Clinical trial NCT04399122
Conditions: Post-operative Pain Control
Keywords: Photorefractive Keratectomy Post-operative Eye Pain Refractive Surgery
Sponsor: 59th Medical Wing
Start date: 2017-03-21; Completion date: 2019-10-28
Enrollment: 200 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Photorefractive keratectomy (PRK) is a refractive error correction procedure that helps eliminate or reduce the dependence on corrective lenses. An important aspect of PRK is post-operative pain management. Post-operative pain can be significant in the first three to five days and is typically controlled utilizing various modalities including narcotic pain medication. Simple observation suggests a difference in the post-operative pain levels of patients utilizing the more potent oxycodone- versus the less potent codeine-containing acetaminophen preparations. There have been no studies performed to explore any differences in perceived pain comparing these two medications when used following PRK. This study is designed to answer this question by means of a pain survey conducted in the first five days post-op. This may help better manage similar patients in the future.

Detailed description:
This will be a prospective pain assessment study utilizing a simple three question survey given to patients undergoing bilateral PRK. Following recruitment and enrollment (see section 4.1 and 4.2 for recruitment and consent process), patients will be randomized to be prescribed either 1) Group 1: codeine 30mg/acetaminophen 300mg (standard of care dosage) or 2) Group 2: oxycodone 5mg/acetaminophen 325mg (standard of care dosage) post-operatively. All post-operative patients will receive standard bandage contact lenses and as needed tetracaine as per standard of care. Patients will be removed from the study if they take other non-study pain medications. They will be asked to record their pain levels four times daily as well as the number of as needed narcotic pain medication taken and the number of tetracaine drops used (to isolate a potential confounding pain control modality). Randomization will be performed with the aid of www.randomizer.org which will generate a randomized assignment to either group 1 or group 2.

All PRK procedures will be performed per standard of care. The procedure will be performed by one of the 4 approved surgeons. All surgeons will use the same technique using either the VISX or the Allegretto laser machines. This technique will include use of a brush for mechanical removal of corneal epithelial cells. The surgeons will take note at this time of the relative adherence of the epithelium to the underlying tissue and grade the adherence on a scale of 0-4 (0=least adherent and 4=most adherent). In the data analysis, differences between surgeons and between operating platform (VISX vs Allegretto) will be compared to account for any possible bias in operating parameters.

The survey will be worded as follows:

1. "Rate your eye pain or level of discomfort at 0800, 1200, 1600 and 2000. Please write the number closest to your response in the table below under the appropriate day and time.
2. "How many tablets of study-related pain medication did you take today in the AM/PM?"
3. "How many times did you use topical tetracaine today in the AM/PM?"
4. "Did you take any other non-study related pain medications?"

Patients will be followed-up post-operatively as per standard of care. This includes follow-up visits at 1 day, 1 week, 1 month, 3 months, 6 months and 12 months. Starting on post-operative day 1, the patients will be asked to record their pain levels using the pain survey at four hour intervals (0800, 1200, 1600, 2000). At the 1 week post-operative visit, the pain surveys will be collected from the patients. Visual acuity data will be extracted from all but the 12 month follow-up appointment and used as a secondary outcome to correlate any possible differences in pain scores to functional outcomes in terms of visual acuity.

Arms: arm 1: codeine 30mg/acetaminophen 325mg Take one to two tablets every 4 to 6 hours as needed for pain for up to 4 days following surgery. arm 2: oxycodone 5mg/acetaminophen 325mg Take one tablet every 4 to 6 hours as needed for pain for up to 4 days following surgery.
Interventions: intervention 1: acetaminophen/codeine vs acetaminophen/oxycodone
Intervention descriptions: intervention 1: pain medications

Protocol documents:
Prot_001.pdf: 
Version: 1 Dec 2012 
Revised by AMD 4 
                                     Non-Exempt Human Research Study 
 
PROTOCOL FOR CLINICAL INVESTIGATION – NON-EXEMPT HUMAN 
(Wilford Hall Ambulatory Surgical Center – WHASC) 
 
PROTOCOL SUMMARY 
1.  Title:  
Post-operative pain control after photorefractive keratectomy comparing acetaminophen/codeine vs 
acetaminophen/oxycodone 
FWH20160007H                                                              
 
2.0. Principal Investigator (PI): 
 
                              WHASC PI: 
 
