The Efficacy of Local Anesthetics to Reduce Shoulder Pain Post-Steroid Injections
Phase: PHASE4
Conditions: Shoulder Pain
Sponsor: Milton S. Hershey Medical Center

Page 1 of 19 (V.08/18/2015) 
 
 
 
 
HRP-592 - Protocol for Human Subject  
Research with Use of Test Article(s) 
 
Protocol Title: 
The Efficacy of Local Anesthetics to Reduce Shoulder Pain Post-Steroid Injections 
 
 
Principal Investigator: 
Name: Robert Gallo, MD 
Department:  Orthopaedics and Rehabilitation 
Telephone: 531-5638 
E-mail Address: rgallo@hmc.psu.edu 
 
Version Date: 
2/8/2016 
 
Clinicaltrials.gov Registration #:  NCT02592629 
 
 

Page 2 of 19 (V.08/18/2015) 
Table of Contents 
1.0 
Objectives 
2.0 
Background 
3.0 
Inclusion and Exclusion Criteria 
4.0 
Recruitment Methods 
5.0 
Consent Process and Documentation 
6.0 
HIPAA Research Authorization and/or Waiver or Alteration of Authorization 
7.0 
Study Design and Procedures 
8.0 
Subject Numbers and Statistical Plan 
9.0 
Confidentiality, Privacy and Data Management 
10.0 
Data and Safety Monitoring Plan 
11.0 
Risks 
12.0 
Potential Benefits to Subjects and Others 
13.0 
Sharing Results with Subjects 
14.0 
Subject Stipend (Compensation) and/or Travel Reimbursements 
15.0 
Economic Burden to Subjects 
16.0 
Resources Available 
17.0 
Other Approvals 
18.0 
Multi-Site Research 
19.0 
Adverse Event Reporting 
20.0 
Study Monitoring, Auditing and Inspecting 
21.0 
Future Undetermined Research: Data and Specimen Banking 
22.0 
References 
 
 
 
 
 

Page 3 of 19 (V.08/18/2015) 
1.0 
Objectives 
 
1.1 
Study Objectives 
The specific aim of this prospective study is to determine whether local anesthetics prior to subacromial 
steroid injections reduce pain and consequently if they are cost-effective in the treatment for shoulder 
pathology. 
 
Hypothesis: Patients undergoing subacromial steroid injections without local anesthetics will have 
significantly increased pain than those who do use anesthetics prior to undergoing the injections. 
 
Standard of Care: Giving local anesthetics in addition to the steroid injection. Both of these treatment 
options are available to patients even if they are not undergoing the study. 
  
 
1.2 
Primary Study Endpoints 
The primary endpoint is to determine whether local anesthetics prior to subacromial injections reduce 
pain, quantified on a 1-10 pain scale. 
 
 
1.3 
Secondary Study Endpoints 
Not applicable 
 
2.0 
Background 
 
2.1 
Scientific Background and Gaps 
Shoulder pain is a common problem that can be estimated to be prevalent in up to 15 percent of the 
patient population registered to general practices and is second only to back pain in patients seeking 
treatment for musculoskeletal issues in the primary care setting. As a common source of distress, 
shoulder pain contributes significantly to health care costs. In the US, it directly attributes $7 billion to 
costs in the year 2000, with a mean cost per care episode of $1667 and $3011 for outpatient and 
hospital-based settings, respectively. 
 
Rotator cuff disease due to impingement, tendonitis or bursitis is a frequent cause of shoulder 
pain and dysfunction. Initial treatment consists of a conservative approach of activity modification, oral 
nonsteroidal anti-inflammatory drugs (NSAIDs) and supervised physical therapy. However, if the 
patients’ symptoms persist, subacromial injections of a local anesthetic such as lidocaine, and a 
corticosteroid may be indicated as a sequential treatment option. 
 
The steroid injection itself can be a painful process, so administering a local anesthetic prior to 
the steroid injection is thought to mitigate pain or reduce possible discomfort during and immediately 
following the procedure. A survey of 835 rheumatologists found that 74.7 percent of those who trained 
after 1985 combined lidocaine and steroids for soft tissue and joint injections. Though there is evidence 
advocating for the benefits of combining local anesthetics and corticosteroids for the treatment of 
subacromial pathologies, it is not conclusive whether local anesthesia prior to steroid injections 
significantly enhances the pain relieving effect of steroids. Should local anesthesia not have a significant 
impact on the patient’s pain intensity, then the use of corticosteroids alone could potentially result in 
reduced costs in care. 
 
