Clinical Utility of Prenatal Whole Exome Sequencing
Phase: NA
Conditions: Structural Anomalies, Cardiac Anomalies, Central Nervous System Anomalies, Thorax Anomalies, Genito-urinary Anomalies, Gastrointestinal Anomalies, Skeletal Anomalies, Multiple Anomalies
Sponsor: University of California, San Francisco

Clinical Utility of Prenatal Whole Exome Sequencing: Study Protocol 
NCT03482141 
Document Approval Date: 9/30/2022 
 
 

 
 
Study Application (Version 1.22) 
 
1.0 
General Information 
2.0 
Add departments 
2.1 and Specify Research Location: 
 
3.0 
List the key study personnel: (Note: external and affiliated collaborators who 
are not in the UCSF directory can be identified later in the Qualifications of 
Key Study Personnel section at the end of the form) 
3.1 *Please add a Principal Investigator for the study: 
Norton, Mary MD, MD 
Select if applicable 
  Department Chair 
  Resident 
  Fellow 
If the Principal Investigator is a Fellow, the name of the Faculty Advisor must be supplied below.  
3.2 If applicable, please select the Research Staff personnel 
A) Additional Investigators 
Ackerman, Sara, PhD, MPH 
Other Investigator 
Beleford, Daniah A MD, PhD 
Other Investigator 
Curry, Cynthia 
Study Clinician 
Keller, Roberta, MD 
Other Investigator 
Koenig, Barbara, PhD 
*Enter the full title of your study: 
Clinical Utility of Prenatal Whole Exome Sequencing 
*Enter the study alias: 
Prenatal WES 
* This field allows you to enter an abbreviated version of the Study Title to quickly identify this 
study. 
Is 
Primary? Department Name 
 
UCSF - 118044 - M_Human Genetics 

Co-Principal Investigator 
Kwok, Pui-Yan Dr., MD, PhD 
Co-Principal Investigator 
Lianoglou, Billie R 
Other Investigator 
Michie, Marsha, PhD 
Other Investigator 
Sanders, Stephan MDPhD 
Other Investigator 
Sherr, Elliott MD, PhD 
Other Investigator 
Shieh, Joseph, MD, PhD 
Other Investigator 
Slavotinek, Anne PhD, PhD 
Co-Principal Investigator 
Sparks, Teresa N 
Study Clinician 
B) Research Support Staff 
Amezcua, Jessica M 
Study Coordinator 
Anguiano, Beatriz 
Research Assistant 
Chang, Jiyoo 
Research Assistant 
Chen, Flavia H 
Research Assistant 
Cullen, Caitlin 
Clinical Research Associate 
Dong, Shan 
Technician 
Downum, Sarah L 
Study Coordinator 
Farrell, Rachel L 
Study Recruiter 
Faubel, Amanda J 
Study Coordinator 
Gosnell, Kristen A 
Study Nurse 
Hoban, Hannah G 
Study Coordinator 
Hutchinson, Romobia 
Study Coordinator 
Michelson, Jeremy 
Research Assistant 
Norstad, Matthew 
Research Assistant 
O'Leary, Allison S 
Study Coordinator 
Oman, Natalie 
Study Coordinator 
Outram, Simon M 
Clinical Research Associate 

Patel, Sachi 
Study Coordinator 
Perry, Rachel L 
Study Nurse 
Rangwala, Naseem A 
Research Assistant 
Rego, Shannon M 
Study Recruiter 
Rigler, Nicole A 
Study Coordinator 
Ryan, Tamara L 
Study Nurse 
Sahin Hodoglugil, Nuriye N 
Study Coordinator 
Schwartz, Grace B 
Technician 
Scudmore, Janice C 
Study Nurse 
Shear, Matthew 
Research Assistant 
Silver, Julia M 
Study Recruiter 
Silver, Julia M 
Study Recruiter 
Thao, Kao N 
Study Coordinator 
Tick, Katherine 
Clinical Research Associate 
Tobias, Sarah E 
Study Recruiter 
Valdez Lopez, Priscila A 
Study Coordinator 
Yamane, Taylor A 
Research Assistant 
Yip, Tiffany A 
Study Recruiter 
3.3 *Please add a Study Contact 
Koenig, Barbara, PhD 
Lianoglou, Billie R 
Norton, Mary MD, MD 
Sahin Hodoglugil, Nuriye N 
The Study Contact(s) will receive all important system notifications along with the Principal 
Investigator. (e.g. The project contact(s) are typically either the Study Coordinator or the Principal 
Investigator themselves). 
3.4 If applicable, please add a Faculty Advisor/Mentor: 
3.5 If applicable, please select the Designated Department Approval(s) 

Add the name of the individual authorized to approve and sign off on this protocol from your 
Department (e.g. the Department Chair or Dean). 
4.0 
Initial Screening Questions 
Updated January 2019 - Revised Common Rule (January 2018) Compliant - v92 
4.1 * PROJECT SUMMARY: (REQUIRED) Give a brief overview of this project (250 words or less). Tell us 
what this study is about, who is being studied, and what it aims to achieve. If you have an NIH 
Abstract, paste it here (Click on the orange question mark to the right for more detailed instructions): 
Genome sequencing, which allows physicians to look at many genes concurrently, has been 
rapidly integrated into the clinical setting but its usefulness remains uncertain. The UCSF Program 
in Prenatal and Pediatric Genome Sequencing (P3EGS) will study the effectiveness of sequencing 
as a tool for 1) diagnosing infants and children with serious developmental disorders, and, 2) 
providing genetic information to parents when a prenatal study reveals a fetus with a structural 
anomaly. We will also address ethical, social and economic issues in the delivery of genomic 
sequencing results to diverse populations, such as under represented minorities and the medically 
underserved. This protocol is specifically focusing on the prenatal aspect of the broader P3EGS 
project. A separate protocol will be submitted simultaeously for the pediatric patients. Other 
studies, such as those using interviews to follow families offered sequencing, will be submitted to 
the IRB as separate protocols. 
4.2 * HUD DEVICE: (REQUIRED) Does this application involve a Humanitarian Use Device (HUD): 
  No 
  Yes, and it includes a research component 
  Yes, and it involves clinical care ONLY 
4.3 * TYPE OF RESEARCH: (REQUIRED) Select the option that best fits your project (Click the orange 
question mark to the right for definitions and guidance): 
  Biomedical research (including medical records review, biospecimen collection and/or use, 
other healthcare or health outcomes related activities, research database, biospecimen bank, 
or recruitment registry) 
  Social, behavioral, educational, and/or public policy research 
  Hybrid - includes aspects of BOTH types of research (check this option if your research is 
mainly social/behavioral but also involves specimen collection or blood draws to look at 
biological measures) 
4.4 * SUBJECT CONTACT: (REQUIRED) Does this study involve ANY contact or interactions with 
participants: 
  Yes (including phone, email or web contact) 
  No (limited to medical records review, biological specimen analysis, and/or data analysis) 
4.5 * RISK LEVEL: (REQUIRED) What is your estimation of the risk level, including all screening 
procedures and study activities: 
  Minimal risk 
  Greater than minimal risk 

4.6 * REVIEW LEVEL: (REQUIRED) Requested review level (Click on the orange question mark to the 
right for definitions and guidance): 
  Full Committee 
  Expedited 
  Exempt 
4.7 * EXPEDITED REVIEW CATEGORIES: (REQUIRED) If you think this study qualifies for expedited 
review, select the regulatory categories that the research falls under: (check all that apply) 
  Category 1: A very limited number of studies of approved drugs and devices 
  Category 2: Blood sampling 
  Category 3: Noninvasive specimen collection (e.g. buccal swabs, urine, hair and nail clippings, 
etc.) 
  Category 4: Noninvasive clinical procedures (e.g. physical sensors such as pulse oximeters, 
MRI, EKG, EEG, ultrasound, moderate exercise testing, etc.) 
  Category 5: Research involving materials (data, documents, records, or specimens) that were 
previously collected for either nonresearch or research purposes 
  Category 6: Use of recordings (voice, video, digital or image) 
  Category 7: Low risk behavioral research or research employing survey, interview, oral 
history, focus group, program evaluation, human factors evaluation, or quality assurance 
methodologies 
* Does the collection of blood samples meet requirements outlined by HHS 
Office for Human Research Protections for Expedited Review Research 
Category 2: (REQUIRED) 
For healthy, nonpregnant adults who weigh at least 110 pounds the 
amounts drawn may not exceed 550 ml in an 8 week period and 
collection may not occur more frequently than 2 times per week; 
From other adults and children, considering the age, weight, and 
health of the subjects, the collection procedure, the amount of blood 
to be collected, and the frequency with which it will be collected, the 
amount drawn may not exceed the lesser of 50 ml or 3 ml per kg in 
an 8 week period and collection may not occur more frequently than 2 
times per week 
  Yes  
 No 
4.9 * DATA/SPECIMEN ANALYSIS ONLY: (REQUIRED) Does this study ONLY involve records review and 
/or biospecimen analysis (do not check 'Yes' if this is a registry, research or recruitment database, or 
biospecimen repository): 
   Yes  
   No 
4.10 * CLINICAL TRIAL: (REQUIRED) 
Is this a clinical trial: 
According to The World Health Organization (WHO) and the 
International Committee of Medical Journal Editors (ICMJE) a 
clinical trial is: 
Any research study that prospectively assigns human participants or 
groups of humans to one or more health-related interventions to 
evaluate the effects on health outcomes. 
 

ICMJE requires registration of a clinical trial in a public database (such as 
ClinicalTrials.gov) prior to enrollment, for eventual publication of results in 
member biomedical journals. 
Guidance: Public Law 110-85 requires that all investigators who perform 
an applicable clinical trial must ensure that the trial is registered on a 
government web site called ClinicalTrials.gov. 
The FDA requires registration for 'applicable clinical trials,' defined 
as follows: 
For any trials of drugs and biologics: controlled clinical investigations, 
other than Phase 1 investigations, of a product subject to FDA 
regulation. 
For trials of biomedical devices: controlled trials with health outcomes 
of devices subject to FDA regulation, other than small feasibility 
studies, and pediatric post-market surveillance. 
For additional information on the ClinicalTrials.gov registration process at 
UCSF and the definition of a clinical trial for purposes of registration, visit 
the ClinicalTrials.gov section of the UCSF Clinical Research Resource 
HUB. 
  Yes  
 No 
Clinical Trial Registration - 'NCT' number for this trial: 
 
NCT03482141 
4.11 * CLINICAL TRIAL PHASE: (REQUIRED) Check the applicable phase(s): 
  Phase 0 
  Phase 1 
  Phase 1/2 
  Phase 2 
  Phase 2/3 
  Phase 3 
  Phase 4 
  Not Applicable 
4.12 * INVESTIGATOR-INITIATED: (REQUIRED) Is this an investigator-initiated study: 
  Yes  
 No 
The UCSF IRB recommends use of the Virtual Regulatory Binder to 
manage your study. 
4.13 * CANCER: (REQUIRED) Does this study involve cancer (e.g., the study involves patients with cancer 
or at risk for cancer, including behavioral research, epidemiological research, public policy research, 
specimen analysis, and chart reviews): 
   Yes  
   No 
 

4.14 * RADIATION EXPOSURE: (REQUIRED) Does your protocol involve any radiation exposure to patients 
/subjects EITHER from standard care OR for research purposes (e.g., x-rays, CT-scans, DEXA, CT- 
guided biopsy, radiation therapy, or nuclear medicine including PET, MUGA or bone scans): 
   Yes  
   No 
4.15 SCIENTIFIC REVIEW: If this study has undergone scientific or scholarly review, please indicate 
which entity performed the review (check all that apply): 
  Cancer Center Protocol Review Committee (PRC) (Full approval is required prior to final IRB 
approval for cancer-related protocols.) 
  CTSI Clinical Research Services (CRS) Advisory Committee 
  CTSI Consultation Services 
  Departmental scientific review 
  Other: 
* Specify Other: (REQUIRED) 
 
NIH 
4.16 * STEM CELLS: (REQUIRED) Does this study involve human stem cells (including iPS cells and adult 
stem cells), gametes or embryos: 
  No 
  Yes, and requires IRB and GESCR review 
  Yes, and requires GESCR review, but NOT IRB review 
4.17 * FINANCIAL INTERESTS: (REQUIRED) Do you or any other responsible personnel (or the spouse, 
registered domestic partner and/or dependent children thereof) have financial interests related to 
this study: 
   Yes  
   No 
5.0 
Funding 
5.1 * FEDERAL FUNDING: (REQUIRED) Is this study currently supported in whole or in part by Federal 
funding, even by a subcontract, OR has it received ANY Federal funding in the past: 
  Yes  
 No 
5.2 * DoD INVOLVEMENT: Is this project linked in any way to the Department of Defense (DoD): 
(REQUIRED) 
   Yes  
   No 
5.3 SPONSORS: Identify all sponsors and provide the funding details. If funding comes from a 
Subcontract, please list only the Prime Sponsor: 
External Sponsors: 
 
View 
Awardee 
Contract Project 
UCSF 
RAS 
System 
Award 

 
Other Funding Sources and Unfunded Research - Gift, Program, 
Departmental or other Internal Funding (check all that apply): 
  Funded by gift (specify source below) 
  Funded by UCSF or UC-wide program (specify source below) 
  Specific departmental funding (specify source below) 
  Unfunded (miscellaneous departmental funding) 
  Unfunded student project 
* Identify the gift, program, departmental, or other internal funding source: 
(REQUIRED) 
 
UCSF Women's Reproductive Health Research (WRHR) Career Development Program 
6.0 
Sites, Programs, Resources, and External IRB Review 
6.1 UCSF AND AFFILIATED SITES (check all that apply): 
  UCSF Benioff Children's Hospital Oakland (BCHO) 
  UCSF China Basin clinics and facilities 
  UCSF Helen Diller Family Comprehensive Cancer Center 
  UCSF Langley Porter Psychiatric Institute (LPPI) 
  UCSF Medical Center at Mission Bay (Benioff Children's Hospital, the Betty Irene Moore 
 