         
 
Co-PI: 
Name 
 
Charisma Evangelista 
 
Rank/Corps or Civilian Rating 
 
Maj/MC 
 
Date of IRB Approved CITI Training  
6 Sep 2017 
 
Branch of Service 
USAF 
 
AD Mil/DoD Civilian/Ctr/Non-DoD Civ 
AD Mil 
 
Department  & Base 
 
Dept of Ophthalmology/Lackland AFB 
 
Phone & Pager #  
292-4700/ 594-0521 
 
E-Mail Address & 
 
AKO/DKO E-Mail Address 
charisma.b.evagelista.mil@mail.mil 
 
DoD Assurance # and Expiration Date 
N/A 
 
 
3.0. Research Plan:  
 
3.1. Purpose:  
To determine any differences in perceived post-operative pain control using different forms of opioid pain medication.  This will 
provide insight into the need to use medications with higher abuse potential. 
 
3.2. Hypotheses, Research Questions or Objectives:  
Is there a difference in the perceived post-operative pain levels of patients undergoing photorefractive keratectomy when using 
codeine versus oxycodone for pain control? 
 
4.  Brief Summary of the study:  
Photorefractive keratectomy (PRK) is a refractive error correction procedure that helps eliminate or reduce the dependence on 
corrective lenses. An important aspect of PRK is post-operative pain management. Post-operative pain can be significant in the 
first three to five days and is typically controlled utilizing various modalities including narcotic pain medication.  Simple 
observation suggests a difference in the post-operative pain levels of patients utilizing the more potent oxycodone- versus the 
less potent codeine-containing acetaminophen preparations. There have been no studies performed to explore any differences 
in perceived pain comparing these two medications when used following PRK.  This study is designed to answer this question by 
means of a pain survey conducted in the first five days post-op. This may help better manage similar patients in the future.   
    
5. Subjects:  
Patients referred to the Joint Warfighter Refractive Surgery Center at WHASC. This population includes active duty members 
but excludes pregnant women, children, military basic trainees, prisoners, and detainees. 
 
6. Inclusion/exclusion criteria:  
Inclusion criteria:  
Patients included for this study will be active duty members and DoD beneficiaries referred to the Joint Warfighter Refractive 
Surgery Center for corrective refractive surgery.  This population generally includes healthy individuals of age groups 21 years of 
age and above. Inclusion criteria are: 
• 
M/F >21 years of age (PRK is not done on anyone under the age of 21 at this surgery center) 
• 
Have met all criteria for bilateral PRK 
Exclusion criteria:  
• 
Patients who do not meet the criteria for refractive surgery 
• 
Patients receiving LASIK 
• 
Patients known to have an allergy to either of the study pain medications 


Version: 1 Dec 2012 
Revised by AMD 4 
                                     Non-Exempt Human Research Study 
• 
Patients receiving refractive surgery on only one eye 
• 
Pregnant women, children, military basic trainees, prisoners and detainees 
• 
Subject has used narcotics in the last 6 months 
 
7.  Number of Subjects:  TOTAL NUMBER OF SUBJECTS (nation-wide/study-wide):  WHASC 200 
 
8.  Use of an Investigational New Drug:  N/A 
 
9.  Use of an Investigational Device:  N/A 
 
10. Use of a Placebo: N/A 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Post-operative pain control after photorefractive keratectomy comparing acetaminophen/codeine vs acetaminophen/oxycodone 
 
Version: 1 Dec 2012 
Revised by AMD 4 
                                     Non-Exempt Human Research Study 
PROTOCOL FOR CLINICAL INVESTIGATION – NON-EXEMPT HUMAN 
(Wilford Hall Ambulatory Surgical Center – WHASC) 
 
1.  Title:  
Post-operative pain control after photorefractive keratectomy comparing acetaminophen/codeine vs 
acetaminophen/oxycodone 
FWH2016007H                                                         
 
2.0. Principal Investigator (PI): 
 
                           WHASC PI:  
 
 
 