2.2 
Previous Data 
Not applicable 
 

Page 4 of 19 (V.08/18/2015) 
2.3 
Study Rationale 
Though there is evidence advocating for the benefits of combining local anesthetics and corticosteroids 
for the treatment of subacromial pathologies, it is not conclusive whether local anesthesia enhances the 
pain relieving effect of steroids. Should local anesthesia not have a significant impact on the patient’s 
pain intensity as detected by self-assessment via pain scale, then the use of corticosteroids alone could 
potentially result in reduced costs in care. 
 
3.0 
Inclusion and Exclusion Criteria 
 
3.1 
Inclusion Criteria 
• 
Adults aged 18-70 
• 
Shoulder pain lasting at least 4 weeks  
• 
Inability to use arm with restriction of movement and loss of full function.  
• 
Able to understand study and provide voluntary, written informed consent 
 
3.2 
Exclusion Criteria 
• 
Less than 18 or greater than 70 years old 
• 
Contraindications of previous injections and previous shoulder surgery 
• 
Unable to understand consent form (in the opinion of the PI) 
• 
Non-English speaking individuals 
• 
Medication contradictions to lidocaine, corticosteroids 
 
3.3 
Early Withdrawal of Subjects 
 
3.3.1 
Criteria for removal from study 
Patients will be withdrawn from the study for safety reasons including severe adverse reactions, 
failure of subject to adhere to protocol requirements, or subject consent withdrawal. 
 
3.3.2 
Follow-up for withdrawn subjects 
The subjects may withdraw at any point prior to the steroid injection. Additionally, they may 
elect not to participate in rating their pain right after they receive the injections. Subjects who 
withdraw and prefer to have a lidocaine injection, may still participate in rating their pain after 
the lidocaine + steroid injection. Any subject who is getting steroid injections for shoulder pain 
may replace subjects who withdrew. 
 
4.0 
Recruitment Methods 
 
4.1 
Identification of subjects 
Subjects will be identified as part of their initial or routine evaluation by one of the study investigators in 
the Bone & Joint Institute.   
 
4.2 
Recruitment process 
If steroid injections are indicated for subjects with shoulder pathologies who come to the Orthopedics 
department, they will be asked to participate in the study. 
 
4.3 
Recruitment materials 
Not applicable. 
 

Page 5 of 19 (V.08/18/2015) 
4.4 
Eligibility/screening of subjects 
Adult patients presenting to the Bone & Joint Institute will be evaluated as part of standard of care.  
Those subjects meeting eligibility requirements will be presented with the opportunity to participate in 
the research study by a member of the research team. 
 
 

Page 6 of 19 (V.08/18/2015) 
5.0 
Consent Process and Documentation 
 
5.1 
Consent Process  
  
5.1.1 
Obtaining Informed Consent 
 
5.1.1.1 
Timing and Location of Consent 
Subjects presenting to the study investigator’s practice site as part of their initial 
or routine evaluation will be given the opportunity to participate in the research 
study.  Patients will be given information about the study and asked to 
participate.  If eligible, based on inclusion and exclusion criteria, informed 
consent will be obtained at the time of the screening visit and the patient will be 
enrolled in the study. 
 
5.1.1.2 
Coercion or Undue Influence during Consent 
Subjects will be given ample time to read and review the consent form on their 
own.  All questions the patient may have will be answered and written consent 
will be obtained.  A member of the research team will assist in the explanation 
and obtaining of the written consent.  A copy of the signed consent will be given 
to the patient and another copy sent to Medical Records. Subjects will be 
informed they do not have to participate in this research study. They will be 
informed that their current and future care at the PSHMC will not be affected by 
their decision to accept or decline participation. 
 
5.1.2 
Waiver or alteration of the informed consent requirement 
Requesting a waiver to screen for eligibility prior to the informed consent document being 
signed. 
 
5.2 
Consent Documentation 
 
5.2.1 
Written Documentation of Consent 
A member of the research team will assist in the explanation and obtaining of the written 
consent.  A copy of the signed consent will be given to the patient and another copy sent to 
Medical Records. 
 
5.2.2 
Waiver of Documentation of Consent (Implied consent, Verbal consent, etc.) 
Not applicable. 
 
5.3 
Consent – Other Considerations  
 
5.3.1 
Non-English Speaking Subjects 
Not applicable. 
 
5.3.2 
Cognitively Impaired Adults 
 
5.3.2.1 Capability of Providing Consent 
Not applicable. 
 
5.3.2.2 
Adults Unable To Consent 
Not applicable. 
 
5.3.2.3 Assent of Adults Unable to Consent 

Page 7 of 19 (V.08/18/2015) 
Not applicable. 
 
