placebo in the published literature. Both of these studies demonstrated that phenylephrine/ketorolac is superior to placebo for the maintenance of mydriasis during cataract surgery. Epinephrine has been the standard of care for intraoperative mydriasis. Phenylephrine/ketorolac (Omidria) is a newly FDA-approved additive for the maintenance of intraoperative mydriasis, but there are currently no published studies comparing epinephrine to phenylephrine/ketorolac for maintenance of mydriasis during cataract surgery.

While both of these drugs have been shown to be superior to placebo for the maintenance of mydriasis, there is a significant cost difference between epinephrine, which has been used for many years, and phenylephrine/ketorolac, which gained FDA approval in 2014. One 4 mL vial of Omidria® is utilized for one cataract surgery, which costs $465.

The primary endpoint to be measured in the study is the mean area under the curve change from baseline in pupil diameter over time to the end of cataract surgery.

Secondary endpoints will be maximum intraoperative pupil constriction, subjects with pupil diameter less than 6.5 mm at any during surgery, subjects with pupil less than 6.0 mm during cortical clean-up, and subjects with greater than 2.5 mm of pupillary constriction at any time during surgery.

Arms: arm 1: Epinephrine is the intracameral additive during cataract surgery. arm 2: Omidria is the intracameral additive during cataract surgery.
Interventions: intervention 1: Phenylephrine-ketorolac intervention 2: Epinephrine
Intervention descriptions: intervention 1: Pehnylephrine-ketorolac is a combination of an alpha-one agonist (phenylephrine) and an NSAID (ketorolac). One 4-mL bottle of 1% phenylephrine/3% ketorolac is added to the irrigation solution during cataract surgery. intervention 2: Epinephrine is a nonselective adrenergic agonist added to the irrigation solution during cataract surgery.

Protocol documents:
Prot_SAP_000.pdf: 
 
Page 1 of 14 (V.06/27/2016)  
                                                                                        
 
HRP-591 - Protocol for  
Human Subject Research 
 
Protocol Title:  
Prospective Comparison of Epinephrine and Phenylephrine/Ketorolac (Omidria®) Additives With Regards to 
Intraoperative Pupil Size 
 
Principal Investigator: 
Name: Seth Pantanelli  
Department: Ophthalmology 
Telephone: 289897 
E-mail Address: spantanelli@hmc.psu.edu 
 
Version Date:  
August 5, 2016 
 
Clinicaltrials.gov Registration #: 
Not applicable 
 
Important Instructions for Using This Protocol Template: 
1. 
Add this completed protocol template to your study in CATS IRB (http://irb.psu.edu) on the “Basic Information” 
page, item 7.  
2. 
This template is provided to help investigators prepare a protocol that includes the necessary information needed 
by the IRB to determine whether a study meets all applicable criteria for approval.  
3. 
Type your protocol responses below the gray instructional boxes of guidance language.  If the section or item is 
not applicable, indicate not applicable. 
4. 
For research being conducted at Penn State Hershey or by Penn State Hershey researchers only, delete the 
instructional boxes from the final version of the protocol prior to upload to CATS IRB (http://irb.psu.edu).  For all 
other research, do not delete the instructional boxes from the final version of the protocol. 
5. 
When making revisions to this protocol as requested by the IRB, please follow the instructions outlined in the Study 
Submission Guide available in the Help Center in CATS IRB (http://irb.psu.edu) for using track changes.  
 
If you need help… 
University Park and other campuses: 
Office for Research Protections Human Research Protection Program 
The 330 Building, Suite 205 
University Park, PA 16802-7014 
Phone: 814-865-1775 
Fax: 814-863-8699 
Email: irb-orp@psu.edu 
College of Medicine and Hershey Medical Center: 
Human Subjects Protection Office 
90 Hope Drive, Mail Code A115, P.O. Box 855 
Hershey, PA 17033 
(Physical Office Location: Academic Support Building Room 1140) 
Phone: 717-531-5687 
Fax number: 717-531-3937 
Email: irb-hspo@psu.edu 
 