Co-PI: 
Name 
 
Charisma Evangelista 
 
Rank/Corps or Civilian Rating 
 
Maj/MC 
 
Date of IRB Approved CITI Training  
6 Sep 2017 
 
Branch of Service 
USAF 
 
AD Mil/DoD Civilian/Ctr/Non-DoD Civ 
AD Mil 
 
Department  & Base 
 
Dept of Ophthalmology/JBSA-Lackland 
 
Phone & Pager #  
292-4700/ 594-0521 
 
E-Mail Address & 
 
AKO/DKO E-Mail Address 
Charisma.b.evangelista.mil@mail.mil 
 
DoD Assurance # and Expiration Date 
N/A 
 
 
 
 
 
 
 
 
 
 
2.1. Associate Investigators (AI):   
Provide the current list of all “engaged” AIs for the study based on 45 CFR 46.102, e.g., for purposes of research the AI: (1) 
obtains data through intervention or interaction with a research subject(s); and/or (2) obtains identifiable private information 
and/or protected health information about the research subject(s); and/or (3) obtains the informed consent of human subjects 
for research.  All “engaged” investigators must complete IRB approved CITI training. 
Name 
AD/DoD Civ/Ctr/ 
Non-DoD Civ 
Rank/Corps or 
Civilian Rating/Title 
Date of CITI Training 
 
Phone & Pager # 
Mathew Caldwell 
AD 
Lt Col 
205 Oct 20185 
292-2010 
Gary Legault 
AD 
MAJ (USA) 
14 Feb 2017 
292-2010 
Darrel Carlton 
AD 
COL (USA) 
25 Jul 2017 
292-4700 
Vasudha Panday 
Ctr 
Ophthalmologist 
045 Oct 20185 
292-2010 
Douglas Apsey 
Ctr 
Optometrist 
127 Sep 20185 
292-2554 
P. David Kohler 
Ctr 
Optometrist 
232 Jan 20185 
292-2584 
Robert E. Smith 
Ctr 
Ophthalmologist 
01 Aug 2017 
292-2010 
Donovan Reed 
AD 
Capt/MC/Ophthal. 
Resident 
07 Jul 18 
292-6995 
 
2.2. Research Assistants (RA) & Coordinators (RC):   
Provide the current list of all “engaged” RAs & RCs for the study based on 45 CFR 46.102, e.g., for purposes of research the RA 
or RC: (1) obtains data through intervention or interaction with a research subject(s); and/or (2) obtains identifiable private 
information and/or protected health information about the research subject(s); and/or (3) obtains the informed consent of 
human subjects for research.  All “engaged” RAs and RCs must complete IRB approved CITI training. 
Name 
AD/DoD Civ/Ctr/ 
Non-DoD Civ 
Rank/Corps or 
Civilian Rating/Title 
Date of CITI Training  
 
Phone & Pager #  
Kathleen Dinan 
Ctr 
Ophthal. Tech/RC 
24 Apr 2018 
292-2565 
Catherine Hale 
Ctr 
Ophthal. Tech/RA 
01 Mar 2017 
292-2483 
Linda Saavedra 
Ctr 
Ophthal. Tech/RA 
05 Oct 2017 
292-2483 
Rita Garza 
Ctr 
Ophthal. Tech/RA 
02 Mar 2017 
292-2483 
Christie Kaden 
Ctr 
Ophthal, Tech/RA 
1 Mar 2017 
292-2483 
 
2.3. The research relevance of this protocol focuses on:  
[] Diagnosis 
[x] Treatment 
[] Medical Utilization/Managed Care 
[] Prevention 
[] Medical Readiness      [] Other  
2.4.  Location(s):  Joint Warfighter Refractive Surgery Center at WHASC 
 
3.  Research Plan:   
 
3.1. Purpose:  


Post-operative pain control after photorefractive keratectomy comparing acetaminophen/codeine vs acetaminophen/oxycodone 
 
Version: 1 Dec 2012 
Revised by AMD 4 
                                     Non-Exempt Human Research Study 
To determine any differences in perceived post-operative pain control using different forms of opioid pain medication.  This will 
provide insight into the need to use medications with higher abuse potential. 
 
3.2. Hypotheses, Research Questions or Objectives:  
Is there a difference in the perceived post-operative pain levels of patients undergoing photorefractive keratectomy (PRK) 
when using codeine versus oxycodone for pain control? 
   
3.3. Significance:   
PRK is a safe and effective method of improving the vision of many patients but is attended by significant post-operative pain.  
Comparing pain management using narcotics with different potencies helps the clinician decide whether a stronger/more 
potentially addictive substance like oxycodone is necessary for adequate pain control. 
 
