Opioid Analgesic Reduction Study (OARS) - Pilot
Phase: PHASE3
Conditions: Post Operative Pain
Sponsor: Rutgers, The State University of New Jersey

 
 
 
 
Protocol Title: OARS Protocol Pilot Multi-Site 
Protocol Version Date: Vr.0.4.06.28.2021 
 
Page 0 of 27 
 
 
INTERVENTIONAL 
RESEARCH PROTOCOL TEMPLATE 
(HRP-503a) 
 
 
 
 
STUDY INFORMATION 
 
▪ 
Title of Project: 
OARS Protocol Pilot- Multi-site 
 
▪ 
Principal Investigator Name 
Cecile Feldman, DMD MBA 
 
▪ 
Principal Investigator Div. & Dept. 
Rutgers School of Dental Medicine 
 
▪ 
Principal Investigator Contact Info:  
feldman@rutgers.edu 
Rutgers School of Dental Medicine 
110 Bergen Street 
Newark, NJ 07103 
(973) 972-1679 
 
▪ 
Protocol Version and Date: 
Vr.0.4.06.28.2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
Protocol Title: OARS Protocol Pilot Multi-Site 
Protocol Version Date: Vr.0.4.06.28.2021 
 
Page 1 of 27 
 
 
 
Table of Contents 
Skip To Section: Hold CTRL + Click (Below) To Follow Link in Blue 
 
1.0 
Research Design 
 
 
1.1 
Purpose/Specific Aims 
 
 
1.2 
Research Significance 
 
 
1.3 
Research Design and Methods 
 
 
1.4 
Preliminary Data 
 
 
1.5 
Sample Size Justification 
 
 
1.6 
Study Variables 
 
 
1.7 
Drugs/Devices/Biologics 
 
 
1.8 
Primary Specimen Collection 
 
 
1.9 
Interviews, Focus Groups, or Surveys 
 
 
1.10 
Timetable/Schedule of Events 
 
 
2.0 
Project Management 
 
 
2.1 
Research Staff and Qualifications 
 
 
2.2 
Resources Available 
 
 
2.3 
Research Sites 
 
 
3.0 
Multi-Site Research Communication & Coordination 
 
 
3.1 
Outside Research 
 
 
4.0 
Research Data Source/s 
 
 
4.1 
Primary Data – Subjects and Specimens 
 
 
4.2 
Subject Selection and Enrollment Considerations 
 
 
4.3 
Subject Randomization 
 
 
4.4 
Secondary Subjects 
 
 
4.5 
Number of Subjects 
 
 
4.6 
Consent Procedures 
 
 
4.7 
Special Consent Populations 
 
 
4.8 
Economic Burden and/or Compensation For Subjects 
 
 
4.9 
Risks to Subjects 
 
 
4.10 
Secondary Data – Record/Chart Reviews, Databases, Tissue Banks, Etc. 
 
 
4.11 
Chart/Record Review Selection 
 
 
4.12 
Secondary Specimen Collection 
 
 
5.0 
Special Considerations 
 
 
5.1 
Health Insurance Portability and Accountability Act (HIPAA) 
 
 
5.2 
Family Educational Rights and Privacy Act (FERPA) 
 
 
5.3 
NJ Access to Medical Research Act 
 
 
5.4 
Code of Federal Regulations Title 45 Part 46 (Vulnerable Populations) 
 
 
6.0 
Research Data Protection and Reporting 
 
 
6.1 
Data Management and Confidentiality 
 
 
6.2 
Data Security 
 
 
6.3 
Data Safety And Monitoring 
 
 
6.4 
Reporting Results 
 
 
6.5 
Data Sharing 
 
 
7.0 
Data and/or Specimen Banking 
 
 
8.0 
Other Approvals/Authorizations 
 
 
9.0 
Bibliography 
 
 
 
 
 

 
 
 
 
Protocol Title: OARS Protocol Pilot Multi-Site 
Protocol Version Date: Vr.0.4.06.28.2021 
 
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1.0 Research Design 
 
1.1 Purpose/Specific Aims 
The purpose of this study is to test protocols being developed for the conduct of a large sale multi-site clinical 
trial which will compare opioids to non-opioids for managing post-surgical impacted 3rd molar extraction pain. 
 
A double-blind randomized clinical trial is being designed.   Subjects will be randomly assigned to either the 
OPIOID or NON-OPIOID group.  Analgesic agents for both the OPIOID and NON-OPIOID group are commonly 
used in practice today.  The OPIOID analgesic (hydrocodone 5mg/acetaminophen 300mg) is available in a 
combination tablet and is the most commonly prescribed opioid analgesic in dentistry.  The NON-OPIOID 
analgesic (ibuprofen 400 mg and acetaminophen 500mg) is not available as a combination tablet in the US at 
that dosage, however components are available separately in the dosages which will be used.  All analgesics are 
FDA approved and are being used according to label. 
 
A.  Objectives  
The objectives of this study are to: 
1. Test refined OARS study instruments.  These instruments include: 
a. Eligibility form 
b. Enrollment form 
c. 
Pre-surgical questionnaire 
d. Post-surgical questionnaire 
e. eDiary 
2. Test REDCap for: 
a. Texting subjects eDiary entry invitations via Twillo 
3. Test Actigraph for: 
a. Capturing activity and sleep activity data 
4. Test SMRxT bottle for: 
a. Capturing date/time that  pill removal from the SMRxT bottle 
b. Texting investigator messages based upon changes in the number of pills in the SMRxT 
bottle 
5. Test the steps for querying the Prescription Database Monitoring Program (PDMP) database. 
6. Test whether female patients are amenable to take a pregnancy test to determine eligibility. 
 
B.  Hypotheses / Research Question(s) 
The following research questions will be answered: 
1. Are patients able to answer the proposed questions on the pre-surgical and post-surgical questionnaire? 
2.  Are patients able to consistently make the eDiary entries via their smart phones? 
3.  Is REDCap easy to use? 
4.  Are patients willing to wear the Actigraph for 72 hours and can data be easily downloaded? 
5. Is data provided by SMRxT reliable and can Nomi accurately send text messages to study investigators? 
6. Are patients willing to consistently take 3 capsules per dose? 
7. Do patients comply with instructions to take one capsule from Bottle #1 and 2 capsules from Bottle #2? 
8. Are female patients willing to take a pregnancy test to determine eligibility to participate? 
 
1.2 Research Significance 
Patients and their clinicians select analgesics to prevent and/or manage post-surgical and acute pain.3   Many young, 
vulnerable, opioid-naive, patients undergoing 3rd molar extraction, and adults experiencing a dental emergency or 
undergoing osseous dental surgery, are exposed to unnecessary opioids.3,4   These exposures create unnecessary 
dangers5-10  and result in unused tablets that may be abused.11-14   Completed studies are limited as they compare 
the analgesic against a placebo, frequently are single dose studies or follow patients for just several hours.15-17  None 

 
 
 
 
Protocol Title: OARS Protocol Pilot Multi-Site 
Protocol Version Date: Vr.0.4.06.28.2021 
 
Page 3 of 27 
 
 
of those studies demonstrate non-inferiority; are pragmatic (prescribe the analgesics as used in practice); follow a 
patient through the entire pain episode; determine tablets remaining  in the patient’s household; and compare the 
patient’s propensity for obtaining future opioid prescriptions.  This pilot will test methodology for a pragmatic clinical 
trial which could demonstrate that a combination of ibuprofen and acetaminophen is at least as good as the most 
commonly prescribed opioid by dentists in managing post-surgical pain.   
 