 
Page 2 of 14 (V.06/27/2016)  
Table of Contents 
 
1. 
Objectives 
2. 
Background  
3. 
Inclusion and Exclusion Criteria 
4. 
Recruitment Methods 
5. 
Consent Process and Documentation  
6. 
HIPAA Research Authorization and/or Waiver or Alteration of Authorization 
7. 
Study Design and Procedures 
8. 
Subject Numbers and Statistical Plan 
9. 
Confidentiality, Privacy and Data Management  
10. 
Data and Safety Monitoring Plan 
11. 
Risks 
12. 
Potential Benefits to Subjects and Others 
13. 
Sharing Results with Subjects 
14. 
Subject Stipend (Compensation) and/or Travel Reimbursements 
15. 
Economic Burden to Subjects 
16. 
Resources Available 
17.0 
12Other Approvals 
18.0 
13Multi-Site Research 
19.0 
13Adverse Event Reporting 
20.0 
13Study Monitoring, Auditing and Inspecting 
21.0 
14Future Undetermined Research: Data and Specimen Banking 
22.0 
14References 
 
 


 
Page 3 of 14 (V.06/27/2016)  
1. 
Objectives 
 
1. 
Study Objectives 
 
The purpose of this study is to compare the efficacy of phenylephrine 1.0%/ketorolac 0.3% (Omidria®) to 
epinephrine for intraoperative mydriasis (pupil dilation).  
 
Our hypothesis is that phenylephrine/ketorolac additive is equal in efficacy to epinephrine with regards 
to its effects on pupil size during cataract surgery. 
 
2. 
Primary Study Endpoints 
 
The primary endpoint to be measured in the study is the mean area under the curve change from 
baseline in pupil diameter over time to the end of cataract surgery.  
 
3. 
Secondary Study Endpoints 
 
Secondary endpoints will be maximum intraoperative pupil constriction, subjects with pupil diameter 
less than 6.5 mm at any during surgery, subjects with pupil less than 6.0 mm during cortical clean-up, 
and subjects with greater than 2.5 mm of pupillary constriction at any time during surgery. 
 
2. 
Background  
 
2.1. 
Scientific Background and Gaps  
 
Cataract remains a leading cause of correctable blindness worldwide. Over 3.5 million cataract surgeries 
in the United States and 20 million cataract surgeries worldwide are performed every year. Cataract 
surgery is performed by making a small incision, removing the cataractous lens, most often through the 
process of phacoemulsification, and replacement with an intraocular lens. Like all surgeries, adequate 
exposure and field of view is vital for a safe and effective surgery. In cataract surgery, the field of view is 
limited by the diameter of the pupil. Several different drugs, such as cyclopentolate, tropicamide, 
phenylephrine, and epinephrine are utilized to maintain dilation (mydriasis) of the pupil during 
surgery1,2. 
 
There are currently two prospective randomized controlled trials comparing phenylephrine/ketorolac to 
placebo in the published literature3,4. Both of these studies demonstrated that phenylephrine/ketorolac 
is superior to placebo for the maintenance of mydriasis during cataract surgery. Epinephrine has been 
the standard of care for intraoperative mydriasis. Phenylephrine/ketorolac (Omidria) is a newly FDA-
approved additive for the maintenance of intraoperative mydriasis, but there are currently no published 
studies comparing epinephrine to phenylephrine/ketorolac for maintenance of mydriasis during cataract 
surgery. 
 
While both of these drugs have been shown to be superior to placebo for the maintenance of mydriasis, 
there is a significant cost difference between epinephrine, which has been used for many years, and 
phenylephrine/ketorolac, which gained FDA approval in 2014. One 4 mL vial of Omidria® is utilized for 
one cataract surgery, which costs $465.  
 


 
Page 4 of 14 (V.06/27/2016)  
2.2. 
Previous Data 
 The two prospective randomized controlled trials comparing phenylephrine/ketorolac to placebo 
reported that phenylephrine/ketorolac was superior to placebo in maintaining intraoperative mydriasis, 
preventing miosis, and reducing postoperative pain. As previously mentioned, there is no currently 
reported data in the literature comparing phenylephrine/ketorolac to other commonly used mydriatic 
agents, such as epinephrine. 
 