3.4. Military Relevance:  
Laser refractive surgery in the United States Air Force has developed into a robust program since its inception in 2001.1  Of the 
different surgical corrective options, PRK has been the most commonly performed refractive surgery in the United States 
Armed Forces.1,2,3 It is utilized in the military to help reduce dependence on corrective eye wear and thus increase readiness and 
mission operations. Improving the overall experience of photorefractive keratectomy including pain control would help 
maintain or increase its perception as a valuable treatment option for refractive error.   
  
3.5. Background and Review of Literature:  
PRK is a surgical procedure that utilizes a laser to reshape the surface (cornea) of the eye, allowing for greater or even complete 
independence from corrective eye wear. It may have less risk of corneal destabilization and dry eye when compared with the 
more commonly performed procedure laser in situ keratomileusis (LASIK).4,5  However, pain and discomfort is an important 
limitation of PRK, particularly post-operatively as pain peaks approximately 24 hours and then gradually subsides as the corneal 
epithelium heals.6 Various strategies to minimize post-operative pain are an ongoing effort.7 At our institution a recent change in 
post-operative analgesic prescribing practices (switching from oxycodone to codeine as the primary narcotic pain controller) 
has led to the anecdotal perception that oxycodone may control pain better than codeine. There are no studies in the literature 
that address subjective pain experienced post-operatively comparing these two pain control modalities when used following 
PRK.  If this survey finds that there is a difference in perceived post-operative pain between patients using oxycodone versus 
codeine, then it may help clarify the post-PRK pain medication regimen. 
 
3.5.1. Bibliography:  
1. 
Panday VA, Reilly CD. Refractive surgery in the United States Air Force. Curr Opin Ophthalmol, 2009; Jul(4):242-246 
2. 
Hammond MD, Madigan WP, Bower KS. Refractive surgery in the United States Army, 2000-2003. Ophthalmology, 
2005; Feb:112(2):184-90. 
3. Stanley PF, Tanzer DJ, Schallhorn SC. Laser refractive surgery in the United States Navy. Curr Opin Ophthalmol, 2009; 
Jul 19(4):321-324. 
4. Spadea L, Cantera E, Cortes M, Conocchia NE, Stewart CW. Corneal ectasia after myopic laser in situ keratomileusis: a 
long-term study. Clin Ophthalmol. 2012;6:1801-13. 
5. Lee HK, Lee KS, Kim HC, Lee SH, Kim EK. Nerve growth factor concentration and implications in photorefractive 
keratectomy vs laser in situ keratomileusis. Am J Ophthalmol. 2005 Jun;139(6):965-71. 
6. McCarty CA, Garrett SK, Aldred GF, et al. Assessment of subjective pain following photorefractive keratectomy. 
Melbourne Excimer Laser Group. J Refrac Surg, 1996; Mar-April 12(3):365-369. 
7. 
Woreta FA, Gupta A, Hoschstetler B, Bower KS. Management of post-photorefractive keratectomy pain. Surv 
Ophthalmol, 2013; Nov-Dec 58(6): 529-535. 
 
3.6. Research Design and Methods:  
This will be a prospective pain assessment study utilizing a simple three question survey given to patients undergoing bilateral 
PRK. Following recruitment and enrollment (see section 4.1 and 4.2 for recruitment and consent process), patients will be 
randomized to be prescribed either 1) Group 1: codeine 30mg/acetaminophen 300mg (standard of care dosage) or 2) Group 2: 
oxycodone 5mg/acetaminophen 325mg (standard of care dosage) post-operatively.  All post-operative patients will receive 
standard bandage contact lenses and as needed tetracaine as per standard of care.  Patients will be removed from the study if 
they take other non-study pain medications.  They will be asked to record their pain levels four times daily as well as the number 
of as needed narcotic pain medication taken and the number of tetracaine drops used (to isolate a potential confounding pain 
control modality).  Randomization will be performed with the aid of www.randomizer.org which will generate a randomized 
assignment to either group 1 or group 2.   
 