Details Sponsor Name 
Sponsor Type 
Institution: Type: 
Number 
Number 
("A" + 
6 
digits) 
NIH Natl Human 
Genome Research 
Inst. 
01 
UCSF 
Grant 
P0518017 
Sponsor Name: 
NIH Natl Human Genome Research Inst. 
Sponsor Type: 
01 
Sponsor Role: 
Funding 
CFDA Number: 
Grant/Contract Number: 
Awardee Institution:: 
UCSF 
Is Institution the Primary 
Grant Holder: 
Yes 
Contract Type: 
Grant 
Project Number: 
P0518017 
UCSF RAS System Award 
Number ("A" + 6 digits): 
Grant Number for Studies Not 
Funded thru UCSF: 
Grant Title: 
Genomic sequencing to aid diagnosis in pediatric and 
prenatal practice: Examining clinical utility, ethical 
implications, payer coverage, and data integration in a 
diverse population. 
PI Name: 
(If PI is not the same as 
identified on the study.) 
Pui-Yan Kwok 
Explain Any Significant 
Discrepancy: 

Women's Hospital, Bakar Cancer Hospital, or outpatient clinics) 
  UCSF Mount Zion 
  UCSF Parnassus (Moffitt-Long hospital, dental clinics or other outpatient clinics) 
  UCSF Other Sites (including Laurel Heights and all the other sites outside the main hospitals) 
  Zuckerberg San Francisco General (ZSFG) 
  SF VA Medical Center (SF VAMC) 
  Fresno - UCSF Fresno OR Community Medical Center (CMC) 
  Gladstone 
  Institute on Aging (IOA) 
  Jewish Home 
  SF Dept of Public Health (DPH) 
  Vitalant (formerly Blood Centers of the Pacific and Blood Systems Research Institute) 
Research involving ZSFG: You are required to obtain additional 
approvals from the ZSFG Dean's Office. Download the ZSFG Protocol 
Application Form and submit the completed form to the 
ZSFG Dean's Office. 
We rely on the Community Medical Center IRB for all research at 
the UCSF Fresno campus and Community Medical Center. Check 
'Yes' to relying on an external IRB in 6.10 below. 
6.2 LOCATIONS: At what locations will study visits and activities occur: 
Study participants will be seen, recruited and followed up with primarily at UCSF Betty Irene 
Moore Women’s Hospital (BIMWH), UCSF Benioff Children’s Hospital Mission Bay (BCHMB), UCSF 
Benioff Children’s Hospital Mission Bay (BCHO), Zuckerberg San Francisco General Hospital 
(ZSFGH) and UCSF Fresno Community Medical Center. 
6.3 OFF-SITE PROCEDURES: Will any study procedures or tests be conducted off-site by non-UCSF 
personnel: 
   Yes  
   No 
6.4 RESEARCH PROGRAMS: Check any UCSF research programs this study is associated with: 
  Cancer Center 
  Center for AIDS Prevention Sciences (CAPS) 
  Global Health Sciences 
  Immune Tolerance Network (ITN) 
  Neurosciences Clinical Research Unit (NCRU) 
  Osher Center 
  Positive Health Program 
6.5 * CTSI CRS SERVICES: (REQUIRED) Will this study be carried out at one of the UCSF Clinical Research 
Services (CRS) units or utilize CRS services: 
   Yes  
   No 
6.6 * MULTI-CENTER TRIAL: (REQUIRED) Is this a multi-center or multi-site research trial: 
By 'multi-center trial' we mean a study where the protocol is developed 
by an lead investigator, an industry sponsor, consortium, a disease-group, 

etc.,and multiple sites across the nation or in different countries participate 
in the trial. The local sites do not have any control over the design of the 
protocol. 
   Yes  
   No 
6.8 OTHER SITE TYPES: Check all the other types of sites not affiliated with UCSF with which you are 
cooperating or collaborating on this project: 
Do NOT check any boxes below if this is a multi-center clinical 
trial, UCSF is just one of the sites, and neither UCSF nor one of its 
faculty-linked affiliates (SF VAMC, Gladstone, ZSFG) are the 
coordinating center. 
  Other UC Campus 
  Other institution 
  Other community-based site 
  Foreign Country 
  Sovereign Native American nation (e.g. Navajo Nation, Oglala Sioux Tribe, Havasupai, etc.) 
6.11 * OUTSIDE RELIANCES: (REQUIRED) Are any of the collaborating sites requesting to rely on UCSF's 
IRB: 
   Yes  
   No 
6.14 * RELYING ON AN EXTERNAL IRB: (REQUIRED) Does this application include a request to rely on an 
external IRB (a central IRB (other than the NCI CIRB) or an external IRB (other UC campus, 
commercial, or institutional): 
   Yes  
   No 
Check 'Yes' since we rely on the Community Medical Center IRB for 
reseach that takes place in Fresno. 
7.0 
Outside Site Information 
7.1 Outside Site Information 
If you have more than 10 sites to add, list the outside sites in the 
Outside Sites List document and upload it in the Other Study 
Documents section of the Initial Review Submission Packet form. 
Any sites requesting to rely on UCSF's IRB must be listed below. 
Click "Add a new row" to enter information for a site. Click it again to add a second site again to 
add a third site, a fourth site, etc. 
 
Outside Site Information 

 
8.0 
Research Plan and Procedures 
8.1 HYPOTHESIS: Describe the hypothesis or what the study hopes to prove: 
In the pediatric population whole exome sequencing is estimated to identify a diagnosis in 
approximately one-third of all cases. Considering the extreme phenotype of cases with congenital 
anomalies and experience from labs that are currently offering prenatal whole exome 
sequencing, we expect the yield to be higher than the pediatric experience. Whole exome 
sequencing is an ideal approach to the prenatal population given its comprehensive nature and 
ability to detect involved genes that may not have initially been suspected. Additionally, initiating 
genetic studies with whole exome sequencing, as opposed to targeted sequential genetic testing, 
would reduce turn around time to facilitate earlier parental understanding of a fetal diagnosis and 
maximize family planning options. 
This research will contribute novel information about the frequency of genetic disorders in fetuse 
with congenital anomalies, enabling providers to more accurately counsel about prognosis, 
individualize antenatal care, allow more informed decision-making, and anticipate specific 
neonatal needs. By examining genotype-phenotype correlations, it will facilitate a precision-based 
approach for future targeted neonatal (and ultimately antenatal) therapies such as enzyme 
replacement or stem cell transplantation. The NIH has recognized the importance of such a 
 
Non-UCSF affiliated site information: 
Site name: 
UCSF Fresno/Community Medical Center 
Contact name: 
Cynthia Curry 
Email: 
cynthia.curry@gmail.com 
Phone: 
559-459-2269 
For Federally-funded studies only, corresponding FWA#: 
* The research at this site will be reviewed by: 
 The non-affiliated site's IRB or a private IRB 
 The non-affiliated site is requesting UCSF to be the IRB of 
record for this study 
 The non-affiliated site is not engaged in the human subjects 
research and has provided a letter of support 
If the other site's IRB approval letter is available now, attach it to 
the application. If the IRB approval letter is not yet available, 
submit it once you receive it. 
Or, if the other site is not engaged in human subjects 
research, attach the letter of support to your application. 

precision-based approach to medical care.21 Further, this research will contribute substantially to 
our understanding of women’s preferences surrounding crucial decision points during an affected 
pregnancy and after delivery. 
8.2 AIMS: List the specific aims: 
Our specific aims will: 
1) examine the clinical utility of exome sequencing, including assessment of a variety of health- 
related and reproductive outcomes, in 400 undiagnosed prenatal cases. 
2) address ethical, social and economic issues in the delivery of genomic sequencing results to 
ancestrally and economically diverse populations through (2.1) a mixed methods, longitudinal 
empirical study of clinical interactions and experiences, (2.2) an economic analysis of insurance 
coverage, price and reimbursement of multigene tests, and (2.3) creation of an Ethics Advisory 
Board to respond to emerging issues and establishment of authentic stakeholder engagement; and 
3) pilot a user-friendly web-based patient/provider application integrating genomic and clinical 
data as a shared evidence base to support result communication, interpretation and clinical 
decision making; the application will be based on the “Bioscreen” model created and successfully 
implemented at UCSF. 
8.3 DESIGN: Briefly describe the study design (e.g., observational, interventional, randomized, placebo - 
controlled, blinded, cross-over, cross-sectional, longitudinal, pharmacokinetic, etc.): 
Any patient with a fetus identified by ultrasound to have a severe congenital anomaly and have 
had or will have prenatal diagnosis for chromosome analysis or microarray analysis will be offered 
the option for additional testing by whole exome sequencing. The patient will be educated 
regarding the anomalies identified on ultrasound and meet with a genetic counselor associated 
with the study to review the risks, benefits and limitations of whole exome sequencing (WES). 
After a comprehensive conversation related to WES the patient will be offered to pursue this 
testing with the cost of testing covered through the study. Because exome sequencing is a new 
approach, a small number of parents and families will be invited to participate in an additional 
study, this would include both patient that pursued WES and those that declined. That study will 
involve being interviewed by a member of our team, by telephone or in person. 
To achieve diversity, patient ascertainment and recruitment will occur at three sites where 
prenatal imaging and counseling take place, these sites that serve a broad range of under- 
represented minority (URM) populations and span the full socio-economic spectrum, including the 
underserved. The sites include UCSF Betty Irene Moore Women’s Hospital (BIMWH), UCSF Benioff 
Children’s Hospital Mission Bay (BCHMB), Zuckerberg San Francisco General Hospital (ZSFGH) 
and UCSF Fresno Community Medical Center; these sites have patient populations representing 
up to 80% URM and 60% from underserved backgrounds. 
Following consent and collection of standardized phenotypic and demographic data, the families 
will undergo WES as part of clinical care. If prenatal testing had been performed at an outside 
laboratory specimen will be coordinated, for WES at UCSF. After counseling, sequencing and 
variant analysis and interpretation by our expert group, study subjects will meet with their 
clinicians to receive results. For pregnancies resulting in a live birth, infants will continue to be 

followed for 6-12 months after birth to assess medical decision-making for the child and provision 
of genetic information for other family members. 
We will examine the following outcomes in order to assess clinical utility in prenatal patients: (i) 
pregnancy termination, (ii) in-utero medical or surgical intervention, (iii) perinatal decision- 
making, e.g. antepartum surveillance, location and mode of delivery, non-intervention or 
perinatal hospice care, (iv) immediate neonatal management, and (v) reproductive decision- 
making subsequent to the index pregnancy. 
Our team of clinicians, molecular genetics specialists and bioinformaticians are highly qualified to 
perform these analyses; we will examine and contrast clinical and personal utility across the 
social spectrum and among under-represented minority groups. In parallel, our bioethics and 
health economics groups will follow and study patient/provider interactions and insurance 
coverage/reimbursement. And to enhance clinical decision making, our clinical and informatics 
groups will design and implement a pilot approach to user-friendly sharing of clinical and genetic 
information to families and health care providers. 
A series of surveys will be administered to the patient at various time points including the time of 
consent, return of results and 6-12 month follow-up. These surveys are designed to further the 
study goals of understanding the personal and clinical utility of exome sequencing. These surveys 
may be done in person, by phone, emailed, or mailed to you after the clinic visit. A $50 total in 
gift cards will be provided to subjects that complete the surveys. $20 will be provided after the 
first survey and $30 for the second. 
8.4 BACKGROUND AND SIGNIFICANCE: Briefly provide the background and significance of this study (e.g. 
why is this study needed) (space limit: one half page): 
If this is a first in humans study, please summarize the safety data from 
the animal studies. For pediatric drug or device studies, please identify if 
this is the first study in pediatric populations. 
Next-generation sequencing (NGS) is changing the paradigm of clinical genetic testing. Unlike 
highly focused single-gene tests, NGS allows one to examine gene panels, the exome, and the 
whole genome. With the broad array of molecular tests now available, ordering physicians face 
the conundrum of selecting the best diagnostic tool for patients with suspected genetic conditions. 
Single-gene testing is often most appropriate for conditions with distinctive clinical features and 
minimal locus heterogeneity. NGS-based gene panel testing, which can be complemented with 
chromosomal microarray analysis (CMA) and other ancillary methods, provides a comprehensive 
and feasible approach for well documented but genetically heterogeneous disorders. Whole 
exome sequencing (WES) and whole genome sequencing (WGS) have the advantage of enabling 
parallel interrogation of most of the genes in the human genome. To some, WES is preferable to 
previously used methods due to higher diagnostic yield, shorter time to diagnosis, and improved 
cost-efficiency. 
The ability to survey the exome opens up both new opportunities and new challenges. For 
example, all coding regions of known genes must be analyzed when applying WES to 
undiagnosed cases with unclear inheritance patterns. Current limitations on variant interpretation 
capabilities and clinical validity raise questions about the clinical utility of WES as either a stand- 
alone or a first-choice diagnostic test. Additional challenges include pre- and post-test counseling 
with appropriate and robust informed consent, bioinformatics analysis setup and validation, 
variant interpretation and classification, the need for policies and protocols concerning the 
discovery and reporting of secondary findings unrelated to the presenting indication, a 
requirement for validation of WES results, assurance of conformation to quality control standards, 
data storage and accessibility, and reimbursement issues. 