5.3.3 
Subjects who are not yet adults (infants, children, teenagers)  
 
5.3.3.1 Parental Permission 
Not applicable. 
 
5.3.3.2 Assent of subjects who are not yet adults 
Not applicable. 
 
6.0 
HIPAA Research Authorization and/or Waiver or Alteration of Authorization 
 
6.1 
Authorization and/or Waiver or Alteration of Authorization for the Uses and Disclosures of PHI 
 
Check all that apply: 
  
Not applicable, no identifiable protected health information (PHI) is accessed, used or 
disclosed in this study. [Mark all parts of sections 6.2 and 6.3 as not applicable] 
 
 
Authorization will be obtained and documented as part of the consent process. [If this is the 
only box checked, mark sections 6.2 and 6.3 as not applicable] 
 
 
Partial waiver is requested for recruitment purposes only (Check this box if patients’ medical 
records will be accessed to determine eligibility before consent/authorization has been 
obtained). [Complete all parts of sections 6.2 and 6.3] 
 
 
Full waiver is requested for entire research study (e.g., medical record review studies). 
[Complete all parts of sections 6.2 and 6.3] 
 
 
Alteration is requested to waive requirement for written documentation of authorization 
(verbal authorization will be obtained). [Complete all parts of sections 6.2 and 6.3] 
 
6.2 
Waiver or Alteration of Authorization for the Uses and Disclosures of PHI 
 
6.2.1 
Access, use or disclosure of PHI representing no more than a minimal risk to the privacy of the 
individual 
 
6.2.1.1 Plan to protect PHI from improper use or disclosure 
Information is included in the “Confidentiality, Privacy and Data Management” 
section of this protocol. 
 
6.2.1.2 Plan to destroy identifiers or a justification for retaining identifiers  
The list will be destroyed upon completion of the study. 
 
6.2.2 
Explanation for why the research could not practicably be conducted without access to and 
use of PHI 
Patient identifiers are necessary for identification and review of the patient’s medical records.  A 
unique study code number will be used for identification of study data.  The linking list will be 
destroyed upon completion of the study. 
 
6.2.3 
Explanation for why the research could not practicably be conducted without the waiver or 
alteration of authorization 
Waiver is required to screen for eligibility. 

Page 8 of 19 (V.08/18/2015) 
 
6.3 
Waiver or alteration of authorization statements of agreement 
Protected health information obtained as part of this research will not be reused or disclosed to any 
other person or entity, except as required by law, for authorized oversight of the research study, or for 
other permitted uses and disclosures according to federal regulations.  
 
The research team will collect only information essential to the study and in accord with the ‘Minimum 
Necessary’ standard (information reasonably necessary to accomplish the objectives of the research) 
per federal regulations.  
 
Access to the information will be limited, to the greatest extent possible, within the research team. All 
disclosures or releases of identifiable information granted under this waiver will be accounted for and 
documented. 
 
7.0 
Study Design and Procedures 
 
7.1 
Study Design 
The trial is a randomized,  prospective study. Patients undergoing steroid injections will be randomized 
into three groups:  
• 
Group A=Injection of 1 ml of 40 mg Kenalog combined with 4 ml of 1% lidocaine 
• 
Group B=Injection of 1 ml of 40 mg Kenalog combined with 4 ml of 1% lidocaine after 2 ml in 
subcutaneous injection 
• 
Group C=Injection of 1 ml of 40 mg Kenalog combined with 4 ml of 1% lidocaine after applying 
ethyl chloride spray for 3 seconds 
 
Patients’ pre and post-procedural pain as well as the pain of the injection itself will be assessed with a 
visual pain scale and the results will be analyzed for statistical significance.  
 
7.2 
Study Procedures 
The study consists of one visit in clinic during their standard of care visit. Patients will be given 
information about the study and asked to participate.  If eligible, based on inclusion and exclusion 
criteria, informed consent will be obtained at the time of the screening visit and the patient will be 
enrolled in the study.   
 
After obtaining informed consent, the patient will be asked to rate their current pain on a visual 1-10 
point scale before injection.  They will then be randomized to one of three treatment groups.  The study 
investigator will randomly draw a sealed envelope containing one of the three treatment groups.  The 
sealed envelopes will be stored in a secure area within the clinic practice site.  The subject will be 
randomized to one of three groups: 
• 
Group A=Injection of 1 ml of 40 mg Kenalog combined with 4 ml of 1% lidocaine 
• 
Group B=Injection of 1 ml of 40 mg Kenalog combined with 4 ml of 1% lidocaine after 2 ml in 
subcutaneous injection 
• 
Group C=Injection of 1 ml of 40 mg Kenalog combined with 4 ml of 1% lidocaine after applying 
ethyl chloride spray for 3 seconds 
 
The needle size will be standardized: 
• 
        25 gauge needle for the subcutaneous lidocaine injection 
• 
        21 gauge needle for the combined injection 
 
Immediately after and ten minutes after the injection is completed, they will also be asked to rate pain 
on the same 1-10 visual scale. 