Post-operative pain control after photorefractive keratectomy comparing acetaminophen/codeine vs acetaminophen/oxycodone 
 
Version: 1 Dec 2012 
Revised by AMD 4 
                                     Non-Exempt Human Research Study 
All PRK procedures will be performed per standard of care. The procedure will be performed by one of the 4 approved 
surgeons. All surgeons will use the same technique using either the VISX or the Allegretto laser machines. This technique will 
include use of a brush for mechanical removal of corneal epithelial cells. The surgeons will take note at this time of the relative 
adherence of the epithelium to the underlying tissue and grade the adherence on a scale of 0-4 (0=least adherent and 4=most 
adherent). In the data analysis, differences between surgeons and between operating platform (VISX vs Allegretto) will be 
compared to account for any possible bias in operating parameters. 
 
The survey will be worded as follows: 
1. 
“Rate your eye pain or level of discomfort at 0800, 1200, 1600 and 2000. Please write the number closest to your 
response in the table below under the appropriate day and time. 
2. 
“How many tablets of study-related pain medication did you take today in the AM/PM?” 
3. “How many times did you use topical tetracaine today in the AM/PM?” 
4. “Did you take any other non-study related pain medications?” 
 
Patients will be followed-up post-operatively as per standard of care. This includes follow-up visits at 1 day, 1 week, 1 month, 3 
months, 6 months and 12 months. Starting on post-operative day 1, the patients will be asked to record their pain levels using 
the pain survey at four hour intervals (0800, 1200, 1600, 2000).  At the 1 week post-operative visit, the pain surveys will be 
collected from the patients.  Visual acuity data will be extracted from all but the 12 month follow-up appointment and used as a 
secondary outcome to correlate any possible differences in pain scores to functional outcomes in terms of visual acuity. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3.6.1. Interventions, Observations, or Data Sought:  
Primary Outcome: Subjective median daily post-operative average pain score following PRK in each eye 
Secondary Outcomes: Post-operative visual acuities (standard of care), which surgeon performed the surgery, adherence of 
epithelium to underlying tissue, which laser platform was used, side effects from the study medications requiring a change or 
cessation of the pain control medication.  
 
3.6.2. Data Collection and Processing:  
The pain surveys will be collected from each subject at the 1 week post-operative visit.  The secondary outcomes listed in 3.6.1. 
are standard of care information and will be recorded from the subjects clinical records. 
 
3.6.3. Setting:  Joint Warfighter Refractive Surgery Center at WHASC 
 
3.6.4. Date(s):  1 December 2015-31 May 2017 
 
3.6.5. Source of Research Material:  
Source of Research Material per Participant (Procedures) 
# Routine Care 
# Research Driven 
# Total Procedures 
Pain Survey (1 day, 1 week) 
0 
8 
8 
JWRSC Clinical Record—Visual Acuity (1 day, 1 week), surgeon, 
laser platform 
5 
0 
5 
200 Enrolled Patients 
Group 2  
Oxycodone + acetaminophen 
Group 1  
Codeine + acetaminophen 
Complete daily survey until 
one week follow up 
Complete daily survey until 
one week follow up 
Randomized 
 


Post-operative pain control after photorefractive keratectomy comparing acetaminophen/codeine vs acetaminophen/oxycodone 
 
Version: 1 Dec 2012 
Revised by AMD 4 
                                     Non-Exempt Human Research Study 
 
 
 
3.6.6. Subjects:  
Patients referred to the Joint Warfighter Refractive Surgery Center at WHASC. This population includes active duty members 
but excludes pregnant women, children (17 and under), military basic trainees, prisoners, and detainees. 
 
3.6.7. Inclusion/Exclusion Criteria: 
Inclusion criteria:  
Subjects included for this study will be active duty members and DoD beneficiaries referred to the Joint Warfighter Refractive 
Surgery Center for corrective refractive surgery.  This population generally includes healthy individuals 21 years of age and older.  
Inclusion criteria are: 
• 
M/F >21 years of age (PRK is not done on anyone under the age of 21 at this surgery center) 
• 
Have met all criteria for bilateral PRK 
Exclusion criteria: 
• 
Patients who do not meet the criteria for refractive surgery 
• 
Patients receiving LASIK 
• 
Patients known to have an allergy to either of the study pain medications 
• 
Patients receiving refractive surgery on only one eye 
• 
Pregnant women, children, military basic trainees, prisoners and detainees 
• 
Subject has used narcotics in the last 6 months 
 
3.6.8. Instrumentation:  
A numeric rating scale will be used to survey patient’s pain/discomfort level experienced during PRK. The numeric pain scale is 
an effective pain assessment tool which has shown reliable and valid results in numerous studies for both acute and chronic 
pain.3 Its’ use is appropriate for discriminating differences in intensity of pain but not in quality of pain. A copy of the pain survey 
can be found at attachment 4 of the protocol package. 
 
