Patient Experiences With the COVID-19 Vaccination After Breast Cancer Treatment
Conditions: Breast Cancer Related Lymphedema, Covid19
Sponsor: Massachusetts General Hospital

 
  
  
PROTOCOL AND STATISTICAL  
ANALAYSIS PLAN 
Protocol Title:   
 
Patient Experiences with the  COVID-19 Vaccination after  
Breast Cancer Treatment  
  
Principal Investigator:   
Alphonse Taghian, MD PhD FASTRO  
  
NCT Number:   
NCT04872738  
  
Version Date:   
March 17, 2023 

 
  
  
PARTNERS HUMAN RESEARCH COMMITTEE PROTOCOL 
SUMMARY  
  
  
Answer all questions accurately and completely in order to provide the PHRC with the relevant 
information to assess the risk-benefit ratio for the study.  Do not leave sections blank.  
  
PRINCIPAL/OVERALL INVESTIGATOR  
  
Alphonse Taghian, MD PhD FASTRO  
  
  
PROTOCOL TITLE  
Patient Experiences with the COVID-19 Vaccination after Breast Cancer  
Treatment  
  
FUNDING  
The project was supported by Award Number R01CA139118 (AG Taghian) 
and Award Number P50CA08393 (AG Taghian) from the National Cancer  
Institute.  The content is solely the responsibility of the authors and does not 
necessarily represent the official views of the National Cancer Institute or 
the National Institute of Health. This program is supported by the Adele 
McKinnon Research Fund for Breast Cancer-Related Lymphedema (AG 
Taghian) the Olayan-Xefos Family Fund for Breast Cancer Research (AG 
Taghian), and the Heinz Family Foundation (AG Taghian).    
  
VERSION DATE  
04.08.2022  
  
SPECIFIC AIMS  
Concisely state the objectives of the study and the hypothesis being tested.  
• 
To elicit patient experiences and side effects associated with the  
COVID-19 vaccine after breast cancer surgery  
• 
Hypothesis 1: Patients will choose to receive the vaccine on the 
arm contralateral to axillary lymph node removal, or in the lower 
extremity if they have had bilateral axillary lymph node removal  
• 
Hypothesis 2: Patients with a history of breast cancer will 
experience axillary lymph node swelling after receiving the 
COVID-19 vaccine at the same rate as the general population  
• 
Hypothesis 3: Patients with axillary surgery who develop lymph 
nodes swelling in the ipsilateral side might be at increased risk of 
developing lymphedema  

Partners Human Subjects Research Application Form  
    
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• 
Hypothesis 4: Patients who had a COVID infection prior to 
receiving the vaccine will experience more vaccine side effects 
than those who were not infected  
  
  
BACKGROUND AND SIGNIFICANCE  
Provide a brief paragraph summarizing prior experience important for understanding the 
proposed study and procedures.  
Breast Cancer-Related Lymphedema: Overview, Incidence, and Risk 
Factors  
Breast cancer-related lymphedema (BCRL) remains a burdensome and 
much feared complication of breast cancer treatment. BCRL may occur after 
lymph node surgery or radiation to the axillary regions, interrupting the 
proper circulation of lymph fluid. This protein-rich fluid then accumulates in 
the interstitial tissues of the arm, shoulder, or hand, and/or the breast or 
trunk, causing swelling that characterizes this condition.[1] Patients may 
experience a range of symptoms, including heaviness, pain, tightness, 
changes in skin quality, decreased range of motion, as well as a higher risk 
for infection in the affected area(s). The morbidity resulting from BCRL is 
significant and negatively impacts almost all aspects of patients’ lives, 
contributing to anxiety and even depression.[2–7]  
Risk factors that have been well established in the literature include 
axillary lymph node dissection (ALND), regional lymph node radiation 
(RLNR), number of pathologically involved lymph nodes, and high Body Mass 
Index (BMI).[8–13] Sentinel lymph node biopsy (SLNB) is favorable to ALND 
for the axillary staging of early disease because it significantly decreases the 
risk for BCRL, although the risk is not entirely eliminated.[8,12,14,15] In 
recent analyses by our team looking at data from over 2,171 women, 
stratified by BC treatment received, the 5-year point estimate of BCRL was 
31.2% after ALND and RLNR, 24.6% after ALND without RLNR, 12.2% after  
SLNB and RLNR and 8.3% after SLNB without RLNR.[16]    
  