1.3 Research Design and Methods 
This pilot study consist of two phases intended to test procedures and instruments that will be used in a large scale, 
multi-site clinical study.  The research design and methods will be identical for subjects enrolled in each of the 
phases. 
• 
Phase 1: Enrolling 24 subjects (12 male and 12 female) at Rutgers School of Dental Medicine Oral Surgery 
Clinic 
• 
Phase 2: Enrolling 8 (4 male and 4 female) subjects at each of the additional clinical sites  
o 
University of Rochester 
o 
University of Maryland 
o 
University of Illinois 
o 
University of Michigan  
Phase 2 will begin any time after the first 10 participants in Phase 1 (at RSDM) have completed Visit 2. 
 
Subjects, who have presented to the Dental Clinic to have at least one impacted lower 3rd molar extracted, will be 
followed at surgery then for 9 (-/+5) days post-surgery in this pilot study.  As this is a pragmatic clinical trial, subjects 
are able to determine when and how much of the study analgesic to use.  Subject compliance is based upon 
completion of the eDiary morning and evening entries and at the post-operative visit.   
Subjects will complete a questionnaire prior to surgery related to their pre-operative pain. 
 
Immediately following surgery, subjects will be given a study material package which contains the following items:  
• 
Pain Medication in SMRxT bottles: Two combination analgesics will be used and subjects will be randomly 
assigned to either the OPIOID (Hydrocodone 5 mg/acetaminophen 300 mg) or NON-OPIOID group 
(ibuprofen 400 mg/acetaminophen 500mg).  Study analgesics will be formulated from powder by the 
compounding pharmacy and provided in 2 different size/color capsules.   
 
Capsule 
Number 
OPIOID Content 
PROTOCOL Z 
NON-OPIOID Content 
PROTOCOL A 
Quantity 
for a Dose 
Total 
Dispensed 
Capsule 
Size 
Color 
1 
Hydrocodone 5mg / 
Acetaminophen 300 mg 
Ibuprofen 400 mg 
 
1 
20 
AA 
Brown 
2 
Placebo 
 
Acetaminophen 500 mg 
1 
20 
00 
White 
* All analgesics are FDA approved and are being used according to label. 
 
Each study package will contain 20 doses.  Subjects will be asked to take the first dose before leaving the 
office as long as they are accompanied.  If they are not accompanied, subjects will be asked to take their 
first dose when they get home.  The remaining study analgesic will be self-administered.  Pain medication 
will be contained in 2 SMRxT bottles, electronic bottles which enable the tracking of capsule removal at any 
given time.   
• 
Actigraph- sleep/ activity monitor worn like a watch that tracks and transmits daily activity data 
 
 In addition to managing their post-operative pain as needed, subjects will be asked to actively participate over the 
post-operative period (time between surgery visit and post-operative visit). Subjects will be asked to complete a pain 
eDiary twice a day during the post-operative period and wear an Actigraph activity/sleep monitor continuously for 
the first 72 hours of the post-operative period.  
• 
eDiary:  

 
 
 
 
Protocol Title: OARS Protocol Pilot Multi-Site 
Protocol Version Date: Vr.0.4.06.28.2021 
 
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o 
Subjects will receive automatic reminders to complete a survey which is linked to their file in 
REDCap  
o 
Using their smart phones, subjects will self-report pain levels, sleep activity, and medications 
used. 
o 
Frequency: once in the morning and once in the evening during each day of the post-operative 
period  
• 
Actigraph- electronically captures activity and sleep data 
o 
Data will be downloaded when the Actigraph is returned 
 
Subjects will return for the post-operative visit, during which they will complete a PostOp Subject Questionnaire and 
a Pilot Participation Questionnaire.  At this visit, subjects will be required to return the Actigraph and 2 SMRxT 
medication bottles containing all unused study medication. The Clinical Research Coordinator will count, record in 
REDCap, and collect/store all unused medication in the double locked drug cabinet.  All unused study medication 
will be collected by to Rutgers School of Dental Medicine (External sites will ship unused study product to Rutgers) 
and destroyed in accordance with policies set forth by Rutgers Environmental Health Services at the conclusion of 
the study.   
 
A follow-up PDMP query taking place 30 days +/- 7 days after completing Visit 1 if permitted by state law.  If the 
subject filled an additional opioid prescription within that month, subject will be offered addiction counseling.  
Contact will be initiated by phone, however, if phone contact is unsuccessful, subject will be emailed the counseling 
information. 
  
A. Research Procedures 
The follow is the order of occurrence: 
 
Order 
Research 
Procedure 
When 
Research 
Protocol  
Where 
By Whom 
1 
Informed consent 
obtained 
Visit 0 
Yes 
Dental 
Clinic 
Clinical Site Research Coordinator/ 
Clinical Co-Investigator 
2 
Eligibility 
determination 
Visit 0 
Yes 
Dental 
Clinic 
Clinical Site Research Coordinator/ 
Clinical Co-Investigator 
3 
Urine Pregnancy 
Test 
Visit 1 
Yes 
Dental 
Clinic 
Clinical Site Research Coordinator/ 
Clinical Co-Investigator 
4 
Protocol Training 
and SMS Test 
Visit 1 
Yes 
Dental 
Clinic 
Clinical Site Research Coordinator/ 
Clinical Co-Investigator 
5 
Pre-Op 
questionnaire 
administered 
Visit 1 
Yes 
Dental 
Clinic 
Clinical Site Research Coordinator/ 
Clinical Co-Investigator 
6 
Treatment or 
surgery performed 
Visit 1 
Standard of 
Care 
Dental 
Clinic 
Clinical Co-Investigator 
7 
Surgical Care 
Report completed 
Visit 1 
Yes 
Dental 
Clinic 
Clinical Site Research Coordinator/ 
Clinical Co-Investigator 
8 
Loading Dose 
taken before 
leaving office  
Visit 1 
Yes 
Dental 
Clinic 
Subject 
9 
Analgesics taken 
and eDiary 
completed 
Days 1-10 
Yes 
Subject’s 
Home 
Subject 
10 
Post-operative 
Examination 
Visit 2 (Day 10 +/- 5 
days after Visit 1) 
Standard or 
Care 
Dental 
Clinic 
Clinical Co-Investigator 
11 
Post-Operative 
Care Report 
completed 
Visit 2 
Yes 
Dental 
Clinic 
Clinical Site Research Coordinator/ 
Clinical Co-Investigator 

 
 
 
 
Protocol Title: OARS Protocol Pilot Multi-Site 
Protocol Version Date: Vr.0.4.06.28.2021 
 
Page 5 of 27 
 
 
12 
Post-Op 
questionnaire 
administered 
Visit 2  
Yes 
Dental 
Clinic 
Clinical Site Research Coordinator/ 
Clinical Co-Investigator 
13 
Unused analgesia 
tablets collected 
Visit 2 
Yes 
Dental 
Clinic 
Clinical Site Research Coordinator/ 
Clinical Co-Investigator  
14 
PDMP Query (if 
permitted by state 
law) 
30 days +/- 7 days 
after Visit 1 
Care offered 
to 
participants 
Dental 
Clinic 
Clinical Site Research Coordinator/ 
Clinical Co-Investigator 
 