At our own center, we are currently performing a retrospective study comparing 
phenylephrine/ketorolac to epinephrine. There is no preliminary data at this time. 
 
2.3. 
Study Rationale 
 
Epinephrine is a current standard of care for intraoperative mydriasis during cataract surgery. 
Phenylephrine/ketorolac was approved by the FDA in 2014 and has been shown to be superior to 
placebo for maintenance of intraoperative mydriasis during cataract surgery. However, there has been 
no published literature on the efficacy of phenylephrine/ketorolac compared to epinephrine. 
 
In addition, there is a significant cost difference between the current standard of care, epinephrine, 
(<$20/dose) and phenylephrine/ketorolac (~$400/dose). 
 
 
3. 
Inclusion and Exclusion Criteria 
 
3.1. 
Inclusion Criteria 
 
 Patients who are older than 18 years of age 
 Patients who are planned to undergo bilateral cataract surgery 
 Patients with baseline IOP of 5 - 22 mm Hg 
 Medicare insurance* 
 
*As discussed in 2.3, there is a significant cost difference between our two study drugs. Therefore, 
Medicare insurance is part of our inclusion criteria, because there is a pass-through reimbursement in 
place to cover the cost of phenylephrine/ketorolac. Other insurances (for example, Aetna Better Health, 
Highmark Freedom, Gateway) have variable or poor coverage for phenylephrine/ketorolac, which would 
leave the medical center responsible for the cost. Patients can never be held responsible for the cost of 
the medication because it is included in “covered services” for cataract surgery billing.  
 
 
3.2. 
Exclusion Criteria 
 
 Patients who are planned to undergo only unilateral cataract surgery 
 Patients who are planned to undergo cataract surgery and another surgical procedure in the same operation 
(eg. combined cataract and glaucoma surgery) 
 Patients with concurrent clinically significant disease, connective tissue disease, abnormal blood pressure at 
screening, narrow-angle or unstable glaucoma or treatment with prostaglandins, uncontrolled chronic eye 
disease or active corneal pathology or scarring 
 Patients with history of iritis or trauma with iris damage 
 Patients with recent eye surgery (non-laser surgery within 3 months or laser surgery within 30 days prior to 
study surgery) 


 
Page 5 of 14 (V.06/27/2016)  
 Patients with clinically significant hypersensitivity to the study medications 
 Patients who have used pilocarpine (a pupil constrictor) within 6 months prior to surgery 
 
3.3. 
Early Withdrawal of Subjects 
 
3.3.1. Criteria for removal from study 
 
Subjects may withdrawal from the study if they no longer wish to participate in the study. 
Subjects may withdrawal from the study if they no longer plan to undergo bilateral cataract 
surgery. There are no anticipated safety reasons for which a subject would need to withdrawal 
from the study. There is no disease progression that would require a subject to withdrawal from 
the study. 
 
3.3.2. Follow-up for withdrawn subjects 
 
Subjects may withdrawal from the study at any point up to their second cataract surgery. Data 
will be collected for the number and the reason for withdrawal of subjects (eg. withdrawal of 
consent). A patient disposition flow diagram will be constructed. Subjects that withdrawal from 
investigational treatment will be treated as any other patient who is undergoing cataract 
surgery outside of the study. 
 
4. 
Recruitment Methods 
 
4.1. Identification of subjects 
 
All patients meeting the inclusion criteria who are seen and evaluated in the ophthalmology clinics of 
the study team physicians and plan to undergo bilateral cataract surgery will be offered to participate in 
the study. 
 
It should be noted that only eligible patients with Medicare insurance are to be offered the opportunity 
to participate in the study. This is because Medicare universally provides adequate reimbursement for 
Omidria, while other carriers (i.e. Gateway Heath or Amerihealth) do not. 
 