Role of Injections in Lymphedema Risk  
As the prevention of lymphedema is preferable to an impairmentbased 
approach, patients treated for BC historically received advice regarding 
precautionary behaviors and lifestyle modifications (e.g. avoiding injections) 
they can adopt, in theory, to reduce their life-long risk of developing this 
condition, many of which remain unsubstantiated by highlevel, scientific 
support.[17,18]   
Given the paucity of evidential support and controversy surrounding 
these measures, our team conducted a literature review[18] and two 

 
prospective analyses[19,20] to assess whether lifestyle risk exposures, 
including injections on the ipsilateral arm, conferred a risk for the 
development of lymphedema. By multivariate analysis in both prospective  

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studies (n=632 and n=327), injections were not associated with an increase 
in arm volume.   
In our literature review in The Lancet Oncology,[18] we looked at 85 
manuscripts to determine whether historical literature has found a tangible 
association between presumed risk-increasing behavioral exposures (including 
ipsilateral skin puncture, cellulitis infections) and BCRL. We found that over 
the past several decades, the majority of published studies have demonstrated 
that the clinical benefit of current precautionary guidelines has not been 
established. Among 31 original studies examining the association between 
these 
exposures 
and 
BCRL, 
only 
eight 
are 
prospective 
cohort 
studies.[10,19,21–24] Among these, four studies demonstrate a significant 
correlation between lymphedema and commonly reported lifestyle-based risk 
factors, in one case, skin puncture.[24] The study that found a correlation 
between skin puncture and lymphedema was composed only of patients with 
ALND (n=188), and based on 8 patients who developed lymphedema after 
skin puncture.   
In summary, skin puncture is not associated with increased arm 
volume based on available evidence.   
  
COVID-19 Vaccine and Lymphedema Risk  
Lymph node swelling is a known and common side effect of both the 
Moderna and Pfizer COVID-19 vaccines. This is the body’s normal reaction to 
the vaccine. According to the Centers for Disease Control and Prevention, 
axillary swelling or tenderness (i.e., lymphadenopathy) was a solicited 
adverse event reported in 11.6% of patients (vs 5.0% for placebo) following 
dose 1 and 16.0% of patients (vs 4.3% for placebo) following dose 2 after 
the Moderna vaccine.[25] This occurred in the arm and neck 2-4 days 
following vaccination with a median duration of 1-2 days. After the 
PfizerBioNTech COVID-19 vaccine, lymphadenopathy was reported as an 
unsolicited adverse event with 58 more cases in the vaccine group than the 
placebo group (64 vs 6 respectively). This occurred in the arm and neck 
within 2-4 days of vaccination and lasted for a mean of 10 days.[26] Rates 
and duration of adenopathy in both trials were based on clinical assessment 
(i.e., physical examination). Anecdotally, mammographically detectable 
axillary adenopathy following COVID-19 vaccinations has been 
unilateral.[27]  
It is worrisome that lymph node swelling after the vaccine mimics that 
found in breast cancer which has spread to the lymph nodes. This side effect 
will cause worry and anxiety amongst patients as a result. For patients who 
have had lymph node removal (ALND or SLNB) and are at risk of 
lymphedema, we are concerned that the lymph node swelling may tax the 
lymphatic system and incite lymphedema in those at risk or worsen it in 
those with BCRL. Fear of lymphedema is high in this population and we need 
to better understand what risk, if any, lymphadenopathy after the COVID-19 
vaccine imparts to BCRL risk.   

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Although our previous research has found that injections were not 
associated with increased arm volume[18,19,28], the COVID-19 vaccine is 
new. We do not know how lymph node swelling associated with the vaccine 
will affect patients at risk for or suffering from lymphedema. We cannot 
therefore apply the results from our previous studies to our 
recommendations for patients around the COVID-19 vaccine.  
   
It is imperative to educate patients about vaccine options, such as 
receiving the vaccine in an alternative location such as the anterolateral 
thigh. It is imperative that we study patient experiences, choices, side 
effects and lymphedema incidence after the COVID-19 vaccine.   
  
Study Summary and Clinical Implications  
This study will be a prospective, longitudinal cohort study incorporating 
patient-reported surveys after vaccine receipt. Given that the COVID-19 
vaccine will likely be required in the long term, this data will inform patient 
recommendations for those receiving the COVID-19 vaccine who are at risk 
for and with lymphedema.   
   