B. Data Points 
Data elements to be collected include: 
When 
Data Points Collected 
Eligibility/Consent Visit - Visit 0 
• Name 
• Date of birth 
• Positive substance abuse history 
• Presence of any chronic pain problem 
• Previous adverse reactions to analgesics 
• PDMP history (previous opioid Rx’s) 
• Significant medical history preventing eligibility 
• Self-reported Pregnancy (if female) 
Treatment Visit (including Surgery) 
- Visit 1 
Gender & Pregnancy 
• 
Gender/gender identify 
• 
Pregnancy Test Results (if female) 
Pre-Operative Questionnaire 
• Race/Ethnicity 
• Education Achieved 
• Sleep ability 
• Swelling 
• Smoking 
• Height/Weight/BMI 
• Current pain level 
• Overall ability to withstand pain 
• Pain Interference 
Protocol Knowledge Test Questionnaire (SMS Test and Training Form) 
• Knowledge of study protocol 
Treatment/Surgery Record 
• Teeth extracted 
• Impaction type 
• Surgical difficulty 
• Surgical treatment time duration 
• Anesthesia 
• Antibiotics 
• Anti-Inflammatory agents 
Days 1-10 +/- 5 days 
(At home) 
Patient Diary (for the first 7 evenings and days) 
• Ability to sleep 
• Time/date and # of study medication capsules taken 
• Other OTC pain medication taken (drug/dosage/tablets) 
• Side effects/adverse events 
• Sleep ability  
• Pain interference 
• Time/date and # tablets taken 
• Pain levels 
• Ability to perform daily functions (pain interference) 
Post Operative Visit- Visit 2  
Post Op Report 

 
 
 
 
Protocol Title: OARS Protocol Pilot Multi-Site 
Protocol Version Date: Vr.0.4.06.28.2021 
 
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(Day 10 +/1 5 days) 
• Date 
• Complications 
End of Study Data Collection 
• Pain Interference 
• Post-op visit time 
• Sleep quality 
• # tablets returned  
• Overall satisfaction with pain control 
• Diary ease of use 
• Suggestions for protocol improvement 
PMDP Query  
(21 days after Visit 2  +/- 7 days) 
Query 
• Date 
• Opioid prescription found (y/n) 
• Date of prescription 
• Prescription details 
 
In addition, should an emergency call be received or an emergency visit take place during the post-operative 
period, the date of the call/visit, reason for the call/visit and any treatment/recommendations provided will 
be recorded.  Should a subject elect to terminate their participation in the study or should the subject be 
hospitalized, the date the subject is terminated from the study along with the reason will be recorded. 
 
C. Study Duration 
The study will be completed over a 4-month period.  Each subject will participate in the study for 10 +/- 5 
days.  A follow-up PDMP query taking place 30 days +/- 7 days after completing Visit 1 if permitted by state 
law.   
. 
D. Endpoints 
Study will end after the PMDP query. 
 
1.4 Preliminary Data 
Not applicable. 
 
1.5 Sample Size Justification 
As this is a pilot to test clinical trial instruments and protocols, no sample size calculation was performed. 
 
1.6 Study Variables 
 
A.   Independent Variables, Interventions, or Predictor Variables  
Independent variables include: 
• 
Intervention group 
• 
Type of smartphone utilized 
• 
Internet carrier 
 
Note:  The surgical treatment provided to the patient is NOT a study intervention.  Subjects are being 
recruited to participate in this study after patients have decided to receive their surgical treatment based 
upon normal clinical practice and is part of normal standard of care.  The intervention in this study is usage 
of a combination of over-the-counter non-opioid analgesics versus the usage of an analgesic containing the 
most commonly prescribed opioid for pain management. 
 
B.  Dependent Variables or Outcome Measures  
 
Source 
Outcome Measure 

 
 
 
 
Protocol Title: OARS Protocol Pilot Multi-Site 
Protocol Version Date: Vr.0.4.06.28.2021 
 
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REDCap 
• 
Completeness of data fields on the questionnaires 
• 
Accuracy of the data 
• 
Accuracy of the Interface with eDiary 
• 
Usability among end-users 
eDiary 
• 
Number of entries by subject 
• 
Frequency of entries by subject 
• 
Completeness of entries 
Actigraph 
• 
Utilization (Subject wearing the device) 
o 
Total duration 
o 
Interrupted verses constant 
• 
Accuracy of data output 
o 
Monitoring activity verses sleep  
SMRxT Bottle 
• 
Accuracy of the data 
o 
Date/time record for capsule removal 
o 
Discernibility of # of Capsules removed per time point 
o 
Nomi text alert to investigator  
PDMP website 
• 
PDMP Data Completeness 
 
 
1.7 Drugs/Devices/Biologics  
OPIOID group contains hydrocodone 5mg/acetaminophen 300mg and a placebo.  The NON-OPIOID group 
contains ibuprofen 400mg and acetaminophen 500mg.  The OPIOID and NON-OPIOID groups will be made by 
over-encapsulating existing FDA approved caplets currently sold in the United States.  Two different color 
capsules will be used.   
 
COLOR 
OPIOID GROUP 
NON-OPIOID GROUP 
Brown  
Hydrocodone 5mg/acetaminophen 300mg 
Ibuprofen 400mg  
White 
Placebo 
Acetaminophen 500mg 
 
Each dose of study analgesic will consist of two capsules, one brown and one white.  Subjects will be instructed 
to take one brown capsule and one white capsule when taking study medication as needed for pain. 
 
Study medication will be purchased from Liberty Drug Compounding Center in Chatham, NJ.  Liberty Drug will 
prepare the study product by over-encapsulation. Capsules used for over-encapsulation will be bovine 
spongiform encephalopathy/transmissible spongiform encephalopathy (BSE/TSE) free. These FDA approved 
analgesics will be used according to label.  Two capsules will be required for each dosage.   
• 
For OPIOID: 
▪ 
One capsule will contain hydrocodone 5mg/acetaminophen 300 mg encapsulated in a 00 capsule 
▪ 
One capsule will contain the placebo formed into a 0 capsule 
• 
For NON-OPIOID: 
▪ 
One capsule will contain acetaminophen 500 mg encapsulated into a 00 capsule 
▪ 
One capsule will contain ibuprofen 400 mg encapsulated into a 0 capsule 
 
Study product will be shipped to the Rutgers School of Dental Medicine Coordinating Core in bottles of 20 
capsules. Each bottle will contain a barcode which contains a unique bottle number, the contents (drug), 
quantity, batch/lot number, manufacture date, and expiration date. Rutgers School of Dental Medicine 
Coordinating Core will be responsible study package assembly for each participant at each site.  These study 
participant packages will be organized in the randomization order generated by the statistician and shipped to 
the sites, ensuring that site personnel are blinded.   
 
When 
preparing 
a 
packet 
of 
materials 
for 
an 
OPIOID 
subject, 
twenty 
(20) 
capsules 
of 
hydrocodone/acetaminophen will be transferred to at SMRxT bottle and twenty (20) capsules of the placebo 

 
 
 
 
Protocol Title: OARS Protocol Pilot Multi-Site 
Protocol Version Date: Vr.0.4.06.28.2021 
 
Page 8 of 27 
 
 
will be transferred to a second SMRxT bottle. For a NON-OPIOID subject, twenty (20) capsules of acetaminophen 
will be transferred to a SMRxT bottle and twenty (20) capsules of ibuprofen will be transferred to a second 
SMRxT bottle.  A label will be affixed to each SMRxT bottles which includes instructions to be followed by the 
subject.   
 
SMRxT bottles are child proof, light protected bottles which weigh the capsules contained within the bottle.  
Each time a pill is removed or replaced and the bottle placed on a flat service, the number of capsules removed 
is transmitted via cellular service to the SMRxT secure cloud. This enables the research staff to track usage of 
capsules in real time.   
 
A. Drug/Device Accountability and Storage Methods 
Study product will be purchased from Liberty Drug Compounding Pharmacy. The compounding pharmacy 
has the license needed to provide the quantity of study medication needed.  All medications (Ibuprofen 
400mg, Acetaminophen 500mg, Hydrocodone 5mg/Acetaminophen 300mg are commercially available in 
the US and will be used according to their labels.  Capsules used to over-encapsulate will be bovine 
spongiform encephalopathy/transmissible spongiform encephalopathy (BSE/TSE) free. These FDA 
approved analgesics will be used according to label.   
 