Page 9 of 19 (V.08/18/2015) 
 
No long-term follow-up will be conducted. 
 
7.3 
Duration of Participation 
The subject will only be participating from the time they receive the injection to when they indicate the 
level of pain on the pain scale; i.e. they will be seen in the clinic site once. 
 
7.4 
Test Article(s) (Study Drug(s) and/or Study Device(s)) 
 
7.4.1 Description 
All of these drugs  and listed dosages are currently FDA approved and considered standard of 
care. 
 
Lidocaine hydrochloride injection: USP is sterile, nonpyrogenic, aqueous solution that contains a 
local anesthetic agents and is administered parenterally by injection. It is FDA approved and 
indicated for production of local or regional anesthesia by infiltration techniques such as steroid 
injections 
 
Ethyl Chloride spray: a vapocoolant (skin refrigerant) intended for topical application to control 
pain associated with injections. It is FDA approved. 
 
 
Kenalog Injection (triamcinolone acetonide): a synthetic glucocorticoid corticosteroid with anti-
inflammatory action. This formulation is FDA approved for intramuscular and intra-articular use 
only 
 
7.4.2 Treatment Regimen 
o Group A=Injection of 1 ml of 40 mg Kenalog combined with 4 ml of 1% lidocaine 
o Group B=Injection of 1 ml of 40 mg Kenalog combined with 4 ml of 1% lidocaine after 2 ml in 
subcutaneous injection 
o Group C=Injection of 1 ml of 40 mg Kenalog combined with 4 ml of 1% lidocaine after applying ethyl 
chloride spray for 3 seconds 
 
7.4.3 Method for Assigning Subject to Treatment Groups 
The subjects will be randomized by drawing a treatment group from a sealed envelope. 
 
7.4.4 Subject Compliance Monitoring 
Subject compliance monitoring is not necessary as there will only be 1 treatment protocol for 
this study. 
 
7.4.5 Blinding of the Test Article 
Not applicable. 
 
7.4.6 
Receiving, Storage, Dispensing and Return  
 
7.4.6.1 
Receipt of Test Article  
The compounds are used in the Bone & Joint Institute as standard of care.   
 
7.4.6.2 
Storage 
The compounds will be stored at room temperature in the Bone & Joint Institute 
as per standard of care instructions.  

Page 10 of 19 (V.08/18/2015) 
7.4.6.3 
Preparation and Dispensing 
The study drug will be prepared by an investigator following standard of care 
protocols. Subject randomization will be performed prior to dispensing of any 
study drugs. Once the needle is in the proper location, the solution of steroid 
will be injected slowly. A 2 mL solution of 1% lidocaine without epinephrine will 
be injected subcutaneously prior to the steroid injection if the subject is 
randomized into group B. If subject is in group C, ethyl chloride spray will be 
applied for 3 seconds prior the steroid injection. 
 
7.4.6.4 
Return or Destruction of the Test Article 
The study drug will be disposed of in clinic following standard procedure for 
disposal of needles. 
 
7.4.6.5 
 Prior and Concomitant Therapy 
No prior and concomitant therapy will be collected. 
 
8.0 
Subject Numbers and Statistical Plan 
 
8.1 
Number of Subjects 
            Approximately 150 subjects (50 per treatment arm). 
 
8.2 
Sample size determination 
The primary endpoint is the change in visual pain scale from baseline (pre-injection) to follow up (0- and 
10-minutes after injection).  The study contains 3 groups:   
o Group A=Injection of 1 ml of 40 mg Kenalog combined with 4 ml of 1% lidocaine 
o Group B=Injection of 1 ml of 40 mg Kenalog combined with 4 ml of 1% lidocaine after 2 ml in 
subcutaneous injection 
o Group C=Injection of 1 ml of 40 mg Kenalog combined with 4 ml of 1% lidocaine after applying ethyl 
chloride spray for 3 seconds 
 
Comparisons will be made for the primary outcome between all 3 study groups: Group B vs. A; Group C 
vs. A; and Group C vs. B.  Thus, we used a Bonferonni corrected Type I error rate for 3 tests to determine 
the sample size required for 80% power.   
 
