A Randomized, Controlled Trial of an Online Health Tool About Down Syndrome
Phase: NA
Conditions: Down Syndrome
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 
BRIAN G. SKOTKO, M.D., M.P.P. 
 
PROTOCOL TITLE 
Down Syndrome Clinic to You (DSC2U) 
 
FUNDING 
PATIENT-CENTERED OUTCOMES RESEARCH INSTITUTE 
 
VERSION DATE 
February 28, 2017 
 
SPECIFIC AIMS 
Concisely state the objectives of the study and the hypothesis being tested. 
Our core objective is to leverage an innovative technology from 
Massachusetts General Hospital (MGH), which engages parents/caregivers, 
so that we can begin to reduce specific health care disparities experienced 
by those underserved patients with Down syndrome (DS). Specifically, 
through a randomized control trial (RCT), we will test whether 
patient/caregiver-initiated online reports with personalized recommendations 
versus usual care will increase caregiver-reported, provider-driven health 
actions consistent with national DS guidelines. While all patients with DS 
have a disparity as defined by their disability, we also intend to mitigate the 
compounding disparities of geographic location, race/ethnicity, and 
socioeconomic factors for the majority of families and overcome the limited 
reach of DS specialty care by taking advantage of the broader reach of the 
Internet. 
 
BACKGROUND AND SIGNIFICANCE 
Provide a brief paragraph summarizing prior experience important for understanding the 
proposed study and procedures. 
Down syndrome (DS) is a rare, chronically debilitating genetic condition 
caused by extra genetic material from chromosome 21. Patients with DS are 
prone to multiple chronic conditions over their lifetime, including congenital 
heart disease, thyroid conditions, gastrointestinal disorders, leukemia, 
obstructive sleep apnea, and accelerated aging, among others. Most patients 
with DS have their medical care managed by their primary care providers 
(PCPs), but a recent study showed that <10% of children and adolescents 
with DS are up-to-date on even the basic recommendations, such as thyroid 
screens, celiac testing, audiograms, eye exams, and sleep apnea testing. 

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Recognizing the challenge that PCPs have in staying current on all of the 
complexities of this condition, 58 Down syndrome specialty clinics have been 
formed in 32 U.S. states since 1967. Yet, despite their documented impact, 
the 58 DS-specialty clinics, combined, only serve about 12,000 patients with 
DS, which is <5% of the estimated population of people with DS living in the 
U.S. 
 
In 2014, the NIH published a revised research plan for DS research stating, 
“For individuals living with Down syndrome and their families, there is an 
ongoing need to study clinical and behavioral treatments and interventions”. 
In 2008, the Centers for Disease Control and Prevention published a “Public 
Health Research Agenda for Down Syndrome” stating that “more research is 
needed to identify optimal methods of monitoring for [the comorbid] 
conditions. In addition, prevention strategies need to be developed for those 
conditions amenable to prevention”. In 2011, the American Academy of 
Pediatrics (AAP) created DS Health Supervision Guidelines, including age-
specific screening tests and procedures. For adults, consensus-based 
guidelines exist. 
 
Our preliminary studies on our rules-based online intake from, which was 
collaboratively developed by MGH Down Syndrome Program (DSP) and MGH 
Laboratory of Computer Science (LCS) has shown potential for a sizeable 
benefit to our users, parents/caregivers and specialists. Our research will be 
both novel and innovative. We will offer our already created and tested 
online intake platform, rebranded as “Down Syndrome Clinic to You 
(DSC2U),” as a direct-to-public, always-available, online service yielding 
comprehensive, yet personalized recommendations for patients with DS who 
have limited access to specialty care. We want to provide game-changing 
care to the overwhelming majority of patients with DS who are underserved. 
 
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 plan to enroll 200 parents/caregivers from around the country in a two-
arm randomized controlled trial (RCT) over 21 months. 
 
Eligibility screening questions include: 
1. Do you have a child or dependent with Down syndrome? 
2. What is your child or dependent’s date of birth? 
3. When is your child or dependent’s next annual well visit (“PCP visit”) 
scheduled with his or her primary care provider? 