Receipt from the Pharmacy 
Liberty Pharmacy will ship study product to the Rutgers School of Dental Medicine in bottles of 20 capsules.   
Each bottle will be clearly marked with a unique ID number, the contents (drug), quantity, batch/lot 
number, manufacture date, and expiration date. Shipments will be recorded as received by scanning each 
bottle into REDCap.  All study product will be stored in a medication safe in the Rutgers Coordinating Core 
at RSDM (Newark, NJ).   
 
Radom assignment  
Subjects will be randomized to either the opioid or non-opioid analgesic group at the 1:1 ratio, stratified by 
gender. Pre-determined random number sequences, will be generated by the statistician. The 
randomization code will be generated and labels will be created during the preparation phase when the 
treatment packets are prepared so that each packet will be prepared and the labeled with the packet 
identification number will be generated and put on the packets according to the randomization sequence. 
Complete randomization code for each site will be stored in REDCap and only the DCC staff have access to 
it. 
 
Subject Package Preparation 
When a subject package is ready to be prepared, the OPIOID/NON-OPIOID designation is obtained by 
looking up on the randomization list for the next site/gender to be prepared.  Study package ID (PID) labels 
will be printed for all materials to be placed into the packet.   
 
Medication Transfer 
When preparing a packet of materials for a participant, there will be a one to one transfer from the 
manufacturer’s bottle to the SMRxT bottles.  Specifically, for OPIOID participant, twenty (20) capsules of 
hydrocodone/acetaminophen will be transferred to at SMRxT bottle and twenty (20) capsules of the 
placebo will be transferred to a second SMRxT bottle.  For a NON-OPIOID participant, twenty (20) capsules 
of acetaminophen will be transferred to a SMRxT bottle and twenty (20) of ibuprofen will be transferred to 
a second SMRxT bottle.  Immediately following the medication transfer, the Coordinator will scan the bar 
code on the manufacturer bottle then the barcode on the SMRxT bottles to record the transfer of study 
product in REDCap, enabling the system to track the study product which has now been placed into a subject 
package. The manufacturer bottles will then be discarded.   
 
Shipment to the Sites 

 
 
 
 
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Subject packages will be shipped to each site in denominations of 4.   When packaging a shipment, the study 
packet being packed will be scanned into REDCap to register the package being sent to a clinical site.   
 
Storage 
Each clinical site will have three locked metal cabinets which will be exclusively used for this study: one 
cabinet will be used to store study materials which have been shipped to the sites by Rutgers, one for 
placement of study materials, including study product, when recharging the SMRxT bottles and Actigraph 
prior to release to a participant and the third cabinet will maintain study materials (including study product) 
which have been returned by the participant and are awaiting shipment to the Rutgers Coordinating Core.   
 
Return of Study Packages to Rutgers Core 
Study packages will be shipped back to the Rutgers Core for processing and medication disposal.  Contents 
of the returned study packages (2 SMRxT bottles with unused study medication and the Actigraph) will be 
individually scanned upon receipt at the Core. Unused study medication will be transferred into a storage 
bins awaiting disposal through REHS.  
 
1.8 Specimen Collection 
 
A. Primary Specimen Collection 
▪ 
Types of Specimens: N/A 
▪ 
Annotation: N/A 
▪ 
Transport: N/A 
▪ 
Processing: N/A 
▪ 
Storage: N/A 
▪ 
Disposition: N/A 
 
B. Secondary Specimen Collection 
▪ 
Types of Specimens: N/A 
▪ 
Annotation: N/A 
▪ 
Transport: N/A 
▪ 
Storage: N/A 
▪ 
Disposition: N/A 
 
1.9 Data Collection 
 
A. Primary Data Collection 
▪ 
Location: Eligibility form, consent, pre-operative questionnaire, gender/pregnancy form, surgical case 
report form, post-operative case report form, post-operative questionnaire will be collected in the 
dental clinic.   Subjects will complete their eDiary on their smart-phones at home.   
 
▪ 
Process of Data Collection: There will be several mechanisms and applications through which the 
data will be collected: 
 
▪ 
REDCap 
The majority of the data will be collected electronically via REDCap forms/surveys.  The eligibility form, 
consent, pre-operative questionnaire and post-operative questionnaire will be administered by study 
personnel.  The surgical case report form and post-operative case report form will be completed by 
study personnel.  The eDaily will be completed by the subject via REDCap web-based surveys on their 
smart phones.   
 
▪ 
NOMI through the use of SMRxT bottles 

 
 
 
 
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Page 10 of 27 
 
 
To collect data on the usage of study analgesics, each study subject will be given 2 SMRxT bottles with 
study product.  SMRxT bottles are electronic bottles which record the date time capsules are removed 
from the bottle or replaced back into the bottle.  One SMRxT will contain the color 1 capsules and the 
2nd SMRxT bottle the color 2 capsules.  SMRxT bottles connect via cellular technology to the NOMI 
website which provides real-time monitoring of study product usage.  No patient identifiers will be 
stored in the NOMI system which operates the SMRxT bottles.   
 
▪ 
Actigraph 
To collect data on a subject’s activity level and sleep, subjects will be asked to wear the Actigraph 
activity/sleep monitor.  Data from the Actigraph will be downloaded from the Actigraph website into 
REDCap.  No patient identifiers will be stored in the Actigraph system. 
 
▪ 
Timing and Frequency: Time and frequency for each instrument is shown in the Study Instruments 
Table below. 
▪ 
Procedures for Audio/Visual Recording: N/A 
▪ 
Study Instruments: The following data collection study instruments will be used: 
 
Instrument 
Methodology 
Measures 
Time 
Frequency 
Location 
Informed 
Consent 
REDCap form 
 
15 minutes 
Once 
Dental Clinic 
Eligibility Form 
REDCap form 
 
5 minutes 
Once 
Dental  Clinic 
Pre-Operative 
Questionnaire 
REDCap form 
Demographics 
pain,  
swelling, 
5 minutes 
Once 
Dental Clinic 
Surgical 
Treatment Case 
Report 
REDCap form 
Extractions 
Surgical time 
Difficulty 
Pharmaceuticals 
used 
5 minutes 
Once 
Dental Clinic 
eDiary 
REDCap 
Surveys 
Pain 
Sleep 
Pain Interference 
Adverse Effects 
2 minutes 
per entry 
7 evening 
entries 
7 mid-day 
entries 
7 evening 
entries 
At Home 
Post-Operative 
Case Report 
REDCap form 
 
3 minutes 
Once 
Dental  Clinic 
Post Operative 
Questionnaire 
REDCap form 
Pain 
Sleep 
Pain Interference 
Adverse Effects 
Pain Interference 
Adverse Effects 
Satisfaction 
10 minutes 
Once 
Dental Clinic 
 
▪ 
Ethnographic Studies, Interviews, Or Observation: N/A  
 
▪ 
Subject Identifiers:  Once a patient is enrolled, a study ID code will be assigned and used on all study 
materials, eliminating the need to place identifiable information on the forms.  Thus, no other study 
material will not contain the patients name or any other identifiable information.  Once the study is 
completed, the log containing patient names will be shredded. 
 
