Clinical trial NCT04822597
Conditions: Breast Cancer Sentinel Lymph Node Breast Neoplasms Breast Cancer Female
Keywords: Sentinel Lymph Node Biopsy Sentinel Lymph Node Mapping Radioactive Tracer Injection Nuclear Medicine Radiocolloid Injection
Sponsor: University of Wisconsin, Madison
Start date: 2021-04-23; Completion date: 2022-05-09
Enrollment: 167 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to compare the effectiveness four different pain treatments for the injection of radioactive tracer that women with breast cancer receive for sentinel lymph node biopsies.

This study will include women who have been diagnosed with breast cancer and who will be undergoing sentinel lymph node biopsy with a standard injection of radioactive tracer before surgery.

A participant's active participation will take place on two separate occasions. In the first occasion, a participant will complete a brief pain assessment on the day of enrollment. The rest of a participant's active participation will take place on one day (the day of surgery) and last approximately 20 minutes, after which active participation will end.

Detailed description:
Primary Objective: To test the effectiveness of four alternative approaches to topical anesthesia on pain associated with radiotracer injection for women diagnosed with breast cancer undergoing sentinel lymph node mapping.

Secondary Objectives:

1. To assess patient satisfaction with pain control modality for radiotracer injection.
2. To identify barriers to implementation of the different pain control interventions.

Arms: arm 1: Ice will be placed on the breast prior to radioactive tracer injection (usual treatment) arm 2: A lidocaine patch (4% topical) will be placed on the breast for at least one hour prior to radioactive tracer injection arm 3: A vibrating distraction device (Buzzy(R)) and ice will be placed on the breast prior to radioactive tracer injection. arm 4: A lidocaine patch (4% topical) will be placed on the breast for at least one hour prior to radioactive tracer injection. This will be removed and a vibrating distraction device (Buzzy(R)) and ice will be placed on the breast just prior to radioactive tracer injection.
Interventions: intervention 1: Lidocaine patch intervention 2: Buzzy(R) intervention 3: Ice pack
Intervention descriptions: intervention 1: Lidocaine is a local anesthetic. intervention 2: Buzzy provides non-invasive pain relief by vibrating and cooling the skin which distracts from pain sensations. intervention 3: Ice cools the skin and can provide some numbing for pain.

Protocol documents:
Prot_SAP_001.pdf: 
1 
 
Optimizing topical pain control for breast cancer patients undergoing preoperative 
radiotracer injection for sentinel lymph node mapping: a randomized clinical trial 
Principal Investigator:  
Heather Neuman, MD, MS, University of Wisconsin School of Medicine and Public 
Health, Department of Surgery, Division of General Surgery 
 
Campus 
Address: 
600 Highland Ave, CSC H4/785D, Madison, WI 53792-7375 
Phone number: 
(608) 262-9060 
Fax: 
(608) 263-7652 
Email address: 
Neuman@surgery.wisc.edu 
 
Co-investigators: Lee Wilke, Laura Bozzuto, Jessica Schumacher, Meeghan Lautner, Scott 
Perlman 
 
Statistician: 
 
Study Coordinator: Alyssa Wiener 
 
Recruitment Personnel: Alyssa Wiener, Catherine Breuer, Grace McKinney 
 
Funding Sponsor: NIH Surgical Oncology Training Program T32 
 
Protocol Version Date: 5/2022 
 
NCT04822597 
 
 


2 
 
1. Project Summary 
We plan a randomized clinical trial comparing four user-friendly, non-invasive topical pain 
treatments, including a novel thermomechanical distraction technique, for breast cancer 
patients undergoing radiotracer injection for sentinel lymph node mapping. There is 
significant variability in how practices approach minimizing pain with radiotracer injection. 
Patients have identified this procedure as particularly painful out of all the procedures they 
undergo related to breast cancer treatment. To date, no best practice approach has been 
identified that is easily implemented into clinical workflows across practice types. Our 
objective is to identify a practical and widely adoptable solution to this persistent problem 
and improve the experience of breast cancer patients starting their treatment trajectory 
within the health system. 
2. Significance  
Each year, over 270,000 American women will be diagnosed with breast cancer, making it 
the most common non-cutaneous malignancy in this population (1). The majority of these 
women have localized disease and will undergo sentinel lymph node (SLN) biopsy for 
cancer staging, as the presence of axillary lymph node metastasis is one of the most 
important prognostic factors for early stage breast cancer. Unfortunately, preoperative 
radiotracer injection for axillary SLN mapping can be extremely painful for some breast 
cancer patients, the pain of which is often severely underestimated by physicians (2). 
Indeed, radiotracer injection has been identified by some patients as the most painful 
experience in the operative day including surgery itself (3). The field of breast surgery has 
made large strides in improving patient experiences of breast surgery, including improving 
localization methods for breast conservation and incorporating regional blocks for the 
operative procedure. However, the pain with preoperative radiotracer injection remains 
distressing for patients. In order to enhance the experience of already anxious patients 
facing breast surgery, it is imperative that we identify methods to optimize pain control. 
Patient experience is an important component of the overall quality of health care and is 
essential for building positive relationships between patients and providers (4). These 
experiences and relationships are especially critical for breast cancer patients who are often 
only starting their treatment trajectory within the healthcare system.  
 
3. Background 
3.1 Periareolar radiotracer injection is the preferred method for SLN identification in 
breast cancer patients (5) but is extremely painful. In current practice, there is wide 
variability on pain management for radiotracer injection with no clear gold-standard. 
Intraoperative injection after initiation of surgical anesthesia would likely minimize pain the 
most. However, although some centers have successfully incorporated intraoperative 
injection of radiotracer into clinical flow (6–8), there are significant implementation 
challenges with this approach, including constraints associated with handling of radioactive 
material and coordination with nuclear medicine staff. For most centers, pre-operative 
injection is a necessity (8).  
 
3.2 Prior studies have demonstrated that the injection of local anesthetic such as 
lidocaine significantly reduces pain associated with subsequent or concomitant 
radiotracer injection (9–11) but may also reduce success of lymphatic mapping 
(Table). While the reduction in pain scores with lidocaine injection is encouraging, studies 
have reported mixed results regarding success of SLN identification (9–11). The largest and 
most recent randomized controlled trial demonstrated markedly lower mapping rates for 
patients receiving lidocaine injections. Furthermore, some of the studies utilized special 
preparations of lidocaine along with the radiotracer, something not feasible for many 


3 
 
practices. As a result, many nuclear medicine radiologists and surgeons are uncomfortable 
using injectable lidocaine and instead rely on topical anesthesia for the radiotracer injection 
(12).  
Table. Summary of Existing Literature on SLN Mapping Rates after Lidocaine Injections 
Author 
Design 
Study 
years 
Sample size Method 
SLN Mapping 
rates 
Stojadinovic 
et al. 
Randomized 
controlled 
trial 
2006-2009 
140 
Prepared 
mixture of 
lidocaine and 
radiotracer (+/- 
bicarbonate) 
injected 
subarerolar 
• 96% EMLA 
cream,  
• 97% sodium 
bicarbonate  
• 90% 1% 
lidocaine 
• 90% 1% 
lidocaine + 
sodium 
bicarbonate 
Stearns et 
al. 
Prospective 
cohort with 
historical 
control 
Prospective 
2011-
2012 , 
historical 
2005-2009 
110 
prospective, 
187 
retrospective 
2cc of 1% 
lidocaine 
injected 
subareolar prior 
to radiotracer 
• 95% 1% 
lidocaine 
• 94% historical 
control 
Hawkins et 
al. 
Randomized 
controlled 
trial 
2009-2010 
49 
6cc of 2% 
buffered 
lidocaine 
injected 
subcutaneous 
• 79% control 
• 72% 1% 
lidocaine + 
sodium 
bicarbonate 
3.3 No topical anesthetic has been proven to be superior for controlling pain associated 
with radiotracer injection. Topical anesthetics such as lidocaine-prilocaine cream (EMLA) 
have limited benefit compared to placebo (13–16). To date, there have been no studies 
investigating the efficacy of an anesthetic patch (e.g. 5% lidocaine) or non-pharmacologic pain 
management for this procedure. Thus, there is still a need to investigate a practical, effective, 
and broadly adoptable intervention that will reduce the distress associated with preoperative 
radiotracer injection in breast cancer patients.  
 