Current clinical standards recommend offering chromosomal microarray (CMA) in the prenatal 
setting when fetal structural anomalies are detected via prenatal ultrasound. In these cases, 
clinically relevant copy number variants have been reported in 6.0-9.1% of fetuses with a normal 
karyotype. However, informed consent processes for prenatal CMA are challenging—particularly in 
cases with ultrasound anomalies, as parents are absorbing challenging news and under 
considerable stress. Women have reported being “blindsided” by positive CMA results, or feeling 
that these results were “toxic information”—information they wished they did not have, 
particularly in cases of uncertain genetic information or uninterpretable variants. Nonetheless, in 
that same study women who were referred for CMA because of ultrasound anomalies reported 
less frequent negative reactions, since they already anticipated abnormal results. 
Introducing WES into prenatal clinical care of underrepresented populations raises additional 
issues and considerations of payment coverage, access, and standards of care. Beyond the sheer 
complexity of the test and its results, clinicians and health systems must address numerous 
considerations, including: private and public insurance coverage; language and culture differences 
and their implications for genetic counseling and clinician-patient relationships; ability to access 
follow-up testing and clinical care; ability to access appropriate treatment and services; and 
particularly in the prenatal setting, local, state, and national abortion laws and decision-making 
about pregnancy termination. These issues and others will affect not only patients’ decision- 
making regarding WES, but also their post-test needs for patient follow up, counseling and 
support. The importance of systematically assessing the clinical utility of NGS is critical for 
determining in which clinical and health care contexts WES will be useful and for commencing 
research on these considerations. 
8.5 PRELIMINARY STUDIES: Briefly summarize any preliminary studies relevant to your proposed 
research (space limit: one half page): 
The UCSF group has gained significant experience over the past 3 years in providing NGS to 
patients through its Personalized Genomics Clinic and the Genomic Medicine Initiative. UCSF 
BCHMB has a specialized clinic that unifies the consent process, results session and follow up for 
patients undergoing WES. The clinic is currently held twice a month and staffed by Drs. 
Slavotinek and Shieh, together with a dedicated genetic counselor, Marta Sabbadini. To date, 
more than 150 patients ranging in age from newborn to adult, referred from numerous providers, 
have been seen in this clinic. Referring indications have included ID, multiple congenital 
anomalies, seizures/encephalopathy, and other neurological presentations, including stroke 
/hemorrhage, chronic pain, ataxia, muscle weakness, central hypoventilation, dysautonomia, 
pontocerebellar hypoplasia, and movement disorders. Over 90% of patients have been sequenced 
as trios (proband and both biological parents). In the first 57 patients taken from the group of 
greater than 150 patients, a possible causative sequence variant was identified, and a definitive 
diagnosis was made in 25/57 (44%). In an assessment of clinical utility for the first 49 positive 
results (excluding fetuses), 24/49 had a result-directed improvement in clinical care, one had 
withdrawal of care, three had the introduction of a targeted treatment or diagnosis related 
therapy, 43/49 received critical reproductive information and 13/49 received reproductive 
information that was directly relevant for testing of other family members or for other family 
members planning children (data not shown).We therefore have experience in the assessment of 
clinical utility from patients undergoing WES. 
IHG Genomics Core Facility and the Genomic Medicine Initiative. Under the auspices of the UCSF 
Genomic Medicine Initiative, we have achieved CLIA certification for next-generation sequencing 
for over one year. The first clinical sequencing test launched was a cancer gene panel that 
compares the tumor and germline DNA of a patient. Over the last year, we have sequenced 2,844 
samples successfully, resulting in many cases where target specific therapies are chosen for the 
patients. We have also obtained WES data for 152 clinical and control samples in the process of 
obtaining CLIA certification for clinical WES at UCSF. The data obtained so far compared favorably 
against sequencing data for the same samples from outside CLIA certified laboratories (including 
that at UCLA and GeneDx). In addition, we have performed WES on 10,768 samples for research 
purposes. With a highly experienced sequencing staff and bioinformatics group, we have 
established a strong team to perform both clinical and research sequencing. 
8.6 * TREATMENT PROTOCOL: Is this a treatment study, i.e. does this study intend to provide treatment 
to individuals with a medical or psychological condition: (REQUIRED) 
   Yes  
   No 

8.7 * BILLABLE PROCEDURES: Does this study involve any procedures, lab tests or imaging studies that 
have a CPT code and could be billable to patients, their insurance, Medi-Cal, Medicare, or any other 
entity (answer 'Yes' even if the study is going to pay for all the procedures): (REQUIRED) 
   Yes  
   No 
If you are not sure if your study involves billable procedures, send 
an email to the UCSF Office of Clinical Research (OCR) for help 
answering this question. 
8.8 * COMMON RESEARCH ACTIVITIES: Types of research activities that will be carried out. Check all that 
apply and describe in more detail in the 'Procedures / Methods' section: (REQUIRED) 
  Interviews, questionnaires, surveys 
  Educational or cognitive tests 
  Focus groups 
  Social media-based research activities 
  Observation 
  Fitness tests or other exertion activities 
  Use of mobile health apps or other apps 
  Collection of data from wearable tech such as Fitbit, Apple Watch, Garmin, motion actigraphs, 
etc.) 
  Non-invasive imaging or testing (MRI, EEG, pulse oximetry, etc.) 
  Imaging procedures or treatment procedures that involve radiation (x-rays, CT scans, CT- 
guided biopsies, DEXA scans, MUGA or PET scan) 
  Administration of contrast agent 
  Randomization to one intervention versus another 
  Use of placebo 
  Biopsy conducted solely for research purposes 
  Sham surgical procedure 
  None of the above 
8.9 * PROCEDURES / METHODS: (REQUIRED) 
Describe the research methods and study activities taking place at each site 
(e.g. what will participants be asked to do and what will members of the 
study team do?). If there will be multiple participant groups or study sites, 
explain what will happen with each group or study sites. 
If some of the activities would occur even if the person were not in the 
study, as in the case of treatment or tests performed for diagnostic 
purposes, clearly differentiate between those activities that will be 
done solely for research purposes and those that are happening as 
part of routine care. 
Please call our office at 415-476-1814 and ask to speak to someone on the 
Expedited Review team if you need help differentiating between what parts 
are research and what parts aren't. 
We anticipate enrolling up to 75-85 participants per year. 
1. Recruitment: 
Personnel within the UCSF Fetal Treatment Center, UCSF Prenatal Diagnosis Center, 
Benioff Children's Hospital Oakland Fetal Treatment Center, Zuckerberg San Francisco 
General Hospital or UCSF Fresno Community Medical Center will identify and recruit 

participants. Additionally, we will offer enrollment to patients consented to exome 
sequencing through a second study our team is offering (IRB 17-21662 (Fetal birth defects 
prospective database: Toward a precision-based approach)). 
2. Consent: 
Personnel at each site will consent to Exome Sequencing. Anticipated enrollment will be 
around 75-85 cases per year from all sites. 
Trio Exome Sequencing obtained for each enrolled participant 
Affected fetus and biological parents are both important for estimating clinical implications 
of variants. The following fetal samples will also be collected: chorionic villli, amniotic fluid, 
cord blood, fetal tissue (stillbirth or Intrauterine Fetal Demise), neonatal blood, or 
extracted fetal/neonatal DNA from the above detailed specimens. Parents saliva or blood 
will suffice for biological parents samples. 
Sample Processing and Reporting 
Consent, sample collection, whole exome sequencing and banking. Findings will be reported to 
clinical staff including physicians and genetic counselors associated with this study. These 
clinicians will review results with the the patient and their family. 
Results from exome sequencing that will be provided to the participants and their families, and 
that could contribute to clinical decision-making include (1) variants known to cause or contribute 
to the birth defect found in the fetus and, (2) in cases where the participant has indicated in the 
consent form that they wish to learn about additional findings with medical significance, variants 
in genes of medical significance outside of the primary indication for testing (additional or 
secondary findings). 
In cases in which a variant is identified that could be either inherited or de novo, if the father has 
declined participation, the potential that this variant could be inherited from the father will not be 
shared with him, given his active declination. 
If the father has declined participation, and a variant is found in the fetus that is likely to have 
been inherited from the father (e.g. an autosomal recessive disorder is diagnosed in the fetus), 
the basic genetic inheritance will be explained to the mother. If the father has declined 
participation, we will not contact him again to share results. 
As part of the consenting process, when talking with the fathers, we will explain these potential 
outcomes to assure they understand the full implications of consenting, or declining to consent. 
We may use exome sequencing to sequence a large proportion of the currently known and 
unknown genes in some affected individuals. Sequencing unknown genes, such as many of the 
tests that will be performed for this study, are considered experimental in nature. As such, the 
accuracy and usefulness of these experimental tests has yet to be determined, and the 
conclusions of these test results may be uncertain. 
We will place the resulting phenotypic and genotypic data in a controlled-access database at the 
National Institutes of Health. Use of the data will not be restricted to any one condition or the 
condition for which the sample was obtained. The patient will have the option to opt out of 
inclusion of their data in this database in the consent process. 
After informed consent has been obtained a series of surveys will be administered to the patient 
at various time points including the time of consent, return of results and 6-12 month follow- 
up. These surveys are designed to further the study goals of understanding the personal and 
clinical utility of exome sequencing.These surveys may be done in person, by phone, emailed, or 
mailed to you after the clinic visit. A $50 total in gift cards will be provided to subjects 
that complete the surveys. $20 will be provided after the first survey and $30 for the second. 
Participation in the study will take a total of about 2-3 hours over a period of 3 or more days. 
In addition: We will contact executives, administrators, managers or clinicians at UCSF via 
email to ask if they are willing to complete a survey about organizational readiness to change 
(ORCA). This survey will be administered once via Redcap or on paper and will not involve any 
personal identifiers. The goal of the survey is to learn more about their views on the potential 
for implementation of clinical sequencing in healthcare systems and communities. The de- 
identified data will be pooled by the University of Washington to include data from the rest of the 
CSER2 consortium. The ORCA will be administered to 6-10 administrators, managers, or clinicians 
at each site participating on our project. 
Consent from the administrators, managers, etc. who will answer the ORCA questionnaire will be 
implicit if they agree to return the surveys that are emailed to them. We have requested a waiver 
of documentation of consent and have attached the email we plan to send to the providers. 

ORCA survey data will be collected anonymously and will be pooled with data from other sites in 
our NIH-funded consortium in order to minimize risk of re-identification. 
The completion of this survey should take approximately 10-15 minutes. 
8.11 INSTRUMENTS: List all questionnaires, surveys, interview, or focus group guides that will be used for 
this study: 
If the instruments are not complete or not available because they will be 
developed as part of this study, describe the basic content or include an 
outline and submit the final versions to the IRB with a modification for 
approval prior to use. 
A series of surveys will be administered to the patient at various time points including the time of 
consent, return of results and 6-12 month follow-up. These surveys are designed to further the 
study goals of understanding the personal and clinical utility of exome sequencing. 
Specifically, after initial consent is obtained the patients will be administered a demographic 
survey to characterize the patient population undergoing exome sequencing through our study. 
Subsequent surveys will be specific to the patient's circumstance and have been tailored to be 
appropriate for patients that have an on-going pregnancy, a pregnancy that has resulted in a live 
birth, or a pregnancy loss due to either elective termination or natural causes. 
After the return of results the patient will be administered a survey that can be conducted in 
patient or through email, or can be return to us by mail. Finally there will be surveys obtained 
after the 6-12 month point of having received results from the exome sequencing. All of these 
surveys are designed to obtain information regaring the patient's experience of having undergone 
genetic sequencing in their pregnancy, what information they understood about the results of 
their testing, where they sought information outside of our clinical service to understand these 
results and how the sewuencing results were incorporated into their understanding of their child's 
health or adverse pregnancy outcome. 
We will contact executives, administrators, managers or clinicans at UCSF via email to ask if they 
are willing to complete a survey about organizational readiness to change (ORCA). This survey 
will be administered once via Redcap or on paper and will not involve any personal identifiers. The 
goal of the survey is to learn more about their views on the potential for implementation of 
clinical sequencing in healthcare systems and communities. The de-identified data will be pooled 
by the University of Washington to include data from the rest of the CSER2 consortium. 
Attach any unpublished instruments in the 'Other Study Documents' 
section of the Initial Review Submission Packet form after 
completing the study application. Published instruments should 
NOT be attached. 
8.12 * BIOSPECIMEN COLLECTION: Are you drawing any blood or collecting other biosamples (e.g. tissue, 
buccal swabs, urine, saliva, hair, etc.) for analysis under this protocol and/or storage for future 
research: (REQUIRED) 
  Yes  
 No 
* Could this study generate genetic data that may be broadly shared (e.g., submitted to 
NIH in compliance with Genomic Data Sharing (GDS)/Genome-Wide Association 
Studies (GWAS) requirements): (REQUIRED) 
  Yes  
 No 
Please make sure your consent form includes the recommended 
genomic data sharing language. 