B. Secondary Data Collection  
▪ 
Type of Records: N/A 
▪ 
Location: N/A 
▪ 
Inclusion/Exclusion: Medical records will be utilized to pre-screen for study eligibility. 
▪ 
Data Abstraction Form(s): N/A    

 
 
 
 
Protocol Title: OARS Protocol Pilot Multi-Site 
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Page 11 of 27 
 
 
 
1.10 Timetable/Schedule of Events 
The following is the study timetable: 
 
 
2.0 Project Management 
 
2.1 Research Staff and Qualifications 
Research Staff 
Training 
Experience  
Role 
Cecile A. Feldman  
DMD, MBA  
Dr. Feldman is a professor in the 
department of Community Health 
and has participated in many 
research protocols over the course 
of her career. 
PI 
As PI, Dr. Feldman is responsible for 
oversight of this pilot project; 
obtaining patient payment cards, 
collecting study instruments, entering 
data, calculating descriptive statistics 
and developing final report. 
Janine Fredericks-
Younger  
DMD 
Dr. Fredericks-Younger is an 
assistant professor in the 
Department of Restorative at the 
Rutgers School of Dental Medicine. 
Co-Investigator 
As co-investigator, Dr. Fredericks-
Younger will serve as the Chief Clinical 
Officer responsible for overseeing 
adherence to the study protocol and 
providing support to the Clinical Co-
Investigators. 
Shou-en Lu 
PhD 
Dr. Lu is an associate professor in 
the department of epidemiology 
and biostatistics at the Rutgers 
School of Public Health. 
Co-Investigator/Statistician 
As co-investigator, Dr. Lu will assist 
with data management, statistical 
analysis and developing the final 
report 
Patricia Greenberg 
MS 
Ms. Greenberg is the administrative 
manager and senior biostatistician 
at the Rutgers School of Public 
Health. 
REDCap Developer and Statistician 
Ms. Greenberg will provide REDCap 
support and assist in data 
management. 
Vincent Ziccardi 
DMD, MD,  
Certificate in Oral 
and Maxillofacial 
Surgery  
Dr. Ziccardi is the chair of the Oral 
and Maxillofacial Surgery 
Department and has been involved 
in several analgesia pain studies. He 
will serve as a Clinical Co-
Investigator. 
Clinical Co-Investigator 
Clinical Co-Investigators are 
responsible for subject recruitment, 
determining eligibility, performing 
necessary treatment, providing 
patient instructions, and completing 
post-operative treatment.   
Brahmleen Kaur 
DMD 
Dr. Kaur is a faculty member in the 
department of Oral and 
Maxillofacial Surgery.  
Clinical Co-Investigator 
Clinical Co-Investigators are 
responsible for subject recruitment, 
determining eligibility, performing 
necessary treatment, providing 
PDMP 
Query
Surgery
Visit 2
(Day 5 to 15)
Visit 1 
(Day 1)
Post-Op
9 Days Later
(+/- 5 days)
Eligibility 
& Consent
Visit 0 
Same Day or
Up to 3 months (93 
days) later
Patient 
Completes Diary
30 days from Visit 1 
+/- 7 days)
For 7 Days
(Post-Op Day or 7 days 
whichever is less)

 
 
 
 
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patient instructions, and completing 
post-operative treatment.   
Megan Ogden 
BSN 
Ms. Ogden is a nurse in the Oral and 
Maxillofacial Surgery Clinic and will 
serve as Clinical Research 
Coordinator. 
Clinical Research Coordinator 
Ms. Ogden is a nurse in the Oral and 
Maxillofacial Surgery Clinic and will 
serve as Clinical Research Coordinator. 
Yosmery Garcia 
RDH 
Ms. Garcia is a dental 
hygienist/research coordinator at 
the Rutgers School of Dental 
Medicine and will serve as Clinical 
Research Coordinator.  
Clinical Research Coordinator 
Clinical Research Coordinator is 
responsible for subject recruitment, 
obtaining consent, providing patient 
instructions, completing REDCap 
forms, and administering subject 
surveys.    
Sandi Grace 
 
Ms. Grace is a dental student at the 
Rutgers School of Dental Medicine 
Data Quality Analyst 
Data Quality Analyst is responsible for 
reviewing the data for accuracy and 
completeness  
Jonathan Vacca 
 
Jonathan Vacca is an RSDM dental 
student 
Data Analyst  
Ayodeji Awopegba 
 
Ayodeji Awopegba is an RSDM 
dental student 
Data Analyst 
Anthony Bishoy 
Doss 
 
Anthony Bishoy Doss is an RSDM 
dental student 
Data Analyst 
Phase 2 Personnel 
Gary Warburton 
DDS, MS 
Dr. Warburton is a faculty member 
in the department of Oral and 
Maxillofacial Surgery at the 
University of Maryland, Baltimore.  
Dr. Warburton will serve as a 
Clinical Co-Investigator. 
Site Clinical Co-Investigator 
Clinical Co-Investigators are 
responsible for subject recruitment, 
determining eligibility, performing 
necessary treatment, providing 
patient instructions, and completing 
post-operative treatment.   
Jane Phillips 
MS 
Ms. Phillips is a research 
coordinator at the University of 
Maryland, Baltimore and will serve 
as Site Clinical Research 
Coordinator. 
Site Clinical Research Coordinator 
Site Clinical Research Coordinator is 
responsible for subject recruitment, 
obtaining consent, providing patient 
instructions, completing REDCap 
forms, and administering subject 
surveys.    
Michael Miloro 
DMD, MD 
Dr. Miloro is the Chair of the Oral 
and Maxillofacial Surgery 
Department at the University of 
Illinois at Chicago, College of 
Dentistry.  Dr. Miloro will serve as a 
Clinical Co-Investigator. 
Site Clinical Co-Investigator 
Clinical Co-Investigators are 
responsible for subject recruitment, 
determining eligibility, performing 
necessary treatment, providing 
patient instructions, and completing 
post-operative treatment.   
Susan Ferguson 
MS 
Ms. Ferguson is a research 
coordinator at the University of 
Illinois at Chicago and will serve as 
Site Clinical Research Coordinator. 
Site Clinical Research Coordinator 
Site Clinical Research Coordinator is 
responsible for subject recruitment, 
obtaining consent, providing patient 
instructions, completing REDCap 
forms, and administering subject 
surveys.    
Brent Ward 
DMD, MD 
Dr. Ward is the Chair of the Oral 
and Maxillofacial Surgery 
Department at the University of 
Site Clinical Co-Investigator 
Clinical Co-Investigators are 
responsible for subject recruitment, 
determining eligibility, performing 

 
 
 
 
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Michigan.  Dr. Ward will serve as a 
Clinical Co-Investigator. 
necessary treatment, providing 
patient instructions, and completing 
post-operative treatment.   
Jennifer Lay-Luskin 
Other 
Ms. Lay-Luskin is a research 
coordinator at the University of 
Michigan and will serve as Site 
Clinical Research Coordinator. 
Site Clinical Research Coordinator 
Site Clinical Research Coordinator is 
responsible for subject recruitment, 
obtaining consent, providing patient 
instructions, completing REDCap 
forms, and administering subject 
surveys.    
Hans Malstrom 
DDS 
Dr. Malstrom is the Chair of 
Eastman Dental’s General Dentistry 
Division at the University of 
Rochester.  Dr. Malstrom will serve 
as a Clinical Co-Investigator. 
Site Clinical Co-Investigator 
Clinical Co-Investigators are 
responsible for subject recruitment, 
determining eligibility, performing 
necessary treatment, providing 
patient instructions, and completing 
post-operative treatment.   
Rita Crosier 
Other 
Ms. Crosier is a research 
coordinator at the University of 
Rochester and will serve as Site 
Clinical Research Coordinator. 
Site Clinical Research Coordinator 
Site Clinical Research Coordinator is 
responsible for subject recruitment, 
obtaining consent, providing patient 
instructions, completing REDCap 
forms, and administering subject 
surveys.    
 
2.2 Research Staff Training 
Before patient recruitment begins, the principal investigator will meet with all Clinical Co-Investigators and the 
Clinical Research Coordinators to train them in the research protocol.  Included will be the training that must be 
provided to subjects so that they know how to complete their diaries.       
 