3. 4 Preliminary observations 
Options for topical anesthetic: Institutionally and in the literature, EMLA cream does not appear 
to reduce pain with radiotracer injection (13–15). The nuclear medicine department at our 
institution discontinued the use of EMLA due to perceived lack of efficacy and workflow 
challenges associated with implementing EMLA application into practice (which may have 
impacted effectiveness).  
The current standard of care at our institution is application of ice to the breast before 
radiotracer injection. Application of ice to the breast has not been directly studied in the setting 
of radiotracer injection, but ice and topical vapocoolant sprays have been found to reduce the 
pain of procedures such as venous and arterial cannulation in adults (17–20). According to 
breast cancer providers at our institution, patients continue to report significant pain with the 
procedure when ice is used as the topical anesthetic.  


4 
 
Lidocaine patches, in contrast to EMLA, are easier for patients and providers to apply and have 
demonstrated efficacy in neuropathic pain as well in aesthetic procedures (21–23). This 
represents a potential option for a topical anesthetic. 
Novel intervention for procedural pain: Topical high frequency vibration combined with topical 
cooling is a novel method to alleviate acute procedural pain. It has been studied and 
implemented largely in the pediatric population. It is thought that mechanoreceptor and noxious 
thermal inhibitory stimulation alter normal pain conduction pathways and offers better pain 
control than cooling alone (24). This combined approach has been found to significantly reduce 
the pain and distress of venipuncture (25). This intervention is the most commonly used non-
pharmacologic intervention for venipuncture pain within our institution’s Children’s Hospital with 
good anecdotal success in reducing pediatric pain. The literature in the adult population of 
combined vibration and cold therapy is much scarcer, but preliminary data suggests that this 
intervention is beneficial especially in those with greater pre-procedural anxiety and is superior 
to cooling alone (24). A combination of vibration and cooling has not been widely implemented 
in our adult population for any acute procedural pain, making it an underexplored and promising 
area of study. Our initial observations are that application of this type of vibration to the 
periareolar breast and even nipple areolar complex is tolerable.      
4. Study Objective and Specific Aims 
Primary Objective: To test the effectiveness of four alternative approaches to topical anesthesia 
on pain associated with radiotracer injection for women diagnosed with breast cancer 
undergoing sentinel lymph node mapping. 
 
Secondary Objectives: 
1. To assess patient satisfaction with pain control modality for radiotracer injection.  
2. To identify barriers to implementation of the different pain control interventions.  
 
5. Research Design and Methods 
5.1 Study Overview and Schema 
This is a randomized clinical trial testing the effectiveness of four alternative approaches to 
topical anesthesia for radiotracer injections for women diagnosed with breast cancer undergoing 
sentinel lymph node mapping. We will test two types of topical anesthetic (ice and lidocaine 
patch) with and without the addition of a topical high frequency vibration device (always 
combined with cooling). Ice is our control group as it reflects current standard of care at our 
institution.  
 
 
Patient schema 


5 
 
 
 
 
 
Nuclear Medicine Provider schema 
 
 
 
 
 
 
 
 
 
 
5.2 Selection of Participants 
Inclusion criteria: 
• 
≥ 18 years of age 
• 
biopsy proven breast cancer 
• 
planned standard radiotracer injection (intradermal injection in the upper outer quadrant 
of the involved breast) for sentinel lymph node biopsy in the nuclear medicine 
department on the same day as surgery; standard versus non-standard injection is 
determined by the surgeon based on patient history at the time of procedure scheduling 
Exclusion criteria: 
• 
males 
• 
pregnancy 
• 
local anesthetic allergy or active use of the following medications 
• 
Abametapir (risk X) 
• 
Conivaptan (risk X) 
• 
Fusidic Acid (risk X) 
• 
Idelalisib (risk X) 
Nuclear Medicine 
Faculty Caring for  
Consented Patient 
care 
End of patient 
recruitment  
End-of-study survey 
(nuclear medicine faculty) 
Baseline pain 
assessment 
Nuclear Medicine 
Provider 
Technologist 
Caring for 
Consented Patient 
Post-procedural provider surveys 
after injection on each consented 
patient  
(nuclear medicine technologist) 
End of patient 
recruitment  
End-of-study survey 
(nuclear medicine 
technologists) 


6 
 
• 
Mifepristone (risk D) 
• 
Stiripentol (risk D) 
• 
Amiodarone (risk C) 
• 
Dofetilide (risk C) 
• 
Dronedarone (risk C) 
• 
Ibutilide (risk C) 
• 
Sotalol (risk C) 
• 
Vernakalant (risk C) 
• 
Non-English speaking/reading 
• 
Unable to provide informed consent 
• 
Unable to participate with surveys 
• 
Undergoing radiotracer injection the day prior to surgery or intra-operatively at the time 
of initial surgical scheduling 
o If patients are initially scheduled for same-day preoperative injection, complete all 
enrollment procedures (including randomization), and surgery is re-scheduled for 
a day prior to surgery or for intra-operative injection, they will be excluded if: 
 
randomized to a lidocaine patch arm (Arms C or D)re-scheduled for an 
intra-operative injection 
• 
Planned non-standard radiotracer injection site 
5.3 Screening and recruitment: 
Screening: 
Introduction of the study: Patients being cared for by breast surgeons within the UW Breast 
Center will be eligible for consideration. Clinic schedules will be reviewed in advance by the 
study team to screen for patients meeting eligibility criteria. Breast surgeons will identify 
additional eligible patients and confirm eligibility of patients identified on study team screening. 
Potential participants will be informed about the study by a member of their clinical care team at 
a standard of care visit or during a standard care phone call. Those interested in learning more 
will be contacted by a member of the study team to further discuss the study.   
Recruitment: 
The study team will offer all interested patients a study information packet (study information 
sheet, consent form, and baseline Wong-Baker FACES pain rating scale). Interested patients 
can receive the packet via email, mail, or in-person at a UWHC visit, according to their 
preference. Only study team members will provide these materials to interested patients and/or 
conduct in-depth discussion of the study. The study team will only email a link or electronic 
information packet after discussion of the inherent risks of email transmission of information and 
the patient has verbally consented to email receipt of this information.  
Patients will be informed that final study eligibility will be determined based on the final 
scheduling of their surgical procedure, specifically whether the radiotracer injection is the same 
day as the surgery. 


7 
 
The study team will review the operating room schedules to identify patients undergoing 
standard preoperative radiotracer injection for sentinel lymph node mapping on the same day as 
breast surgery. 
Interested patients who are fully eligible will be contacted by study team members to further 
discuss the study and consent. 5.4 Consent process: 
5.4.1 Patient consent 
We request a waiver of signed consent and alteration of HIPAA authorization such that 
participant signature is not required for consent and authorization. Informed consent will be 
verbally obtained and documented prior to any research activities. After a patient expresses 
desire to enroll, informed consent will be obtained. Patients will have already received a copy of 
the informed consent and authorization document. If a new copy is required, this will be emailed 
or mailed to the patient based on their preference. If the patient will be at the hospital or clinic 
for another reason, they can also obtain a copy of the consent and authorization from the study 
team at that time. As much time as needed will be given for potential subjects to decide whether 
or not to participate in this study. Subjects will be informed that they are not obligated to 
participate in the study.   
 
Waiver of signed consent: 
The research presents no more than minimal risk of harm to subjects and involves no 
procedures for which written consent is normally required outside of the research context. Use 
of lidocaine patches and the Buzzy device for local pain control are not procedures that require 
written consent under non-research settings. Similarly, the surveys in this protocol present low 
psychological risk and would not require written consent under a non-research setting. The 
waiver of signed consent will not adversely affect the rights and welfare of subjects. The 
research cannot be practicably carried out without waiver of signed consent. Not all participants 
will enroll at the time of initial clinic visit. For patients who choose to enroll remotely over the 
phone, the short time between surgical scheduling and surgery date impedes their ability to 
return a signed consent before their surgery date and therefore formally enroll in the 
study. Subjects will be provided with a consent document to guide the informed consent process 
and will be given the opportunity to have all questions answered.    
 