RESEARCH DESIGN AND METHODS  
Briefly describe study design and anticipated enrollment, i.e., number of subjects to be enrolled 
by researchers study-wide and by Partners researchers.  Provide a brief summary of the eligibility 
criteria (for example, age range, gender, medical condition).  Include any local site restrictions, 
for example, “Enrollment at Partners will be limited to adults although the sponsor’s protocol is 
open to both children and adults.” 
  
This is a prospective, longitudinal observational cohort study incorporating 
patient-reported surveys before and/or after vaccine receipt. Female patients 
who are ≥18 years of age and have a history of breast cancer will be eligible. 
For the MGH site, patients must have received some breast cancer treatment 
at MGH or its affiliates and received perometry measurements to measure 
arm volume to be eligible for this study. Per our MGH lymphedema screening 
records, there are a minimum of 4,947 patients who will qualify for this 
study.  Based on an anticipated survey response of 20%, we anticipate 
minimal accrual at MGH to be approximately 989 patients.  
Briefly describe study procedures.  Include any local site restrictions, for example, “Subjects 
enrolled at Partners will not participate in the pharmacokinetic portion of the study.”  Describe 
study endpoints. 
  
REDCap was used to develop surveys to be sent electronically to patients. 
We will use the surveys to elicit patient choices around receiving/not 
receiving the vaccine, injection site of choice and side effects. Complete 
versions of all survey involved in this study have been attached to this 
application, but not all questions will be relevant to each patient. Therefore, 
branching logic is built into our REDCap database to ensure patients only 

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have to answer the questions that are relevant to them. For example, a 
patient who receives a COVID-19 vaccine that only has one dose will not 
need to fill out symptoms information for their second dose as it is not 
applicable to them.  
For all eligible patients from MGH who use MGB Patient Gateway, they will be 
sent a recruitment letter via MGB Patient Gateway with a REDCap survey link 
embedded. We have been working with the Partners eCare team to build this 
recruitment report.   
The invitation to participate was previously resent a second time after 72 
hours with no response, and then a third time at seven days after initial 
contact (prior to new IRB regulations regarding reminders). An updated 
version of the recruitment letter was sent with the booster survey once this 
dose becomes available. The letter includes a new second survey link to 
questions about the booster vaccine. It is stated in the recruitment letter 
that this is an updated version of the study which makes the survey more 
user friendly and includes the booster dose. For this reason, all participants 
will receive the invitation to participate unless they have specifically asked 
not to be contacted about our study again. A follow up phone call may be 
made if we do not hear back in 2 weeks. For patients who do not complete 
the surveys after consenting to participate (either due to forgetting to finish 
the surveys or having technical difficulties finding the surveys), the Clinical 
Research Coordinator will call the participant at the phone number in the  
EPIC chart to assist in completing all surveys. A telephone script is attached.    
  
Since booster doses of all vaccines are recommended by health officials at 
differing times, we will contact participants securely through Patient Gateway 
who have already completed survey(s) about their 1st/2nd doses asking them 
to complete the booster survey as well. This updated booster letter will 
include information regarding optional arm measurements as well. This 
states that we would like participants to make appointments for arm 
measurements 1-2 weeks before the booster, 7-14 days after the booster, 4-
6 weeks after the booster, and 3 months after the booster, +/- 2 weeks. This 
is an optional component of participation in this study. The letter will be sent 
through patient gateway. The letter will be sent again to participants who 
have completed surveys about their 1st/2nd doses in March of 2022 as we 
anticipate many more responses now as the booster had become more 
widespread. Depending on response rates, we may reach out by phone, 
using the attached letter as a script, to help participants complete the 
booster survey.   
  
98 participants are eligible for our study as well as the CANVAX: Cancer, 
COVID and Vaccination study (2021P000746). We have been collaborating 
with the CANVAX team and would like for as many participants as possible of 
these 98 to complete both studies. In the future, both teams will collaborate 

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on how best to share our data (perhaps by applying for a data use 
agreement). Therefore, we will send an additional letter through Patient  
Gateway to these participants explaining why we would specifically  
appreciate their participation in the study, signed by the CANVAX PI. These 
participants have not opted out of being contacted for future research. The 
Lymphedema Research Program Clinical Research Coordinators are listed as 
Research Assistants on the CANVAX protocol. If a CANVAX patient is seen in 
the Breast Cancer Center for routine follow ups or arm measurements, CRCs 
will offer to have the patient fill out the survey during the visit. Depending 
on response rate from the Patient Gateway letter, CRCs may also call these 
patients (a script is attached) unless they decline to participate.   
  