A total of N=50 patients per group (N=150 total) yields 80% power for a t-test conducted at the 
Bonferonni corrected Type I error rate of 1.7%, which holds the overall Type I error rate for the study at 
5%, to detect a 2-point difference in pain scale changes between groups, assuming a common standard 
deviation of 3 points.  The standard deviation was calculated after making a conservative assumption 
that visual pain scores would be uniformly distributed across 0-10. 
 
8.3 
Statistical methods 
A one-way analysis of variance (ANOVA) model will be used to test whether changes in pain scores differ 
by study group. The outcome variable for the model will be the change in pain scores, and the 
independent variables will be indicators of each study group.  The overall F-test for study group will be 
used to determine whether study groups differ with respect to mean changes in visual pain scores.  If 
the F-test is significant, then follow up tests comparing each set of groups will be conducted using the 
Bonferonni-adjusted Type I error rate of 1.7%.    
 
9.0 
Confidentiality, Privacy and Data Management  
See the Research Data Plan Review Form 
 

Page 11 of 19 (V.08/18/2015) 
9.1 
Confidentiality 
 
9.1.1 
Identifiers associated with data and/or specimens 
 
9.1.1.1 Use of Codes, Master List 
 
9.1.2 
Storage of Data and/or Specimens 
 
9.1.3 
Access to Data and/or Specimens 
 
9.1.4 
Transferring Data and/or Specimens 
 
9.2 
Subject Privacy 
 
10.0 Data and Safety Monitoring Plan 
 
10.1 
Periodic evaluation of data 
The research coordinator will complete the appropriate report form and logs; assist the 
principal investigator to prepare reports and notify the IRB and any applicable reporting 
agencies of all unanticipated problems / adverse events. 
 
The research coordinator and principal investigator will confirm that all adverse events are 
correctly entered in the AE log; be available to answer any questions concerning AEs; notify the 
IRB and any applicable reporting agencies of unanticipated problems and AEs as appropriate.  
All assessments of AEs will be made by a licensed medical professional who is an investigator on 
the research. 
 
10.2 
Data that are reviewed 
Data to be reviewed includes incidence of adverse effects collected data. 
 
10.3 
Method of collection of safety information 
Not applicable. 
 
10.4 
Frequency of data collection 
Not applicable. 
 
10.5 
Individuals reviewing the data 
Not applicable. 
 
10.6 
Frequency of review of cumulative data 
There will be an interim analysis in this study after 50% of patients are enrolled and have completed all 
study requirements. Adverse events will be reviewed as they occur. 
 
10.7 
Statistical tests 
A one-way analysis of variance (ANOVA) model will be used to test whether changes in pain scores differ 
by study group. The outcome variable for the model will be the change in pain scores, and the 
independent variables will be indicators of each study group.  The overall F-test for study group will be 
used to determine whether study groups differ with respect to mean changes in visual pain scores.  If 
the F-test is significant, then follow up tests comparing each set of groups will be conducted using the 
Bonferonni-adjusted Type I error rate of 1.7%.   
 

Page 12 of 19 (V.08/18/2015) 
10.8 
Suspension of research 
There will be no stopping rules in this study as all medications are FDA approved and safe for patient 
use.   
 
If a patient, at any point in the course of their treatment demonstrates a significant adverse event 
related to the study medication, then the adverse event will be addressed. 
 
 

Page 13 of 19 (V.08/18/2015) 
11.0 Risks 
Loss of confidentiality will be minimized as the research team will only have access to the research data and all 
information will be kept in a shared research file in Hersheymed.net on a password-protected computer, in the 
Orthopaedic research office locked filing cabinets. 
 
Subjects will be assigned to a treatment program by chance. The treatment received may prove to be less 
effective or to have more side effects than the other research treatment(s) or other available treatments.   
 
Ethyl Chloride - freezing may alter skin pigment 
 
Kenalog - joint tissue damage, swelling in your veins, allergic reaction, infection, increase in blood sugar.   
 
Lidocaine - itching, rash, swelling of the skin, pain at the injection site, numbness, dizziness, and allergic 
reactions.  Rarely, when injected into the blood stream lidocaine can cause confusion, coma, seizures, 
respiratory arrest, heart beat irregularities, and toxicities; however, in this study lidocaine will not be injected 
into your bloodstream. 
 
Nerve damage for a period of time after the injection. 
 
12.0 Potential Benefits to Subjects and Others 
 
12.1 
Potential Benefits to Subjects 
The treatment received may prove to be less or more effective or to have more side effects than the 
other research treatment or other available treatments. 
 
12.2 
Potential Benefits to Others 
The potential benefit may be a way to reduce healthcare cost by decreasing the over-utilization of 
unnecessary materials/procedures. The results of this study will guide future treatment decisions. 
 