4.2. 
Recruitment process 
 
All patients will be offered the opportunity to participate in the study, will be provided information in 
person while being consented for cataract surgery, and will be given an informed consent form 
regarding the study. 
 
4.3. 
Recruitment materials 
 
An informed consent form will be used to recruit subjects.  
 
4.4. 
Eligibility/screening of subjects 
 
Patients will be asked eligibility questions before obtaining informed consent. Those who meet exclusion 
criteria will not be consented for the study. 
 


 
Page 6 of 14 (V.06/27/2016)  
5. 
Consent Process and Documentation  
 
5.1. 
Consent Process  
  
5.1.1.Obtaining Informed Consent 
 
5.1.1.1. Timing and Location of Consent 
 
Informed consent is a process.  Consent will take place in the ophthalmology 
clinic when a patient would be regularly consented to undergo cataract surgery 
(within 60 days of surgery date). The average wait time for cataract surgery in 
our ophthalmology clinic is currently 30-60 days.  As the patient presents for 
surgery, the consent will be reviewed once again and any additional questions 
will be addressed to confirm they still want to participate in the study. 
 
5.1.1.2. Coercion or Undue Influence during Consent 
 
All patients consenting for cataract surgery that meet inclusion criteria will be 
offered to participate in the study. They will not be persuaded to participate. 
 
5.1.2.Waiver or alteration of the informed consent requirement 
 
Not applicable 
 
5.2. 
Consent Documentation 
 
5.2.1. Written Documentation of Consent 
 
Consent will be documented in writing through a consent document. This document will be 
uploaded and available for the study in CATS IRB.  
 
5.2.2. Waiver of Documentation of Consent (Implied consent, Verbal consent, etc.) 
 
Not applicable. Written consent will be obtained. 
 
5.3. 
Consent – Other Considerations  
 
5.3.1. Non-English Speaking Subjects 
 
Not applicable 
 
5.3.2. Cognitively Impaired Adults 
 
5.3.2.1. Capability of Providing Consent 
 
Not applicable 
 
5.3.2.2. Adults Unable To Consent 
 
Not applicable 
 


 
Page 7 of 14 (V.06/27/2016)  
5.3.2.3. Assent of Adults Unable to Consent 
 
Not applicable 
 
5.3.3. Subjects who are not yet adults (infants, children, teenagers)  
 
5.3.3.1. Parental Permission 
 
Not applicable. 
 
5.3.3.2. Assent of subjects who are not yet adults 
 
Not applicable. 
 
6. 
HIPAA Research Authorization and/or Waiver or Alteration of Authorization 
 
6.1. 
Authorization and/or Waiver or Alteration of Authorization for the Uses and Disclosures of PHI 
 
Check all that apply: 
 
 
x Authorization will be obtained and documented as part of the consent process. [If this is the 
only box checked, mark sections 6.2 and 6.3 as not applicable] 
 
 
x Partial waiver is requested for recruitment purposes only (Check this box if patients’ medical 
records will be accessed to determine eligibility before consent/authorization has been 
obtained). [Complete all parts of sections 6.2 and 6.3] 
 
 
6.2. 
Waiver or Alteration of Authorization for the Uses and Disclosures of PHI 
 
6.2.1. Access, use or disclosure of PHI representing no more than a minimal risk to the privacy of the 
individual 
 
6.2.1.1. Plan to protect PHI from improper use or disclosure 
 
Information is included in the “Confidentiality, Privacy and Data Management” 
section of this protocol. 
 
6.2.1.2. Plan to destroy identifiers or a justification for retaining identifiers  
 
Identifiers will not be recorded or retained.  
 
6.2.2. Explanation for why the research could not practicably be conducted without access to and 
use of PHI 
 
Access to PHI will be necessary to determine inclusion/exclusion criteria for a subject to enroll in 
the study. 
 