2.3 Resources Available 
For Phase 1, emergency services through the Rutgers School of Dental Medicine and University Hospital will be 
available.  For Phase 2 clinical sites, emergency services will be offered through the dental clinics at which care 
was provided. Note that surgical treatment and post-operative care is following normal standard of care. 
 
2.4 Research Sites 
Phase 1 
Subjects will be seen at the Rutgers School of Dental Medicine, Oral and Maxillofacial Surgery Clinic.  
 
Phase 2 
Subjects will be seen at the following clinical sites: 
o 
University of Maryland, School of Dentistry, Department of Oral and Maxillofacial Surgery 
o 
University of Illinois at Chicago, College of Dentistry, Department of Oral and Maxillofacial 
Dentistry 
o 
University of Michigan, School of Dentistry, Department of Oral and Maxillofacial Surgery  
o 
University of Rochester, Eastman’s School of Dentistry, General Practice Residency Clinic 
  
 
3.0 Multi-Center Research 
This pilot study is a single protocol that will be implemented at the following institutions: University of Maryland, 
School of Dentistry, Department of Oral and Maxillofacial Surgery, University of Illinois at Chicago, College of 
Dentistry, Department of Oral and Maxillofacial Dentistry, University of Michigan, School of Dentistry, 

 
 
 
 
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Department of Oral and Maxillofacial Surgery, and University of Rochester, Eastman’s School of Dentistry, 
General Practice Residency Clinic. 
 
4.0 Subject Considerations 
 
4.1 Subject Selection and Enrollment Considerations  
 
A. Method to Identify Potential Subjects 
The schedule for patients being seen at the dental school for 3rd molar extracts will be reviewed by study 
investigators so that study personnel can be present when the patients reports for a consult and inquire 
about interest in participating in the study.  The site may advertise for the study by word of mouth and/or 
advertising through flyers, social media, e-mail and/or ads in local/college newspapers. 
 
B. Recruitment Details 
The Clinical Co-Investigators will have identified patients presenting for impacted 3rd molar extraction.  A 
Clinical Co-Investigator will approach the patient and determine if he/she is interested in finding out about 
a clinical trial about pain medications.  After asking if the patient is interested in participating in the trial 
comparing the effectiveness of two pain medications, an explanation will be provided along with the 
consent form.  The patient will be provided 15 minutes to review the informed consent and then discuss it 
with the clinical co-investigator associated with the respective clinic.   
C. Subject Screening 
If after reviewing the informed consent and discussing the trial with the clinical co-investigator the patient 
is still interested in participating, the patient will be asked to sign the informed consent. Screening will be 
initiated to determine if inclusions criteria have been meet and no exclusion criteria exist which would 
exclude them from the study.  If during the eligibility process an exclusion is found, the patient will be 
deemed ineligible to participate. 
▪ 
Inclusion Criteria 
Adult men and non-pregnant women who are at least 18 years of age, who are able to refrain from 
driving or operating heavy machinery while taking the study medication will be able to participate.  
Subjects who are English speaking and are able to provide consent will be considered.  Subjects must 
be in generally good health and able to take ibuprofen, paracetamol (acetaminophen), and 
hydrocodone. 
▪ 
Exclusion Criteria 
Subjects who self-report the following history will be excluded from participating: 
• 
Individual under the age of 18 
• 
History of gastrointestinal bleeding and/or peptic ulcer 
• 
History of renal disease (excluding kidney stones) 
• 
History of hepatic disease 
• 
History of bleeding disorder 
• 
History of respiratory depression 
• 
Any prior respiratory effect of an opioid or other anesthetic drug that required respiratory support 
postoperatively 
• 
Active or untreated asthma 
• 
History of known allergic reaction to ibuprofen, acetaminophen, hydrocodone, and/or anesthesia 
• 
Currently taking any of the following medications: 
▪ 
CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal 
agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), which may increase 
plasma concentrations of hydrocodone bitartrate and acetaminophen and prolong opioid 
adverse reactions, and which may cause potentially fatal respiratory depression 
▪ 
CNS depressants. 
• 
Consumes 3 or more alcoholic drinks every day and/or has a history of alcoholism 

 
 
 
 
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• 
History of drug or alcohol abuse (excludes marijuana use) 
• 
Family history of drug or alcohol abuse in a first degree relative 
• 
Has had one or more opioid prescription filled within the past 6 months 
• 
Currently pregnant or lactating 
 
Patients would also be excluded due to any additional criteria that would place the individual at 
increased risk or preclude the individual’s full compliance with or completion of the study which 
includes: 
• 
Prior participation in this study 
• 
Inability or refusal to provide informed consent 
  
4.2 Secondary Subjects 
N/A 
 
4.3 Number of Subjects 
 
A. Total Number of Subjects 
Phase 1: A maximum of 24 subjects will be enrolled, 12 males and 12 females. 
Phase 2: A maximum of 8 subjects will be enrolled, 4 males and 4 females at each clinical site. 
 
B. Total Number of Subjects If Multicenter Study 
Total study enrollment: 56 subjects 
 
C. Feasibility 
Phase 1: The RSDM Oral and Maxillofacial Surgery Clinic has performed previous 3rd molar pain studies.  These 
studies have enrolled about 5 patients per week.  Thus it is not anticipated that there will be any problem 
recruiting 24 patients over a 2 month period enabling the study to be completed within 4 months. 
 
Phase 2: The other institutional sites are enrolling 8 patients each and, like RSDM, have adequate patient flow 
to meet the 8 subject enrollment over the student period. 
 
4.4 Consent Procedures 
 
A. Consent Process 
▪ 
Location of Consent Process 
Consent will be obtained while the patient is being seen in the dental clinic.  This is the same location 
in which informed consent is obtained for all dental procedures being performed at the dental school. 
▪ 
Ongoing Consent 
Study objectives, risks and benefits will be reviewed with the patient at the beginning of the Treatment 
Visit if the Treatment Visit is Separate from the Screening Visit and at the beginning of the Post-
Operative Visit.  While patients can withdraw their consent at any time, it is not expected that this will 
happen as the study protocol lasts for only 10 days.  Should a patient withdraw their consent, they will 
be instructed to immediately stop taking the study medication and return all unused medication to the 
Clinical Co-Investigator.  
▪ 
Individual Roles for Researchers Involved in Consent 
The Clinical Co-Investigators and the Research Coordinator will obtain the informed consent.   
▪ 
Consent Discussion Duration 
It is estimated that it will take about 10-15 minutes to discuss the study purpose and obtain informed 
consent. 
▪ 
Coercion or Undue Influence 
The Clinical Co-Investigators will be asked to emphasize that participation in this study protocol is 
purely voluntarily.  They will be told to emphasize, that the dental treatment they will receive will not 

 
 
 
 
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be influenced in any way by their participation or non-participation in the study.  Patients participating 
in this pilot study will not be given free care, thus limiting the possibility of coercion or undue influence. 
▪ 
Subject Understanding 
Subjects will be asked to summarize in their own words the purpose of the study, the risks and the 
benefits in order to ensure their understanding and willingness to participate.   
 