If the participant consents, they will immediately begin a survey asking     
for information about their first dose and symptoms and second dose and 
symptoms, if applicable.  For participants who have had all doses of their 
respective vaccines, their participation is complete after responding to a 
survey about all applicable doses. For participants who have had one dose of 
their vaccine and plan to have a second, they will fill out the expected date 
of their second dose and told that the invitation will be resent on that date 
via Patient Gateway for them to fill out a second survey on that dose. A 
second link will be available in the recruitment letter directing participants to 
fill out experiences with the booster dose of the vaccine if they receive it. 
Copies of both surveys (first/second dose experience and booster dose 
experience) are attached.   
  
Additionally, we will reach out to participants through Patient Gateway who 
have consented to the study and experienced some form of swelling and 
provide them with contact information if they would like to schedule arm 
measurements before and/or after receiving the booster vaccination. All 
participants are aware that arm measurements remain available to them as 
they have in the past. Language for this letter is attached. We will resend an 
updated letter to participants who reported lymph node swelling after any of 
the three doses. The updated language is attached. As has been conducted 
with the booster arm measurements, parking will be compensated for those 
coming in for additional appointments outside of regular oncology visits. 
Depending on response rates, we may also reach out to participants by 
phone using the attached letter as a script.   
  
An additional survey asking questions about prior SARS-CoV-2 infection will 
be sent to all participants who have consented to participate through 
answering questions on any doses of the vaccine. The CANVAX study 
recently published results that prior infection was associated with higher 
systemic, but not local, symptoms43. We would like to test this in our 
population and therefore must collect data on any prior infections to 

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compare with the data we have on vaccine experiences. The invitation to 
complete this survey, attached, will be sent securely through patient 
gateway, and we may reach out by phone depending on response rates at 
the discretion of the PI. A consent addendum is included in the survey 
language, attached. No new subjects will be enrolled through this survey.   
  
Participants will be aware (explained in consent fact sheet) that we may 
review their medical records for the purposes of this study and that we will 
analyze their survey data in conjunction with their breast cancer treatment 
information and lymphedema screening data.   
Upon completion of the survey study, we may apply for secondary use of 
data from our Screening Program to analyze perometry and 
clinicopathological data for participants who have responded to surveys 
regarding their COVID-19 vaccinations and who are established participants 
in our MGH Breast Cancer-Related Lymphedema Screening Program 
(2008P000540 and 1999P009256). We have applied for and been granted 
secondary use under Insight number 2021P003414. This program routinely 
screens patients starting at pre-operative baseline, throughout and beyond 
treatment at their oncology follow-up visits. Screening consists of perometry 
measurements, a valid and reliable measure of arm volume used for 
lymphedema screening[29], as well as a patient-reported outcome measure, 
the Symptoms Experience Index (SEI), a validated measure of symptoms 
after breast cancer surgery. Analysis of this data will inform BCRL risk after 
COVID-19 vaccination versus that from our historical control data.   
 
For studies involving treatment or diagnosis, provide information about standard of care at  
Partners (e.g., BWH, MGH) and indicate how the study procedures differ from standard care.  
Provide information on available alternative treatments, procedures, or methods of diagnosis. 
  
Not applicable: this study does not involve treatment or diagnosis.   
  
Describe how risks to subjects are minimized, for example, by using procedures which are 
consistent with sound research design and which do not unnecessarily expose subjects to risk or 
by using procedures already being performed on the subject for diagnostic or treatment purposes. 
  
  
  

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The surveys sent, the main research components of this study, do not 
present risk to patients. We will protect patients by inviting the majority of 
the study participants through secure Patient Gateway contact. All surveys 
will be completed in REDCap and all survey responses will be stored in our 
secure REDCap database. All patients who are offered to participate in this 
study are already familiar with the MGH Lymphedema Research Program.   
  