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4. What is the PCP’s contact information (first name, last name, city, and 
state)? 
5. Does your child or dependent currently receive care at a DS specialty 
clinic? (If the child is actively followed in a DS specialty clinic, he or 
she would be ineligible.) 
6. What is the name and e-mail address of the caregiver or legal 
guardian who will be participating in this research? 
a. Will this person be attending the PCP visit with the child or 
dependent? Yes/No 
b. If “No”, will this person be committed to seeing that the letters of 
recommendation generated from this study get delivered to the PCP 
during this visit? Yes/No 
7. What is your child or dependent’s race? 
8. What is your child or dependent’s ethnicity? 
9. What is your child or dependent’s sex? 
10. If I am eligible to participate in this study, I prefer to receive study 
materials, such as forms to fill out and my caregiver checklist, in: 1) 
English or 2) Spanish 
 
In order to be eligible, the parent/caregiver need to respond “Yes” to 
questions #1, “No” to question #5, and must provide information to #2, #3, 
#4, #6, #7, #8, #9, and #10 as well as a valid e-mail address for all study 
communication purpose. In addition, we can only allow one patient’s 
caregiver for each participating PCP since multiple patients seen by the same 
PCP would not be independent events. 
 
Down syndrome occurs naturally and proportionally in all races and 
ethnicities, so our estimates are proportional to the racial/ethnic distribution 
of the U.S., as reported in the 2010 U.S. Census. 
 
We would like to achieve this diversity in our enrolled participants. To this 
extent, we will then use a quota system in offering enrollment. Based on our 
idealized Enrollment Table (below), we will enroll no more than 144 whites 
and no fewer than 32 Hispanics (Latinos/Latinas) and 26 Blacks/African 
Americans. We will also enroll no more than 102 participants of either sex. 
 

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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.
Potential eligible participants will be directed to our study recruitment 
website (www.downsyndromeclinictoyou.com) to complete the eligibility 
screening questionnaire (Appendix A). Information of frequently asked 
questions and answers will also be provided on our study recruitment 
website (Appendix B). After a questionnaire is submitted and a 
parent/caregiver is deemed eligible, our study personnel will send an email 
notification containing a unique link to our online consent form in REDCap 
(Appendix C). Once they have provided consent, the parent/caregiver will 
continue on to complete the baseline assessment. Our study personnel will 
then be notified by e-mail, after which we will randomize the participant 1:1 
to either the Intervention or Control arm (Appendix D). 
 
To limit chance confounding between variables that might influence guideline 
compliance, we will stratify randomization based on two variables (six 
strata) collected prior to randomization during the Baseline assessment 
when data are gathered only from parents (PCPs are first surveyed after 
their appointment with the patient who has Down syndrome): 
 
 Travel time to primary care physician: < 30 minutes; 30–60 minutes; 
> 60 minutes 
 Primary insurance: public (e.g., Medicaid, Medicare) or private 
 
Given the sequence of study procedures, we will not stratify on any variables 
reported by the PCP. With 200 participants randomized, we expect to 

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achieve effective mixing of PCP characteristics that might be associated with 
differential guideline compliance. Moreover, by not conditioning on PCP 
characteristics, findings from our primary analysis will be most broadly 
generalizable. However, we do want to increase precision in our secondary 
analyses by accounting for relevant sources of variation among PCP 
practices. To this extent, we will collect the following variables for inclusion 
as covariates: 
 
 PCP practice size: < 5 MDs; 5–9 MDs; 10+ MDs (collected in PCP 
Experience Survey during Post-visit Assessment 1) 
 PCP practicing in a federally qualified community health center: yes or 
no (collected in PCP Experience Survey during Post-visit Assessment 1) 
 Years of PCP practice (collected in PCP Experience Survey during Post-
visit Assessment 1) 
 Number of patients with Down syndrome cared for by PCP (collected in 
PCP Experience Survey during Post-visit Assessment 1) 
 
Baseline Assessment (Intervention & Control Arms) 
The intervention and control groups will both complete a Baseline 
Assessment; up to 3 e-mail reminders will be sent to the parent/caregiver 
every 1 week. The Baseline Assessment, implemented using REDCap 
(Research Electronic Data Capture), a secure, NIH-funded, and Health 
Insurance Portability and Accountability Act (HIPAA) compliant web-based 
application hosted by Partners HealthCare Research Computing, will request 
the following information: 
 