Alteration of HIPAA Authorization: 
The use of protected health information involves no more than minimal risk to the privacy of 
individuals. Data privacy practices will protect identifiers from improper use and disclosure (see 
11 Records to be kept, Privacy, and Confidentiality). Identifiers will be destroyed at the earliest 
opportunity consistent with research conduct. Participants will receive a consent and 
authorization document for their records detailing how protected information will not be reused 
or disclosed. Research cannot be practicably conducted without the alteration of HIPAA 
authorization. Not all participants will enroll at the time of initial clinic visit. For patients who 
choose to enroll remotely over the phone, the short time between surgical scheduling and 
surgery date impedes their ability to return a signed authorization before their surgery date and 
therefore formally enroll in the study. The research cannot be practicably conducted without 
access to and use of protected health information. Protected health information is required to 
access participant medical records for data elements of medical/surgical history and surgery 
data.    
 


8 
 
Consent can occur in one of the following ways: 
1) In-person in the breast center: If the patient agrees to participate in the study after 
discussing with the breast surgeon and would like to undergo informed consent at the 
time of their clinic consultation, informed consent will be obtained in a closed, private 
room by a member of the study team at the Breast Center. A verbal consent and 
authorization will be obtained and documented. The patient will be given a copy of the 
consent form for their records. Patients will be informed that their final study eligibility will 
be determined after the surgery is scheduled and it is confirmed that the radiotracer 
injection will happen on the same day as surgery.   
2) In-person at another location in the hospital or clinic: If the patient agrees to participate 
and has another appointment at the UW hospital and clinic, the study team can meet 
with the patient to obtain informed consent. The consent would be obtained in a closed, 
private location by a member of the study team. A verbal consent and authorization will 
be obtained and documented. The patient will be given a copy of the consent form for 
their records. 
3) By telephone:  The study team will review details of the study with the patient. Patient 
identity will be verified by verbally stated full name and date of birth. A verbal consent 
and authorization will be obtained and documented. 
 
 
Subjects will receive a copy of the consent form and will be given contact information for study 
coordinator and PI for any additional questions. 
 
5.5 Randomization: 
After consent for enrollment has been obtained and eligibility confirmed, patients will be 
randomized to one of four intervention arms. Patients will be stratified by whether or not they are 
scheduled to undergo a breast radiology procedure (eg. wire localization, seed localization, 
elucent clip) prior to nuclear medicine injection. Treatment group allocation will be 
communicated to nuclear medicine providers with a colored paper printout that travels with the 
patient on the day of surgery.  
 
5.6 Study procedures: 
Intervention Arms 
Intervention Group A (control and current standard of care)- Topical cooling: An ice pack will be 
applied to the upper outer quadrant of the areola/breast for 1.5 minutes immediately prior to 
radiotracer injection(s). 
Intervention Group B- Topical cooling plus vibration distraction device application: An ice pack 
will be applied to the upper outer quadrant of the areola for 1.5 minutes immediately prior to 
radiotracer injection. For the last minute, the vibrating distraction device (Buzzy®) will be placed 
over the ice. The vibrating distraction device (Buzzy®) will be moved lateral at the time of the 
surgical prep but kept on the breast during the injection. In the event that a patient requires 
additional injections for adequate mapping, as determined by the image interpreting staff, the 
Buzzy® and ice treatment will be repeated prior to each additional injection. 
Intervention Group C- lidocaine patch: A 4% lidocaine patch will be applied in the preoperative 
holding area to the upper outer quadrant at least 1 hour prior to radiotracer injection. Lidocaine 


9 
 
patches will be prescribed at the time of study enrollment. If a patient arrives for injection and 
does not have a lidocaine patch in place, they will be treated according to the standard of care 
(ice). In the event that a patient requires additional injections for adequate mapping, as 
determined by the image interpreting staff, the patient will receive the standard of care treatment 
(ice) prior to each additional injection. 
Intervention Group D- lidocaine patch along with topical cooling plus vibration distraction device: 
A 4% lidocaine patch will be applied in the preoperative holding area to the upper outer 
quadrant at least 1 hour prior to radiotracer injection. The patch will be removed and the ice 
pack will be applied for 1.5 minutes prior to prep. For the last minute, the vibrating distraction 
device (Buzzy®) will be placed over the ice. The vibrating distraction device (Buzzy®) will be 
moved lateral at the time of the surgical prep but kept on the breast during the injection. 
Lidocaine patches will be prescribed at the time of study enrollment. If a patient arrives for 
injection and does not have a lidocaine patch in place, they will be treated with the Buzzy® and 
ice intervention prior to injection. In the event that a patient requires additional injections for 
adequate mapping, as determined by the image interpreting staff, the Buzzy® and ice treatment 
will be repeated prior to each additional injection. 
 
Device: 
Buzzy®: The Buzzy® device is IDE exempt under 21 CFR Part 812.2(c)(2) as an approved 
device being investigated in accordance with its labeling. Buzzy® has received FDA 510(k) 
clearance for pain control with injections. Buzzy® is a battery-powered device that produces 
high frequency vibration and is to be combined with a cooling element (e.g. ice pack) when 
applied to the skin for pain control. Buzzy® is thought to work by simultaneous stimulation of 
mechanoreceptor and noxious thermal inhibitory neurons which together modulate the 
transmission of pain.(26) 
Drug: 
Lidocaine patch 4% OTC: The patch provides 4g of lidocaine per 100g patch and is applied to 
the skin. This drug is exempt from IND 21 CFR Part 312.2(b)(1) as a lawfully marketed drug 
used in clinical investigation. This study is not intended to identify a new indication for the drug 
or for change in drug labeling. This investigation does not involve a route of administration or 
dosage level or use in a patient population or other factor that significantly increases the risks 
(or decreases the acceptability of the risks) associated with the use of the drug product. The 
dosage level used in the study is the standard dosage level of one patch of 4% lidocaine. The 
route of administration is the approved topical route of administration. The patient population in 
the study is not at increased risk from the drug related to any specific population factors.   
5.6.1 Surgical re-scheduling: 
If a participant is enrolled after meeting all eligibility criteria but the surgery is rescheduled, the 
participant’s surgery date eligibility will be re-evaluated. If the participant is rescheduled for 
surgery with same-day preoperative nuclear medicine injection, then study procedures will be 
carried out per protocol. If the participant is rescheduled for surgery with intraoperative nuclear 
medicine injection, she will be withdrawn from the study as she will be unable to undergo study 
procedures. If the participant is rescheduled for surgery with a day-before surgery nuclear 
medicine injection she will undergo study procedures only if she was originally randomized to 
either the ice (arm A) or the ice + buzzy (Arm B) arms. If the participant is rescheduled for 


10 
 
surgery with a day-before surgery nuclear medicine injection she will be withdrawn from the 
study if she was originally randomized to either the lidocaine patch (arm C) or the lidocaine 
patch + ice + buzzy (Arm D) arms as lidocaine patches cannot be administered the day before 
surgery for logistical reasons. 
5.7 Data Collection:  
5.7.1 Patient-level data collection: 
Patient surveys: Patients will complete one brief pain assessment and one survey during the 
study period.  
Baseline pain assessment: Patients will complete a baseline pain assessment at the time of 
enrollment using the Wong-Baker FACES pain rating scale (Appendix A). The patients will have 
been given the Wong-Baker FACES pain rating scale at the time of their initial clinic visit. They 
will be referred to this scale during the enrollment phone call, and baseline pain score will be 
recorded.  
Post-procedural survey: Patients will also complete a brief survey (<10 minutes) after the 
radiotracer injection but before initiation of anesthesia (Appendix B). Patients should complete 
the survey within three hours of receipt of radiotracer injection. This will either occur in the 
nuclear medicine suite or in the preoperative holding area with an iPad device or paper/pen. 
This post-procedural survey has intentionally been kept brief to decrease patient burden, which 
is especially critical as it will be completed on the day of surgery. 
 
Chart review: We will record information including: age, race/ethnicity, medical history of chronic 
pain or fibromyalgia (yes/no), history of prior breast and axillary procedures (biopsy, surgery), 
history of prior breast cancer, active narcotic or other pain medication usage (over the past 
week, use of narcotics including tramadol at least twice weekly and/or daily use of Tylenol, 
NSAIDs, gabapentin, and/or amitriptyline), breast cancer laterality, tumor histology, grade and 
size, clinical and pathologic AJCC 8th edition cancer stage, hormone receptor status (estrogen 
receptor, progesterone receptor, Her2neu), and receipt of neoadjuvant chemotherapy. 
Additionally, we will record any pain medications taken on the day of surgery prior to the arrival 
to nuclear medicine (narcotics, Tylenol, NSAIDs, gabapentin, amitriptyline), the time of lidocaine 
patch application, breast radiology procedure prior to nuclear medicine injection, and sentinel 
lymph node identification on pathology report. We will also record type of radiotracer received.  
 