4.0. Human Subject Protection 
 
4.1. Recruitment:  
Subject recruitment will occur during the initial pre-operative briefing at the Joint Warfighter Refractive Surgery Center. As 
standard of care, all persons undergoing refractive surgery are brought together for a group educational meeting regarding 
refractive surgery. At this meeting subjects who plan on undergoing PRK will be informed of the opportunity to take part in this 
study. Those interested in participating in the study will be given an informed consent and HIPAA authorization form to take 
home and review. This will allow at least 24 hours for the patient to discuss the study with friends, relatives, or a physician prior 
to their surgery. The next day patients who agree to participate in the study will undergo the consent/enrollment process for 
the study. The PI (who is a resident and will not be the surgeon), an AI, or a research coordinator/assistant will present the 
information about the study to the prospective subjects.  AI’s who will also be the surgeon will not recruit any of his/her own 
patients for the study. 
 
4.2. Consent Processes:  
No study specific procedures will be performed without a written and signed informed consent document. If the patient is 
found eligible and chooses to participate in the study, written informed consent will be obtained by the PI, a non-surgeon AI, or 
an approved research coordinator/assistant on the day of surgery at the Joint Warfighter Refractive Surgery Center. All aspects 
of the study will be explained to the subject including any risks and benefits about the study and consent will be obtained only 
after the subject has had an opportunity to ask questions and discuss the study with the PI, an AI, or assistant. Any subject 
unable to demonstrate the ability to understand or willingness to sign the informed consent or HIPAA authorization form will be 
excluded from the study. 
 
4.3 Participation Compensation:  Subjects will not be paid for participation in this study. 
 
4.4. Assent Process: N/A 
 
4.5. Benefits:  
There is no direct benefit to the patients in the study.  This study will only indirectly benefit the patient by contributing to the 
pool of general medical knowledge which may contribute to future patient care. 
 


Post-operative pain control after photorefractive keratectomy comparing acetaminophen/codeine vs acetaminophen/oxycodone 
 
Version: 1 Dec 2012 
Revised by AMD 4 
                                     Non-Exempt Human Research Study 
4.6. Risks:  
As a post-operative pain control study comparing two previously utilized and accepted methods for pain control, there is 
minimal inherent risk.  Patients will receive either one or the other pain medication and will record their perceived pain levels.   
 
With collection of any patient data, there is a risk of inadvertent breach of confidentiality.  
 
To summarize, the risks involved with this study include: 
    1. Inadvertent breach of confidentiality 
 
4.7. Costs: N/A 
 
4.8. Safeguards for Protecting Information:  
Each subject’s research record including a copy of the ICD, HIPAA Authorization and the intra-operative pain survey will be 
stored in a locked cabinet in a locked room.  All research data including patient demographics will be kept in a firewall protected 
electronic database, which will be encrypted, double password protected and the access will be restricted.  The research data 
will be de-identified prior to analysis by the statistician and any links to identifiable data including the Master Key of PII, will be 
destroyed as soon as possible. There are no planned linkages with external databases, nor is transmission of the data for 
collaborative use anticipated.  The research data will not be utilized for further research activity beyond the protocol 
stipulations without additional IRB approval. 
 
4.9. Safeguards for Protecting Subjects: 
The principal investigator will be responsible for the protocol safety monitoring.  The PI will make study documents (e.g., 
consent forms, data pulls) and pertinent hospital or clinical records readily available for inspection by the local IRB and over 
sight staff for confirmation of the study data. 
 
4.9.1. Minimizing Risks:  
Patients at the Joint Warfighter Refractive Center have traditionally received acetaminophen/oxycodone but more recently 
began receiving acetaminophen/codeine for post-operative pain instead and therefore this study would not change the Center’s 
accepted practices except to compare the pain control differences of the these two pain medications. 
   
4.9.2. Vulnerable Populations: N/A 
 
4.9.3. Clinical Care: N/A 
 
4.9.4. Injury Compensation: N/A 
 
4.9.5. Data Safety Monitoring: N/A 
 
5.0. Alternatives:  Choosing to have surgery but not to participate in this study is an alternative to volunteering for the study. 
 
