PREMIER: PREvention of Metabolic Illness Through prEcision nutRition
Phase: NA
Conditions: Obesity, Type 2 Diabetes, Metabolic Syndrome, Diet Habit, Nutritional and Metabolic Disease, Food Preferences
Sponsor: Massachusetts General Hospital

PARTNERS HUMAN RESEARCH COMMITTEE 
PROTOCOL SUMMARY 
Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
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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 
Sara Cromer, MD  
Research Staff, Diabetes Unit and Center for Genomic Medicine 
Richard B. Simches Research Center 
Massachusetts General Hospital (MGH) 
185 Cambridge Street 
Boston, MA 02114 
 
PROTOCOL TITLE 
PREMIER: PREvention of Metabolic Illness through prEcision nutRition 
 
FUNDING 
Pilot and Feasibility Award program from the Nutrition Obesity Research Center at Harvard 
(NORCH) 
 
VERSION DATE 
08/15/2023 
 
 
NCT ID number:  
2019P002638 
 
SPECIFIC AIMS 
Concisely state the objectives of the study and the hypothesis being tested. 
 
The proposed study will examine interpersonal post-prandial responses to specific foods and 
meals based on personal features and characterize their variability across study groups. We 
propose to conduct a recall-by-genotype study among individuals with extremes genotypes 
influencing dietary intake from the Partners Healthcare Biobank to study the glycemic and 
metabolomic responses to a standardized and an election meal in a full-day clinic visit. 
The specific objective of the PREMIER study is to carry out an interventional dietary study to 
measure the response of blood glucose and other biomarkers to a standardized meal or an 
election meal of varying nutritional content.  
The specific hypothesis of this study is that deep molecular, physiological, and behavioral 
profiling can identify mechanisms underlying variable responses to specific foods and meals. 
The study will deliver preliminary data to link underlying genetic influences for food preferences 
with variable metabolic responses to different types of meals. If successful, it is foreseen that this 
data could be used to inform personalized dietary interventions focused on optimizing substrate 
metabolism and body weight. 
 

Partners Human Subjects Research Application Form 
  
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
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BACKGROUND AND SIGNIFICANCE 
Provide a brief paragraph summarizing prior experience important for understanding the 
proposed study and procedures. 
 
Dietary intake is a major driving force behind the escalating obesity and type 2 diabetes (T2D) 
epidemics and is shaped by the confluence of social and environmental factors acting on a 
background of inherited biological differences (Atasoy et al., 2012; Rankinen and Bouchard, 
2006; Swinburn et al., 2011; van der Klaauw and Farooqi, 2015). To inform more effective 
obesity and T2D prevention strategies, it is crucial to better understand the biological, 
environmental, and social factors that influence how people interact and respond to specific 
foods (Cefalu et al., 2015; Hawkes et al., 2015; Unwin et al., 2010; White, 2016).  
In a recent large-scale genome-wide association study, our research team has identified 96 
genomic regions associated with overall variation in dietary intake (Merino et al., 2019). These 
findings provided insight into specific brain regions, cell types, and neural processes regulating 
food intake and intermediary metabolism. However, the clinical utility of this information 
remains largely unknown. Two recent advances in the genetics of complex traits could offer 
translational opportunities. First, the development of modern computational methods to cluster 
genetic variants based on underlying similarities, and collapsing them into cluster-specific 
polygenic scores (PSs), represents an efficient approach to capture genetic susceptibility and has 
the potential to deliver clinical benefit through enhanced capacity to maximize response to 
tailored behavioral interventions for the prevention and management of obesity and T2D (Udler 
et al., 2018; Udler et al., 2019). Second, the advent of recall-by-genotype studies, an approach to 
recall participants from clinical studies based on their specific genotype, can be used to identify 
people with the desired genotypes for clinical interventions and deep phenotyping (Corbin et al., 
2018). 
Connecting knowledge about human genetic variants with information from circulating 
metabolites can be particularly useful in understanding the mechanisms by which some people 
experience a detrimental response to specific foods. Large clinical trials have shown that close 
adherence to healthy lifestyle interventions can prevent or delay the progression to T2D by ~50% 
(Knowler et al., 2002; Pan et al., 1997; Ramachandran et al., 2006; Tuomilehto et al., 2001). 
However, large variability exists in response to dietary interventions (Korem et al., 2017; PW; 
Spector; Zeevi et al., 2015). Understanding the links between food intake signaling mechanisms 
and intermediate metabolism may help optimize the beneficial impact of dietary interventions 
and strengthen adherence to personalized dietary recommendations. 
 