5.7.2 Provider-level data collection: Nuclear medicine staff surveys: Nuclear medicine 
technologists will be asked to complete two sets of surveys. Nuclear medicine faculty will be 
asked to complete the end-of-study survey only. 
Post-procedural survey: The first survey will be to assess the nuclear medicine technologists’ 
immediate perception of the ease of administration of the intervention and the patient’s post 
procedural pain (Appendix D). Each post-procedural survey will be linked to the patient study ID. 
This will be completed by the technologist assisting with each enrolled patient.  
 
Nuclear Medicine Technologists will be providing ancillary and/or standard of care services that 
are within their normal scope of clinical practice. As part of their normal scope of practice and 
standard of care, technologists assist Nuclear Medicine MD, DOs with radiotracer injections and 
associated pain control/pain mitigation procedures. Technologists who assist with study 
participants will be included in the study team. 
 


11 
 
End-of-study survey: We will also administer a brief survey at the end of the trial to the nuclear 
medicine faculty and technologists involved in the radiotracer injection and associated pain 
control for patients on the trial. The nuclear medicine faculty and technologists will be the staff 
most consistently involved in the injections throughout the study time period and therefore would 
be most reliably able to reflect on implementation of the interventions. (Appendix E). 
Nuclear Medicine faculty are ultimately responsible for and supervise each radiotracer injection 
and associated pain control. They serve an integral role in the conduct of research-specific 
study procedures and are included in the study team.  
  
 
 


12 
 
5.8 Schedule of Events 
 
Time of 
new breast 
cancer 
diagnosis 
First clinic 
visit with 
breast 
surgeon 
Telephone 
call after 
first clinic 
visit & 
surgical 
scheduling 
Following 
radiotracer 
injection 
Following 
final 
surgical 
procedure 
Following 
study 
accrual 
Assess inclusion/exclusion 
criteria 
X 
X 
X 
 
 
 
Introduce study, offer 
participation 
 
X 
X 
 
 
 
Verbal consent and 
authorization ) 
 
X 
X 
 
 
 
Baseline pain assessment 
 
X 
X 
 
 
 
Post-procedural patient 
survey 
 
 
 
X 
 
 
Assessment of sentinel 
lymph node identification 
via chart review 
 
 
 
 
X 
 
Nuclear medicine staff 
questionnaire 
 
 
 
X 
 
X 
 
7. MEAUSRES 
Primary patient outcome measure: The Wong-Baker FACES pain rating scale is a standardized 
10-point Likert scale that is validated and has utility for patients with lower health literacy 
(27,28). It has been used in prior studies assessing pain with radiotracer injection for SLN 
mapping (9–11) (Appendix A). 
Secondary patient survey outcome measures: 
 
• 
Short Form McGill questionnaire: This is a validated pain questionnaire taking an 
average of 2-5 minutes to complete that captures subjective experiences of pain in 
both sensory and affective categories on a 4-point Likert scale. A total score out of 45 
is calculated with sensory and affective sub-scores (29) and has been used in prior 
studies assessing pain with radiotracer injection for SLN identification (9–11) 
(Appendix B). 
• 
We will ask questions to determine whether the patient received their intervention as 
assigned (Appendix B). 
• 
Questions to assess patient experience and satisfaction were drawn from the 
following: 
o Consumer Assessment of Healthcare Providers and Systems (CAHPS®) 
questions Surgical Care survey (30) (Appendix B).  
o The American Society of Anesthesiologists Satisfaction with Anesthesia 
Questions (31) (Appendix B). 
o Studies of patient experience/satisfaction with local analgesia using validated 
surveys (32–34)(Appendix B) 
• 
Recommendation of topical anesthetic option: We will ask patients whether they 
would recommend the topical anesthetic option that they received to others (yes/no) 
and inquire why or why not (open ended)(Appendix B).  
 
Secondary staff outcome measures: 


13 
 
• 
Intervention usability and perceived patient pain: 
o The question to assess intervention usability is adapted from the Single Ease 
Question developed for assessment of usability after the completion of a task 
(31). The question addressing perceived patient pain utilizes the Numeric 
Rating scale (NRS), a validated pain rating scale used previously in provider 
assessment of patient pain with radiotracer injection (2,32). (Appendix C) 
• 
End of study assessment: 
o The goal of the survey will be to assess experiences with implementing each 
arm of the study and any identified barriers. Nuclear medicine providers will 
be asked to rank order the usability and perceived efficacy of the different 
interventions. Space will be provided for open ended comments on benefits 
or barriers related to the interventions. (Appendix D) 
 
8. Statistical Considerations 
8.1 Analysis 
Data will be analyzed with intervention arms masked. All scales will be constructed in a manner 
consistent with scale development, including item non-response. We will compare mean post-
procedural pain scores (primary outcome) and other continuous secondary outcomes with 
ANOVA, testing the null hypothesis that mean post-procedural pain scores will not statistically 
differ between the control and intervention arms. Pairwise differences between each of the 
intervention arms and the control arm will be assessed with t-tests. Differences in potential 
control measures between patients randomized to the control and intervention arms that arise 
by chance will be examined using a chi-square test or Fisher’s exact test for categorical 
variables and analysis of variance (ANOVA) or Kruskal-Wallis test for continuous variables 
(depending on distribution), respectively. Should there be significant differences in control 
measures between arms, an analysis of covariance (ANCOVA) will be used to assess the 
primary outcome, including significant covariates. Differences in the secondary dichotomous 
measures (sentinel lymph node mapping, patient recommendation) will be assessed with Chi-
Square analysis. We will summarize responses to open ended questions in the patient survey 
and adherence to intervention. All analyses will follow an intention to treat approach. We will 
summarize the responses from the nuclear medicine providers/staff to determine what arm was 
perceived to be the most effective method for pain control and the easiest to administer. 
Secondary analysis will be performed on the type of radiotracer received and pain scores. 8.2 
Sample size 
Power is calculated for our primary outcome variable, the Wong-Baker FACES pain scale. We 
assume patients randomly assigned to the control arm will have a Wong-Baker score consistent 
with scores reported for breast cancer patients in prior studies (mean=6.0, standard 
deviation=2.6) (10) and that the standard deviation across arms will be similar (2.6). A 
difference in 2 points in the Wong-Baker score between the standard care/control arm and the 
arm with the greatest reduction in pain score is considered clinically significant (27,37,38). A 
Monte Carlo power simulation of this one-way ANOVA design under an assumption of a sample 
with 40 patients per group, two point difference between usual care and the arm with the 
greatest difference, and alpha=0.05 yields 85% power to detect a difference of 2 points on the 
10-point pain scale. Based on prior experience, we assume an enrollment rate of 60% 
(accounting for both declining to participate and drop-out after randomization) and plan to 
approach 270 patients and enroll 180 patients to allow for drop out to a target sample size of 
160 patients. 
9. Registration Procedures 


14 
 
Summary accrual information will be entered directly into the UW Paul P. Carbone 
Comprehensive Cancer Center OnCore database by the Study Coordinator. 
 
A description of the clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. 
 
10. Risks and Discomforts to Research Subjects 
Patients 
Adverse reaction to pain control modality: Patients will be excluded based on presence of 
lidocaine or other local anesthetic allergy/contraindication. However, it is still possible that a 
patient develops an adverse reaction to placement of a lidocaine patch. Patients may also have 
a skin reaction or discomfort associated with other intervention arms. Currently, if patients do 
not tolerate ice pack application (the standard of care at the institution), it can be promptly 
removed. Likewise, patients will be encouraged to communicate any discomfort or intolerance of 
intervention arm, at which time the intervention can be easily and promptly discontinued. We 
anticipate any skin reaction to be self-limited. 
Loss of patient confidentiality: This risk has been minimized through data protection efforts. 
These include storing data sheets used to collect the clinical information and paper 
questionnaires in a locked drawer within a locked office when not utilized. Data will ultimately be 
transferred into a password protected database stored on the Department of Surgery server. 
Only individuals directly involved in the development and analysis of the research project will 
have access to the data. After transfer of information from the data sheet to the database, all 
data sheets will be destroyed. No direct or identifying PHI will be included in the final analysis or 
final manuscript. Patients who wish to sign electronic consent and receive an electronic copy of 
the signed consent will be educated regarding the security risks of transmitting information via 
email.  
Distress from survey questions: It is unlikely that patients will experience distress associated 
with the pain assessment or satisfaction/experience questions. However, patients will have the 
opportunity to contact study staff regarding any concerns that arise related to the survey 
questions.  
11. Records to be kept, Privacy, and Confidentiality 
All hard copy research files (including randomization lists, questionnaires, and data collection 
forms) will be kept in a secure, locked office in a locked filing cabinet and data will be 
transferred into a password protected computer and database stored on the Department of 
Surgery server. Only the minimum amount of patient and subject data that is necessary to 
achieve the aims of the research will be collected.   
Patients: Directly identifiable information will not be collected on patient study questionnaires. 
To better protect patient information, electronic study data will be kept in two separate 
spreadsheets. The first spreadsheet will be a master code that includes the subject’s name and 
medical record and an associated random study subject ID number. This subject ID will be kept 
in a password protected REDcap database on the Department of Surgery server (in a place 
separate from the data collection database). The data collection database will have the subject’s 
ID number only, without subject (patient or provider) identifying information. When questionnaire 
data is then transferred into the database, only the subject ID will be included (no identifying 
information).  
 


