Effect of a Patient-Centered Decision App on TOLAC: An RCT
Phase: NA
Conditions: Pregnancy, Repeat Cesarean Section, Vaginal Births After Cesarean
Sponsor: University of California, San Francisco

PROCEED Study Protocol 
 
1. Original Study Protocol (January 6, 2016) 
2. Final (V2) Study Protocol (September 28, 2018) with changes noted on title page. 
 
 

 
 
 
 
 
 
 
Effect of a Patient-Centered Decision App on 
TOLAC: An RCT 
 
 
 
The PRiOr CEsarEan Decision App (PROCEED) Study 
 
 
 
Sponsored by: 
US National Institute of Health 
Grant #1R01HD078748 
January 6, 2016 
 
IRB Approvals 
UCSF/Marin Community Clinic: CHR #13-11707 
Massachusetts General Hospital: IRB #2015P002284 
Northwestern University Medical Center: IRB #STU00104496 
 
NCT02646423 
 
 
 
Principal Investigator: Miriam Kuppermann, PhD, MPH 
Professor and Vice Chair for Clinical Research 
Department of Obstetrics, Gynecology & Reproductive Sciences 
School of Medicine 
University of California, San Francisco 
 

PROCEED Study Protocol………………           -3- 
06 January 2016 
 
TABLE OF CONTENTS 
 
STUDY TEAM ROSTER .................................................................................................................................... 4 
PERSONNEL AND DUTIES .............................................................................................................................. 5 
STUDY SCHEMA ............................................................................................................................................. 6 
OVERVIEW OF STUDY DESIGN AND RANDOMIZATION SCHEME .................................................................. 8 
1.0 
INTRODUCTION ................................................................................................................................. 8 
1.1. 
Background and Prior Research ................................................................................................... 8 
2.0 
STUDY HYPOTHESES AND DESIGN .................................................................................................. 10 
2.1. 
Primary Hypothesis ..................................................................................................................... 10 
2.2. 
Secondary Hypotheses ............................................................................................................... 10 
2.3. 
Study Design ............................................................................................................................... 10 
2.3.1. 
Timeline ...................................................................................................................................... 12 
2.3.2. 
Randomization ............................................................................................................................ 12 
3.0 
STUDY POPULATION ....................................................................................................................... 12 
3.1. 
Inclusion Criteria ......................................................................................................................... 12 
3.2. 
Exclusion Criteria ........................................................................................................................ 13 
3.3. 
Participant Retention .................................................................................................................. 13 
3.4. 
Participant Withdrawal ............................................................................................................... 13 
4.0 
STUDY ARMS ................................................................................................................................... 13 
4.1. 
Standard of Care ......................................................................................................................... 13 
4.2. 
Intervention ................................................................................................................................ 16 
5.0 
STUDY PROCEDURES ....................................................................................................................... 16 
5.1. 
Overview ..................................................................................................................................... 16 
5.1.1. 
Chart audit (<25 weeks gestation) .............................................................................................. 17 
5.1.2. 
Opt-in form (<25 weeks gestation) ............................................................................................. 17 
5.1.3. 
Baseline Screening and Enrollment interview  (12 weeks 0 days-24 weeks 6 days gestation) .. 17 
5.1.4. 
Phone Follow-up interview (34- to 37 weeks gestation) ............................................................ 18 
5.1.5. 
Chart audits (after due date) ...................................................................................................... 19 
5.1.6. 
Post-delivery Phone interview for outside deliveries (after due date) ...................................... 20 
6.0 
SAFETY MONITORING AND ADVERSE EVENT REPORTING .............................................................. 20 
6.1. 
Safety Monitoring and Clinical Data Review .............................................................................. 20 
6.2. 
Reporting Requirements for this Study ...................................................................................... 21 
7.0 
STATISTICAL CONSIDERATIONS ....................................................................................................... 21 
7.1. 
Endpoints .................................................................................................................................... 21 
7.1.1. 
Primary Endpoint ........................................................................................................................ 21 
7.1.2. 
Secondary Endpoints .................................................................................................................. 21 
7.2. 
Sample Size ................................................................................................................................. 22 
7.3. 
Blinding ....................................................................................................................................... 23 
7.4. 
Data Analysis ............................................................................................................................... 23 
8.0 
HUMAN SUBJECTS CONSIDERATIONS ............................................................................................. 23 
8.1. 
Ethical Review ............................................................................................................................. 23 
8.2. 
Informed Consent ....................................................................................................................... 24 
8.3. 
HIPAA .......................................................................................................................................... 24 
8.4. 
Risks ............................................................................................................................................ 24 
8.5. 
Benefits ....................................................................................................................................... 24 
8.6. 
Incentives .................................................................................................................................... 24 
8.7. 
Confidentiality ............................................................................................................................ 24 