 
8.13 STATISTICAL METHODS: Briefly summarize the methods and types of analyses that will be 
performed: 
Our study design will allow several statistical comparisons that will generate useful data regarding 
exome sequencing implementation. Clinical outcomes will be scored across multiple domains; for 
example, assigning one point for changes in care or interventions that are deemed to have minor 
clinical utility, two points for those with moderate utility and three points for those with high 
clinical utility. The scoring will be independently performed by two clinicians who did not see the 
patient or family, and who are not familiar with the case. The clinical information will derive from 
a compilation of material derived from direct examinations that occurred prior to study initiation 
and all clinical information available in the EHRs. Results for parents and/or family will be based 
on interviews. The study coordinator or a research assistant will prepare this information for 
review by the clinicians and will remove, when possible, all statements that could reveal whether 
the subject had a positive or negative exome result (i.e. unblind the raters). The two raters will 
reconcile any differences in their scores, or simply average them if agreement does not occur. 
Our group will work with the CSER consortium to develop the specific clinical utility outcomes that 
will be scored. 
After all scores are made for each patient, scores will be totaled within and across domains. The 
analyst will also have the results of the exome sequencing, and separate the patients into two 
groups – one with a positive (i.e. diagnostic) test result, and the other without such a result 
(negative test result). We will compare the scores of those with a positive test result versus those 
with a negative test result. By comparing these two groups, we are not evaluating the overall 
clinical utility that may derive from having any exome sequencing test performed (i.e. we have no 
comparison group of those without exome sequencing). We have chosen to focus instead on only 
those benefits that may derive from having a diagnostic exome sequencing result. 
The size of the “positive” and “negative” groups will depend on the diagnostic success rate of 
exome sequencing in our cohort. Based on prior experience in the Personalized Genomics Clinic 
(see Preliminary Results), we anticipate a minimum of 17% of subjects will have a positive result 
– but that rate could be as high as 38%. In any event, assuming a low rate of 20%, we expect a 
minimum of 220 individuals/families with a positive test result, which should be adequate for the 
analyses we propose. 
It is also important to determine how clinical utility may vary based on a number of factors, 
including setting (prenatal, neonatal, pediatric), by disease indication, by race/ethnicity, and by 
socioeconomic status. Such stratified analyses will depend on the actual observed sample sizes 
within each stratum. 
8.14 REFERENCES: List only the 5-10 most relevant references (a separate bibliography can be attached 
for reference purposes if this study involves novel approaches, agents, or an emerging technology 
that the IRB may not be familiar with): 
1. Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, 
Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, 
Ding Y, Plon SE, Lupski JR, Beaudet AL, Gibbs RA, Eng CM. Clinical whole-exome 
sequencing for the diagnosis of mendelian disorders. N Engl J Med. 2013;369(16):1502- 
1511. PubMed PMID: 24088041; PubMed Central PMCID: PMC4211433. 
2. Norton ME, Rink BD. Changing indications for invasive testing in an era of improved 
screening. Seminars in Perinatology. 2016;40(1):56-66. PubMed PMID: 26725145 
3. Cowan RS. Aspects of the history of prenatal diagnosis. Fetal Diagnosis and Therapy. 1993; 
8(Suppl. 1):10-17. PubMed PMID: 11653011. 
4. Chervenak FA, McCullough LB. Ethical issues in perinatal genetics. Seminars in Fetal and 
Neonatal Medicine. 2011;16(2):70-73. PubMed PMID: 21051301. 
5. Donley G, Hull SC, Berkman BE. Prenatal Whole Genome Sequencing: Just because we 
can, should we? Hastings Center Report. 2012;42(4):28-40. PubMed Central PMCID: 
PMC4113095. 
6. American College of Obstetricians and Gynecologists Committee on Genetics, Society for 
Maternal- Fetal Medicine. Committee Opinion No. 581: the use of chromosomal microarray 
analysis in prenatal diagnosis. Obstet Gynecol. 2013;122(6):1374-1377. PubMed PMID: 
24264715. 
7. Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, Savage M, Platt LD, 
Saltzman D, Grobman WA, Klugman S, Scholl T, Simpson JL, McCall K, Aggarwal VS, 
Bunke B, Nahum O, Patel A, Lamb AN, Thom EA, Beaudet AL, Ledbetter DH, Shaffer LG, 
Jackson L. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J 

Med. 2012;367(23):2175-2184. PubMed PMID: 23215555; PubMed Central PMCID: 
PMC3549418. 
8. de Wit MC, Srebniak MI, Govaerts LC, Van Opstal D, Galjaard RJ, Go AT. Additional value 
of prenatal genomic array testing in fetuses with isolated structural ultrasound 
abnormalities and a normal karyotype: a systematic review of the literature. Ultrasound 
Obstet Gynecol. 2014;43(2):139-146. PubMed PMID: 23897843. 
9. Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, Church DM, Crolla 
JA, Eichler EE, Epstein CJ, Faucett WA, Feuk L, Friedman JM, Hamosh A, Jackson L, 
Kaminsky EB, Kok K, Krantz ID, Kuhn RM, Lee C, Ostell JM, Rosenberg C, Scherer SW, 
Spinner NB, Stavropoulos DJ, Tepperberg JH, Thorland EC, Vermeesch JR, Waggoner DJ, 
Watson MS, Martin CL, Ledbetter DH. Consensus statement: chromosomal microarray is a 
first-tier clinical diagnostic test for individuals with developmental disabilities or congenital 
anomalies. Am J Hum Genet. 2010;86(5):749-764. PubMed PMID: 20466091; PubMed 
Central PMCID: PMC2869000. 
10. Hussain-Gambles M, Atkin K, Leese B. Why ethnic minority groups are under-represented 
in clinical trials: a review of the literature. Health & Social Care in the Community. 2004;12 
(5):382-388. 
11. Robinson JO, Carroll TM, Feuerman LZ, Perry DL, Hoffman-Andrews L, Walsh RC, 
Christensen KD. 
12. Green RC, McGuire AL. Participants and Study Decliners' Perspectives About the Risks of 
Participating in a Clinical Trial of Whole Genome Sequencing. J Empir Res Hum Res Ethics. 
2016;11(1):21-30. PubMed PMID: 26928896; PubMed Central PMCID: PMC4842131. 
13. Lupo PJ, Robinson JO, Diamond PM, Jamal L, Danysh HE, Blumenthal-Barby J, Lehmann 
LS, Vassy JL, Christensen KD, Green RC, McGuire AL. Patients' perceived utility of whole- 
genome sequencing for their healthcare: findings from the MedSeq project. Per Med. 2016; 
13(1):13-20. PubMed PMID:27019659; PubMed Central PMCID: PMC4806392. 
14. Kohane IS. Ten things we have to do to achieve precision medicine. Science. 2015;349 
(6243):37-38. 
15. Reiff M, Bernhardt BA, Mulchandani S, Soucier D, Cornell D, Pyeritz RE, Spinner NB. "What 
does it mean?": uncertainties in understanding results of chromosomal microarray testing. 
Genet Med. 2012;14(2):250-258. PubMed PMID: 22241091; PubMed Central PMCID: 
PMC3445036. 
9.0 
Biospecimen Collection and/or Bank Administration 
9.1 * TYPE OF SPECIMENS (check all that apply): (REQUIRED) 
  Blood (provide amount below) 
  Tissue (describe below) 
  Other type of biospecimen, such as sputum, cerebrospinal fluid, buccal swabs, etc. (describe 
below) 
  Existing/archival materials (name source below) 
Briefly describe the types of biospecimens that will be collected. Provide the 
amount of blood, if applicable. For leftover/existing/archival material, 
identify the source: 
Exome sequencing of prenatal specimens will include either cultured cells or extracted DNA from 
chorionic villi, amniocytes of products of conception including fetal tissue, fetal cord blood or 
neonatal blood. These specimens would have been left over from previous testing, no additional 
procedure would be performed to obtain fetal specimen. Maternal and paternal samples will also 
be requested and can be blood, bucchal swab or saliva samples. For particpants of IRB 17-21662 ( 
Fetal birth defects prospective database: Toward a precision-based approach) we will only be 
collecting a single sample to perform exome sequencing for participation in both studies. No 
additional sample will be obtained for the purposes of enrollment in this study if they elect to 
participate in both. 
9.2 * SPECIMENS ARE: (check all that apply): (REQUIRED) 
  Leftover specimens from a clinical diagnostic or therapeutic procedure 
  Specimens collected for research purposes only (including extra samples taken during a 
clinical procedure) 

  Other 
9.3 * FUTURE SPECIMEN USE: Will any specimens or portions of specimens be retained after the study is 
over for possible use in future research studies: (REQUIRED) 
  Yes  
 No 
9.4 * SPECIMEN BANKING - CONSENT METHOD: Consent for retaining specimens for future research 
studies will be obtained via (check all that apply): (REQUIRED) 
  Specimen section within a main research study consent form 
  Separate specimen consent form 
  UCSF surgical consent form with tissue donation brochure 
9.5 * SPECIMEN DESTINATION: Indicate where specimens will ultimately be stored: (REQUIRED) 
Outside Entities: Indicate where specimens will be sent if they will not 
remain at UCSF (choose at least one; check all that apply): 
  Cooperative group bank 
  NIH 
  Other university or collaborator 
  Industry sponsor 
  Other 
  N/A - all specimens will remain at UCSF 
Internal Storage: If specimens will remain at UCSF, in what kind of 
facility will they reside (choose at least one; check all that apply): 
  UCSF repository/bank being established under this protocol 
  Existing UCSF specimen repository/bank with IRB approval 
  National cooperative group bank housed at UCSF 
  Other location at UCSF (please describe) 
  N/A - no specimens will be retained at UCSF facilities 
Please provide the name of the department, the program, and the physical 
location where the specimens will be housed. If the specimens will be 
stored in an already established bank, provide the name of the bank and its 
iRIS approval number.: 
 
UCSF Genomic Medicine Laboratories 
University of California, San Francisco 
Institute for Human Genetics 
513 Parnassus Ave., HSW 901A 
San Francisco, CA 94143 
9.7 * CLINICAL FOLLOW-UP DATA: Will clinical follow-up data be linked to specimens (i.e., will medical 
record information continue to be abstracted after the specimen is collected): (REQUIRED) 
  Yes  
 No 
Provide duration of follow-up or 'indefinitely': 
 
12 months after delivery 
 

 
9.8 * UCSF-BANKED SPECIMENS - LINKING AND SHARING OF IDENTIFIERS: (REQUIRED) 
  Samples are completely de-identified before being added to the bank/repository. There is no 
way to link the specimens back to the subjects. 
  Samples are coded and researchers are able to link the specimens to specific subjects. 
  Samples are stored with direct identifiers in the repository. 
Explain under what circumstances identifiers may be released with 
specimens or say 'None' if identifiers will NEVER be released with 
specimens: 
The samples will be stored with the UCSF Genomic Medicine Laboratories. Upon lab recipt specime 
ns receive non-PHI lab identifiers and will be maintained in that way. 
9.9 UCSF-BANKED SPECIMENS – IDENTIFIERS: List the identifiers that will be collected, stored, or 
linked with the specimens: 
  Name 
  Date of birth 
  Social Security number 
  Medical record number 
  Address 
  Phone number 
  Email address 
  Other dates (dates of surgery, visit dates) 
9.10 DISTRIBUTION: Specimens banked at UCSF may be made available to (check all that apply): 
  UCSF researchers 
  Non-UCSF researchers 
  Industry 
  None of the above - specimens will be retained and used within our own research program 
9.11 UTILIZATION REVIEW: Is there a formal utilization review process for distribution of specimens:  
   Yes  
   No 
10.0 
Drugs and Devices 
10.1 * DRUGS AND/OR BIOLOGICS: Are you STUDYING any drugs and/or biologics that are either 
approved or unapproved: (REQUIRED) 
   Yes  
   No 
Note: This question is frequently answered incorrectly. If any drugs 
or biologics, approved or unapproved, are being administered under 
this protocol, you should check 'Yes' unless you are absolutely sure 
that NONE of the drugs are part of the research protocol. Tip: Ask 
the PI or the sponsor if you are not sure how to answer this 
question. 
10.3 * MEDICAL DEVICES: Are you STUDYING any medical devices, in vitro diagnostics, or assays that are 
either approved or unapproved:(REQUIRED) 

  Yes  
 No 
10.4 * NSR: Are you requesting a Non-Significant Risk (NSR) determination for an investigational device: 
(REQUIRED) Note: an NSR determination is different from an Investigational Device Exemption 
(IDE). Check the Help link for more guidance on what types of devices can qualify for an NSR 
determination. 
  Yes  
 No 
* Explain why the use of the device in this study poses a non-significant 
risk: (REQUIRED) 
1) We plan to use exome sequencing to clarify a possible genetic cause of congenital anomalies 
identified clinically by fetal anatomic ultrasound. As an entry criterion for the study, all 
participants will have previously undergone prenatal genetic diagnosis by established methods of 
chromosome analysis and microarray. DNA samples submitted for WES in this study will be 
derived from a previously obtained specimen. No invasive procedures are connected with the use 
of the exome sequencing test in our study. 
Thus, our use of exome sequencing meets the “non-significant risk” criteria: 
1) Exome sequencing testing is non-invasive, and is done on previously obtained samples. 
2) Exome sequencing presents no risk to the health or welfare of the subject; results provide 
information only. 
3) and 4) 
We first address “informational risks” associated with return of results relevant to the primary 
finding of a fetal anomaly. 
We believe this use constitutes “non-significant risk” to study participants as they will only be 
asked to participate in research after the clinical diagnosis of a severe congenital anomaly has 
been made. Any genetic finding revealed by sequencing of the trio (fetus plus parents) will inform 
the clinician’s understanding of the etiology of the anomalies identified, but will not modify the  
severity of the already-diagnosed physical anomaly. 
All clinically significant findings identified through whole exome sequencing will be confirmed by a 
secondary sequencing method, specifically Sanger sequencing. 
Although information will be returned to the family based on the exome sequencing testing, we 
believe this constitutes non-significant risk because results based on CLIA-approved tests for 
single genes and gene panels are routinely offered to pregnant women. Thus our use of exome 
sequencing— findings confirmed by an orthogonal method— to obtain genetic information does 
not convey additional risk to the fetus or pregnant women. 
We next address “informational risks” associated with return of results not relevant to the primary 
finding of a fetal anomaly, referred to here as secondary or additional findings. 
Results, including “additional findings,” will be returned to the pregnant woman in order to assess 
their utility (one of the study aims). These results will be returned in accord with our established 
clinical pathway. That policy includes an allowance for return of secondary/additional findings in 
accord with the American College of Medical Genetics recommendations. We will follow that 
clinical policy, which is available on request. In all cases, all family members sequenced are 
given the option to “opt out” of receiving all secondary findings. 
The purpose of this study is to determine if exome sequencing can help identify the etiology of 
structural fetal anomalies in pregnancy, to clarify additional benefits to the family and/or fetus 
from identifying risks to the fetus secondary to a pathogenic result from exome sequencing, and 
to clarify reproductive risks for future pregnancies, or cascade testing of other family members. 
Attach any documentation you have from the manufacturer and/or 
FDA to support this determination. 
10.5 
 

LIST THE DEVICES: List the medical devices or in vitro diagnostics to be studied or used. In the 
device details screen you will be asked questions such as: 
Whether the device is FDA approved or investigational 
Medicare device category 
If the device will be provided at no cost 
If an IDE is necessary, the IDE number, and who holds the IDE 
Risk category of the device 
FDA status of the device 
Please see the UCSF IRB website for more details about the use of devices in research, including the 
Investigator Checklist for Significant Risk, Non-Significant Risk, and/or IDE Exempt Device Studies 
Verification of IDE numbers: If the sponsor’s protocol does not list the IDE number, you must submit 
documentation from the sponsor or FDA identifying the IDE number for this study. Attach this 
documentation in the Other Study Documents section of the Initial Review Submission Packet.  If  
you have any correspondence from the FDA or sponsor regarding this device, 
please attach it to the application. 
 