B. Waiver or Alteration of Consent Process  
▪ 
Waiver or Alteration Details 
N/A 
▪ 
Destruction of Identifiers 
N/A 
▪ 
Use of Deception/Concealment 
N/A 
a. Minimal Risk Justification 
N/A 
b. Alternatives 
N/A 
c. Subject Debriefing 
N/A 
 
C. Documentation of Consent 
▪ 
Documenting Consent 
Consent will be obtained by electronic signature in REDCap.  A printed copy of the signed consent will 
be provided to the patient.   
▪ 
Waiver of Documentation Of Consent (i.e., will not obtain subject’s signature) 
N/A 
 
4.5 Special Consent/Populations 
 
A. Minors-Subjects Who Are Not Yet Adults  
▪ 
Parental Permission 
N/A 
▪ 
Non-Parental Permission 
N/A 
▪ 
Assent Process 
N/A 
▪ 
Documentation of Assent 
N/A.  
▪ 
Reaching Age of Majority During Study 
N/A 
 
B. Wards of the State 
N/A 
▪ 
Research Outside of NJ Involving Minors 
N/A 
 
C. Non-English-Speaking Subjects 
Only English speaking subjects will be enrolled. 
▪ 
Process for Non-English-Speaking Subjects 
N/A 
▪ 
Short Form Consent for Non-English Speakers 
N/A 
 

 
 
 
 
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D. Adults Unable to Consent / Cognitively Impaired Adults (for interventional studies) 
N/A] 
▪ 
NJ Law-Assessment of Regaining the Capacity to Consent 
N/A 
▪ 
Capacity to Consent 
N/A 
a. NJ Law-Selecting A Witness  
N/A 
b. Removing a Subject 
N/A 
 
4.6 Economic Burden and/or Compensation for Subjects 
 
A. Expenses  
Subjects will not be responsible for any costs associated with this research or for any expenses above 
what they would normally be responsible for should they not be a participant in this research.   
 
B. Compensation/Incentives 
Subjects will receive $125 in compensation in the form of a Visa gift card to compensate for the time in 
completing all of the following: the pre-operative survey, e-Diary entries (at least the first 3 morning and 
3 evening entries), and the post-operative survey.   
 
C.  Compensation Documentation 
The principle investigator will obtain all payment cards. Subjects will provide an electronic signature (on a 
REDCap form) to indicate receipt of their payment card.  This will be done as the last question on the post-
operative REDCap survey form.   
 
4.7 Risks of Harm/Potential for Benefits to Subjects 
 
A. Description of Risks of Harm to Subjects 
▪ 
Reasonably Foreseeable Risks of Harm 
Each proposed analgesic has potential side effects.  These side effects include: 
• 
excessive fatigue or drowsiness 
• 
inability to concentrate 
• 
dizziness 
• 
euphoria (intense feeling of well-being & happiness) 
• 
headache  
• 
nausea 
• 
vomiting 
• 
diarrhea 
• 
constipation 
• 
stomach aches 
• 
heartburn 
• 
itching 
• 
skin rashes 
• 
urinary retention 
• 
unintentional weight gain 
Should these side effects become significant or bothersome, the patient will be instructed to stop taking 
the prescribed medication.   If additional analgesia is required, the subject will be instructed to call the 
emergency number.  Should the subject experience shortness of breath, or tachycardia, the subject will be 
instructed to immediately stop taking the study medication and call the emergency number.  Subjects will 
also be counseled on the addictive nature of opioids.   

 
 
 
 
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▪ 
Risk of Harm from an Intervention on a Subject with an Existing Condition 
All study analgesics are commonly used to control post-operative pain today.  To be eligible to 
participate, subject must meet all inclusion and not have any exclusion criteria.  Thus subjects with 
existing conditions are not eligible to participate.  
▪ 
Other Foreseeable Risks of Harm 
Opioids provided are minimal number of capsules and unused capsules will be collected to minimize 
the possibility of diversion.  Care provided will include a PMDP query 30 days after surgery. If an opioid 
prescription has been filled, the subject will be able to speak to an addiction counselor.  Other 
foreseeable risks may include risks associated with a possible loss of confidentiality.   
▪ 
Observation and Sensitive Information 
All information will be as confidential. . 
B. Procedures which Risk Harm to Embryo, Fetus, and/or Pregnant Subjects 
Third molar surgery is the standard of care for patients who require third molar removal. All study analgesic 
medication is part of normal standard of care for post-surgical pain management for men and for women 
who self-report not being pregnant.  Exposure is limited to a short post-operative period, generally 2-5 days 
as needed. 
 
While not a universal standard of care, female subjects will be required to take a point-of-service pregnancy 
test on the day of surgery to provide an extra level of safety.  Only females testing negative will be allowed 
to participate.  In addition, while not a standard of care, female subjects will be counseled on the 
importance of not becoming pregnant while taking study medication and that they should use some form 
of birth control if sexually active. Standard post-op procedures are being followed which includes a clinical 
exam at one week post-op. 
C. Risks of Harm to Non-Subjects 
Subjects will be instructed to not allow others, including members of their household, to use their study 
medication.   Medication will be dispensed with childproof caps.  If patients follow these instructions, there 
are no known risk to non-subjects.   
D. Assessment of Social Behavior Considerations 
Individuals who have an individual or immediate family history (parents, siblings, children or spouse) of 
substance abuse are not eligible to participate as subjects thereby minimizing any foreseeable risks. 
Subjects will be instructed to not allow others, including members of their household, to use their study 
medication.   Medication will be dispensed with childproof caps.  If patients follow these instructions, there 
are no known risk to non-subjects.  
E. Minimizing Risks of Harm 
To minimize risks, patients are being instructed to take their assigned analgesic medication only as needed 
after the first dose.  This will minimize exposure to subjects.  In addition, Individuals who have a personal 
or immediate family history (parents, siblings, children or spouse) of substance abuse are not eligible to 
participate as subjects thereby minimizing any foreseeable risks.   Subjects will be instructed to not allow 
others, including members of their household, to use their study medication.   Medication will be dispensed 
with childproof caps.  
▪ 
Certificate of Confidentiality 
A Certificate of Confidentiality will be issued automatically by NIH as the study utilizes identifiable, 
sensitive information. 
▪ 
Provisions to Protect the Privacy Interests of Subjects 
Data will be de-identified to protect subjects.  
F. Potential Benefits to Subjects 
There is no direct benefit to subjects. 
 
5.0 Special Considerations 
 
5.1 Health Insurance Portability and Accountability Act (HIPAA) 

 
 
 
 
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The following data will be utilized in this study: 
• 
Gender, race, ethnicity, age 
• 
Eligibility criteria 
• 
Pain levels, ability to sleep, ability to perform daily functions, overall satisfaction 
• 
Treatment procedures and treatment notes 
• 
Medications taken 
• 
Any opioid prescriptions filled after surgery 
 
As the study protocol includes the prescribing of an opioid, the state Prescription Data Monitoring Program (PDMP) 
database will be consulted before enrolling a subject into the study.  New Jersey, New York, Illinois, Michigan, and 
Maryland all currently have an operational PDMP that is collects data from dispensers and reporting information 
from the database to authorized users. The patient’s name and birth date is required for this inquiry.  The inquiry 
will be conducted by the Clinical Co-Investigator.  The subject’s number of previous opioid prescriptions will be 
recorded on the Subject Eligibility Form.  A second query will be done 30 days after surgery if the state PDMP allows.  
The PDMP query will be discussed with the subject during the consent process and subjects will consent to the 
prescription drug database will be queried 30 days after surgery on the research study consent form if permitted by 
state regulations. Study participants should be aware that opioids can be addictive. If the state’s Prescription Drug 
Monitoring Database query reflects an opioid being prescribed after the surgical visit, the subject will be offered the 
ability to talk to an addiction counselor. If state regulations prohibit a post-surgery PDMP query at 30 days, an email 
will be send to all subjects from that locale 30 days after surgery to remind them of the availability of an addiction 
counseling session if needed. 
 