6.0. Data Analysis:  
The median daily pain scores for first group (codeine + acetaminophen) will be compared to the median pain score of the 
second group (oxycodone + acetaminophen) using a Wilcoxon signed rank test.  Also, median pain scores will be compared 
between operating physicians and between operating machine (VISX vs Allegretto) using a Wilcoxon signed rank test.  In 
addition, a qualitative analysis will be performed on data obtained. Visual acuities will also be compared between groups if any 
differences are found in pain scores. 
 
6.1. Outcome Measures:  
Post-operative median daily pain scores between two groups using different narcotic medication for pain control. 
 
6.2. Sample size estimation/power analysis:  
A power of 0.8 (1-β) was arrived at based on an assumed false negative rate of 0.20 (4 x the assumed false positive rate of 0.05).  
Effect size of 2/square root of 10 (assumed clinical significance of 2 on a 0-10 numerical pain scale) combined with a false positive 
rate of 0.05 and a power of 0.8 leads to an N of 41 per group using a two-sided T test or a minimum total number enrolled of 82.  
Assuming a 18% drop out rate, a total number of 100 patients would make for 45 per group.  Based on similar studies showing 
that only 50% of participants use the narcotic pain control medication, a doubling of the number enrolled should provide for an 
adequately powered study. 
 


Post-operative pain control after photorefractive keratectomy comparing acetaminophen/codeine vs acetaminophen/oxycodone 
 
Version: 1 Dec 2012 
Revised by AMD 4 
                                     Non-Exempt Human Research Study 
6.3. Statistical Analysis:  
Support from the 59 CRD or 59 MDW ST office statistician will be obtained in performing analysis of data. 
 
6.4 Number of Subjects:   
Number of subjects planned for WHMC 
Enrolled in Study   200 
to result in 
180 
Completing the 
study. 
TOTAL NUMBER OF SUBJECTS (nation-wide/study-wide): 200 
 
7. Duration of Study:  Approximate duration of the study: 1.5 years 
 
8.  Local and External Support Services:  None   
 
9.  Intramural (GME) and Extramural Funding Support:  None 
 
10. Conflict of Interest: None 
 
11.  Use of an Investigational New Drug, use of a Drug for a non-FDA approved purpose, use of an investigative device or use of a 
placebo:   
This research uses an Investigational New Drug 
 
 
 
 
 
[] YES 
[x] NO 
This research uses a FDA approved drug for a non-FDA approved purpose                                                                          [] YES [x] NO 
This research uses an Investigational Device       
 
 
 
 
 
[] YES 
[x] NO 
This research uses a placebo. 
 
 
                                                                                    
[] YES 
[x] NO 
 
12.  Medical Research Area for the Study:  (Pick as many as appropriate) 
[] Analytical Chemistry 
[] Anatomy 
[] Anesthesiology 
[] Biochemistry 
[] Cardiovascular Surgery 
[] Cardiology 
[] Cell Biology 
[] Dentistry 
[] Dermatology 
[] Dietetics 
[] Electrophysiology 
[] Endocrinology 
[] Emergency medicine 
[] Gastroenterology 
[] General Surgery 
[] Hematology 
[] Histology 
[] Immunology/Allergy 
[] Infectious Disease 
[] Microbiology 
[] Molecular Biology 
[] Neonatology 
[] Neurology 
[] Neurosurgery 
[] Nursing 
[] OB/GYN 
[] Occupational Medicine 
[] Occupational Therapy 
[] Oncology 
[x] Ophthalmology 
[] Oral/Maxillofacial Surgery 
[] Orthopedics 
[] Pathology 
[] Pediatrics 
[] Pharmacology 
[] Physical Therapy 
[] Mental Health 
[] Radiology/Imaging 
[] Urology 
[] Wellness 
[] Other (state): 
 
 
13. Attachments:  
1. 
Form A; Certificate of Compliance 
2. 
Informed Consent Document 
3. 
HIPAA Authorization Document 
4. 
Research Questionnaire (Pain Scale) 
5. 
Form A-2; Study Personnel List 
6. 
Form O; Use of a Drug in Research with 2 attachments (Drug Package Inserts) 
7. 
Data Collection Worksheet 
8. 
PII Master Key 
9. 
PI’s CITI training certificate 
10. PI’s CV