 
10.6 * EXPANDED ACCESS: Is this an expanded access or compassionate use protocol, meaning the 
primary purpose is to diagnose, monitor or treat a patient's condition, rather than the collection of 
safety and efficacy data of the experimental agent: (REQUIRED) 
   Yes  
   No 
11.0 
Sample Size and Eligibility Criteria 
11.1 ENROLLMENT TARGET: How many people will you enroll: 
 
View 
Details Device Name 
Is the Device 
FDA Approved 
Is this a new 
device or a new 
use of an already 
approved device 
IDE Number 
Illumina Sequencer 
No 
Yes 
Manufacturer/Supplier of 
Device 
UCSF 
Medicare Category 
A 
B 
Where will the Devices Be 
Stored 
Will Devices be supplied at no 
Cost 
Yes 
Is this a HUD (HDE) 
No 
HDE Number 
Is the Device FDA Approved 
No 
Is this a new device or a new 
use of an already approved 
device 
Yes 
Is an IDE necessary 
No 
IDE Number 
Who holds the IDE 
N/A 
IDE details 
In the opinion of the sponsor, 
select the level of risk 
associated with this device 
No Significant Risk 

 
400 
 
If there are multiple participant groups, indicate how many people will be 
in each group: 
1. The key clinicians from each of our study sites will ascertain and recruit patients together with 
dedicated genetic counselors and research assistants who will be located on-site. We will recruit 
individuals with African American, Latino, Native American, Asian/Pacific Islander, and mixed 
ancestries, with a target of 75% underrepresented minorities (URM) overall, but at a minimum 
60%. Our anticipated breakdown is approximately 40% Latino, 20% African American, 15% other 
URM; 25% non-Hispanic white and non-URM Asian patients based on current clinical composition 
(see Enrollment form). More than 500 cases of fetal anomalies identified by ultrasound are seen 
per year, indicating an easily achieved recruitment rate of 14% overall, 20% for URM and 8% for 
non-URM. 
2. We anticipate recruiting 6-10 administrators, managers or clinicians at each participating site 
to complete the Organizational Readiness for Change (ORCA) survey. 
11.3 SAMPLE SIZE JUSTIFICATION: Explain how and why the number of people was chosen. For multi-site 
studies, this is referring to the number that will be enrolled across all sites: 
UCSF Fetal Treatment Center at UCSF Betty Irene Moore Women's Hospital. Pregnant women 
carrying fetuses with anomalous ultrasound findings will be recruited through the UCSF Fetal 
Treatment Center (FTC). The FTC was the first such program in the world, established nearly 30 
years ago, and sees a diverse patient population with a broad spectrum of congenital anomalies 
and suspected genetic disorders. Approximately 500 patients per year are seen through the FTC, 
which has a long history of participation in clinical studies involving fetal abnormalities.63-65 
Recently, the Center for Maternal-Fetal Precision Medicine (CMFPM) has been established to 
conduct clinical and translational research through the FTC; Dr. Norton is a co-Director of the 
CMFPM and an active member of the FTC clinical team. The FTC includes a genetic counselor that 
is actively involved in research efforts, and a team of research nurses who are supportive of, and 
experienced in, the recruitment of patients and the conduct of clinical research. A protocol is in 
place for recruitment of women with fetal anomalies for WES 
ZSFGH will also be a site for recruitment of fetal cases. The obstetrical service at ZSFGH cares for 
approximately 1,200 pregnant women per year from a very diverse patient population, and these 
women all undergo obstetrical ultrasound on site. When fetal anomalies are detected, patients will 
be counseled by a genetic counselor and a perinatologist or obstetrical specialist with genetics 
training. Dr. Juan Vargas, the Director of Obstetrics at ZSFGH, is very supportive of this project. 
Our teams have collaborated on a large number of clinical studies and our research staff screen 
and recruit patients at ZSFGH for a number of clinical trials, having access to the electronic 
medical record (EMR) and the clinics for patient recruitment. We anticipate recruitment of 
approximately 50 antenatal patients from ZSFGH over the 4 years of the project; recruitment 
efforts will be supported by the genetic counselor and research assistants who are enrolling at the 
FTC. 
UCSF Fresno Community Medical Center will also be a site for recruitment of fetal cases. UCSF 
Fresno Community Medical Center serves a diverse patient population, and these women all 
undergo obstetrical ultrasound on site. When fetal anomalies are detected, patients will be 
counseled by a genetic counselor and a perinatologist or obstetrical specialist with genetics 
training. We anticipate recruitment of approximately 30 antenatal patients from UCSF Fresno 
Community Medical Center over the remaining 2 years of the project; recruitment efforts will be 
supported by the genetic counselor and research assistants who are enrolling at the FTC. 
We are electing to recruit patients participating in an analogous study (17-21662 (Fetal birth 
defects prospective database: Toward a precision-based approach)) as this study is also offering 
exome sequencing in pregnancies affected by a specific anomaly called non-immune hydrops 
fetalis. The additional participation in this protocol would involve these participants completing 
the surveys related to clinical utility of the test. There is no additional procedures other than 
these study surveys. 
11.4 * PARTICIPANT AGE RANGE: Eligible age ranges: (REQUIRED) 

  0-6 years 
  7-12 years 
  13-17 years 
  18-64 years 
  65+ 
11.5 * STUDY POPULATIONS: Data will be collected from or about the following types of people (check all 
that apply): (REQUIRED) 
  Inpatients
 Outpatients 
  Family members or caregivers 
  Providers 
  People who have a condition but who are not being seen as patients 
  Healthy volunteers 
  Students 
  Staff of UCSF or affiliated institutions 
  None of the above 
11.6 * SPECIAL SUBJECT GROUPS: Check the populations that may be enrolled: (REQUIRED) 
  Children / Minors 
  Adult subjects unable to consent for themselves 
  Adult subjects unable to consent for themselves (emergency setting) 
  Subjects with diminished capacity to consent 
  Subjects unable to read, speak or understand English 
  Pregnant women 
  Fetuses
 Neonates
 Prisoners 
  Economically or educationally disadvantaged persons 
  None of the above 
If not already addressed in the Background and Significance questions in 
the Research Plan section or elsewhere, explain why it is appropriate to 
include the types of subjects checked above in this particular study: 
Describe the additional safeguards that have been included in the study to 
protect the rights and welfare of these subjects and minimize coercion or 
undue influence: 
Here are some examples: 
evaluating capacity to consent for individuals who may be decisionally 
impaired (specify how) 
calibrating payment amounts to be non-coercive for the financially 
disadvantaged 
conducting more in-depth evaluations of subjects’ understanding of 
the study and the voluntary nature of participation 
involving advocates in the consent process 
More information and other safeguards are described here: Vulnerable 
Subject Populations and Recruiting Staff and Students. 
 

We will be offering whole exome sequencing to potential research subjects who have already 
completed a prenatal diagnostic procedure and would be performing this testing on the previously 
obtained specimen. Study subjects will be educated using non-directive counseling by a board 
certified and licensed genetic counselor who is trained in educating patients on complex genetic 
topics and providing information including the risks, benefits and limitations of genomic analysis. 
11.7 INCLUSION CRITERIA: Briefly describe the population(s) that will be involved in this study. Include 
anyone that data will be collected from or about (e.g. patients, healthy controls, caregivers, 
providers, administrators, students, parents, family members, etc.): 
Women carrying a pregnancy with an ultrasound diagnosis of a major structural anomaly (or 
multiple anomalies) in a major organ system (cardiac, central nervous system, thorax, genito- 
urinary, gastrointestinal/ventral wall, skeletal and or multiple anomalies ) 
Clnical concern for a potential underlying genetic condition 
Completed or plan to complete CVS or amniocentesis with chromosome analysis or microarray 
(including VOUS) or this testing on products of conception 
Available maternal sample 
11.8 EXCLUSION CRITERIA: List any exclusion criteria (e.g. reasons why someone would not be included 
in the study): 
Prior exome sequencing performed for a clinical or research indication 
Lack of phenotypic indication of a likely underlying genetic etiology 
Mother unwilling or unable to provide a specimen 
11.9 * RESEARCH CONDUCTED ON PATIENT CARE WARDS: Do any study activities take place on any 
patient care units including inpatient wards, peri- or post-operative care units, operating rooms, or 
in the Emergency Department at UCSF Health medical facilities: (REQUIRED) 
  Yes  
 No 
Attach a letter of acknowledgement for the study from the involved 
patient care manager. If you don't know who the patient care 
manager is, click here to send an email to the nursing group. 
11.10 * INTENSIVE CARE NURSERY (ICN): Will you be enrolling any babies who are admitted to the 
Intensive Care Nursery (ICN) (this includes critically ill babies as well as lower acuity patients who 
need overnight monitoring and support): (REQUIRED) 
   Yes  
   No 
11.11 * EMERGENCY DEPARTMENT: Does your protocol or study involve any of the following patient 
related activities in the emergency department (e.g. subject identification, recruitment, consent, 
blood draws, specimen retrieval, involvement of ED staff (nursing, tech, and/or physician), or any 
other ED based procedures): (REQUIRED) 
   Yes  
   No 
12.0 
Inclusion of Minors in Research 
 

12.1 REGULATORY CATEGORIES OF RESEARCH: Select all the regulatory categories that apply: 
  No greater than minimal risk (45 CFR 46.404, 21 CFR 50.51) 
  Greater than minimal risk but presenting prospect of direct benefit (45 CFR 46.405, 21 CFR 
50.52) 
  Greater than minimal risk (though only a minor increase over minimal risk) and no prospect 
of direct benefit but likely to yield generalizable knowledge about the subjects disorder or 
condition (45 CFR 46.406, 21 CFR 50.53) 
  Research not otherwise approvable which presents an opportunity to understand, prevent, or 
alleviate a serious problem affecting the health or welfare of children (45 CFR 46.407, 21 CFR 
50.54) 
Explain why the research in this study falls under the above category or 
categories: 
12.2 
MINORS CONSENTING: Will this study enroll minors who can legally consent for themselves (as in 
the case of emancipated minors or minors being treated for pregnancy or drug use without their 
parents knowing). This is different from agreeing to be in the study even when their parents are the 
ones providing 'official' consent, which we refer to as 'providing assent': 
Note: This is very rare and the answer is usually 'No.' 
   Yes  
   No 
12.3 
PARENTAL PERMISSION VS. WAIVER: Please review the guidance to see under what circumstances 
the IRB can waive parental permission. 
  Parental permission will be obtained 
  Waiver of parental permission is requested: The waiver meets the provisions for a waiver of 
consent (i.e., the research poses minimal risk, it could not practicably be carried out without 
the waiver of parental permission, AND the waiver will not adversely affect the rights and 
welfare of the minor participants (45 CFR 46.116(d)) 
  Waiver of parental permission is requested: Parental permission is not a reasonable 
requirement to protect the minor (e.g. neglected or abused children) or parental knowledge 
of the study may endanger the health or welfare of the minor (45 CRF 46.408(c)) 
Provide details on the other protections that will be in place: 
12.4 ASSENT OF MINORS OR WAIVER: Please review the guidance to see under what circumstances the 
IRB can waive assent. 
  Assent of children developmentally and psychologically able to provide assent will be obtained 
  Waiver of assent is requested: The capability of some or all of the children is so limited that 
they cannot reasonably be consulted 
  Waiver of assent is requested: The research holds out a prospect of direct benefit that is 
important to the health or well-being of the children and is available only in the context of the 
research 
  Waiver of assent is requested: The activities involving the minor are limited to chart review or 
the something equally innocuous 
  Waiver of assent is requested: It is not culturally appropriate to involve the minor in the 
decision to participate (e.g. some foreign research) 
12.5 DOCUMENTATION OF PERMISSION AND ASSENT: (select all that will be used): 
  Permission form addressed to the parents 

  Simplified assent form addressed to the child, 7-12 years old (parents get separate form) 
  Assent form addressed to the child, 13 years and older (for subjects and parents) 
  Assent form addressed to the child, 13 years and older (parents get separate form) 
Check one: 
  One parent's signature will be obtained 
  Two parents' signatures will be obtained 
If this study is approvable under regulatory category .405 and you plan to get permission from 
only one parent, explain why you think one parent's permission is sufficient: 
12.6 WARDS OF THE STATE: Might this study enroll wards of the state: 
   Yes  
   No 
13.0 
Recruitment and Consent 
13.1 * COMPETITIVE ENROLLMENT: Is this a competitive enrollment clinical trial? By competitive 
enrollment, we mean that sites who do not enroll participants early may not get to participate at all: 
(REQUIRED) 
   Yes  
   No 
13.2 * SUBJECT IDENTIFICATION METHODS: What kinds of methods will be used to identify potential 
participants for recruitment (check all that apply): (REQUIRED) 
  Review of patients' conditions, history, test results, etc. (includes patients seen in clinic, 
scheduled for surgery, a procedure, imaging, or tests, or seen in the Emergency Department 
as well as searching through medical record data for possible cohort identification) 
  Already approved recruitment registry 
  Re-contact of participants from the investigators' previous studies 
  Referrals from colleagues (attach the 'Dear Colleague' letter or other recruitment materials 
you will provide to colleagues) 
  Referrals from the community / word of mouth 
  Advertisements (flyers, brochures, radio or t.v. ads, posting on clinical research sites or social 
media, presentation of the study at community events/media, etc.) 
  Online recruiting tool (describe below) 
  CTSI Recruitment Services unit 
  Posting on UCSF Clinical Trials, ClinicalTrials.gov or other publicly available clinical trial website 
  Other method (describe below) 
Attach your recruitment materials (e.g., flyers, ads, recruitment 
letter templates, email text, etc.) in the Other Study Documents 
section of the Initial Review Submission Packet Form. 
* Provide details about the subject identification methods: (REQUIRED) 
Potentail referring providers have been sent the study brochure and heard about the study by 
word of mouth. We will use the attached exome sequencing recruitment script to reach out to 
patients that have been identified by their provider that is not directly involved in the study 
recruitment. We will also use this brochure to offer enrollment to this study for patients enrolled 
and consented under IRB 17-21662 (Fetal birth defects prospective database: Toward a precision- 
based approach). 
Our principal investigators have identified a list of potential respondents who meet the criteria for 
completion of the Organization Readiness for Change (ORCA) survey. 