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.”
 
We will recruit 30 healthy adults, 21-65 years of age for this study. Participants will be recruited 
from the Partners Healthcare Biobank, an electronic health records biorepository with clinical 

Partners Human Subjects Research Application Form 
  
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Version Date:  October 15, 2014 
 
  
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and genetic data from ~36,000 individuals, who have consented to re-contact and through Patient 
Research Invitation (PRI).  Participants will be excluded if they: 
● Refuse or are unable to give informed consent to participate in the study.  
● Have type I or type II diabetes mellitus or are taking medications for type II diabetes 
mellitus. Those not on medications but having a capillary glucose level of >126 mg/dL 
based on fingertip glucose measurements will be excluded.  
● Are obese (BMI>30.0kg/m2) or underweight (BMI≤18.5kg/m2). 
● Have had a heart attack (myocardial infarction) or stroke in the last 3 years.  
● Have had cancer in the last 3 years, excluding skin cancer.  
● Have an ongoing inflammatory disease i.e. Rheumatoid arthritis, systemic lupus 
erythematosus, polymyalgia and other connective tissue diseases.  
● History of cirrhosis and/or aspartate aminotransferase (AST) or alanine aminotransferase 
(ALT) more than 3 times the upper limit of normal (ULN). 
● No known sickle cell disease or anemia. 
● Are currently suffering from acute clinically diagnosed depression. 
● Currently taking or intending to take during the study duration any medication known to 
affect glycemic parameters, such as glucocorticoids or fluoroquinolones. 
● Are unable to fast from 9pm the night before the clinic visit until 9am on the clinic day 
● Are pregnant or breastfeeding. 
● Are participating in another clinical study. 
● Are vegan, suffering from an eating disorder or unwilling to eat foods that are part of the 
study.  
 
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.
 
Eligible participants who have reconsented to contact from the Partners HealthCare Biobank 
with desired genotypes and through Patient Research Invitation (PRI) will be contacted by study 
coordinators via our IRB approved contact letter. 
Eligible participants will then be invited to attend the Translational and Clinical Research Center 
at MGH for their visit. Before the visit, participants will be sent pre-visit instructions, 
questionnaires and consent forms. Informed consent will be taken at the visit. After participants 
have given informed consent to take part they will have a fasting blood sample taken. In the 
event that a participant does not provide informed consent, no samples will be collected from the 
participants. Participants will then undergo a brief medical examination to measure BP, waist 
circumference, weight and height. During the clinical visit, participants will be cannulated, 
consume a set breakfast and an election lunch and provide blood samples at 9 time points (at 
baseline, [Breakfast meal], 30, 60, 120, 180, 240, [Lunch meal], 270, 300, 360 minutes (all 
minute intervals are relative to their first bite of the breakfast test meal)).  
The subjects will also be asked to collect a stool sample the day of the visit or within 48 hours. In 
the event that a participant cannot produce a stool specimen during the visit, arrangements will 
be made to have the stool sample returned by mail. The participant will be given a stool 
collection kit containing illustrated instructions and all materials required to collect the stool 
specimen. The stool specimens will be collected into preservative-containing specimen tubes 

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using standard Human Microbiome Project protocols. There are no discernible risks associated 
with stool collection.  
 
 
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.
 
N/A 
 
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.
 