 
Page 8 of 14 (V.06/27/2016)  
6.2.3. Explanation for why the research could not practicably be conducted without the waiver or 
alteration of authorization 
 
Not applicable 
 
6.3 
Waiver or alteration of authorization statements of agreement 
 
Not applicable 
 
7. 
Study Design and Procedures 
 
7.1. 
Study Design 
 
This is a double-blinded prospective randomized controlled study of patients who are undergoing 
bilateral cataract surgery (separate unilateral operations performed within several weeks of each other. 
Patients will be selected to participate in the study based on inclusion/exclusion criteria. Each patient in 
the study will be randomly assigned to intracameral phenylephrine/ketorolac in one eye and 
intracameral epinephrine in the other eye for intraoperative mydriasis. A video will be recorded of the 
surgical eye for the entire duration of cataract surgery. A single reviewer will watch the video and record 
the pupil diameter for every minute during the duration of the surgery. The reviewer will be blinded to 
which eye received which mydriatic agent intraoperatively. 
 
It should be noted that video recording of surgical procedures is a routine practice for many of the 
participating surgeons and is not limited to only those participating in the study. Thus, it is not 
considered a ‘study procedure,’ but instead is routine practice. 
 
7.2. 
Study Procedures 
 
 
7.2.1. EXAMPLE: Visit 1 or Day 1 or Pre-test, etc. (format accordingly) 
 
Pre-operative visit: Inclusion/exclusion criteria will be assessed. Consent will be obtained from 
eligible subjects who wish to participate in the study. Demographic and baseline characteristics 
will be recorded. 
 
7.2.2. EXAMPLE: Visit 2 or Day 2 or Post-test, etc. (format accordingly) 
 
 
Day of surgery: Video recording of the surgical eye during the entire duration of  surgery will be 
obtained. 
 
Post-operative visits: Patients will be followed routinely post-operatively. No data will  
 
be collected from post-operative visits. 
 
7.3. 
Duration of Participation 
 
The individual subject will participate in the study for two cataract surgeries. 
 
8. 
Subject Numbers and Statistical Plan 
 


 
Page 9 of 14 (V.06/27/2016)  
8.1. 
Number of Subjects 
 
At least 106 subjects will need to be accrued. This is assuming that no subjects will drop out of the study 
once they are accrued.  
 
8.2. 
Sample size determination 
 
106 subjects assumes there will be a 0.3 mm difference between the two treatment arms, alpha = 0.05, 
power = 95%. A difference of 0.3 mm was assumed based on the results of two previous trials that had a 
difference of 0.6 mm comparing phenylephrine/ketorolac to placebo3,4.  
 
8.3. 
Statistical methods 
 
The trapezoidal rule will be used to calculate the AUC of pupil diameter from surgical baseline to wound 
closure. The result will be divided by time of the last pupil diameter value to determine mean AUC. 
Baseline pupil diameter will then be subtracted from the mean AUC. A chi-square test will be used to 
compare continuous data between the two treatment arms.  
 
9. 
Confidentiality, Privacy and Data Management  
 
9.1. 
Confidentiality 
 
9.1.1. Identifiers associated with data and/or specimens 
 
See the Research Data Plan Review Form 
 
9.1.1.1. Use of Codes, Master List 
 
See the Research Data Plan Review Form 
 
9.1.2. Storage of Data and/or Specimens 
 
See the Research Data Plan Review Form 
 
9.1.3. Access to Data and/or Specimens 
 
See the Research Data Plan Review Form 
 
9.1.4. Transferring Data and/or Specimens 
 
See the Research Data Plan Review Form 
 
9.2. 
Subject Privacy 
 
See the Research Data Plan Review Form 
 


 
Page 10 of 14 (V.06/27/2016)  
10. 
Data and Safety Monitoring Plan 
10.1. Periodic evaluation of data 
 
Not applicable 
 
10.2. Data that are reviewed 
 
Not applicable 
 
10.3. Method of collection of safety information 
 
Not applicable 
 
10.4. Frequency of data collection 
 
Not applicable 
 
10.5. Individuals reviewing the data 
 
Not applicable 
 
10.6. Frequency of review of cumulative data 
 
Not applicable 
 
10.7. Statistical tests 
 
Not applicable 
 
10.8. Suspension of research 
 
Not applicable 
 
11. 
Risks 
 
Both of the study drugs are currently routinely used in cataract surgery. There are no risks in addition to the 
small risks associated with routine cataract surgery. There is a minimal risk of loss of confidentiality.  
 