13.3 * SEARCHING OF MEDICAL RECORDS: (REQUIRED) 
Whose patients are they: 
  Investigators' own patients or patients seen within the same practice 
  Patients not under the care of the investigators 
How and by whom will records be accessed and searched (check all that 
apply): 
  Self-search in APeX or other medical records source 
  Self-search using UCSF's Research Cohort Selection Tool 
  CTSI Consultation Service Recruitment Services 
  UCSF Academic Research Services (ARS) 
  University of California Research Exchange (UC ReX) 
  Other method (describe below) 
13.4 DETERMINATION OF ELIGIBILITY: How, when, and by whom will eligibility for recruitment be 
determined: 
The key clinicians from each of our study sites will ascertain and recruit patients together with 
dedicated genetic counselors and research assistants who will be located on-site. This will occur 
at the time of a prenatal clinical visit and involve review of ultrasound findings and previously 
completed prenatal diagnosis procedures. 
Our principal investigators have identified a list of potential respondents who meet the criteria for 
completion of the Organization Readiness for Change (ORCA) survey. 
13.5 * INITIATION OF CONTACT: Who initiates contact (check all that apply): (REQUIRED) 
  Investigators/study team 
  UCSF recruitment unit (e.g. CTSI Consultation Services) 
  Potential participant 
  Other (explain below) 
13.6 * HOW IS CONTACT INITIATED: (check all that apply): (REQUIRED) 
  In person 
  Phone 
  Letter / email 
  Website or app 
  Other (explain below) 
Attach the telephone recruitment script in the Other Study 
Documents section of the Initial Review Submission Packet Form. If 
potential participants will initiate contact, attach the telephone 
screening script that will be used to provide more information about 
the study and determine if callers are eligible to participate. 
Attach the recruitment letter or email template in the Other Study 
Documents section of the Initial Review Submission Packet Form. 
13.7 RECRUITMENT PLAN: Based on the checkboxes you chose above, please provide a narrative 
describing your recruitment plan. We want to know: 

Who is conducting the search for potential participants, and how? 
How are potential subjects being approached for recruitment? By whom, and when? 
If there will be more than one participant group (e.g. patients, healthy controls, caregivers, family 
members, providers, etc.), provide details about the recruitment plans for each group. 
(Recommended length - 100-250 words) 
For fetal cases, patients will be approached by a clinician, typically a maternal-fetal specialist, 
who has counseled the patient regarding the fetal anomaly that has been detected. At the time of 
recognizing a potential study participant they will be educated regsarding the option for research 
participation and provided an informational study specific brochure. Written informed consent will 
be obtained by the study prenatal genetic counselor. Many patients will have undergone prenatal 
diagnostic testing in an outside laboratory; in such cases, cells or extracted DNA from the original 
fetal sample will be used for the purpose of this study. The consent process for prenatal WES will 
include pre-test counseling and the option of choosing whether or not to receive uncertain results 
and secondary findings. A study brochure, informing prospective participants of the aims of the 
study and whole exome sequencing procedure has been created and will be provided for review. 
This study is specific to UCSF/ZSFGH and UCSF Fresno Community Medical Center locations. We 
will educate providers in our MFM and genetic counseling program through the already 
established methods of information dissemination in these teams. We will educate the UCSF MFM 
community that services the prenatal diagnosis center in their quarterly PDC meeting. The 
genetic counselors in the UCSF prenatal diagnosis center also service the genetic counseling 
needs of ZSFGH. They will be educated and given updates regarding this study in their weekly 
meeting held Wednesdays. This meeting is devoted to discussing complex cases, testing 
strategies and/or research opportunities to offer to patients. 
We will not be actively recruiting from sites outside of UCSF, however, patients sent to UCSF for a 
second opinion with concern for a fetal anomaly that is confirmed will be offered enrollment 
during their visit to UCSF. 
Finally, study participants pursuing exome sequencing under IRB 17-21662 (Fetal birth defects 
prospective database: Toward a precision-based approach) will be offered enrollment in this study 
as well. These participants will be recruited for the purposed of enabling us to incude their health 
data and exome sequencing results in our database, there will not be any study procedures such 
as blood draw or exome duplicated by participating in both projects. Those that have consented 
to IRB 17-21662 and agree to also enroll in this study will also be asked to complete the surveys 
associated with this study protocol. 
We will also be recruiting 6-10 administrators, managers or clinicians at each participating site to 
complete the Organizational Readiness for Change (ORCA) survey, which will be emailed to these 
potential participants. Completion of the survey reflects these participants consent since these 
surveys are anonymous and project activities do not involve the collection of personal information 
about the respondent. 
13.8 * CONSENT METHODS: How will permission to participate (i.e., informed consent) be obtained from 
each potential participant. If there will be multiple groups and different plans for consenting each, 
check all that apply. See the orange Help bubble to the right for more detailed guidance. 
Participants will (check all that apply): (REQUIRED) 
  Sign a consent form at the end of the consent discussion (signed consent) 
  Provide online 'eConsent' using an E-Signature system 
  Click through a link in a survey or email after reading about the study and then complete the 
study online (electronic consent) 
  Be told about the study and be given a handout/information sheet and be asked if they agree 
to participate (verbal consent) 
  Complete the study activities and turn in materials, as in the case of a completed survey that 
is placed in a drop box or mailed to the study team (implied consent) 
  Not be able to provide consent and will have a family member consent for them, as in the 
case of a critically ill or unconscious patient (surrogate consent) 
  Not be able to provide consent (emergency waiver of consent - allowed for minimal risk 
research or greater than minimal risk research with an approved community consultation plan) 
  Not know about the study, as in the case of chart reviews or observations of public behavior 
(waiver of consent) 
 

  Other method (describe below) 
Attach your consent form, information sheet, or electronic consent 
text in the Informed Consent Documents section of the Initial 
Review Submission Packet Form. 
13.9 * CONSENT PROCESS: Describe the process for obtaining informed consent, including details such as 
who will have the consent discussion and when participants will be asked to sign the consent form in 
relation to finding out about the study: (REQUIRED) We encourage researchers to review our 
guidance on obtaining and documenting informed consent. 
If there are multiple groups being consented differently, provide details about the consent 
process for each group. 
If you are relying on verbal or implied consent, provide details about how that will happen. 
For studies using online recruitment and consent or consent via mail, provide details here. 
The patient will be educated regarding the anomalies identified on ultrasound in their pregnancy 
and meet with a genetic counselor associated with the study to review the testing completed so 
far in the pregnancy and how it contrasts from whole exome sequencing. A detailed explaination 
of the risks, benefits and limitations of whole exome sequencing (WES) will take place. After this 
discussion the patient will be offered to pursue this testing with the cost of testing covered 
through the study. Because exome sequencing is a new approach, a small number of parents and 
families will be invited to participate in an additional study, this would include both patient that 
pursued exome sequencing and those that declined. That study will involve being interviewed by 
a member of our team, by telephone or in person. For those patients being consented remotely 
we will be using Docusign as the e-consent platform. 
Regarding the ORCA survey for administrators, managers or clinicians, these participants will be 
sent and email explaining the survey. Completion of the survey reflects these participants 
consent since these surveys are anonymous and project activities do not involve the collection of 
personal information about the respondent. 
* It is important that the people obtaining consent are qualified to do so. 
Briefly describe the training and experience these individuals have in 
obtaining informed consent: (REQUIRED) 
Informed consent will be obtained by genetic counselors supporting this study. Genetic counselors 
are uniquely trained to educate patients on complex genetic information to ensure informed 
decision making regarding the benefits, limits and risks for pursing this tesitng that may be 
related to the fetus, their parents and other family members, 
13.10 * CONSENT COMPREHENSION: Indicate how the study team will assess and enhance the subjects' 
understanding of study procedures, risks, and benefits prior to signing the consent form (check all 
that apply): (REQUIRED) Tip: Review the Consent Comprehension - Learning Notes in the Help 
bubble at the right for specific questions that can be asked to assess comprehension, consider 
using the UCSF Decision-Making Capacity Assesment Tool, and review our guidance on obtaining 
written or verbal informed consent for more detail on how to conduct the assessment. 
  The study team will engage the potential participant in a dialogue, using open-ended 
questions about the nature of the study or the experimental treatment, the risks and benefits 
of participating, and the voluntary nature of participation 
  Potential participants will be asked or shown a series of questions to assess their 
understanding of the study purpose, procedures, risks and benefits, as well as the voluntary 
nature of participation (especially appropriate when the consent process happens online or 
through a mobile health app) 
  Other method (describe below): 
Provide details of the other approaches that will be used, if using another 
method to assess comprehension: 
 

13.11 * DECEPTION: Does this study rely on some deception or misinformation about what the 
researchers are observing to get valid data? (REQUIRED) 
   Yes  
   No 
13.13 * WAIVER OF DOCUMENTATION OF SIGNED CONSENT: Select the regulatory category under which 
the IRB may waive the requirement to obtain signed consent for this study: 
  The only record linking the subject and the research would be the consent document and the 
principal risk would be potential harm resulting from a breach of confidentiality. Each subject 
will be asked whether they want documentation linking them with the research. 46.117(c) 
(1) 
  The research presents no more than minimal risk of harm to subjects and involves no 
procedures for which written consent is normally required outside of the research context. 
46.117(c) (2) 
13.14 TIME: What is the estimated time commitment for participants (per visit and in total): 
Initial participation in the study will take a total of 2-3 hours on 2 different days. One of these 
visits will be devoted to education around the benefits, limits and risks of whole exome 
sequencing, as well as patient consent. The second visit will be edvoted to review results. The 
follow up interviews and visits will take 5 minutes to one hour during several follow up visits. 
Participation in this study will take place over 12-18 months. 
IMPORTANT TIP: Ensure this information is consistent with the 
information provided in the consent form. 
13.17 OTHER ALTERNATIVES: Describe other alternatives to study participation, if any, that are available 
to prospective subjects: 
For study participants that declined whole exome sequencing a small number of parents and 
families will be invited to participate in an additional study. That study will involve being 
interviewed by a member of our team, by telephone or in person. This interview is expected to 
take about 20 minutes. 
Potential study participants may also pursue clinical prenatal whole exome sequencing outside of 
this study. 
14.0 
Waiver of Consent/Authorization for Recruitment 
Purposes 
This section is required when medical records may be reviewed to 
determine eligibility for recruitment. 
14.1 * PRACTICABILITY OF OBTAINING CONSENT PRIOR TO ACCESS: Study personnel need to access 
protected health information (PHI) during the recruitment process and it is not practicable to obtain 
informed consent until potential subjects have been identified: (REQUIRED) 
  Yes 
If no, a waiver of consent/authorization is NOT needed. 
14.2 * RISK TO PRIVACY: A waiver for screening of health records to identify potential subjects poses no 
more than minimal risk to privacy for participants: 

  Yes 
If no, a waiver of authorization can NOT be granted. 
14.3 * RIGHTS/WELFARE: Screening health records prior to obtaining consent will not adversely affect 
subjects' rights and welfare: 
  Yes 
If no, a waiver of authorization can NOT be granted. 
14.4 * IDENTIFIERS: Check all the identifiers that will be collected prior to obtaining informed consent: 
  Names
 Dates 
  Postal addresses 
  Phone numbers 
  Fax numbers 
  Email addresses 
  Social Security Numbers* 
  Medical record numbers 
  Health plan numbers 
  Account numbers 
  License or certificate numbers 
  Vehicle ID numbers 
  Device identifiers or serial numbers 
  Web URLs 
  IP address numbers 
  Biometric identifiers 
  Facial photos or other identifiable images 
  Any other unique identifier 
  None 
Note: HIPAA rules require that you collect the minimum necessary. 
14.5 * HEALTH INFORMATION: Describe any health information that will be collected prior to obtaining 
informed consent: 
Prior to obtaining informed consent the patients prenatal ultrsaound reports and results from 
prenatal diagnosis will be reviewed. 
Note: HIPAA requires that you collect the minimum necessary. 
14.6 * DATA RETENTION/DESTRUCTION PLAN: Describe your plan to destroy any identifiable data 
collected to determine eligibility for recruitment. This should be done at the earliest opportunity. If 
you plan to retain identifiable recruitment data, provide the justification for doing so: 
All study participants will be assigned a study number and clinical information for data analysis 
will be performed using that assigned study number. There will be a locked master list that will 
include a key to identify study subjects with their study number. 
15.0 
Risks and Benefits 
15.1 RESEARCH-RELATED RISKS: Check if your study involves any of these specific research-related risks 