This study has been designed to reduce participant burden as much as possible while allowing 
for the robust data/specimen collection necessary to obtain predictive measures of dietary 
responses. All clinical procedures are routine and carry minimal risk, but are voluntary and 
participants can withdraw consent at any time.  
The risks associated with collecting blood anthropometrics and questionnaires, present minimal 
risks. Total blood volume is 134ml at the point it reaches the lab, and a total of 170 ml taken 
from participant. As this is below 300ml over at least 6 hours, this does not result in added risk. 
Normal blood donation volume is 450-500ml. If nursing staff have any reason to be concerned 
with this volume of blood draw for any individual participant then they will discharge the 
participant. A total of 170 ml is calculated as 134ml for sampling, plus up to 36 mL discarded 
when removing flush from the cannula (4mls at each blood draw except at baseline to remove the 
flush so 4mlx9=36ml). Randomized study IDs will be assigned to participants to protect the 
patients’ sensitive health information. Since these patients are healthy no adverse events are 
anticipated, however given that there is a dietary intervention involved participants will be 
monitored closely by study staff for possible adverse events during the visit day. 
 
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.
 
Participants can withdraw their consent at any time during the course of the study without giving 
any reason by contacting the study contact number. Similarly, the participant can withdraw their 
consent for the continued retention and use of their samples even after they have been collected, 
without giving a reason. Reason for discontinuation from the study will be asked about 
sensitively and recorded.  
If a subject withdraws consent to the use of donated biological samples, any retained samples 
will be disposed of/destroyed. If these samples have already been used for data analysis (e.g. 
sequencing or metabolite measurement) it will not be possible to destroy this data and it will 
remain as a part of the study, but any data that is retained will be anonymized.  

Partners Human Subjects Research Application Form 
  
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Version Date:  October 15, 2014 
 
  
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The Principal Investigator:  
● Will ensure subjects’ withdrawal of informed consent is recorded. Will ensure that 
biological samples from that subject, if stored at the study site, are immediately 
identified, disposed of/destroyed and the action documented.  
● Will ensure that the laboratory(ies) holding the samples is/are informed about the 
withdrawn consent immediately and that samples are disposed of/destroyed and the 
action documented.   
All participants must consume the baseline breakfast and provide baseline fasting bloods. Failure 
to meet these two requirements will result in termination of continued study participation as 
other endpoints will be unevaluable. If any other sample collections, dietary interventions, or 
blood timepoints are missed or unable to be completed, the subjects may continue with 
participation and these missing items will be logged by the study staff. 
 
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.
 
The risks associated with collecting blood, anthropometrics and questionnaires, present minimal 
risks. Potential risks and discomforts include phlebotomy, stress from abnormal laboratory 
values, and loss of confidentiality. 
Drawing blood involves minor risks and discomforts including brief pain and possibly a bruise at 
the needle/cannulation site. Occasionally, a person may feel faint when their blood is drawn. 
Infections rarely develop and are treatable.  
Some participants in this study will carry genetic risk and clinical factors for diabetes and it is 
therefore possible that some will have undiagnosed pre-diabetes or diabetes; some may have 
other unrecognized conditions that may come to attention through routine blood work during this 
study. Participants with laboratory values deemed by the study physicians to be clinically 
actionable will be informed by phone and letter and asked to follow up with their primary care 
physician, who may also be notified if the participant agrees. Physician’s phone and email will 
be listed on the letter so the subject can reach out to us if they have any questions about their 
results.  
Randomized study IDs will be assigned to participants to protect the patients’ sensitive health 
information, however there could be a breach in confidentiality involving protected health 
information, and the information collected from taking part in a genetic study could influence 
insurance companies or employers regarding a patient’s health. The privacy of all subjects will 
be protected and confidentiality maintained.  
 
EXPECTED BENEFITS 

Partners Human Subjects Research Application Form 
  
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Version Date:  October 15, 2014 
 
  
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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. 
 
There is no specific individual health benefit expected as a direct result of participating in this 
study. However, participants will be provided information about the laboratory results of their 
individual participation in the research study. We will provide lab results from the visit day that 
include glucose and insulin levels, kidney and liver function test, and lipid panel results that we 
will measure. The research we are doing is only a stepping stone in understanding metabolic 
responses to foods. Most of the findings that come from the study will not be relevant to personal 
health. These studies will help advance our clinical and scientific understanding of how 
metabolic processes in the body are influenced by diet and our microbiome and ultimately how 
these processes may contribute to factors influencing human health and disease. 
Participants will be remunerated for their time (US $70) following successful completion of the 
study. The remuneration will be in the form of general use, credit-card style (e.g. American 
Express or Visa) pre-loaded gift cards. Participants will receive two free meals during the study 
visit. They will also receive a voucher for your transportation to the study visit, which will cover 
the cost of parking or 2 passes on the MBTA. 
 