13.0 Sharing Results with Subjects 
            The results will not be shared. 
 
14.0 Subject Stipend (Compensation) and/or Travel Reimbursements 
Not applicable 
 
15.0 Economic Burden to Subjects 
 
15.1 
Costs  
All procedures are standard of care and will be billed to insurance. The subjects will be liable for any co-
pays, deductibles, or other fees associated with their insurance policy. 
 
15.2 
Compensation for research-related injury 
It is the policy of the institution to provide neither financial compensation nor free medical treatment 
for research-related injury. In the event of injury resulting from this research, medical treatment is 
available but will be provided at the usual charge. Costs for the treatment of research-related injuries 
will be charged to subjects or their insurance carriers.  
 

Page 14 of 19 (V.08/18/2015) 
16.0 Resources Available 
 
16.1 
Facilities and locations 
Research will be conducted at the Penn State Hershey Bone and Joint Institute. 
 
16.2 
Feasibility of recruiting the required number of subjects 
The Penn State Hershey Bone and Joint Institute cares for many patients with shoulder problems that 
need to get steroid injections to relieve pain. The PI does 1-2 injections per clinic and has 2 clinics a 
week. After 52 weeks the sample size would be around 150, which is above the 138 subject sample size 
calculated by the edited stats analysis.  
 
16.3 
PI Time devoted to conducting the research 
Dr. Gallo has research time determined in his agreement with the Orthopaedic Department.  
 
16.4 
Availability of medical or psychological resources 
If any medical or psychological care is needed for a subject, they will be directed for standard of care 
treatment at Hershey Medical Center. 
 
16.5 
Process for informing Study Team 
All team members have been given copies of all IRB approved documents – protocol, data collection 
tools, approval memos, etc.  The team meets regularly to review data and any updates. 
 
17.0 Other Approvals 
 
17.1 
Other Approvals from External Entities 
Not applicable. 
 
17.2 
Internal PSU Committee Approvals 
 
Check all that apply: 
  Anatomic Pathology – Hershey only – Research involves the collection of tissues or use of pathologic 
specimens. Upload a copy of the Use of Human Tissue For Research Form on the “Supporting 
Documents” page in CATS IRB. This form is available on the IRB website at: 
http://www.pennstatehershey.org/web/irb/home/resources/forms 
 
  Animal Care and Use – All campuses – Human research involves animals and humans or the use of 
human tissues in animals 
 
  Biosafety – All campuses – Research involves biohazardous materials (human biological specimens 
in a PSU research lab, biological toxins, carcinogens, infectious agents, recombinant viruses or DNA or 
gene therapy).  
 
  Conflict of Interest Review – All campuses – Research has one or more of study team members 
indicated as having a financial interest. 
 
  Radiation Safety – Hershey only – Research involves research-related radiation procedures. All 
research involving radiation procedures (standard of care and/or research-related) must upload the 
Radiation Review Form on the “Supporting Documents” page in CATS IRB. This form is available on the 
IRB website at: http://www.pennstatehershey.org/web/irb/home/resources/forms 
 

Page 15 of 19 (V.08/18/2015) 
  IND/IDE Audit – All campuses – Research in which the PSU researcher holds the IND or IDE or 
intends to hold the IND or IDE. 
 
  Scientific Review – Hershey only – All investigator-written research studies requiring review by the 
convened IRB must provide documentation of scientific review with the IRB submission. The scientific 
review requirement may be fulfilled by one of the following: (1) external peer-review process; (2) 
department/institute scientific review committee; or (3) scientific review by the Clinical Research Center 
Advisory committee.  NOTE: Review by the Penn State Hershey Cancer Institute Scientific Review 
Committee is required if the study involves cancer prevention studies or cancer patients, records and/or 
tissues. For more information about this requirement see the IRB website at: 
http://www.pennstatehershey.org/web/irb/home/resources/investigator  
 