12. 
Potential Benefits to Subjects and Others 
 
12.1. Potential Benefits to Subjects 
 
There is no direct benefit to individual subjects, as both of the study drugs are routinely used during 
cataract surgery. 
 
12.2. Potential Benefits to Others 
 


 
Page 11 of 14 (V.06/27/2016)  
Better mydriasis allows for a better view and operating field for the ophthalmologist, potentially leading 
to decreased difficulty of surgery and potentially better surgical outcomes. Benefits to society include 
potentially identifying an equally efficacious drug that is significantly cheaper. During a time when 
healthcare costs continue to rise, this is extremely relevant.  
 
13. 
Sharing Results with Subjects 
 
Not applicable 
 
14. 
Subject Stipend (Compensation) and/or Travel Reimbursements 
 
Not applicable 
 
15. 
Economic Burden to Subjects 
 
15.1. Costs  
 
The subjects will not be responsible for any additional costs for participating in the research.  
 
15.2. Compensation for research-related injury 
 
There is no risk in addition to that of routine cataract surgery. 
 
16. 
Resources Available 
 
16.1. Facilities and locations 
 
Patients will be recruited from the Penn State Hershey Eye Center Clinic (UPC 1, Suite 800). All cataract 
surgeries for the study will be performed at Hershey Outpatient Surgery Center (HOSC).  
 
 
16.2. Feasibility of recruiting the required number of subjects 
 
The study team has access to approximately 10-20 potential subjects per week. At a minimum, 10% of 
subjects (1-2 per week) would need to be recruited in a one year period to reach the required number of 
participants for the desired study power. 
 
16.3. PI Time devoted to conducting the research 
 
The PI has 20% academic time and will be contributing half of this to research activities, for a total 
percentage effort of 10%. 
 
16.4. Availability of medical or psychological resources 
 
Not applicable 


 
Page 12 of 14 (V.06/27/2016)  
 
16.5. Process for informing Study Team 
 
Team members will meet with the PI every second and fourth Monday of each month during the course 
of the study to ensure proper training on study protocol and duties. 
17.0 Other Approvals 
17.1 
Other Approvals from External Entities 
 
Not applicable 
 
17.2 
Internal PSU Committee Approvals 
 
Check all that apply: 
  Anatomic Pathology – Hershey only – Research involves the collection of tissues or use of pathologic 
specimens. Upload a copy of HRP-902 - Human Tissue For Research Form on the “Supporting 
Documents” page in CATS IRB. This form is available in the CATS IRB Library.   
 
  Animal Care and Use – All campuses – Human research involves animals and humans or the use of 
human tissues in animals 
 
  Biosafety – All campuses – Research involves biohazardous materials (human biological specimens in a 
PSU research lab, biological toxins, carcinogens, infectious agents, recombinant viruses or DNA or 
gene therapy). 
 
  Clinical Laboratories – Hershey only – Collection, processing and/or storage of extra tubes of body fluid 
specimens for research purposes by the Clinical Laboratories; and/or use of body fluids that had 
been collected for clinical purposes, but are no longer needed for clinical use. Upload a copy of HRP-
901 - Human Body Fluids for Research Form on the “Supporting Documents” page in CATS IRB. This 
form is available in the CATS IRB Library.  
 
  Clinical Research Center (CRC) Advisory Committee – All campuses – Research involves the use of CRC 
services in any way. 
 
  Conflict of Interest Review – All campuses – Research has one or more of study team members 
indicated as having a financial interest. 
 
  Radiation Safety – Hershey only – Research involves research-related radiation procedures. All research 
involving radiation procedures (standard of care and/or research-related) must upload a copy of 
HRP-903 - Radiation Review Form on the “Supporting Documents” page in CATS IRB. This form is 
available in the CATS IRB Library. 
 