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.
 
Both men and women and persons of all races and ethnicities will be included. Pregnant women 
and those six months after giving birth or still breastfeeding will be excluded due to the potential 
for confounding on biomarkers/metabolites for dietary prediction models. 
 
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 nature of the recruitment and study procedures will require continuous and unscheduled 
patient interactions and the limitations of our study staff in speaking languages other than 
English preclude us from enrolling non-English speaking participants at this time. 
 
For guidance, refer to the following Partners policy: 
          Obtaining and Documenting Informed Consent of Subjects who do not Speak English

Partners Human Subjects Research Application Form 
  
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
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          https://www.partners.org/Assets/Documents/Medical-Research/Clinical-
Research/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.
 
The Partners HealthCare Biobank is a large research data and sample repository working within 
the framework of Partners Personalized Medicine. It provides Partners investigators with 
required approval from the Partners Institutional Review board (IRB) access to high quality, 
consented samples linked to clinical data stored, some additional health information and survey 
data, and genomic data. Participants will be contacted via a contact letter, and an opt-in/opt-out 
card. The first recruitment efforts will be with individuals who have given permission for re-
contact from the Partners HealthCare Biobank. We plan to recruit all required individuals from 
those who participated in the biorepository.  
Patient Research Invitation (PRI): RPDR will be used to pre-select MGB patients who have not 
yet opted-out from PRI, enrolled in Partners Biobank, between the ages of 18-79.  We will first 
perform chart reviews and RPDR queries to screen for potentially eligible subjects using the 
inclusion and exclusion criteria for this study.  Eligible potential subjects will then be contacted 
directly by researcher about the study via Patient Gateway message or letter or announcement.  
The patient gateway message/letter or announcement will explain the study in simple terms and 
include contact information (i.e. phone number and email for study team), so that the patients can 
choose to “opt-out”.  If the potential research subject has not declined further contact within 7 days 
of the Patient Gateway message and/or letter, the research coordinator will contact the patient via 
telephone to determine their interest in participating in the study and confirm their eligibility using 
a screening form based on the inclusion and exclusion criteria.  The research coordinator will send 
further information and an informed consent form via mail or email to eligible participants, inviting 
them to come to the first visit. 
The individuals who opt-in will be screened over the phone by the study team (see Call Script 
#1). Individuals who do not return the card will be called by the study team to gauge interest and, 
if interested, screened over the phone by the study team. Individuals who opt-out or who indicate 
they are not interested during the phone call will not be contacted further regarding this study. 
Potential participants who wish to participate in the study and meet no exclusion criteria will be 
mailed instructions for the first visit, and a copy of the consent form with encouragement for 
review prior to the first study visit. Any interim questions regarding the protocol will be 
answered over the phone. After reading the study protocol and consent form, potential 
participants who still wish to participate will be invited to attend the Visit. 
If the patient contacts the study coordinator by phone, the study coordinator will outline the 
study using a call script and assess eligibility (inclusion criteria) and minor exclusion criteria 
(e.g. pregnancy, food allergies to dietary components; see questionnaire script) and answer any 

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questions the patient may have. Additionally, if the patient does not contact the study coordinator 
within 2 weeks of sending the letter, they will be contacted by phone and the study will be 
outlined. If the patient indicates that they do not wish to learn more about the study, they will not 
be contacted further. If it becomes apparent during our recruitment that women or minorities are 
underrepresented, focused effort will be made to recruit additional members of these groups 
according to the demographics of the greater Boston area.  
If the participants are still interested and have met the initial screen, they will undergo a more 
detailed eligibility assessment performed by a study coordinator over the phone (see script). At 
this point the participants will be given an informational booklet, the Participant Information 
Sheet (PIS), and consent form, electronically or sent via mail, that fully describes the study. This 
booklet will assist in the informed consent process. If individuals remain interested in 
participating, the participants will be invited and scheduled to attend their clinical day at which 
time they will sign the informed consent.  
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
 
Participants will be remunerated for their time (US $70) following successful completion of the 
study. The remuneration will be in the form of general use, credit-card style (e.g. American 
Express or Visa) pre-loaded gift cards. 
 