to participants that may need to be disclosed in the consent form: 
  Physical discomforts or pain 
  Risks to employment, or social or legal standing 
  Risk that the study team may observe possible evidence of child abuse, elder abuse, or a 
threat to self or others that they are required to report 
* For any boxes checked above, describe how you will minimize these risks 
and discomforts, e.g., adding or increasing the frequency 
of monitoring, additional screening to identify and exclude people with 
diminished kidney or liver function, or modification of procedures such as 
changing imaging studies to avoid giving contrast agent to people who are 
more likely to suffer side effects from it, etc.: (REQUIRED) 
Physical discomfort or pain from blood draws: 
Risks to employment, or social or legal standing from genetic research: 
Possible personal discomfort due to sensitive topics (genetic testing in pregnancy) 
15.2 * RISKS: Describe any anticipated risks and discomforts not listed above: (REQUIRED) 
Sometimes people feel anxiety about learning new or uncertain genetic information about 
their pregnancy or their family. Uncertain results in a pregnancy can be especially 
challenging to incorporate into prenatal decision making.Information about biological 
relationships will not be shared by the researchers, unless this information is of 
medical importance to you or your family. 
Information about family relationships can be learned during testing. Testing may reveal 
unexpected information about blood-relatedness. It may reveal situations where a father 
or another relative has no biological relationship with a child. 
Genetic testing can also cause stress to family relationships when different family 
members disagree about the need for testing. 
The Genetic Information Nondiscrimination Act (GINA) is a federal law that protects 
patients against employment and health insurance discrimination. That means that 
employers and health insurance companies cannot use genetic information when making 
hiring or coverage decisions. The law has limits, however. Life insurance, long-term care 
insurance, and disability insurance, are not included in the law’s protections. GINA does 
not cover those serving in the military. Some state laws also include protection against 
genetic discrimination but safeguards are not completed 
We will take appropriate steps to ensure that personal health information is kept 
private, however, unforeseen events could result in a loss of privacy. 
15.3 
MINIMIZING RISKS: Describe the steps you have taken to minimize the risks/discomforts to 
subjects. Examples include: 
designing the study to make use of procedures involving less risk when appropriate 
minimizing study procedures by taking advantage of clinical procedures conducted on the 
study participants 
mitigating risks by planning special monitoring or conducting supportive interventions for the 
study 
having a plan for evaluation and possible referral of subjects who report suicidal ideation 
We will take extensive precautions to maintain participant confidentiality throughout the 
study. First, lists of individuals who will be participating will be kept in a locked drawer and in 
password protected computer files in the office of the study coordinator. Used consent forms will 
also be locked in a filing cabinet in the office of the study coordinator, and electronic forms of the 
transcripts will be maintained securely on her computer. Confidentiality of all study-related 
records will be maintained in accordance with State and Federal laws. Only the PI and a limited 
number of study personnel will have access to data which will be encrypted and stored on a 
 

secure server. De-identified data will be stored in a secure HIPAA compliant database. Datasets 
used for analysis will be de-identified. Participant identities will not be revealed in any publication 
that may result from the proposed study. 
While there is a risk of emotional distress should be acknowledged, women are only eligible for 
this study if they have already elected to undergo prenatal genetic diagnosis, where the potential 
pychological and personal/family health risks upfront for patient consideration and informed 
decision making regarindg research participation by a consultation with a licensed and certified 
genetic counselorwhere the potential risk for false negative and positive results are typically 
discussed with a genetic counselor. Every effort will be made to educate study subjects and 
provide information about the study in a way that mitigates this risk. 
To mitigate risks for inaccurate information from the technology we will confirm all variants using 
a secondary Sanger sequencing. 
15.5 * BENEFITS: (REQUIRED) Note: These are the benefits that the IRB will consider during their review. 
They are not necessarily appropriate to include in the consent form. 
Possible immediate and/or direct benefits to participants and society at 
large (check all that apply): 
  Positive health outcome (e.g. improvement of condition, relief of pain, increased mobility, 
etc.) 
  Closer follow-up than standard care may lead to improved outcomes or patient engagement 
  Health and lifestyle changes may occur as a result of participation 
  Knowledge may be gained about their health and health conditions 
  Feeling of contribution to knowledge in the health or social sciences field 
  The research presents a reasonable opportunity to further the understanding, prevention, or 
alleviation of a serious problem affecting the health or welfare of children 
  Other benefit (describe below) 
  None 
15.6 RISK TO BENEFIT RATIO: Explain why the risks to subjects are reasonable in relation to anticipated 
benefits, if any, to the participant or society: 
We may find a gene variant or variants that are important to the health of the 
patient's pregnancy and/or the health of their family. 
If a variant is found to explain the birth defects identified in the pregnancy this information may 
be valuable to enable providers to more accurately counsel about long term outcomes, 
individualize antenatal care, allow more informed decision-making, and improve the ability of the 
care team to plan for specific neonatal needs. 
15.7 * DATA AND SAFETY MONITORING: Do you have a Data and Safety Monitoring Plan (DSMP) for this 
study (A DSMP is required for Greater than Minimal Risk research): (Click the Help link for guidance 
on risk determination) (REQUIRED) 
   Yes  
   No 
This is not required for minimal risk research but the UCSF IRB strongly recommends 
one to ensure the data collected are adequate to meet the research aims: 
16.0 
Confidentiality, Privacy, and Data Security 
16.1 PROTECTING PRIVACY: Indicate how subject privacy will be protected: 
  Conduct conversations about the research in a private room 
  Ask the subject how they wish to be communicated with – what phone numbers can be 
called, can messages be left, can they receive mail about the study at home, etc. 

  Take special measures to ensure that data collected about sensitive issues do not get added 
to their medical records or shared with others without the subject’s permission 
  Other methods (describe below) 
16.2 SENSITIVE DATA: Do any of the instruments ask about illegal or stigmatized behavior: 
   Yes  
   No 
16.3 SIGNIFICANT CONSEQUENCES OF A LOSS OF PRIVACY OR CONFIDENTIALITY: Could a breach of 
privacy or confidentiality result in any significant consequences to participants, such as criminal or 
civil liability, loss of state or federal benefits, or be damaging to the participant's financial standing, 
employability, or reputation: 
  Yes  
 No 
Check all that apply: 
  Embarrassment 
  Criminal or civil liability 
  Loss of state or federal benefits 
  Damaging to the participant's financial standing, employability, or reputation 
  Potential risks to insurability (health, disability, or life insurance) 
Describe the potential consequences: 
The Genetic Information Nondiscrimination Act (GINA) is a federal law that protects patients 
against employment and health insurance discrimination. That means that employers and health 
insurance companies cannot use genetic information when making hiring or coverage decisions. 
The law has limits, however. Life insurance, long-term care insurance, and disability insurance, 
are not included in the law’s protections. GINA does not cover those serving in the military. Some 
state laws also include protection against genetic discrimination but safeguards are not completed 
16.4 EXTRA CONFIDENTIALITY MEASURES: Explain any extra steps that will be taken to assure 
confidentiality and protect identifiable information from improper use and disclosure, if any: 
For our analysis all study subjects including their clinical information (ultrasound findings in the 
pregnancy, prenatal health records, pregnancy decision making and long term pregnancy 
outcome) and whole exome sequencing test results will be fully de-identified and assigned a 
study number. The master key that identifies study subject with their study number will be 
maintained in a locked folder with only a small amount of study staff including key researchers to 
have access to this key. 
16.5 * REPORTABILITY: Do you anticipate that this study may collect information that State or Federal 
law requires to be reported to other officials, such as elder abuse, child abuse, or threat to self or 
others: (REQUIRED) 
   Yes  
   No 
16.6 CERTIFICATE OF CONFIDENTIALITY: Will this study obain a Certificate of Confidentiality: 
  Yes  
 No 
Please include the recommended Certificate of Confidentiality 
language in the consent form. 
16.7 SHARING OF RESEARCH RESULTS: Will there be any sharing of EXPERIMENTAL research test results 

with subjects or their care providers: 
  Yes  
 No 
Note: This is unusual and not recommended, particularly in cases 
where the tests are carried out in a non-CLIA certified laboratory, 
the results are of unproven clinical significance, or where there are 
not known preventative strategies and/or treatments. If these are 
the most likely scenarios for your study, you should check 'No.' 
If you have an incidental finding of clear clinical significance, call 
the HRPP QIU at 415-476-1814 for a consult. 
Explain under what circumstances research results may be shared: 
This testing will be performed in a CLIA certified lab to perform prenatal clinical whole exome 
sequencing. These results will therefore be shared with both the patient and their care team per 
patient consent indications. 
16.9 * HIPAA APPLICABILITY: Study data will be: (REQUIRED) 
  Derived from a medical record (e.g. APeX, OnCore, etc. Identify source below) 
  Added to the hospital or clinical medical record 
  Created or collected as part of health care 
  Used to make health care decisions 
  Obtained from the subject, including interviews, questionnaires 
  Obtained ONLY from a foreign country or countries 
  Obtained ONLY from records open to the public 
  Obtained from existing research records 
  None of the above 
  Derived from the Integrated Data Repository (IDR) or The Health Record Data Service 
(THREDS) at SFGH 
In addition to signing a consent form, each subject will have to sign 
the UCSF Research Subject Authorization Form (HIPAA Form). 
Upload the HIPAA Authorization Form in the Other Study 
Documents section of the Initial Review Submission Packet Form. 
Failure to have patients sign the HIPAA Authorization is one of the 
most common findings from QIU Routine Site Visits. Please call 
the IRB office at 415-476-1814 if you have questions about HIPAA 
research requirements. 
If derived from a medical record, identify source: 
 
APeX, Epic systems 
16.10 * IDENTIFIERS: Check all identifiers that will be collected and included in the research records, 
even temporarily: (REQUIRED) 
  Names
 Dates 
  Postal addresses 
  Phone numbers 
  Fax numbers 
  Email addresses 
 

  Social Security Numbers* 
  Medical record numbers 
  Health plan numbers 
  Account numbers 
  License or certificate numbers 
  Vehicle ID numbers 
  Device identifiers or serial numbers 
  Web URLs 
  IP address numbers 
  Biometric identifiers 
  Facial photos or other identifiable images 
  Any other unique identifier 
  None 
* Could study records include ANY photos or images (even 'unidentifiable' 
ones): (REQUIRED) 
   Yes  
   No 
16.11 * PATIENT RECORDS: Will health information or other clinical data be accessed from UCSF Health, 
Benioff Children's Hospital Oakland, or Zuckerberg San Francisco General (ZSFG): (REQUIRED) 
  Yes  
 No 
16.12  * CLINICAL DATA - GENERAL DESCRIPTION: Provide a general description of the types of clinical 
data that you are requesting access to: (REQUIRED) 
We will be collecting data regarding fetal ultrasound findings, postnatal phenotype 
information, maternal prenatal labwork and any genetic testing results including microarray 
analysis, other specific genetic testing if pursued and the results of the exome sequencing that is 
coordinated as a part of the study participation. 
16.13 * CHART/CLINIC NOTES AND OTHER FREE TEXT FIELDS: Will the medical record data include any 
information extracted from free text fields: (REQUIRED) 
  Yes  
 No 
Data sets that include free text from fields such as chart notes, 
clinic notes, and other text fields are considered identifiable, even 
without direct identifiers. 
16.14 * HIPAA - PERMISSION TO ACCESS SENSITIVE DATA: Does the research require access to any of 
the following types of health information from the medical record: (check all that apply) 
(REQUIRED) 
  Drug or alcohol abuse, diagnosis or treatment 
  HIV/AIDS testing information 
  Genetic testing information 
  Mental health diagnosis or treatment 
  None of the above 
Important note: Ensure that participants initial the corresponding 
line(s) in Section C of the HIPAA authorization form during the 
consent process. 
 

16.15 * ACCESS TO OTHER SENSITIVE OR PROTECTED DATA: Are you requesting access to any 
sensitive health data not protected under HIPAA (any other health history that patients would 
expect to be kept private such as records relating to treatment for obesity, STDs, compulsive 
behaviors, embarrassing health conditions, sexual orientation and practices, etc.): (REQUIRED) 
   Yes  
   No 
16.17 * IDENTIFIABILITY OF FINAL DATA SET: (REQUIRED) 
Which type of data set are you requesting IRB approval for: 
A de-identified data set does not include ANY of the 18 HIPAA 
identifiers in the list above or any free text fields. 
A limited data set (LDS) is described as health information that 
excludes direct identifiers but that may include: 
City 
State 
ZIP Code 
Elements of date (including dates such as admission, discharge, 
service, month and year) 
Other numbers, characteristics, or codes not listed as direct 
identifiers, including ages in years, months or days or hours 
Identifiable data sets include direct identifiers and/or information from 
free text fields. 
Review the HIPAA FAQs on the IRB website for more details about 
identifiability of data sets. 
  De-identified data set 
  Limited data set 
  Identifiable data set without direct identifiers (includes free text fields) 
  Identifiable data set with direct identifiers (may or may not also include free text fields) 
16.18 * DATA COLLECTION AND STORAGE: (check all that apply): (REQUIRED) 
Collection methods: 
  Electronic case report form systems (eCRFs), such as OnCore or sponsor-provided clinical trial 
management portal 
  UCSF ITS approved Web-based online survey tools: Qualtrics or RedCap 
  Other web-based online surveys or computer-assisted interview tool 
  Mobile applications (mobile or tablet-based) 
  Text Messaging 
  Wearable devices 
  Audio/video recordings 
  Photographs 
  Paper-based (surveys, logs, diaries, etc.) 
  Other: 
* What online survey or computer assisted interview tool will you use: 
(REQUIRED) 
  Qualtrics (Recommended) 
  RedCAP (Recommended) 
  Survey Monkey (NOT recommended and may require UCSF ITS Security review) 
  Other 
 

* Data will be collected/stored in systems owned by (check all that apply): 
(REQUIRED) 
  Study sponsor 
  UCSF data center (including OnCore, RedCap, Qualtrics, and MyResearch) 
  UCSF encrypted server, workstation, or laptop residing outside of UCSF data center 
  Personal devices, such as laptops or tablets that are not owned or managed by UCSF 
  SF VAMC 
  Zuckerberg San Francisco General Hospital 
  Benioff Children's Hospital Oakland 
  Langley Porter Psychiatric Institution 
  Other UCSF affiliate clinic or location (specify below) 
  Cloud vendor such as Amazon Web Services (AWS), Salesforce, etc. (specify below) 
  Other academic institution 
  3rd party vendor (business entity) 
  Other (explain below) 
16.19 * ADDITION OF RECORDS TO A REGISTRY: Will patient records reviewed under this approval be 
added to a research database, repository, or registry (either already existing or established under 
this protocol): (REQUIRED) 
  Yes  
 No 
This activity generally requires patient consent and HIPAA 
Authorization. A Waiver of Consent/Authorization may be granted 
for patients who are deceased or lost to follow up, but ongoing 
patients should be consented at their next clinic visit prior to 
accessing their health records or they may provide consent and 
HIPAA authorization for research use of their health information by 
mail or through a certified E-Signature system such as 
DocuSign. You may be asked to revise your consent plans. 
16.20 * DATA SHARING: During the lifecycle of data collection, transmission, and storage, will identifiable 
information be shared with or be accessible to anyone outside of UCSF: (REQUIRED) 
   Yes  
   No 
17.0 
Financial Considerations 
17.1 * PAYMENT: Will subjects be paid for participation, reimbursed for time or expenses, or receive any 
other kind of compensation: (REQUIRED) 
  Yes  
 No 
17.2 PAYMENT METHODS: Subjects payment or compensation method (check all that apply): 
Payments will be (check all that apply): 
  Cash
 Check 
  Gift card 
  Debit card 
  UCSF Research Subject Payment Card 