Describe explicitly the methods for ensuring the safety of subjects.  Provide objective criteria for 
removing a subject from the study, for example, objective criteria for worsening disease/lack of 
improvement and/or unacceptable adverse events.  The inclusion of objective drop criteria is 
especially important in studies designed with placebo control groups. 
  
Given minimal risk to patients and the fact that it is an observational study, 
the main criteria for removing a subject from the study would be patient 
withdrawal from the study.   
  
FORESEEABLE RISKS AND DISCOMFORTS  
Provide a brief description of any foreseeable risks and discomforts to subjects.  Include those 
related to drugs/devices/procedures being studied and/or administered/performed solely for 
research purposes.  In addition, include psychosocial risks, and risks related to privacy and 
confidentiality.  When applicable, describe risks to a developing fetus or nursing infant. 
  
Psychosocial risks may include frustration associated with receiving survey 
prompts as to whether the patient has received the first dose of the 
COVID19 vaccine, given this is an emotional topic currently. There could also 
be distress associated with the potential for the known side effect of lymph 
node swelling after receiving the COVID-19 vaccine in patients at risk for 
lymphedema.   
  
EXPECTED BENEFITS  
Describe both the expected benefits to individual subjects participating in the research and the 
importance of the knowledge that may reasonably be expected to result from the study.  Provide 
a brief, realistic summary of potential benefits to subjects, for example, “It is hoped that the 
treatment will result in a partial reduction in tumor size in at least 25% of the enrolled subjects.”  
Indicate how the results of the study will benefit future patients with the disease/condition being 
studied and/or society, e.g., through increased knowledge of human physiology or behavior, 
improved safety, or technological advances.  
  
Benefits to society would include wide distribution of important patient 
education regarding the side effects and recommendations for safe receipt of 
the COVID-19 vaccine. This will minimize distress in our patients who 
experience a potentially alarming symptom such as lymph node swelling, 
which may concern patients who underwent lymph node removal. Since we 

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will be monitoring for symptoms, we will be able to direct patients to seek 
medical care in the event lymph node swelling symptoms persists to six 
weeks after the second dose. If there is clinical concern that persists ≥ 6 
weeks after the final vaccine dose, axillary ultrasound is recommended per 
current MGH Breast Imaging standard of care. There are no direct benefits 
to patients who do not experience lymph node swelling.  
  
EQUITABLE SELECTION OF SUBJECTS  
The risks and benefits of the research must be fairly distributed among the populations that stand 
to benefit from it.  No group of persons, for example, men, women, pregnant women, children, 
and minorities, should be categorically excluded from the research without a good scientific or 
ethical reason to do so.  Please provide the basis for concluding that the study population is 
representative of the population that stands to potentially benefit from this research. 
  
The proposed study will be limited to the enrollment of female subjects who 
are ≥ 18 years of age. Breast cancer is exceedingly rare in the population 
under 18 years of age, with only a 0.02% malignancy rate for pediatric 
breast masses.[30–33] Additionally, less than 1% of all breast cancer 
patients are male.[33,34] Therefore, accrual of children and males would be 
limited and would not allow for statistical analysis or comparison. All patients 
who meet eligibility requirements will be offered the study. This includes all 
newly diagnosed patients who will be accrued to the pre-existing screening 
program during the duration of the study. No exclusions will be made on the 
basis of race, ethnicity, sexual orientation. The clinical staff will make all 
efforts to enroll eligible patients, including minority subjects.  
  
When people who do not speak English are excluded from participation in the research, provide 
the scientific rationale for doing so.  Individuals who do not speak English should not be denied 
participation in research simply because it is inconvenient to translate the consent form in 
different languages and to have an interpreter present. 
  
The survey will be given to participants who are able to read and consent to 
the study in English. Given technological REDCap limitations, we will be 
unable to retroactively add surveys in different languages after the initial 
survey invitations have been sent out on Patient Gateway.  Given that the 
vast majority of patients in our database speaks English, we believe the 
imperative nature of beginning this study supports this approach.   
  
It is imperative to translate the COVID-19 vaccine information sheet into 
several languages as it is crucial that patients receive this education 
regardless of language spoken. Prior to this, we can have an interpreter 
present as needed for the screening visits so CRCs can explain the guidelines 
to patients as they come in for measurements. This will be done per our 

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clinical service and will be distributed to any patients in the Breast Cancer 
Center, regardless of their participation in research.  
  