 Caregiver information: first name, last name, gender, date of birth, 
relationship to patient, phone number, address, and email address 
 Child or dependent’s information: first name, last name, gender, date of 
birth, race/ethnicity (NIH standardized format) 
 PCP information: first name, last name, gender, office phone, office 
address and e-mail (if available) 
 Travel time to primary care physician: < 30 minutes; 30–60 minutes; > 
60 minutes 
 Primary insurance: public (e.g., Medicaid, Medicare) or private 
 Date of annual well visit (“PCP visit”) appointment 
 Symptoms indicating need for celiac disease testing or sleep study. We 
plan to assess these symptoms among other symptoms not related to 
these conditions so as to minimize any priming effects.  For example, 
“Does your child snore at night?” might be asked next to “Does your 
child have any rashes?”  (A sleep study might be warranted for snoring, 
but not for rashes.) (Appendix E) 
 Health Care Outcome Survey (Metrics measuring adherence to national 
health care guidelines): thyroid screening, celiac disease screening, sleep 
apnea testing, ophthalmology exams, and audiograms (Appendix F) 

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 Secondary outcome measures: PedsQL 2.0 Family Impact Module and 
PedsQL 4.0 parent-proxy, standard Short Form 15 Generic Core Scales 
(Appendix G) 
 
Intervention Arm 
After submission of the Baseline Assessment, the parents/caregivers will be 
e-mailed a unique link to their DSC2U intervention form. The 
parent/caregiver will need to enter the month and day of birth of the person 
with Down syndrome to access their form. Using that information and their 
unique link, they can return to and complete the DSC2U form (Appendix H) 
at their convenience. Reminder e-mails to complete the DSC2U form will be 
sent at 4, 3, and 2 weeks prior to their son’s/daughter’s scheduled PCP 
annual well visit appointment. After they have completed DSC2U form, the 
system will send the parent/caregiver a link to their Caregiver Checklist 
(Appendix I) and Primary Care Provider Plan (Appendix J), which they will 
access by entering the month and day of birth of the person with Down 
syndrome. The DSC2U Caregiver Checklist and Primary Care Provider Plan 
will be accessible online until the end of the study period and may be 
downloaded and printed at the user’s discretion. 
 
Control Arm 
After submission of the Baseline Assessment, parents/caregivers in the 
Control arm will be sent an e-mail message thanking them for their 
participation in the study. Included will be a reminder to let study personnel 
know if their son’s/daughter's scheduled appointment with the PCP changes. 
Control arm participants will be receiving usual care—that is, the natural 
advice and recommendations that would be offered by their PCPs. (Upon 
conclusion of the RCT, control group participants will be offered the same 
Caregiver Checklist and Primary Care Provider Plan intervention.) 
 
PCP Visit 
Prior to each patient’s scheduled PCP visit, the parent/caregiver will receive 
2 reminders for their upcoming appointment, including a request to let our 
study personnel know if the date of the appointment has changed. Because 
the timing between study enrollment and scheduled PCP visit will vary 
among participants, we will plan to send these appointment reminders at 
approximately 4 weeks, then 1 week prior to the scheduled appointment. 
 
Post-Visit Assessments (Both Intervention and Control Arms) 
 Secondary outcome measures: PedsQL 2.0 Family Impact Module; 
PedsQL 4.0 parent-proxy, standard Short Form 15 Generic Core Scales 
(Appendix G) 
 
In addition, with direct input from our Patient/Caregiver working group (WG) 
and PCP WG, we will be designing three novel surveys: 

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 Health Care Outcome Survey (for parents/caregivers) (for Primary 
Outcomes) (Appendix F) 
 Parent/Caregiver Experience Survey (for Secondary Outcomes) 
(Appendix K) 
 Primary Care Provider Experience Survey (for Secondary Outcomes) 
(Appendix L) 
 