 
For guidance, refer to the following Partners policies: 
          Recruitment of Research Subjects 
          https://www.partners.org/Assets/Documents/Medical-Research/Clinical-
Research/Recruitment-Of-Research-Subjects.pdf
 
          Guidelines for Advertisements for Recruiting Subjects
          https://www.partners.org/Assets/Documents/Medical-Research/Clinical-
Research/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.

Partners Human Subjects Research Application Form 
  
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Interested participants will be sent an information sheet (see Participant Information Sheet and 
Pre-visit instructions) and informed consent form by mail or by email, at least 2 weeks before 
their baseline visit is scheduled. At the baseline visit or the day before the first visit (if 
consenting remotely), it will be the responsibility of the researcher to obtain written (signed and 
dated by the participant and researcher) informed consent from each individual participating in 
the study after adequate explanation of the aims, methods, objectives, benefits and potential risks 
of the study. The researcher will also discuss the procedures that will happen as part of the study 
prior to consent taking and if the volunteers are willing, the relevant box on the consent form will 
be ticked. The researcher will also explain to the participants that they are completely free to 
refuse to enter the study or to withdraw from it at any time without obligation to give a reason. 
Participants will have the opportunity to ask questions before they sign the consent form. The 
participant will be provided with a copy of their signed and dated consent form and any other 
written information which they should be instructed to retain.  
In the event that a potential participant is known to one of the study investigators, (for example a 
work colleague or personal acquaintance) the study team will ensure that the informed consent 
procedures will be conducted by an alternative investigator who has no relationship with the 
volunteer. 
Consent will be taken by the designated trained researchers responsible for conducting the study 
and experienced in patient communication and consent taking. All potential participants will 
have been given the informed consent document and will have had adequate time to read it, 
understand the protocol, the risks and burdens and benefits, and will have had time to ask 
questions. The researchers will reiterate this information in person prior to taking consent. Only 
participants who have capacity to provide consent for themselves will be recruited. 
It is essential that participants fully understand the requirements of the study and therefore 
participants without a good understanding of verbal or written English will not be included in the 
study as there is not the provision for translation or interpreters. 
 
NOTE: When subjects are unable to give consent due to age (minors) or impaired decision-
making 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/Clinical-
Research/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 

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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. 
 
We do not anticipate safety issues since this study does not include a therapeutic intervention, 
beyond the risks outlined above for blood draws. The principal investigator will monitor data 
quality and integrity, review subject enrollment, and address any subject-related issues that might 
arise. It will be the discretion of the principal investigator and the sponsor to determine whether 
the research should be altered or stopped. 
 
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
 
 
 
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.
 
As this study is a dietary intervention study, safety monitoring will focus on unanticipated events 
involving risks to participants, including unanticipated problems that meet the definition of a 
serious adverse event.  

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Adverse event (AE): any untoward medical occurrence in a patient or study subject  
Serious adverse event (SAE): any untoward and unexpected medical occurrence or event that: 
 
1. Result in death  
2. Is life threatening  
3. Requires hospitalization or prolongation of existing in-patient hospitalization  
4. Results in persistent or significant disability or incapacity  
 