15 
 
Only approved study personnel will have access to the identifiers (personnel approved for 
identification and recruitment and interaction with subjects will need access to update the 
master code/spreadsheet). Those who will not be interacting with subjects and/or who are only 
helping with analysis will only have access to the coded study data.  
Nuclear medicine providers: Data from the nuclear medicine technologist post-procedure 
surveys will be linked to the patient subject ID. They will not contain additional patient-identifying 
information. These data will be stored on a password protected database on the Department of 
Surgery server. 
After data analysis of the questionnaires is complete and the manuscript has been accepted for 
publication, all hard copies of research files will be destroyed. Other research materials and 
data are maintained in on the secure Department of Surgery server for a minimum of 7 years 
post publication. Data from this study will be stored for future research projects. 
 
12. Data & Safety Monitoring 
The PI and study team will be responsible for data and safety monitoring.  
The PI and/or a member of the research team will be available to the patient for any questions 
or concerns related to the study.  Standard quality assurance will be conducted prior to data 
analysis. 
In accordance with federal regulations, the PI will monitor for, review, and promptly report to the 
IRB, appropriate institutional officials, sponsor, coordinating center and the appropriate regulatory 
agency head all unanticipated problems involving risks to subjects or others that occur in the 
course of a subject’s participation in a research study (45 CFR 46.103(b)(5)(i) and 21 CFR 
56.108(b)(1)), all AE reports will be reported per the UW IRB policies. 
13. References 
1.  
Cancer of the Breast (Female) - Cancer Stat Facts [Internet]. SEER. [cited 2020 Aug 18]. 
Available from: https://seer.cancer.gov/statfacts/html/breast.html 
2.  
Radowsky JS, Baines L, Howard RS, Shriver CD, Iii CCB, Stojadinovic A. Pain Ratings by 
Patients and Their Providers of Radionucleotide Injection for Breast Cancer Lymphatic 
Mapping. Pain Med. 2012;13(5):670–6.  
3.  
O’Connor JM, Helmer SD, Osland JS, Cusick TE, Tenofsky PL. Do topical anesthetics 
reduce periareolar injectional pain before sentinel lymph node biopsy? Am J Surg. 2011 
Dec;202(6):707–11; discussion 711-712.  
4.  
What Is Patient Experience? [Internet]. [cited 2020 Aug 21]. Available from: 
http://www.ahrq.gov/cahps/about-cahps/patient-experience/index.html 
5.  
Povoski SP, Olsen JO, Young DC, Clarke J, Burak WE, Walker MJ, et al. Prospective 
randomized clinical trial comparing intradermal, intraparenchymal, and subareolar injection 
routes for sentinel lymph node mapping and biopsy in breast cancer. Ann Surg Oncol. 
2006 Nov;13(11):1412–21.  
6.  
Stell VH, Flippo-Morton TS, Norton HJ, White RL. Effect of intraoperative radiocolloid 
injection on sentinel lymph node biopsy in patients with breast cancer. Ann Surg Oncol. 
2009 Aug;16(8):2300–4.  


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7.  
Layeeque R, Kepple J, Henry-Tillman RS, Adkins L, Kass R, Colvert M, et al. 
Intraoperative Subareolar Radioisotope Injection for Immediate Sentinel Lymph Node 
Biopsy. Ann Surg. 2004 Jun;239(6):841–8.  
8.  
Berrocal J, Saperstein L, Grube B, Horowitz NR, Chagpar AB, Killelea BK, et al. 
Intraoperative Injection of Technetium-99m Sulfur Colloid for Sentinel Lymph Node Biopsy 
in Breast Cancer Patients: A Single Institution Experience. Surg Res Pract [Internet]. 2017 
[cited 2020 Jul 28];2017. Available from: 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406738/ 
9.  
Stearns V, Blackford A, Kessler J, Sbaity E, Habibi M, Khouri N, et al. Diagnostic accuracy 
of sentinel node identification is maintained with the addition of local lidocaine and 
subareolar radioactive colloid injection. Breast Cancer Res Treat. 2015 Apr;150(3):589–95.  
10.  Stojadinovic A, Peoples GE, Jurgens JS, Howard RS, Schuyler B, Kwon KH, et al. 
Standard versus pH-adjusted and lidocaine supplemented radiocolloid for patients 
undergoing sentinel-lymph-node mapping and biopsy for early breast cancer (PASSION-P 
trial): a double-blind, randomised controlled trial. Lancet Oncol. 2009 Sep;10(9):849–54.  
11.  Hawkins AS, Yoo DC, Movson JS, Noto RB, Powers K, Baird GL. Administration of 
subcutaneous buffered lidocaine prior to breast lymphoscintigraphy reduces pain without 
decreasing lymph node visualization. J Nucl Med Technol. 2014 Dec;42(4):260–4.  
12.  Arciero CA, Henry LR, Howard RS, Peoples GE, Bilchik AJ, Avital I, et al. Technical effects 
of adding 1 % lidocaine to technetium sulfur colloid for sentinel lymphatic mapping in early 
breast cancer: analysis of data from a double-blind randomized controlled trial. Ann Surg 
Oncol. 2013 Aug;20(8):2548–55.  
13.  Canning S, Bryson-Campbell M, Suryavanshi R. Effect of Topical Anesthetic Cream on 
Pain During Periareolar Injection of Technetium Tc99m Sulfur Colloid for Sentinel Lymph 
Node Biopsy in Breast Cancer: A Randomized Control Trial. J Med Imaging Radiat Sci. 
2018;49(1):44–8.  
14.  Chandler KJ, Hunt CH, Morreale R, Johnson GB, Peller PJ. Effect of Patient Age, Breast 
Density, and Topical Anesthetic Cream on Perceived Pain with Sentinel Lymph Node 
Scintigraphy. J Nucl Med Technol. 2012 Mar 1;40(1):44–7.  
15.  Virk J, Smock B, Nadeem M, Chung C, Maynor C, Becker-Weidman D, et al. The Use of 
Periareolar Topical Lidocaine Jelly After Needle Localization May Reduce Pain of 
Subsequent Lymphoscintigraphy. Cureus [Internet]. [cited 2020 Jul 29];12(4). Available 
from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255066/ 
16.  Fetzer S, Holmes S. Relieving the pain of sentinel lymph node biopsy tracer injection. Clin 
J Oncol Nurs. 2008 Aug;12(4):668–70.  
17.  Shah V, Taddio A, McMurtry CM, Halperin SA, Noel M, Pillai Riddell R, et al. 
Pharmacological and Combined Interventions to Reduce Vaccine Injection Pain in Children 
and Adults. Clin J Pain. 2015 Oct;31(Suppl 10):S38–63.  
18.  Dalvandi A, Ranjbar H, Hatamizadeh M, Rahgoi A, Bernstein C. Comparing the 
effectiveness of vapocoolant spray and lidocaine/procaine cream in reducing pain of 