  Reimbursement for parking and other expenses 
  Other: 
Specify other payment/compensation method: 
Exome sequencing test will be covered for by the study. 
17.3 PAYMENT SCHEDULE: Describe the schedule and amounts of payments, including the total subjects 
can receive for completing the study: 
If there are multiple visits over time, explain how payments will be prorated for partial 
completion 
If deviating from recommendations in Subject Payment Guidelines, include specific 
justification below 
Patient are asked to complete mutliple surveys in the study period. They will be compensated $50 
total in gift cardsall surveys are completed. $20 after the first survey and $30 for the second. 
17.4 COSTS TO SUBJECTS: Will subjects or their insurance be charged for any study activities: 
   Yes  
   No 
18.0 
Other Approvals and Registrations 
18.4 OTHER APPROVALS: Indicate if this study involves other regulated materials and requires approval 
and/or authorization from the following regulatory committees: 
  Institutional Biological Safety Committee (IBC) 
Specify BUA #: 
  Institutional Animal Care and Use Committee (IACUC) 
Specify IACUC #: 
  Controlled Substances 
19.0 
Qualifications of Key Study Personnel and Affiliated 
Personnel 
NEW: January 2019 - Affiliated personnel who do not 
need access to iRIS no longer need to get a UCSF ID. 
Instead, add them below in the Affiliated Personnel 
table below. 
19.1 
Qualifications of Key Study Personnel: 
Instructions: 
For UCSF Key Study Personnel (KSP)* listed in Section 3.0, select the KSP 
from the drop down list and add a description of their study responsibilities, 
 

qualifications and training. In study responsibilities, identify every individual 
who will be involved in the consent process. Under qualifications, please 
include: 
Academic Title 
Institutional Affiliation (UCSF, SFGH, VAMC, etc.) 
Department 
Certifications 
NOTE: This information is required and your application will be 
considered incomplete without it. If this study involves invasive or 
risky procedures, or procedures requiring special training or 
certification, please identify who will be conducting these 
procedures and provide details about their qualifications and 
training. Click the orange question mark for more information and 
examples. 
Training Requirements: 
The IRB requires that all Key Study Personnel complete Human Subjects 
Protection Training through CITI prior to approval of a new study, or a 
modification in which KSP are being added. More information on the CITI 
training requirement can be found on our website. 
 
* Definition of Key Study Personnel and CITI Training Requirements (Nov, 
2015): UCSF Key Study Personnel include the Principal Investigator, other investigators 
and research personnel who are directly involved in conducting research with study 
participants or who are directly involved in using study participants’ identifiable private 
information during the course of the research. Key Personnel also include faculty mentors 
/advisors who provide direct oversight to Postdoctoral Fellows, Residents and Clinical 
Fellows serving as PI on the IRB application. 
 
 
The Principal 
Investigator, Mary 
Norton MD, is a Professor 
in the Department of 
Obstetrics, Gynecology 
and Reproductive 
Sciences at UCSF. She 
has been the principal 
and co-investigator of 
numerous clinical 
studies, which have 
involved recruiting, 
consenting, enrolling, 
and following thousands 
of pregnant women from 
throughout the San 
Francisco Bay area. 
Dr. Norton, Mary MD, MD 
Qualifications, Licensure, and 
Training 
Description of Study 
Responsibilities - Briefly 
describe what will each 
person be doing on the study. 
If there are procedures 
requiring special expertise or 
certification, identify who will 
be carrying these out. Also 
identify who will be obtaining 
informed consent. 
KSP Name 
Kao Thao earned her 
As Principal Investigator, 
Dr. Norton will be 
responsible for 
overseeing development 
and implementation of 
study guidelines and 
protocols, as well as the 
analysis and publication 
of data. 

 
 
 
 
Thao, Kao N 
Bachelors of Art in 
Integrative Biology from 
University of California, 
Berkeley. She will be 
involved with 
coordinating patient 
recruitment at UCSF. She 
has experience as a 
research assistant in 
multiple studies in a 
women's health setting. 
 
 
 
 
Lianoglou, Billie R 
 
 
 
 
Dr. Slavotinek, Anne PhD, 
PhD 
 
 
Dr. Shieh, Joseph, MD, 
PhD 
 
Medical Geneticist 
 
 
 
Dr. Kwok, Pui-Yan Ph.D., 
MD, PhD 
 
Dermatologist 
 
 
 
Gosnell, Kristen A 
Clinical Nurse Specialist 
 
 
 
 
Dr. Koenig, Barbara, PhD 
Medical Anthrologist 
 
 
 
 
Scudmore, Janice C 
 
 
 
Dr. Keller, Roberta, MD 
Neonatologist 
 
 
 
 
Dr. Michie, Marsha, PhD 
Anthropologist 
 
 
 
 
O'Leary, Allison S 
 
 
 
Dr. Sherr, Elliott MD, PhD 
Pediatric Neurologist 
 
 
 
 
Michelson, Jeremy 
Study Coordinator 
Mr. Michelson is certified 
in human subject 
research 
Dr. Sherr is certified in 
human subject research 
Ms. O'Leary is certified in 
human subject research 
Study Coordinator, 
Research Assistant 
Dr. Michie is certified in 
human subject research 
Dr. Keller is certified in 
human subject research 
Nurse Practitioner 
Mrs. Scudmore is 
certified in human 
subject research 
Dr. Koenig is certified in 
human subject research 
Ms. Gosnell is certified in 
human subject research 
Dr. Kwok is certified in 
human subject research 
Dr. Shieh is certified in 
human subject research 
Medical Geneticist 
Dr. Slavotinek is certified 
in human subject 
research 
Study Recruiter: 
Recruitment and Consent 
patients 
Billie Lianoglou is a board 
certified and licensed 
genetic counselor at the 
UCSF Fetal Treatment 
Center and is certified in 
human subject research. 
Study Coordinator, 
Research Assistant 

 
Anguiano, Beatriz 
Ms. Anguiano is certified 
in human subject 
research 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sahin Hodoglugil, Nuriye N 
Program Manager 
 
 
Dr. Nuriye Nalan Sahin 
Hodoglugil, MD, MA, 
DrPH is the Program 
Manager for the P3EGS 
Project. Previously she 
worked in global health, 
and collaborated with 
partners in academia, 
Ministries of Health and 
international health 
organizations to generate 
evidence to guide 
programs and policy for 
improving women's 
health. She worked in 
reproductive health 
programs and research in 
several countries in sub- 
saharan Africa and Asia, 
as well as monitoring and 
evaluation of large scale 
maternal health 
interventions. She has 
also worked as a 
researher at UC San 
Francisco and UC 
Berkeley, and as a Senior 
Reproductive Health 
Technical Advisor at 
Johns Hopkins University. 
She holds an MD from 
Hacettepe University 
Faculty of Medicine, 
Turkey; an MA in cultural 
anthropology from 
Hacettepe University 
Institute of Social 
Sciences, and a DrPH 
from University of 
California, Berkeley. 
 
 
Dong, Shan 
bioinformatician 
 
 
 
 
Rangwala, Naseem A 
study coordinator 
 
 
 
 
 
 
 
 
 
Outram, Simon M 
Dr. Outram is also a 
study coordinator and 
will conduct ethnographic 
observations and 
interviews. 
Dr. Outram is certified in 
human subject’s 
research. He has done 
research in Cultural 
Anthropology, Qualitative 
Social Research, Science 
and Technology Studies, 
and Bioethics. He has 
experience with multiple 
social science research 
methodologies, including 
in-depth interviewing and 
ethnographic observation. 
certified in human 
subject research 
certified in human 
subject research 
Study coorinator 

Dr. Sanders, Stephan 
MDPhD 
Bioinformatician 
 
Dr. Sanders Dr Sanders 
trained as a pediatric 
physician at Nottingham 
and London in the UK 
before undertaking a PhD 
and postdoctoral 
research position at Yale. 
His research focuses on 
using genomics and 
bioinformatics to 
understand the etiology 
of human disease, 
especially autism 
spectrum disorder (ASD). 
He is certified in human 
subject research 
Schwartz, Grace B 
lab technician 
 
certified in human 
subject research 
Tobias, Sarah E 
Study Recruiter: 
Recruitment and Consent 
patients 
Sarah Tobias is a board 
certified and licensed 
genetic counselor at the 
UCSF Fetal Treatment 
Center and is certified in 
human subject research. 
Farrell, Rachel L 
Study Recruiter: 
Recruitment and Consent 
patients 
Rachel Farrell is a board 
certified and licensed 
genetic counselor at the 
UCSF Prenatal Diagnosis 
Center and is certified in 
human subject research. 
Hoban, Hannah G 
study coordinator 
 
certified in human 
subject research 
Rego, Shannon M 
Study Recruiter: 
Recruitment and Consent 
patients 
Shannon Rego is a board 
certified and licensed 
genetic counselor 
working as the lead 
genetic counselor in the 
Program for Prenatal and 
Pediatric Genomic 
Sequencing study. She is 
certified in human 
subject research. 
Ackerman, Sara, PhD, MPH 
Medical Anthropologist 
Dr. Ackerman is certified 
in human subject 
research 
Norstad, Matthew 
Study coordinator 
 
Certified in human 
subject research 
Chen, Flavia H 
Study coordinator 
 
Certified in human 
subjects research 
 

Yip, Tiffany A 
Study Recruiter: 
Recruitment and Consent 
patients 
Tiffany Yip is a licensed 
genetic counselor, and 
the assistant genetic 
counselor in the Program 
for Prenatal and Pediatric 
Genomic Sequencing 
study. She is experienced 
in consenting for exome 
testing and certified in 
human subject research. 
Silver, Julia M 
Study Recruiter: 
Recruitment and Consent 
patients 
Julia Silver is a board 
certified and licensed 
genetic counselor at the 
UCSF Prenatal Diagnosis 
Center and is certified in 
human subject research. 
Patel, Sachi 
Study coordinator 
 
Certified in human 
subjects research 
Curry, Cynthia 
Medical Geneticist 
 
Dr. Cynthia Curry is a 
Board-certified Clinical 
Geneticist at UCSF 
Fresno. She will recruit 
patients for this study 
from those seen at 
Community Regional 
Medical Center. Board- 
certified Clinical 
Geneticist who has 
experience with consent 
for exome sequencing. 
Amezcua, Jessica M 
Study coordinator 
 
Certified in human 
subjects research 
Faubel, Amanda J 
Study coordinator 
 
Certified in human 
subjects research 
Rigler, Nicole A 
Study coordinator 
 
Certified in human 
subjects research 
Oman, Natalie 
Study coordinator 
 
Certified in human 
subjects research 
Downum, Sarah L 
Study coordinator 
 
Certified in human 
subjects research 
Yamane, Taylor A 
Study coordinator 
 
Certified in human 
subjects research 
Cullen, Caitlin 
Study coordinator 
 
Certified in human 
subjects research 
Tick, Katherine 
Study coordinator 
 
Certified in human 
subjects research 
 

 
 
19.2 Affiliated Personnel: 
 
Instructions: 
 
This section is for personnel who are not listed in Section 3.0: Grant Key 
Personnel Access to the Study because their names were not found in 
the User Directory when both the iRIS Database and MyAccess directories 
were searched. Add any study personnel who fit ALL of the following criteria 
in the table below: 
They meet the definition of Key Study Personnel (see above), and 
They are associated with a UCSF-affiliated institution (e.g., VAMC, 
Gladstone, Institute on Aging, Vitalant, NCIRE, SFDPH, or ZSFG), and 
They do not have a UCSF ID, and 
They do not need access to the study application and other study 
materials in iRIS. 
Note: Attach a CITI Certificate for all persons listed below in the Other 
Study Documents section of the Initial Review Submission Packet 
Form after completing the Study Application. 
 
Click the orange question mark icon to the right for more information on 
who to include and who not to include in this section. 
Do not list personnel from outside sites/non-UCSF-affiliated institutions. 
Contacts for those sites (i.e. other institution, community-based site, 
foreign country, or Sovereign Native American nation) should be listed in 
the Outside Sites section of the application. 
 
If there are no personnel on your study that meet the above 
criteria, leave this section blank. 
 
 
Name 
Institution 
Telephone 
E-mail 
Role 
No External Personnel has been added to this IRB Study 
 
Please describe the study responsibilities and qualifications of each affiliated 
person listed above: 
 
 
20.0 
End of Study Application 
 
End of Study Application Form 
 
To continue working on the Study Application: 
Click on the section you need to edit in the left-hand menu. Remember to save through 
the entire Study Application after making changes. 
 
If you are done working on the Study Application: 
Important: Before proceeding, please go back to Section 4.0 Initial Screening 
Questions and Save and Continue through the form to make sure all the relevant 

 
sections and questions have been included. If you've changed any answers since you 
started, the branching may have changed. Your application will be incomplete and it will 
have to be returned for corrections. 
Once you are sure the form is complete, click Save and Continue. If this is a new 
study, you will automatically enter the Initial Review Submission Packet Form, 
where you can attach consent forms or other study documents. Review the Initial 
Review Submission Checklist for a list of required attachments. 
Answer all questions and attach all required documents to speed up your 
approval. 
The UCSF IRB welcomes feedback about the IRB Study Application Form. Please click the link to 
answer a survey about the application form.