Survey Implementation 
The Experience Surveys (for both the parents/caregivers and PCPs) will be 
administered approximately 2 weeks after the PCP visit at Post-visit 
Assessment 1 (T1) (Figure 1). Parents/Caregivers will be invited by e-mail to 
complete their experience survey through REDCap. PCPs will receive their 
experience survey by mail, with an option to complete the survey 
electronically on REDCap. PCPs whose e-mails were provided by the 
parents/caregivers will also receive a direct invitation by e-mail to complete 
their survey. In order to minimize loss to follow-up, reminder e-mails will be 
sent 3 times about 2 weeks apart, concluding with a phone call in the eighth 
week by our study personnel. We certainly hope to maximize the PCP 
response rate, but our primary outcomes are not dependent on their 
responses. 
 
Parents/Caregivers will be asked by e-mail to complete the Health Care 
Outcomes Survey through REDCap approximately seven months after the 
PCP visit at Post-visit Assessment 2 (T2) (Figure 1). In order to minimize 
loss to follow-up, reminder e-mails will be sent 3 times about every 2 weeks 
apart, concluding with a phone call in the 8th week by our study personnel. 
 
Figure 1. Survey implementation at various points.  
 
Baseline: Health Care Outcome Survey, PedsQL 2.0 Family Impact Module and PedsQL 4.0 
parent-proxy, standard Short Form 15 Generic Core Scales 
 
T0 (PCP Visit) 
 
T1 (Post-visit Assessment 1): PedsQL 2.0 Family Impact Module and PedsQL 4.0 parent-proxy, 
standard Short Form 15 Generic Core Scales, Parent/Caregiver Experience Survey, and PCP 
Experience Survey 
 
T2 (Post-visit Assessment 2): Health Care Outcome Survey, PedsQL 2.0 Family Impact Module 
and PedsQL 4.0 parent-proxy, standard Short Form 15 Generic Core Scales 
 
Validation Assessment 
Ten percent of the respondents across both groups will be asked to validate 
their self-report by providing documentation of laboratory and procedural 
results. For example, if parents attest to thyroid checks being done for their 

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sons/daughters, they will be asked to send documentation of the primary 
outcomes (e.g. study report or physician sign off). These participants will 
also receive 3 reminder e-mails and a phone call every 2 weeks. 
 
If discrepancies are identified between parental report and source 
verification in more than 10% of these samples, then our team will perform 
a full verification of all 200 participants. Verification will be made by source 
documentation (e.g., sleep study reports) or verbal confirmation through 
telephone calls to primary care physicians. 
 
Primary Outcomes:  
We will be measuring adherence to detect improvement in: thyroid 
screening, celiac disease screening, sleep apnea testing, ophthalmology 
exams, and audiograms 
 
 Thyroid: TSH should be checked annually beginning at age 1 
 Celiac disease: if symptoms present, obtain tTG-IgA and total IgA 
annually 
 Sleep study: performed by 4 years of age and, again, if symptomatic 
 Ophthalmology exam: annually, ages 1-5; every 2 years, ages 5-13; 
every 3 years, ages 13-21; every 2 years, ages 21 and older 
 Audiograms: annually up to age 21, every 2 years thereafter 
 
The indication for 1, 2, 3, 4, or 5 evaluations for a given participant at the 
time of their PCP visit based on age, history, and symptoms will be collected 
prior to randomization as described in the “Baseline Assessment” section. 
 
Secondary Outcomes:  
We also want to determine whether the intervention improves quality of life 
as measured by the nationally validated PedsQL survey instruments. 
 
Six summary scores will be derived from the two PedsQL instruments: 
measures of (1) psychosocial health, (2) physical health, and (3) an overall 
total score from the PedsQL 4.0 parent-proxy, standard Short Form 15 
Generic Core Scales; and measures of (4) parental health-related quality of 
life, (5) family functioning, and an (6) overall total score from the PedsQL 
2.0 Family Impact Module. 
 