  IND/IDE Audit – All campuses – Research in which the PSU researcher holds the IND or IDE or intends to 
hold the IND or IDE. 
 
X Scientific Review – Hershey only – All investigator-written research studies requiring review by the 
convened IRB must provide documentation of scientific review with the IRB submission. The 
scientific review requirement may be fulfilled by one of the following: (1) external peer-review 
process; (2) department/institute scientific review committee; or (3) scientific review by the Clinical 
Research Center Advisory committee.  NOTE: Review by the Penn State Hershey Cancer Institute 


 
Page 13 of 14 (V.06/27/2016)  
Scientific Review Committee is required if the study involves cancer prevention studies or cancer 
patients, records and/or tissues. For more information about this requirement see the IRB website 
at: http://www.pennstatehershey.org/web/irb/home/resources/investigator  
 
18.0 Multi-Site Research 
 
18.1 
Communication Plans 
 
Not applicable 
 
18.2 
Data Submission and Security Plan 
 
Not applicable 
 
18.3 
Subject Enrollment 
 
Not applicable 
 
18.4 
Reporting of Adverse Events and New Information 
 
Not applicable 
 
18.5 
Audit and Monitoring Plans 
 
Not applicable 
 
19.0 Adverse Event Reporting 
 
19.1 
Reporting Adverse Reactions and Unanticipated Problems to the Responsible IRB 
 
In accordance with applicable policies of The Pennsylvania State University Institutional Review Board 
(IRB), the investigator will report, to the IRB, any observed or reported harm (adverse event) 
experienced by a subject or other individual, which in the opinion of the investigator is determined to be 
(1) unexpected; and (2) probably related to the research procedures. Harms (adverse events) will be 
submitted to the IRB in accordance with the IRB policies and procedures. 
 
20.0 Study Monitoring, Auditing and Inspecting 
 
20.1 
Auditing and Inspecting 
 
The investigator will permit study-related monitoring, audits, and inspections by the Penn State quality 
assurance program office(s), IRB, the sponsor, and government regulatory bodies, of all study related 
documents (e.g., source documents, regulatory documents, data collection instruments, study data 
etc.).  The investigator will ensure the capability for inspections of applicable study-related facilities 
(e.g., pharmacy, diagnostic laboratory, etc.). 
 


 
Page 14 of 14 (V.06/27/2016)  
21.0 Future Undetermined Research: Data and Specimen Banking 
 
21.1 
Data and/or specimens being stored 
 
Not applicable 
 
21.2 
Location of storage 
 
Not applicable 
 
21.3 
Duration of storage 
 
Not applicable 
 
21.4 
Access to data and/or specimens 
 
Not applicable 
 
21.5 
Procedures to release data or specimens 
 
Not applicable 
 
21.6 
Process for returning results 
 
Not applicable 
 
22.0 References 
 
1Grob SR, Gonzalez-Gonzalez LA, Daly MK. Management of mydriasis and pain in cataract and intraocular lens 
surgery: review of current medications and future directions. Clin Ophthalmol. 2014; 8: 1281-1289. 
 
2Lawuyi LE, Gurbaxani A. The clinical utility of new combination phenylephrine/ketorolac injection in cataract 
surgery. Clin Ophthalmol. 2015; 9: 1249-1254. 
 
3Hovanesian JA, Sheppard JD, Trattler WB, et al. Intracameral phenylephrine and ketorolac during cataract 
surgery to maintain intraoperative mydriasis and reduce postoperative ocular pain: integrated results from 2 
pivotal phase 3 studies. J Cataract Refract Surg. 2015; 41: 2060-2068. 
 
4Lindstrom RL, Loden JC, Walters TR, et al. Itracameral phenylephrine and ketorolac injection (OMS302) for 
maintenance of intraoperative pupil diameter and reduction of postoperative pain in intraocular lens 
replacement with phacoemulsification. Clin Ophthalmol. 2014; 8: 1735-1744.