For guidance, refer to the following Partners policy:  
          Obtaining and Documenting Informed Consent of Subjects who do not Speak English           
https://www.partners.org/Assets/Documents/Medical-Research/ClinicalResearch/Non-
English-Speaking-Subjects.pdf  
  
  
  
RECRUITMENT PROCEDURES  
Explain in detail the specific methodology that will be used to recruit subjects.  Specifically 
address how, when, where and by whom subjects will be identified and approached about 
participation.  Include any specific recruitment methods used to enhance recruitment of women 
and minorities. 
  
There are multiple recruitment methods for this study:   
- The majority of patients will be accrued via recruitment letter sent 
through MGB Patient Gateway. We will send this letter to all MGH 
patients who are eligible (≥18, female, treated for breast cancer at 
MGH, have been measured with perometry for BCRL) and are in our 
database (1999P009256/2008P000540). For patients who are okay 
with receiving research opportunities, the original letter directly from 
our study team will be sent to them. For all patients who are not 
enrolled at the time of the initial survey invitations, but become 
eligible, they may be accrued either by provider referral or when they 
are in clinic seeing our Clinical Research Coordinators for a perometry 
measurement. This group of patients includes those diagnosed with 
breast cancer after the surveys have been sent out or those who have 
received perometry measurements for clinical purposes. CRCs will 
mention the study during a regular screening visit and send the email 
to the patient if they are interested or give them a flyer (attached) so 
a patient can decide if they would like to join after the visit is over and 
they have time to think about it. The same could happen if a provider 
mentions the study to a patient who then approaches our team about 
the study.  
- For participants who are eligible for our study (MGH patients ≥18, 
female, treated for breast cancer at MGH, have been measured with 
perometry for BCRL) who also participated in the CANVAX: Cancer, 
COVID and Vaccination study (2021P000746), the CRC will send an 
additional letter through Patient Gateway to describe the crossover 
between the two studies. If a CANVAX patient is seen in the Breast 
Cancer Center for routine follow ups or arm measurements, CRCs will 
offer to have the patient fill out the survey during the visit.  

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Provide details of remuneration, when applicable.  Even when subjects may derive medical 
benefit from participation, it is often the case that extra hospital visits, meals at the hospital, 
parking fees or other inconveniences will result in additional out-of-pocket expenses related to 
study participation.  Investigators may wish to consider providing reimbursement for such 
expenses when funding is available 
  
Parking fees will be reimbursed for the optional visit for arm measurements 
before/after receiving the booster vaccination. Participants will be given a 
parking pass for a 0-4 hour visit.   
  
 For guidance, refer to the following Partners policies:  
          Recruitment of Research Subjects  
          https://www.partners.org/Assets/Documents/Medical-
Research/ClinicalResearch/Recruitment-Of-Research-Subjects.pdf 
  
          Guidelines for Advertisements for Recruiting Subjects 
          https://www.partners.org/Assets/Documents/Medical-
Research/ClinicalResearch/Guidelines-for-Advertisements.pdf  
  
          Remuneration for Research Subjects           https://www.partners.org/Assets/Documents/Medical-
Research/Clinical-Research/Remuneration-for- 
Research-Subjects.pdf  
  
  
CONSENT PROCEDURES  
Explain in detail how, when, where, and by whom consent is obtained, and the timing of consent 
(i.e., how long subjects will be given to consider participation).  For most studies involving more 
than minimal risk and all studies involving investigational drugs/devices, a licensed physician 
investigator must obtain informed consent.  When subjects are to be enrolled from among the 
investigators’ own patients, describe how the potential for coercion will be avoided. 
Although this is a minimal risk study, we will ask patients to consent 
(yes/no) via the initial REDCap survey. There are multiple ways a participant 
can be recruited to the study, all study patients will first fill out a consent 
survey that includes the language below.  
  
Are you interested in taking part in this study?  
  
By responding yes, you are confirming your willingness to receive 
unencrypted emails, complete surveys, that you are over the age of 18, 
have been diagnosed with breast cancer and received some treatment at 
MGH or its affiliates, and you have been measured with perometry for 
lymphedema at MGH. A copy of all the information listed above will be 
provided to you for your records.  
  

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By responding no, you will not be contacted again about this study. Thank 
you for your time. As a reminder, choosing not to participate in this study 
will not affect your care at MGH.  
  