The research team may use or share the subject’s information collected or created for this study with the following 
people and institutions: 
• 
Rutgers University Investigators Involved In the Study 
• 
The Rutgers University Institutional Review Board and Compliance Boards 
• 
Study personnel and institutional review boards form the following institutions: 
o 
University of Maryland, School of Dentistry 
o 
University of Illinois at Chicago, College of Dentistry 
o 
University of Michigan, School of Dentistry  
o 
University of Rochester, Eastman School of Dentistry 
• 
The Office for Human Research Protections in the U.S. Dept. of Health and Human Services 
• 
Federal Drug Administration 
• 
National Institutes of Health (NIH) - National Institute of Dental and Craniofacial Research (NIDCR) 
Those persons or organizations that receive your information may not be required by Federal privacy laws to protect 
it and may share your information with others without your permission, if permitted by the laws governing them.   
 
The subject’s name and birthday will be deleted 3 months after the last patient completes the protocol or 1 year 
from the date the first enrolled subject completed the protocol, whichever comes first.    
 
5.2 Family Educational Rights and Privacy Act (FERPA) 
N/A 
 
5.3 NJ Access to Medical Research Act (Surrogate Consent) 
N/A 
 
5.4 General Data Protection Regulation (GDPR) 
N/A  
 
5.5 Code of Federal Regulations Title 45 Part 46 (Vulnerable Populations) 
N/A 

 
 
 
 
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A. Special Populations 
▪ 
N/A 
 
6.0 Data Management Plan 
 
6.1 Data Analysis 
As the main purpose of this pilot study is to test the pragmatic study methodology, descriptive statistics 
including frequencies and means will be calculated for the independent and dependent variables.  No power 
analysis was completed. 
 
6.2 Data Security 
Study data will be collected using REDCap, a secure system housed on Rutgers University servers.  System access 
requires a NetID and is password protected.  Personal identifiers are required in order to contact the subject 
during the research protocol.  Links to personal identifiers (name, e-mail address, mobile phone number) will 
be deleted once all subjects have completed the protocol or a year from completing the first subject, whichever 
comes first. 
 
There could a breach of confidentiality but measures are in place to try and protect the subjects’ privacy.   
Provision of identifiable personal information will be limited to the log maintained should the need to un-blind 
the medication become necessary.  Once a patient is enrolled, a study ID code will be assigned and used on all 
study materials, eliminating the need to place identifiable information on the forms.  Thus, no other study 
material will not contain the patients name or any other identifiable information.  Once the study is completed, 
the log containing patient names will be shredded. 
 
All study personnel have taken both HIPAA and CITI training.  All paper records, including the informed consents, 
subject logs, screening forms, medication logs, and patient diaries, will be stored in the PI’s office in locked file 
cabinets.  Electronic data will only be stored on drives which follow university security policies.  Transmission of 
data will be through the RBHS e-mail system which transmits data in encrypted format.  Data will only be used 
on university computers which are password protected.   No identifiable patient information will be stored in 
any of the electronic files.   
 
6.3 Data and Safety Monitoring 
All Unanticipated problems (UP) and SAEs and will be reported to NIDCR, and the IRB.   
 
A. Data/Safety Monitoring Plan 
Subject record review activities are done in real-time via checks programmed into REDCap, as well as, manual 
reviews conducted by the Research Coordinator. 
 
Pre-programmed quality checks 
• 
Structured responses are required for the CRFs so only valid responses can be recorded.  In addition, 
REDCap has been programmed with all responses being required at time of completion.  
• 
Validation rules are employed where possible 
• 
Eligibility Criteria and Prohibited Medications: On the Eligibility Determination Form branching logic has 
been employed to sequentially review eligibility requirements and eliminate subjective eligibility scoring 
by the Research Coordinator 
o 
As an extra measure of quality control, before eligibility determination is started, the Research 
Coordinator will confirm the subject received a printed signed copy of the informed consent 
form.  This attestation is contained on the Eligibility Determination REDcap form.   
 

 
 
 
 
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Quality management activities will also include a real-time review of subject records, adherence to the protocol, 
adherence to onboarding of study personnel protocols, and proper tracking of study product.  These reviews will 
be conducted after the first 10 subjects have competed the protocol. As part of this record review audit, the 
Research Coordinator and the PI will review of all forms, questionnaires and case reports which make up a 
participant’s study record for the 10 subjects.  Results of the review and corrective actions will be provided in a 
summary report.  The data query process will be managed in REDCap via the Query Form and utilized to rectify 
identified issues in an appropriate time frame.   
 
AE and SAE Identification and Reporting:  Adverse events are expected due to the known nature of the FDA 
approved analgesics.  An adverse event will be documented the Adverse Event form while a serious adverse event 
(SAE) will be recorded on the Serious Adverse Event form in REDCap.  Likewise, unanticipated problems will be 
reported on the Unanticipated Problems Form in REDCap.  Protocol Deviations and violations will be recorded on 
the Protocol Deviation/Violation Reporting Form in REDCap.  Reporting information is found below: 
 
 
 
 
Characteristics of an Adverse Event 
Each event will be recorded on an appropriate case report form that includes assessment of the characteristics 
defined below. These characteristics, along with the frequency of an event’s occurrence, will be considered in 
determining if the event is an unanticipated problem. 
To assess relationship of an event to study intervention the following guidelines are used: 
1. 
Related (Possible, Probable, Definite) 
a.  The event is known to occur with the study intervention, and/or 
b.  There is a temporal relationship between the intervention and event onset and/or 
c.  The event abates when the intervention is discontinued, and/or 
d.  The event reappears upon a re-challenge with the intervention. 
2. 
Not Related (Unlikely, Not Related) 
a.  There is no temporal relationship between the intervention and event onset, and/or 
b.  An alternate etiology has been established. 
 
The Study PI and/or study-appointed, clinically/medically responsible individual will determine whether an AE 
is expected or unexpected. The following are considered expected adverse events (associated with known 
adverse events from the study product): 
a.  excessive fatigue or drowsiness 

 
 
 
 
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b.  inability to concentrate 
c.  dizziness 
d.  euphoria (intense feeling of well-being & happiness) 
e.  headache  
f.  nausea 
g.  vomiting 
h.  diarrhea 
i.  constipation 
j.  stomach aches 
k.  heartburn 
l.  itching 
m.  skin rashes 
n.  urinary retention 
o.  unintentional weight gain 
 
Other Adverse Events will be considered unexpected if the nature, severity, or frequency of the event is not 
consistent with the risk information previously described for the intervention.   
 
Severity of Adverse Event 
The severity of the adverse events will be graded by the extent to which the subject is bothered by the event.  
Subject will determine whether they were bothered by the event to a minor (no impact or minimal impact on 
activities of daily living and no intervention required) or major extent (moderate or significant impact on 
activities of daily living which may require the subject to stop taking the study analgesic or subject seeks medical 
attention.)   
Serious adverse events will be considered severe in extent as the symptoms are significant requiring 
hospitalization and invasive intervention. 
 
 
 
 
B. Data/Safety Monitoring Board Details 
N/A  
 

 
 
 
 
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6.4 Reporting Results 
 
A. Individual Subjects’ Results  
Individual subject results will not be made available. 
B. Aggregate Results 
Aggregate results will not be made available to the subjects as this is a pilot study to test out study 
methodology only.  
C. Professional Reporting 
Results of this study will be used to finalize methodology for grant documentation to NIH.  In addition, 
results of this pilot project may be published as abstract or journal articles and/or presented at professional 
meetings. 
D. Clinical Trials Registration, Results Reporting and Consent Posting 
This pilot study to test methodology.  All analgesics are FDA approved and are being used according to label. 
Thus, this protocol will not be registered on clinicaltrials.gov. 
6.5 Secondary Use of the Data    
There is no planned secondary use of the data. 
 
7.0 Research Repositories – Specimens and/or Data 
 
N/A 
 
8.0 Approvals/Authorizations 
 
HRP 1812 and SMART IRB are being used to obtain a reliance agreement. 
 
9.0 Bibliography 
 
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