18.0 Multi-Site Research 
 
18.1 
Communication Plans 
not applicable 
 
18.2 
Data Submission and Security Plan 
not applicable 
 
18.3 
Subject Enrollment 
not applicable 
 
18.4 
Reporting of Adverse Events and New Information 
not applicable 
 
18.5 
Audit and Monitoring Plans 
not applicable 
 
19.0 Adverse Event Reporting 
 
19.1 
Adverse Event Definitions 
 
 
Adverse event 
Any untoward medical occurrence associated with the use of the drug in 
humans, whether or not considered drug related 
Adverse reaction 
Any adverse event caused by a drug 
Suspected adverse 
reaction 
Any adverse event for which there is a reasonable possibility that the drug 
caused the adverse event.  Suspected adverse reaction implies a lesser degree of 
certainty about causality than “adverse reaction”. 
• 
Reasonable possibility.  For the purpose of IND safety reporting, 
“reasonable possibility” means there is evidence to suggest a causal 
relationship between the drug and the adverse event. 
Serious adverse 
event or Serious 
suspected adverse 
reaction 
Serious adverse event or Serious suspected adverse reaction: An adverse event 
or suspected adverse reaction that in the view of either the investigator or 
sponsor, it results in any of the following outcomes: Death, a life-threatening 
adverse event, inpatient hospitalization or prolongation of existing 
hospitalization, a persistent or significant incapacity or substantial disruption of 
the ability to conduct normal life functions, or a congenital anomaly/birth defect. 
Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered serious when, based upon appropriate 

Page 16 of 19 (V.08/18/2015) 
medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this 
definition.  
Life-threatening 
adverse event or 
life-threatening 
suspected adverse 
reaction 
An adverse event or suspected adverse reaction is considered “life-threatening” 
if, in the view of either the Investigator (i.e., the study site principal investigator) 
or Sponsor, its occurrence places the patient or research subject at immediate 
risk of death.  It does not include an adverse event or suspected adverse reaction 
that had it occurred in a more severe form, might have caused death. 
Unexpected 
adverse event or 
Unexpected 
suspected adverse 
reaction.   
An adverse event or suspected adverse reaction is considered “unexpected” if it 
is not listed in the investigator brochure, general investigational plan, clinical 
protocol, or elsewhere in the current IND application; or is not listed at the 
specificity or severity that has been previously observed and/or specified. 
 
 
 
For device studies, incorporate the following definitions into the below responses, as written: 
Unanticipated 
adverse device 
effect 
Any serious adverse effect on health or safety or any life-threatening problem or 
death caused by, or associated with, a device, if that effect, problem, or death 
was not previously identified in nature, severity, or degree of incidence in the 
investigational plan or IDE application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a 
device that relates to the rights, safety, or welfare of subjects. 
 
19.2 
Recording of Adverse Events 
All adverse events (serious or non-serious) and abnormal test findings observed or reported to study 
team believed to be associated with the study drug(s) or device(s) will be followed until the event (or its 
sequelae) or the abnormal test finding resolves or stabilizes at a level acceptable to the investigator. 
 
An abnormal test finding will be classified as an adverse event if one or more of the following criteria are 
met: 
• 
The test finding is accompanied by clinical symptoms 
• 
The test finding necessitates additional diagnostic evaluation(s) or medical/surgical intervention; 
including significant additional concomitant drug treatment or other therapy 
NOTE: Simply repeating a test finding, in the absence of any of the other listed criteria, does not 
constitute an adverse event. 
• 
The test finding leads to a change in study drug dosing or discontinuation of subject 
participation in the clinical research study 
The test finding is considered an adverse event by the investigator. 
 
19.3 
Causality and Severity Assessments 
The investigator will promptly review documented adverse events and abnormal test findings to 
determine 1) if the abnormal test finding should be classified as an adverse event; 2) if there is a 
reasonable possibility that the adverse event was caused by the study drug(s) or device(s); and 3) if the 
adverse event meets the criteria for a serious adverse event. 
 
If the investigator’s final determination of causality is “unknown and of questionable relationship to the 
study drug(s) or device(s)”, the adverse event will be classified as associated with the use of the study 
drug(s) or device(s) for reporting purposes.  If the investigator’s final determination of causality is 
“unknown but not related to the study drug(s) or device(s)”, this determination and the rationale for the 
determination will be documented in the respective subject’s case history. 
 

Page 17 of 19 (V.08/18/2015) 
19.4 
Reporting of Adverse Reactions and Unanticipated Problems to the FDA   
 
19.4.1 Written IND/IDE Safety Reports 
Not applicable. 
 
19.4.2 Telephoned IND Safety Reports – Fatal or Life-threatening Suspected Adverse Reactions 
Not applicable. 
 
19.5 
Reporting Adverse Reactions and Unanticipated Problems to the Responsible IRB 
In accordance with applicable policies of The Pennsylvania State University Institutional Review Board 
(IRB), the investigator will report, to the IRB, any observed or reported harm (adverse event) 
experienced by a subject or other individual, which in the opinion of the investigator is determined to be 
(1) unexpected; and (2) probably related to the research procedures. Harms (adverse events) will be 
submitted to the IRB in accordance with the IRB policies and procedures. 
 
19.6 
Unblinding Procedures 
Not applicable. 
 
19.7 
Stopping Rules 
The study will be stopped if one method is found to be clearly superior or if there are adverse reactions. 
 