We will also measure the quality of experience with the intervention from 
parents and PCPs and identify ways that the Caregiver Checklist and Primary 
Care Provider Plan could best serve the needs of underserved patients with 
DS. For this assessment, rather than assuming we know which questions to 
ask to best assess their experience, we will engage our Parent/Caregiver and 
PCP WGs to help us pose relevant questions. Our expectation is that the 
assessments will ask for their level of satisfaction with the content and 

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guidance offered by the Caregiver Checklist and Primary Care Provider Plan, 
similar to the voluntary questionnaire used in our preliminary study 
described above. We also anticipate including open-text responses solicited 
from caregivers and providers about their experience using the system. 
 
Data Analysis Plan 
Our primary analysis will compare the mean number of caregiver-reported 
evaluations completed within 7 months of the index PCP visit between the 
intervention and usual care arms. We will analyze the data using a 
generalized linear model assuming beta-binomial distributed counts of 
evaluations among those indicated with parameters estimated by maximum 
likelihood. We will confirm our inference using a permutation test by direct 
randomization of assigned treatment labels. Significant benefit will be 
declared if the mean number of recommended tests is greater among 
participants randomized to the intervention and a two-tailed p-value for the 
treatment comparison is less than 0.05. A significant effect of the 
intervention will be declared only if the permutation test concurs with 
inference from the beta-binomial regression as the permutation test makes 
no assumptions concerning the true distribution of the data. We will analyze 
longitudinal changes in our secondary outcome measures using a shared-
baseline repeated-measures ANOVA for each of 6 quality of life outcomes 
derived from the two PedsQL instruments. Linear contrasts will be used to 
test for treatment-specific improvements over time. As a sensitivity analysis, 
we will also use simple two-group Wilcoxon ranksum tests to compare 
changes from baseline in each follow-up assessment individually. With 6 
secondary outcomes, we will test each secondary outcome at alpha = 0.008 
two-tailed to control for multiple comparisons. 
 
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 
 
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.
Our study does not involve any diagnostic or treatment procedures. The risk 
associated with participating in this study is considered to be minimal and 
commensurate with everyday risks. No physical or economic harm is 
anticipated. A foreseeable risk and discomfort of participating in this study is 
the time and effort of filling out “Down Syndrome Clinic to You” and study 
questionnaires. It will be made clear during the recruitment and consent 
process that the participation is totally voluntary, and parent/caregivers may 
discontinue participation at any time during the study period. Deciding not 
be part of the study will not change participants’ regular medical care in any 

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way. We will also implement several safety measures (storing de-identified 
participant data in password-protected databases and limiting access to 
study data to only study team) to ensure that personal data is protected. 
Study participants will be assured that no information will be published in 
any manner that would personally identify them. 
 
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.
The attribution of any adverse events to this study is categorized as 
Unlikely. The principal investigator will, however, evaluate any adverse 
events and report these to the Partners Human Research Committee 
(PHRC). Any serious adverse events will be reported within 24 hours of the 
event, followed by a complete written report within 10 working days. 
Adverse events considered to be mild or moderate will be summarized in the 
progress report for the continuing review, as specified by the PHRC adverse 
event reporting guidelines. 
 
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 risk associated with participating in this study is considered to be 
minimal and commensurate with everyday risks. Our research activities will 
not cause any physical, psychological, financial, or legal harm to 
participants. The only study-related risks that participants could be exposed 
to are those relating to privacy and confidentiality. We have implemented 
several safety measures (storing de-identified participant data in password-
protected databases and limiting access to study data to only study team) to 
ensure that personal data is protected. The likelihood that this data will 
remain secure is very high. Study participants will be assured that no 
information will be published in any manner that would personally identify 
them. 
 
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. 

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Study participants who are assigned to the intervention group to complete  
DSC2U form then receive customized “Caregiver Checklist” and “Primary 
Care Provider Plan” will have a greater likelihood of an improvement in 
adherence to the national Down syndrome guidelines. Study participants 
who are assigned to the control group will receive current standard of care 
and there will be no immediate potential benefits to this group of 
participants during the RCT period. However, participants in the control 
group will be offered the opportunity to complete the DSC2U form and 
receive a personalized “Caregiver Checklist” and “Primary Care Provider 
Plan” upon conclusion of the study. In addition, the “Primary Care Provider 
Plan” would potentially improve PCP’s practice behaviors by providing 
personalized information based on evidence-based guidelines. 
 