Medical judgement will be exercised in deciding whether an AE is serious. Important AEs that 
are not immediately life-threatening or do not result in death or hospitalization but may 
jeopardize the subject or may require intervention to prevent one of the other outcomes listed in 
the definition above will also be considered serious.  
Adverse events will be recorded and reported to the Principal Investigator. The event will also be 
documented and discussed with all members of the research group in the research departmental 
meetings and with the sponsor.  
All SAEs (both related and unrelated) will be recorded and reported immediately to the Principal 
Investigator and the sponsor. Relapse and death due to an unrelated or pre-existing condition, 
and hospitalization for treatment of a pre-existing condition do not require reporting as SAEs. 
All SAEs should be reported to the research ethics committee within 15 days of the Principal 
Investigator becoming aware where in the opinion of the Principal Investigator, the event was:  
1. Related i.e. resulted from administration of any of the research procedures  
2. Unexpected i.e. an event that is not listed in the protocol as an expected occurrence 
Although no formal adverse event reporting will take part in this study, any significant events 
relating to the procedures surrounding this study that the Investigator feels are important, will be 
documented as a Serious Adverse Event (SAE). Details of the SAE will then be kept in the 
Investigator site file and the Study Master File and notified to the IRB and sponsors as 
appropriate. 
The principal investigator will be reviewing each subject’s data periodically throughout the 
duration of the study for quality, validity and integrity assurance and for adherence to the IRB 
approved protocol. In addition, the study coordinators will monitor subject documents on an 
ongoing basis.  All source data will be organized and filed into subject binders.  Any pertinent 
notes to file regarding the subject will be documented by the study coordinator and kept in the 
applicable subject binder.  All subjects will be assigned a study identification number. In 
addition, interim and final data and safety monitoring reports performed twice during the study 
(at 1/3 and 2/3rds enrollment) by the principal investigator will include the following: 
● Changes to protocol including 
● Amendments to the protocol 
● Investigator/key personnel changes 
● Changes to the consent document and communications to participants 
regarding changes 
● Cumulative adverse event summary  
● Review and analysis of adverse events 
● A summary of any other safety issues 

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● Monitoring the progress of the study 
● Narrative summary of interim or final data analyses  
● Protocol adherence  
● Protocol violations 
● Protocol deviations 
● Recruitment and retention summaries 
● Enrollment numbers 
● Withdrawals (provide summary of reason(s) for withdrawal) 
● Dropouts (provide summary of reason(s) for dropouts) 
 
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-in-
Human-Subjects-Research.pdf 
 
          Reporting Unanticipated Problems (including Adverse Events)
          https://www.partners.org/Assets/Documents/Medical-Research/Clinical-
Research/Reporting-Unanticipated-Problems-including-Adverse-Events.pdf
 
 
 
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.
 
Personal information along with study data will be kept in REDCap, an online Partners approved 
data storage site or using an electronic clinical research form Microsoft Access database that is 
stored locally. Only study coordinators and Investigators will have access to this information. 
The In-study engagement team that interacts with participants during the study will have access 
to a participant’s name, phone number, and email address for the purposes of interacting with the 
participant, answering their questions and troubleshooting issues. However, any and all data 
stored at the completion of the study will be void of any personal health identifiers and only 
labelled with their study ID numbers. Only investigators and study staff will have access to the 
data stored in password protected computer databases. All laboratory samples will be labeled 
with a unique, non-identifying label.  
We may send deidentified samples to a third party, such as the Broad Institute or other suppliers 
for analysis. These specimens will not be linked to any individual identifiers associated with the 
patients. For sending deidentified samples to third party, we will generate a contract for this 
purpose through hospital supply chain. 

Partners Human Subjects Research Application Form 
  
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
13 
 
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.
 
Deidentified study data may be shared with our direct collaborators at the Broad Institute who 
will profile samples for metabolomics studies. We may collaborate with investigators at the 
Harvard T.H. Chan School of Public Health, or other instates for research purposes, laboratory 
assays, or analysis. Any biospecimens sent to collaborators, including blood, serum or stool 
samples for laboratory measurements or analysis will not be linked to any individual identifiers 
associated with the patients. Similarly, any data sent to collaborators for research purposes will 
be de-identified. Any additional collaborators outside Partners will be added through amendment 
of this protocol. We will obtain letter of agreement between academic collaborators prior to 
transfer of samples.  
 
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.
 
All specimens and data will be stored and maintained in the laboratory of Dr. Jose C. Florez (Co-
Investigator) at MGH 
 
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.
 
Data derived from eternal collaborators on specimens curated as part of this study, specifically 
from the Broad Institute or other suppliers for analysis, will be shared as agreed upon in the 
contracts negotiated with Partners.