20.0 Study Monitoring, Auditing and Inspecting 
 
20.1 
Study Monitoring Plan  
 
 
20.1.1 Quality Assurance and Quality Control 
Study data will be recorded and kept in a shared folder on hersheymed.net in a restricted file 
accessible by investigators on the study.  The Principal Investigator will oversee all aspects of the 
study including monitoring. 
 
20.1.2 Safety Monitoring 
The Principal Investigator will confirm that all adverse events (AE) are correctly entered into the 
AE case report forms by the coordinator; be available to answer any questions that the 
coordinators may have concerning AEs; and will notify the IRB, FDA, sponsor and/or DSMB of all 
applicable AEs as appropriate. All assessments of AEs will be made by a licensed medical 
professional who is an investigator on the research. 
 
The Research Coordinator will complete the appropriate report form and logs; assist the PI to 
prepare reports and notify the IRB, FDA and/or DSMB of all Unanticipated Problems/SAE’s. 
 
The Monitor will confirm that the AEs are correctly entered into the case report forms. The 
Monitor will also confirm that the adverse events are consistent with the source documents and 
are reported to the appropriate regulatory bodies as required. 
 
20.2 
Data and/or specimens being stored 
Regulatory work, paper copies of data, electronic copies of data. 
 
20.3 
Location of storage 
Paper regulatory work and data will be kept at 30 Hope dr. suite 2900 in locked files. 
Electronic data will be kept in hersheymed.net investigator accessible shared files. 
 

Page 18 of 19 (V.08/18/2015) 
20.4 
Duration of storage 
Data will be kept at least 6 years, and disposed as per the PI. 
 
20.5 
Access to data and/or specimens 
Data will only be accessible by investigators listed on the study. 
 
20.6 
Procedures to release data or specimens 
not applicable 
 
20.7 
Process for returning results 
not applicable 
 

Page 19 of 19 (V.08/18/2015) 
21.0 References 
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distress? Ann Rheum Dis 2002; 61: 128–131 
Steinfeld R, Valente RM, Stuart MJ. A common sense approach to shoulder problems. Mayo Clin Proc. 
199974(8):785–794. 
2. 
Johnson MP, Crossley KL, O’Neil ME, Al-Zakwani IS. Estimates of direct health care expenditures among 
individuals with shoulder dysfunction in the United States; Paper presented at the 2004 Annual Meeting of the 
American Society of Shoulder and Elbow Therapists; September 29–October 2, 2004; New York, NY. 
3. 
Burbank, K, Stevenson J, Czarnecki G, Dorfman J. Chronic Shoulder Pain: Part II. Treatment. Am Fam 
Physician. 2008 Feb 15;77(4):493-497. 
4. 
Radnovich R, Marriott T, Int J Gen Med. 2013; 6: 641–646. Published online 2013 July 30. doi: 
10.2147/IJGM.S47084 
5. 
Centeno LM, Moore ME. Preferred intraarticular corticosteroids and associated practice: a survey of 
members of the American College of Rheumatology. Arthritis Care Res. 1994;7(3):151–155. 
6. 
Arroll, B. and F. Goodyear-Smith (2005). "Corticosteroid injections for painful shoulder: a meta-analysis." 
Br J Gen Pract 55(512): 224-228. 
7. 
Yu, C. M., et al. (2006). "Subacromial injections of corticosteroids and xylocaine for painful subacromial 
impingement syndrome." Chang Gung Med J 29(5): 474-479. 
8. 
Gaujoux-Viala, C., et al. (2009). "Efficacy and safety of steroid injections for shoulder and elbow 
tendonitis: a meta-analysis of randomised controlled trials." Ann Rheum Dis 68(12): 1843-1849 
9. 
Gruson, K. I., et al. (2008). "Subacromial corticosteroid injections." J Shoulder Elbow Surg 17(1 Suppl): 
118S-130S  
10. 
van Riet, R. P., et al. (2012). "The long term effect of an intra-articular injection of corticosteroids in the 
acromioclavicular joint." J Shoulder Elbow Surg 21(3): 376-379. 
11. 
Gutierrez, G., et al. (2004). "Clinical inquiries. Does injection of steroids and lidocaine in the shoulder 
relieve bursitis?" J Fam Pract 53(6): 488-492. 
12. 
Price, R., et al. (1991). "Local injection treatment of tennis elbow--hydrocortisone, triamcinolone and 
lignocaine compared." Br J Rheumatol 30(1): 39-44. 
13. 
Stanton-Hicks, MD. Local anesthetics: Pharmacology and clinical applications. Hosp Formul 1987; 
22:156.