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.
For the RCT, parents/caregivers who have sons and/or daughters with DS, of 
all ages, living in the U.S. who do not have access to a DS specialty clinic 
are eligible for this study. To emphasize, we are enrolling the 
parents/caregivers and not their sons/daughters with DS. Both English-
speaking and Spanish-speaking families will be recruited. All genders, races, 
and ethnicities will be given the same opportunities to participate in research 
activities. Participants will have equal exposure to recruitment through our 
recruitment website. Our “Down Syndrome Clinic to You” (DSC2U) will be 
developed both in English and Spanish. 
 
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.
As our “Down Syndrome Clinic to You” (DSC2U) will be developed both in 
English and Spanish, both English-speaking and Spanish-speaking families 
will be recruited. 
 
For guidance, refer to the following Partners policy: 
          Obtaining and Documenting Informed Consent of Subjects who do not Speak English
          https://partnershealthcare-public.sharepoint.com/ClinicalResearch/Non-
English_Speaking_Subjects.1.10.pdf
 
 
 

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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.
We plan to enroll 200 total parents/caregivers for the RCT. 
 
In order to capture participants who do not have access to a DS specialty 
clinic, we plan to recruit our participants through multiple mechanisms and 
media (Appendix M): (1) the NIH’s DSConnect®, a national contact registry, 
where parents/caregivers from around the country have indicated that they 
are interested in being contacted for potential research opportunities about 
DS, (2) e-newsletters, Facebook, and Twitter postings of DS advocacy 
groups around the country, (3) our own Facebook and Twitter postings, and 
(4) registering at the NIH’s Clinicaltrials.gov. States/regions without a DS 
specialty clinic will be targeted initially and preferentially. While all patients 
with DS have a disparity as defined by their disability, we intend to mitigate 
the compounding disparities of geographic location, race/ethnicity, and 
socioeconomic factors for the majority. We have incorporated a strategy to 
maximize our study participants’ retention by reaching out to study 
participants via up to 3 follow-up e-mails and a reminder phone call at 
various study points. 
 
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
Parent/caregiver participants of our RCT will receive $50 total for completion 
of the study: $10 after completing the Baseline Assessment, $10 after 
completing the two-week post-visit assessment 1, and $30 after completing 
the seven-month post-visit assessment 2. An additional $20 will be given to 
parents/caregiver participants in the validation set. PCPs will receive $40 
after completing the two-week post-visit experience questionnaire. We will 
purchase online gift cards through Partners reloadable gift card service or 
from Amazon.com or other national retailer.  The electronic links to these 
activated gift cards will be sent electronically to the caregivers after survey 
completion. 
 
For guidance, refer to the following Partners policies: 
          Recruitment of Research Subjects 
          https://partnershealthcare-
public.sharepoint.com/ClinicalResearch/Recruitment_Of_Research_Subjects.pdf
 
          Guidelines for Advertisements for Recruiting Subjects

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          https://partnershealthcare-
public.sharepoint.com/ClinicalResearch/Guidelines_For_Advertisements.1.11.pdf
 
          Remuneration for Research Subjects
          https://partnershealthcare-
public.sharepoint.com/ClinicalResearch/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.
Online consent form will be sent to all eligible participants via email. Eligible 
participants (parents/caregivers) will be able to view all of the elements of 
informed consent online in REDCap (Appendix C). Questions for the study 
could be sent to our study personnel via email. All consent will be obtained 
via REDCap. Two buttons (Yes and No) will be located at the end of study 
consent page. By click on the “YES, I AGREE TO PARTICIPATE IN THIS 
RESEARCH” button, parents/caregivers will be enrolled to our study. By click 
on “NO, EXIT THE PROGRAM” button, parents/caregivers will not be enrolled 
to the study and will be redirected to our study recruitment website main 
page. Online consent form can be printed and/or saved as PDF file. Eligible 
participants will have up to 5 days to provide his/her consent. 
 