17 
 
intravenous cannulation: A randomized clinical trial. Am J Emerg Med. 2017 
Aug;35(8):1064–8.  
19.  Haynes JM. Randomized controlled trial of cryoanalgesia (ice bag) to reduce pain 
associated with arterial puncture. Respir Care. 2015 Jan;60(1):1–5.  
20.  Bastami M, Azadi A, Mayel M. The Use of Ice Pack for Pain Associated with Arterial 
Punctures. J Clin Diagn Res JCDR. 2015 Aug;9(8):JC07–9.  
21.  Katz NP, Gammaitoni AR, Davis MW, Dworkin RH, Lidoderm Patch Study Group. 
Lidocaine patch 5% reduces pain intensity and interference with quality of life in patients 
with postherpetic neuralgia: an effectiveness trial. Pain Med Malden Mass. 2002 
Dec;3(4):324–32.  
22.  Krumova EK, Zeller M, Westermann A, Maier C. Lidocaine patch (5%) produces a 
selective, but incomplete block of Aδ and C fibers. Pain. 2012 Feb;153(2):273–80.  
23.  Tadicherla S, Berman B. Percutaneous dermal drug delivery for local pain control. Ther 
Clin Risk Manag. 2006 Mar;2(1):99–113.  
24.  Baxter AL, Leong T, Mathew B. External thermomechanical stimulation versus vapocoolant 
for adult venipuncture pain: pilot data on a novel device. Clin J Pain. 2009 Oct;25(8):705–
10.  
25.  Baxter AL, Cohen LL, McElvery HL, Lawson ML, von Baeyer CL. An Integration of 
Vibration and Cold Relieves Venipuncture Pain in a Pediatric Emergency Department: 
Pediatr Emerg Care. 2011 Dec;27(12):1151–6.  
26.  Ballard A, Khadra C, Adler S, D Trottier E, Bailey B, Poonai N, et al. External cold and 
vibration for pain management of children undergoing needle-related procedures in the 
emergency department: a randomised controlled non-inferiority trial protocol. BMJ Open 
[Internet]. 2019 Jan 15 [cited 2020 Aug 12];9(1). Available from: 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340451/ 
27.  Garra G, Singer AJ, Taira BR, Chohan J, Cardoz H, Chisena E, et al. Validation of the 
Wong-Baker FACES Pain Rating Scale in Pediatric Emergency Department Patients. Acad 
Emerg Med. 2010;17(1):50–4.  
28.  Instructions for Use [Internet]. Wong-Baker FACES Foundation. [cited 2020 Aug 21]. 
Available from: https://wongbakerfaces.org/instructions-use/ 
29.  Melzack R. The short-form McGill Pain Questionnaire. Pain. 1987 Aug;30(2):191–7.  
30.  Consumer Assessment of Healthcare Providers & Systems (CAHPS) | CMS [Internet]. 
[cited 2020 Aug 21]. Available from: https://www.cms.gov/Research-Statistics-Data-and-
Systems/Research/CAHPS 
31.  ASA_Membership_Patient_Satisfaction.pdf [Internet]. [cited 2020 Aug 24]. Available from: 
http://www.aqihq.org/files/ASA_Membership_Patient_Satisfaction.pdf 


18 
 
32.  Capuzzo M, Landi F, Bassani A, Grassi L, Volta CA, Alvisi R. Emotional and interpersonal 
factors are most important for patient satisfaction with anaesthesia. Acta Anaesthesiol 
Scand. 2005;49(6):735–42.  
33.  McCarthy RJ, Trigg R, John C, Gough MJ, Horrocks M. Patient Satisfaction for Carotid 
Endarterectomy Performed under Local Anaesthesia. Eur J Vasc Endovasc Surg. 2004 
Jun 1;27(6):654–9.  
34.  Barnett SF, Alagar RK, Grocott MPW, Giannaris S, Dick JR, Moonesinghe SR. Patient-
Satisfaction Measures in AnesthesiaQualitative Systematic Review. Anesthesiology. 2013 
Aug 1;119(2):452–78.  
35.  Sauro J, Dumas JS. Comparison of three one-question, post-task usability questionnaires. 
In: Proceedings of the 27th international conference on Human factors in computing 
systems - CHI 09 [Internet]. Boston, MA, USA: ACM Press; 2009 [cited 2020 Nov 16]. p. 
1599. Available from: http://dl.acm.org/citation.cfm?doid=1518701.1518946 
36.  McCaffery M, Beebe A. Pain: Clinical manual for nursing practice. St Louis, Missouri: 
Mosby; 1989.  
37.  Bird SB, Dickson EW. Clinically significant changes in pain along the visual analog scale. 
Ann Emerg Med. 2001 Dec;38(6):639–43.  
38.  Kelly AM. Does the clinically significant difference in visual analog scale pain scores vary 
with gender, age, or cause of pain? Acad Emerg Med Off J Soc Acad Emerg Med. 1998 
Nov;5(11):1086–90.  
 
 
 


19 
 
Appendix A. Baseline Pain Assessment 
Note: this baseline assessment sheet will be provided to patients with the study materials so 
that it would be available for them to review over the phone. 
 
 
 
 
 
 
 
 
The following question will be reviewed with you if you decide to enroll in the study.  It will be 
reviewed when a member of the study team calls you to discuss the study. Please save this 
paper to help with that discussion.  
 
 
The following faces respresent a person who has no pain, or some, or a lot of pain. Indicate the 
face that shows the pain you are experiencing right now.  
 
 
 
 
Pain Control for Breast Cancer Patients Undergoing Sentinel 
Lymph Node Biopsy Research Study 
Patient Baseline Pain Assessment 


20 
 
Appendix B. Post-procedural patient survey 
 
 
   Study ID___________ 
 
 
 
 
 
 
 
 
 
This survey has questions about what the injection of radioactive tracer was like for you. Your 
answers will help us learn what is the best method of controlling pain for this procedure. 
 
 
The following faces respresent a person who has no pain, or some, or a lot of pain. Circle the 
face that shows the pain you experienced with the injection of radioactive tracer: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pain Control for Breast Cancer Patients Undergoing Sentinel 
Lymph Node Biopsy Research Study 
Patient Post-Injection Survey 


21 
 
Study ID___________ 
 
Please fill out the following items about the pain you experienced with the injection of 
radioactive tracer. All questions about “pain” are asking ONLY about the pain you experienced 
in the breast with the injection and not other pain. Please answer questions about the pain you 
experienced in the breast DURING the injection, not other pain you may be feeling when you 
are filling out this form. 
 
 
 
Indicate on this line how bad your pain is—at the left end of line means no pain at all, at right 
end means worst pain possible. 
 
 
 
 
 
 
 
 
 
 


22 
 
Study ID___________ 
 
The following are questions about the pain control you received for the injection of radioactive 
tracer. Please mark your answers with check mark(s) or circles. 
 
1) Please mark with check mark(s) which of the following pain treatment(s) you received before 
your injection of radioactive tracer: 
□ Lidocaine patch on breast 
□ Ice on breast 
□ Vibrating device on breast 
 
If you received a lidocaine patch, was it still on your breast right before your 
breast was cleaned for the injection of radioactive tracer? 
□ Yes 
□ No 
□ Not Sure 
□ Did not receive the lidocaine patch 
 
 
 
Please answer questions 2-4 by circling the number that matches your level of satisfaction or 
dissatisfaction with different parts of your care for the injection of radioactive tracer.  
 
How satisfied are you with:  
 
Very 
Satisfied 
Satisfied 
Somewhat 
Satisfied 
Somewhat 
Dissatisfied 
Dissatisfied 
Very 
Dissatisfied 
2) how the staff paid attention to your 
complaints like discomfort or pain with 
the injection? 
1 
2 
3 
4 
5 
6 
3) the care provided by the staff 
performing your injection? 
1 
2 
3 
4 
5 
6 
4) the pain control you received for the 
injection?  
1 
2 
3 
4 
5 
6 
 
 
 
 
 
 
 
 


23 
 
Study ID___________ 
 
5) Please circle the answer that matches your anxiety during the injection: 
 
Very Anxious 
Moderately Anxious 
Slightly anxious 
Not at all anxious 
1 
2 
3 
4 
 
 
6) Please mark your answer to the following statement with a check mark.  
 