NOTE: When subjects are unable to give consent due to age (minors) or impaired 
decisionmaking capacity, complete the forms for Research Involving Children as Subjects of 
Research and/or Research Involving Individuals with Impaired Decision-making Capacity, 
available on the New Submissions page on the PHRC website:  
      https://partnershealthcare.sharepoint.com/sites/phrmApply/aieipa/irb  
  
For guidance, refer to the following Partners policy:  
     Informed Consent of Research Subjects:      
https://www.partners.org/Assets/Documents/Medical-Research/ClinicalResearch/Informed-
Consent-of-Research-Subjects.pdf 
  
DATA AND SAFETY MONITORING  
Describe the plan for monitoring the data to ensure the safety of subjects.  The plan should 
include a brief description of (1) the safety and/or efficacy data that will be reviewed; (2) the 
planned frequency of review; and (3) who will be responsible for this review and for determining 
whether the research should be altered or stopped.  Include a brief description of any stopping 
rules for the study, when appropriate.  Depending upon the risk, size and complexity of the study, 
the investigator, an expert group, an independent Data and Safety Monitoring Board (DSMB) or 
others might be assigned primary responsibility for this monitoring activity.         
  
NOTE: Regardless of data and safety monitoring plans by the sponsor or others, the principal 
investigator is ultimately responsible for protecting the rights, safety, and welfare of subjects 
under his/her care.  
  
Data monitoring will be completed by the Senior Lymphedema Clinical  
Research Coordinator. Furthermore, the Senior Lymphedema Clinical 
Research Coordinator and the PI will assure compliance with all MGH IRB 
requirements as set forth by the institution to protect the rights, safety, and 
welfare of subjects.  
  

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 Describe the plan to be followed by the Principal Investigator/study staff for review of adverse 
events experienced by subjects under his/her care, and when applicable, for review of sponsor 
safety reports and DSMB reports.  Describe the plan for reporting adverse events to the sponsor 
and the Partners’ IRB and, when applicable, for submitting sponsor safety reports and DSMB 
reports to the Partners’ IRBs.  When the investigator is also the sponsor of the IND/IDE, include 
the plan for reporting of adverse events to the FDA and, when applicable, to investigators at 
other sites.    
  
NOTE: In addition to the adverse event reporting requirements of the sponsor, the principal 
investigator must follow the Partners Human Research Committee guidelines for Adverse Event  
Reporting 
  
The Senior Lymphedema Clinical Research Coordinator will review all adverse 
events as they occur and will work with the Principal Investigator regarding 
the grade and attribution of events. Adverse events are not anticipated in 
this study given it is low risk. In the event they do happen, they will be 
reported to the MGH IRB in accordance with the institution’s Adverse Event 
Reporting Guidelines.  
  
MONITORING AND QUALITY ASSURANCE  
 Describe the plan to be followed by the principal investigator/study staff to monitor and assure 
the validity and integrity of the data and adherence to the IRB-approved protocol.  Specify who 
will be responsible for monitoring, and the planned frequency of monitoring.  For example,  
 specify who will review the accuracy and completeness of case report form entries, source 
documents, and informed consent.    
  
NOTE: Regardless of monitoring plans by the sponsor or others, the principal investigator is 
ultimately responsible for ensuring that the study is conducted at his/her investigative site in 
accordance with the IRB-approved protocol, and applicable regulations and requirements of the 
IRB. 
  
The Senior Lymphedema Clinical Research Coordinator will monitor and 
assure the validity and integrity of the data and adherence to the 
IRBapproved protocol. This will include reviewing REDCap survey data every 
8 weeks for accurateness and completeness. The Principal Investigator will 
oversee this monitoring at regular monthly protocol meetings.  
For guidance, refer to the following Partners policies:           Data and Safety Monitoring Plans 
and Quality Assurance          https://www.partners.org/Assets/Documents/Medical-
Research/Clinical-Research/DSMP-inHuman-Subjects-Research.pdf  
  
          Reporting Unanticipated Problems (including Adverse Events)           
https://www.partners.org/Assets/Documents/Medical-
Research/ClinicalResearch/Reporting-Unanticipated-Problems-including-Adverse-
Events.pdf 
  

Partners Human Subjects Research Application Form  
    
Filename: Protocol Summary  
Version Date:  October 15, 2014  
  
   
15  
PRIVACY AND CONFIDENTIALITY  
Describe methods used to protect the privacy of subjects and maintain confidentiality of data 
collected.  This typically includes such practices as substituting codes for names and/or medical 
record numbers; removing face sheets or other identifiers from completed 
surveys/questionnaires; proper disposal of printed computer data; limited access to study data; 
use of password-protected computer databases; training for research staff on the importance of 
confidentiality of data, and storing research records in a secure location.    
  