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://partnershealthcare-
public.sharepoint.com/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 

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14 
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 will use REDCap (Research Electronic Data Capture), a secure, NIH-
funded, and Health Insurance Portability and Accountability Act (HIPAA) 
compliant web-based application hosted by Partners HealthCare Research 
Computing to collect parent/caregiver baseline assessment, parent/caregiver 
post-visit assessment 1, and parent/caregiver post-visit assessment 2. 
Primary care providers can submit their PCP post-visit experience via regular 
mail or through REDCap. Parents/caregivers can submit their 
documentations of laboratory and procedural results via regular mail or e-
mail. 
 
Data collected via REDCap are secured and stored behind the Partners 
firewall and follow Partners Healthcare Information Security policies for 
authenticated, minimum access. Data collected via regular mail will be 
scanned and stored electronically in our secure, access-limited, password-
protected research folder on the Partners shared drive, same as data that 
are collected via e-mail. Original copies of data collected via regular mail will 
then be disposed in the HIPAA-compliant bins at Massachusetts General 
Hospital. 
 
We will use a secure, web-based application, SproutScribe, to support the 
DSC2U intervention. SproutScribe was developed by the MGH Lab of 
Computer Science to support the intelligent transformation of collected 
structured data into custom narratives. The application has been reviewed 
and approved by Partners Information Security and is currently used to 
support clinical care reporting in the MGH Down Syndrome Program, the 
MGH Lurie Center for Autism and MGH Cardiology. Structured data collected 
from the DSC2U intervention form itself is secure and stored behind the 
Partners firewall and follows Partners Information Security policies for 
authenticated, minimum access. 
 
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.   
 

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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 attribution of any adverse events to this study is categorized as 
Unlikely. The principal investigator will, however, evaluate any adverse 
events and report these to the Partners Human Research Committee 
(PHRC). Any serious adverse events will be reported within 24 hours of the 
event, followed by a complete written report within 10 working days. 
Adverse events considered to be mild or moderate will be summarized in the 
progress report for the continuing review, as specified by the PHRC 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.
Only Principal Investigator (PI) and the study’s research staffs directly 
involved in the data collection will have access to the identifiable information 
about study participants. 
 
Data collected from the RCT will be stored electronically in our secure, 
access-limited, password-protected research folder on our hospital’s secured 
drive. The original paper copies of any study-related materials will be 
discarded, after scanning, in the designated HIPAA-compliant blue recycling 
bins at MGH for confidential materials. Partners Information Services (IS), a 
division within Partner Healthcare Systems (PHS), manages all data and 
voice communication networks as well as other core infrastructure systems 
and applications across the Partners environment. All systems are secured 
behind the Partners firewall and follow Partners Healthcare Information 
Security policies for authenticated, minimum access. All systems are 
patched, monitored, and scanned routinely for vulnerabilities and intrusions 
by the systems administrator and PHS Information Security. All configuration 
changes that could affect accessibility or security are approved by 
management. All systems administrative personnel and support staff have 
completed the NIH training program in Computer Security and have 
additionally completed their certification in the Collaborative Institutional 
Training Initiative (CITI) program. CITI was developed by experts at PHS, 
MGH, and Brigham and Women’s Hospital and with outside institutions in the 

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Summary 
Version Date:  October 15, 2014 
 
  
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"IRB community" and consists of courses in the Protection of Human 
Research Subjects for Biomedical Research. 
 
For guidance, refer to the following Partners policies: 
          Data and Safety Monitoring Plans and Quality Assurance
            https://partnershealthcare-
public.sharepoint.com/ClinicalResearch/DSMP_in_Human_Subjects_Research.pdf  
          
          Reporting Unanticipated Problems (including Adverse Events)
          https://partnershealthcare-
public.sharepoint.com/ClinicalResearch/Reporting_Unanticipated_Problems_including_A
dverse_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.
Data collected via REDCap are secured and stored behind the Partners 
firewall and follow Partners Healthcare Information Security policies for 
authenticated, minimum access. Data collected via regular mail will be 
scanned and stored electronically in our secure, access-limited, password-
protected research folder on the Partners shared drive, same as data that 
are collected via e-mail. Original copies of data collected via regular mail will 
then be disposed in the HIPAA-compliant bins at Massachusetts General 
Hospital. 
 
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 

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 Filename: Protocol 
Summary 
Version Date:  October 15, 2014 
 
  
17 
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