I would recommend the pain control I received to others undergoing the same 
procedure.  
□ Yes 
□ No 
□ Not Sure 
 
Why or why not? 
__________________________________________
__________________________________________
__________________________________________
__________________________________________
__________________________________________
__________________________________________
__________________________________________
__________________________________________
__________________________________________
__________________________________________
__________________________________________ 
 
 
 
 


24 
 
Appendix C. Nuclear medicine staff questionnaire for post-procedural pain 
 
Patient Study ID___________ 
 
 
 
 
 
 
 
1) Did the patient arrive with a lidocaine patch on the breast? 
□ Yes 
□ No but patient in a lidocaine patch treatment arm 
□ Not applicable- patient NOT in lidocaine patch treatment arm 
 
2) 
Did the patient require more than one radiocolloid injection? 
□ Yes 
□ No 
 
3) Ease of administration: 
Overall, how difficult or easy was it to administer the intervention? Circle a number on the 7-
point rating scale below: 
 
Very difficult 
 
 
 
 
 
Very easy 
1 
2 
3 
4 
5 
6 
7 
 
 
 
4) Pain score of patient: 
This question is interested in your perspective of the patient’s pain intensity during the injection. 
Please do not ask the patient for a numeric pain score for the purposes of answering this 
question. 
 
Please indicate on the following scale with an X where you think the patient’s pain intensity was 
related to the radiotracer injection.  
 
Pain Control for Breast Cancer Patients Undergoing Sentinel 
Lymph Node Biopsy Research Study 
Provider Survey for Post-Injection Patients 


25 
 
Appendix D. Nuclear medicine staff questionnaire upon study completion 
Provider study ID _____________ 
 
 
 
 
 
 
 
The following questions are regarding the randomized study of topical pain treatments for the 
radiotracer injections for sentinel lymph node mapping in breast cancer patients.  
 
1) Rank the following pain treatments in order of easiest (1) to administer to hardest (4) to 
administer. Use each number 1-4 only once.  
 
______ Ice pack to the breast 
 
______ Lidocaine patch to the breast 
 
______ Ice pack to the breast with Buzzy 
 
______ Lidocaine patch to the breast followed by ice pack to the breast with Buzzy 
 
2) Rank the following pain treatments in order of what you think provided the best pain control 
(1) to what you think provided the least pain control (4). Use each number 1-4 only once.  
 
______ Ice pack to the breast 
 
______ Lidocaine patch to the breast 
 
______ Ice pack to the breast with Buzzy 
 
______ Lidocaine patch to the breast followed by ice pack to the breast with Buzzy 
 
3) Please describe any challenges, if applicable, to implementing any of the pain treatments 
(open response): 
 
 
 
Pain Control for Breast Cancer Patients Undergoing Sentinel 
Lymph Node Biopsy Research Study 
Provider End-of-Study Survey 

ICF_000.pdf: 
Version Date: 4/7/2021
1
University of Wisconsin (UW) - Madison
Research Participant Information and Consent and Authorization Form
                 
Study Title: 
Optimizing topical pain control for breast cancer patients 
undergoing preoperative radiotracer injection for sentinel 
lymph node mapping: a randomized clinical trial
Principal Investigator: 
Heather Neuman, MD
Phone: (608) 262-2025
Email: neuman@surgery.wisc.edu
Research Fellow: 
Alyssa Wiener, MD
Phone: (608) 262-0688
Email: aawiener@wisc.edu 
      
Invitation
You are invited to take part in a research study about pain control for injections of 
radioactive tracer before sentinel lymph node biopsy. You are invited because you will 
be or are scheduled to have a sentinel lymph node biopsy as part of your breast cancer 
treatment. Your participation is completely voluntary. About 180 patients will 
participate in this study at UW Health University Hospital/University of Wisconsin.
What is the purpose of this form?
The purpose of this consent and authorization form is to give you the information you 
need to decide whether you’d like to be in the study. It also explains how health 
information will be used for this study and requests your permission to use your health 
information. Please ask questions about anything in this form that is not clear. If you 
want to talk to your family and friends before making your decision, you can. Once we 
have answered all of your questions, you can decide whether or not you’d like to 
participate in this study. This process is called “informed consent.”  
What is the purpose of the study?
Patients who have a sentinel lymph node biopsy for breast cancer have a safe 
radioactive tracer liquid injected in the breast the day of surgery or the day before 
surgery. The radioactive tracer collects in the sentinel lymph nodes. Surgeons can 
then find and remove the sentinel lymph nodes with the help of the radioactive tracer. 
Some patients say the injection of radioactive tracer is quite painful. We are studying 
different pain treatments for the injection of radioactive tracer.
The purpose of this study is to compare four different pain treatments for the injection 
of radioactive tracer that breast cancer patients receive for sentinel lymph node 
biopsies. These pain treatments have all been used for other minor procedures. 
However, they have not been compared with each other to see whether they 
specifically reduce pain with the injections of radioactive tracer.
This study is funded by a grant from the National Institutes of Health.
What will my participation involve?
If you decide to participate in this research, we will ask you to sign and date this 
consent form. We will then ask one brief question about any current pain you are 
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2
experiencing. The rest of the study occurs on the day of your sentinel lymph node 
surgery. 
Before you receive the injection of radioactive tracer on the day of your sentinel lymph 
node surgery, the hospital staff involved in the injection will explain to you the pain 
treatment you will receive. You will then receive the pain treatment, followed by the 
injection of radioactive tracer. After you receive the injection but before your surgery, 
you will be asked to complete a short survey about your experience with the 
radioactive injection. The survey should take less than 10 minutes to complete. Your 
active participation in the study will be over after you complete the survey. 
The research staff will also review your medical record to collect basic information 
about you and your cancer (such as your age, medical conditions, use of medications, 
cancer stage and treatment, and other information).
What are the study groups?
In this research study, 180 people will be registered and randomized to four study 
groups. If you decide to participate in this study, you will be assigned through a process 
called randomization to one of four study groups:
<0000>
Ice on the breast (usual treatment)
 
Lidocaine patch on the breast
 
A vibrating distraction device (Buzzy®) and ice on the breast 
 
Lidocaine patch on the breast followed by a vibrating distraction device 
(Buzzy®) and ice on the breast
Randomization means neither you nor the study doctor or study staff will be able to 
pick which study group you are in.  If you agree to be randomized, you will have an 
equal chance of being assigned to either study group. You will be informed of your 
study group assignment on the day of your surgery.
The usual treatment that all patients currently receive at UW Health University Hospital 
is ice on the breast. If you do not participate in the study, you will receive ice on the 
breast as part of routine care. The other possible treatments listed above have not 
been studied before for this specific injection and involve a pain control device and/or 
medicine placed on the breast.
Who can be a part of this study?
This study will include women who have been diagnosed with breast cancer and who 
will be undergoing sentinel lymph node biopsy with a standard injection of radioactive 
tracer before surgery. 
You may not participate in this study if you:
 
Are pregnant 
 
Are younger than 18 years of age
 
Have an allergy to lidocaine or other topical anesthetics
 
Have a medical contraindication to lidocaine or other topical anesthetics (for 
example, individuals taking certain drugs to control heart rhythm would not be 
eligible)
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3
 
Are scheduled to have your radioactive injection happen the day before surgery 
or during surgery
When and where will this study happen?
This research will be conducted on the day of your surgery at the UW Health University 
Hospital on 600 Highland Ave.
How long will I be in this study?
Your active participation will take place on two separate occasions. In the first occasion, 
after you agree to participate in the study, we will spend one minute or less on a brief 
question about any current pain you are experiencing. The rest of your active 
participation will take place on one day (the day of your surgery) and last approximately 
20 minutes. Participation in the study includes receiving your pain treatment and 
completing a short survey within 3 hours of receiving the injection. The survey should 
take less than 10 minutes to complete. Your active participation will end after you 
complete the survey and before your surgery.
How is being in this study different from my regular health care?
All breast cancer patients who need sentinel lymph node biopsy surgery get an 
injection of radioactive tracer to help identify the sentinel lymph nodes. At the UW 
Health University Hospital, patients get one standard pain treatment with this injection 
unless they are getting the injection during their surgery. By being in this study, you 
may get a different pain treatment for the injection than what you would get if you were 
not in the study. It is also possible that you would get the same pain treatment that you 
would get if you were not in the study. You will be asked to complete a brief one-
question pain assessment on the day you agree to participate in the study. On the day 
of your surgery, you will also be asked to complete a second survey about your 
experience with the radioactive tracer injection if you are in this study.
 