NOTE: Additional measures, such as obtaining a Certificate of Confidentiality, should be 
considered and are strongly encouraged when the research involves the collection of sensitive 
data, such as sexual, criminal or illegal behaviors. 
  
In order to protect the privacy of subjects and maintain confidentiality of 
data collected, we will be using a secure MGB Patient Gateway 
communication to recruit the majority of patients.  Access to study data will 
be limited to the Lymphedema Research staff. It is possible de-identified 
data may be shared with statisticians in the future without the additional 
informed consent of participants.   
  
SENDING SPECIMENS/DATA TO RESEARCH COLLABORATORS OUTSIDE 
PARTNERS  
Specimens or data collected by Partners investigators will be sent to research collaborators 
outside Partners, indicate to whom specimens/data will be sent, what information will be sent, 
and whether the specimens/data will contain identifiers that could be used by the outside 
collaborators to link the specimens/data to individual subjects. 
Not applicable  
  
  
Specifically address whether specimens/data will be stored at collaborating sites outside 
Partners for future use not described in the protocol.  Include whether subjects can withdraw 
their specimens/data, and how they would do so.  When appropriate, submit documentation of 
IRB approval from the recipient institution. 
Not applicable  
  
  
RECEIVING SPECIMENS/DATA FROM RESEARCH COLLABORATORS OUTSIDE 
PARTNERS  
When specimens or data collected by research collaborators outside Partners will be sent to 
Partners investigators, indicate from where the specimens/data will be obtained and whether the 
specimens/data will contain identifiers that could be used by Partners investigators to link the 
specimens/data to individual subjects.  When appropriate, submit documentation of IRB approval 
and a copy of the IRB-approved consent form from the institution where the specimens/data 
were collected. 
Not applicable  

Partners Human Subjects Research Application Form  
    
Filename: Protocol Summary  
Version Date:  October 15, 2014  
  
   
16  
  
  
 

Partners Human Subjects Research Application Form  
    
Filename: Protocol Summary  
Version Date:  October 15, 2014  
  
   
17  
References  
  
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Factors associated with fear of lymphedema after treatment for breast cancer. Oncol. 
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[3] 
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Psychological consequences of lymphoedema associated with breast cancer: A 
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[4] 
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[10] Bevilacqua JLB, Kattan MW, Changhong Y, Koifman S, Mattos IE, Koifman RJ, et al. 
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Timing of Lymphedema After Treatment for Breast Cancer: When Are Patients Most At  
Risk? Int. J. Radiat. Oncol. Biol. Phys. 103, 62–70.  
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[17] NLN Medical Advisory Committee. 2012 Position Statement of the National 
Lymphedema Network: Risk Reduction. Natl. Lymphedema Netw.   
[18] Asdourian MS, Skolny MN, Brunelle C, Seward CE, Salama L, Taghian AG. 2016 
Precautions for breast cancer-related lymphoedema: Risk from air travel, ipsilateral 
arm blood pressure measurements, skin puncture, extreme temperatures, and 
cellulitis. Lancet Oncol. 17, e392–e405. (doi:10.1016/S1470-2045(16)30204-2)  
[19] Ferguson CM, Swaroop MN, Horick N, Skolny MN, Miller CL, Jammallo LS, et al. 2016 
Impact of ipsilateral blood draws, injections, blood pressure measurements, and air 
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The Statistical Analysis Plan (SAP) is included above in the Statistical Methods section and is 
part of our published paper which is cited below.   
Juhel, B. C., Brunelle, C. L., Bernstein, M. C., Smith, L. H., Jung, A. W., Ababneh, H. S., 
Hausman, E. K., Bucci, L. K., Bernstein, T., Naoum, G. E., & Taghian, A. G. (2023). Side 
effects of COVID-19 vaccinations in patients treated for breast cancer. Clinical and  
Experimental Medicine, 23(7), 3671–3680. https://doi.org/10.1007/s10238-023-01050-z