If you decide not to participate in this study, you will receive the usual pain treatment 
for the injection of radioactive tracer. You will not be asked to complete any surveys. 
What are my other choices if I do not take part in this study?
You do not have to be in this research study to get care for your breast cancer. If you 
decide to not take part in the study, you will continue to get care for your breast cancer 
according to usual practice.
Are there any benefits to me?
There are no direct benefits to participation in this research. Some people may 
experience improved perceptions of pain with the radioactive tracer injection. Your 
participation is likely to help us identify the most effective pain treatment. There may 
not be any benefit to the society at this stage of the research. However, future breast 
cancer patients are likely to benefit.
Will I be paid or receive anything for being in this study?
●
You will not be paid to take part in this study. 
●
Researchers may develop products from the information you provide for this 
study. Some of these products may have commercial value. If the research 
team or others use your information to develop products of commercial value, 
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Version Date: 4/7/2021
4
you will not receive any profits from products created from your samples or 
information.
Will being in this study cost me anything?
●
There will be no cost to you for any of the study activities or procedures. 
●
You or your insurance company will have to pay for all costs for medical care 
related to your treatment for your breast cancer, including co-payments and 
deductibles. You will have to pay for any costs your insurance does not cover. 
If you have any questions about these costs, or what out-of-pocket expenses 
you may have, you should contact your insurance company. If you do not have 
health insurance, you will have to pay all costs for your medical care just as you 
would if you did not take part in this study. 
Are there any risks to me?
There is a risk that your information could become known to someone not involved in 
this study. However, the study team makes every effort to protect your privacy.
In addition, there is a small risk that you could have a skin reaction to the pain 
treatment you receive. A skin reaction could include redness, itchiness, swelling, or 
pain. We expect any skin reactions to be temporary and to go away on their own. If 
you experience significant discomfort from the pain treatment, let your care team know, 
and the pain treatment can be immediately stopped. It is also possible that you develop 
an allergic reaction to the pain treatment you receive. An allergic reaction could range 
from something as small as a rash to difficulty swallowing. If you were to develop any 
severe allergic reaction, you would be treated with the appropriate allergy medicines.
Do I have to be in the study? What if I say “yes” now and change my mind later?
No, you do not have to be in this study. Taking part in research is voluntary. This 
means that you decide if you want to be in the study. If you decide to take part now 
but later change your mind, you can choose to leave the study at any time. Let the 
researchers know if you choose to leave the study.
If you decide not to take part in the study, or if you choose to leave the study, your 
choice will not affect any treatment relationship you have with your healthcare 
providers at UW-Madison, UW Health, or any affiliated organizations, or any services 
you receive from them. No matter what decision you make, and even if your decision 
changes, there will be no penalty to you. You will not lose medical care or any legal 
rights.
Your authorization for researchers to use your protected health information (PHI) will 
last until the research study is complete. However:
 
You can choose to take back your authorization for researchers to use your 
health information. You can do this at any time before or during your participation 
in the study. 
 
If you take back your authorization, information that was already collected may 
still be used and shared with others; however, the researchers will no longer be 
able to collect NEW information about you.  
 
If you take back your authorization, you will not be able to take part in the 
research study. To take back your authorization, you will need to tell the Lead 
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5
Researcher by writing to Heather B. Neuman, K6/142 CSC, 600 Highland Ave, 
Madison, WI  53792-1690.
Protected health information (PHI) used in this study
Protected health information, also called PHI, is information about your physical or 
mental health that includes your name or other information that can identify you, such 
as your date of birth or medical record number. To do this study, we will use the 
following kinds of PHI:
 
Things you tell the researchers about your health.
 
Information currently in your medical record as well as information added to 
your medical record during the course of this study. This information could 
include demographics (such as age and race), pain medications you take, pain 
conditions you have, type of axillary surgery, cancer stage and receptor status, 
and prior cancer treatments. Operative data will also be collected, such as the 
number of lymph nodes removed during surgery.  
                 
How will my confidentiality be protected?
We have strict rules to protect your personal information and protected health 
information (PHI). We will limit who has access to your name, address, phone number, 
and other information that can identify you. We will also store this information securely.  
We may publish and present what we learn from this study, but none of this information 
will identify you directly without your permission.
The information that we collect from this research project will be kept confidential in 
password-protected and secure computers and servers. Information about you that 
will be collected during the research will be put away, and no-one but the researchers 
will be able to see it. Any information about you will have a number on it instead of 
your name. Only the researchers will know what your number is and this information 
will also be password-protected on secure computers and servers. It will not be shared 
with or given to anyone except those involved in the research. Any physical documents 
involved with research (e.g., paper surveys) will be locked in a secure location and 
destroyed at the end of the study. 
However, we cannot promise complete confidentiality. Federal or state laws may 
permit or require us to show information to university or government officials and the 
National Cancer Institute responsible for monitoring this study. We may also have to 
tell appropriate authorities, such as child protective services or health care providers, 
if we learn during the study that you or others are at risk of harm (for example, due to 
child or elder abuse, or suicidal thoughts).
Authorizing the research team to use your PHI means that we can release it to the 
people or groups listed below for the purposes described in this form. Once your health 
information is released outside UW-Madison or UW Health it may not be protected by 
privacy laws and might be shared with others. Also, with appropriate institutional 
permissions and confidentiality protections, we might use information that we collect 
during this study for other research or share with other researchers without additional 
consent or authorization from you or your legally authorized representative.  
Who at UW-Madison can use my information?
 
Members of the research team 
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Offices and committees responsible for the oversight of research
Who outside the UW-Madison may receive my information?
 
U.S. Office for Human Research Protections 
 
The U. S. Food and Drug Administration (FDA)
 
A 
description 
of 
this 
clinical 
trial 
will 
be 
available 
on 
http://www.ClinicalTrials.gov, as required by U.S. Law. This website will not 
include information that can identify you. At most, the website will include a 
summary of the results. You can search this website at any time.
 
The study team has a Certificate of Confidentiality from the National Institutes 
of Health for this study. A Certificate of Confidentiality prohibits researchers 
from disclosing information [or biospecimens] that may identify you in a legal 
proceeding or in response to a legal request without your consent.
Will information from this study go in my medical record?
 
Some of the information we collect for this study may go in your medical record. 
Depending on which pain treatment you receive, the fact that you received a 
certain treatment will be included in your medical record. 
What happens if I am injured or get sick because of this study?
If you are injured or get sick because of this study, medical care is available to you 
through UW Health, your local provider, or emergency services – as it is to all sick or 
injured people. 
 
If it is an emergency, call 911 right away or go to the emergency room. 
 
For non-emergency medical problems, contact the UW Breast Center. 
 
Call the Lead Researcher, Dr. Heather Neuman, at 608-262-2025 to report your 
sickness or injury.
Here are some things you need to know if you get sick or are injured because of this 
research: 
 
If the sickness or injury requires medical care, the costs for the care will be 
billed to you or your insurance, just like any other medical costs. 
 
Your health insurance company may or may not pay for this care.
 
No other compensation (such as lost wages or damages) is usually available.
 
UW-Madison and UW Health do not have a program to pay you if you get sick 
or are injured because of this study.
 
By signing this consent form and taking part in this study, you are not giving up 
any legal rights you may have. You keep your legal rights to seek payment for 
care required because of a sickness or injury resulting from this study. 
                 
Whom should I contact if I have questions?
You may ask any questions about the research at any time. If you have questions 
about the research after today, you should contact the Principal Investigator Heather 
Neuman at (608) 262-2025.
If you have any questions about your rights as a research subject or have complaints 
about the research study or study team, contact UW Health Patient Relations at 608-
263-8009. The Patient Relations Representatives work with research subjects to 
address concerns about research participation and assist in resolving problems.
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If you would like to email us your scanned or photographed consent document, we will 
request your email address. Email is generally not a secure way to communicate about 
your health as there are many ways for unauthorized users to access email. You 
should avoid sending sensitive, detailed personal information by email. Email should 
also not be used to convey information of an urgent nature. If you need to talk to 
someone immediately, please contact Principal Investigator Heather Neuman at (608) 
262-2025. You do not have to provide your email address to participate in this study.
                 
Agreement to participate in the research study
You do not have to verbally agree to participate in this study. If you refuse to verbally 
agree to participate in this study, you cannot take part in this research study.
If you verbally agree to participate in this study, it means that:
●
You have read this consent and authorization form.
●
You have had a chance to ask questions about the research study, and the 
researchers have answered your questions.   
●
You want to be in this study.
●
You give authorization for your protected health information to be used and 
shared as described in this form.
If you agree to participate in this study, please state your full name, date of birth and 
the following:
“I hereby verbally agree to participate in the study as outlined in this consent and 
authorization document.”
**You will receive a copy of this form**
IRB Approval Date: 4/9/2021              
University of Wisconsin – Madison