9.0 
ADMINISTRATIVE PROCEDURES ...................................................................................................... 24 
9.1. 
Study Coordination ..................................................................................................................... 24 
9.1.1. 
Trainings ..................................................................................................................................... 24 
9.1.2. 
Study Communication ................................................................................................................ 25 
9.1.3. 
Database Management and Data Quality Monitoring ............................................................... 26 
9.2. 
Use of Information and Publications .......................................................................................... 27 
10.0 
REFERENCES .................................................................................................................................... 27 
11.0 
APPENDIX ........................................................................................................................................ 30 
 
 

 
STUDY TEAM ROSTER 
University of California, San Francisco 
Miriam Kuppermann, PhD, 
MPH 
Principal Investigator 
miriam.kuppermann@ucsf.edu 
Peter Bacchetti, PhD 
Statistician/Co-investigator 
peter.bacchetti@ucsf.edu 
Juan Gonzalez, MD, PhD 
Co-investigator 
juan.gonzalez@ucsf.edu 
Mari-Paule Thiet, MD 
Co-investigator 
mari-paule.thiet@ucsf.edu 
Allie O’Leary, MPH 
Project manager 
allison.o’leary@ucsf.edu 
Cinthia Blat, MPH 
Data manager/statistical 
analyst 
cinthia.blat@ucsf.edu 
Priscila Valdez Lopez 
Research coordinator 
priscila.valdezlopez@ucsf.edu 
Marin Community Clinic 
Yamilee Bermingham, MD 
Co-investigator 
ybermingham@marinclinic.org 
Massachusetts General Hospital 
Anjali Kaimal, MD, MAS 
Site PI/Co-investigator 
akaimal@mgh.harvard.edu 
Allison Bryant, MD, MPH 
Co-investigator 
abryant@partners.org 
Emily Behrend, BA 
Research coordinator 
ebehrendmgh.harvard.edu 
Northwestern University Medical Center 
William Grobman, MD, MBA 
Site PI/Co-investigator 
w-grobman@northwestern.edu 
Brittney Williams, MPH 
Research coordinator 
brittney.williams@northwestern.edu 
 
 
 
 

PERSONNEL AND DUTIES 
Principal Investigator (PI) 
The PI is experienced in all aspects of the design, conduct and oversight of randomized 
controlled trials and prospective studies at multiple clinical sites and is an expert in the fields of 
medical decision-making, preference (utility) measurement, and decision-assisting tool creation 
and evaluation. The PI will take a lead role in all aspects of the proposed project, working with 
the site PIs, other co-investigators, and staff members to ensure timely and accurate completion 
of the project. The PI will direct day-to-day activities and provide overall governance and 
scientific leadership to the study. 
Statistician Co-investigator 
The statistician co-investigator will direct analysis strategy for study design and manuscript 
preparation. The statistician will also oversee data analysis by the analyst and advise the PI and 
other co-investigators on methodological issues. 
Site Principal Investigator (site PIs) 
The site PIs will meet monthly by phone and biannually in person (along with the other co-
investigators) to contribute to the overall study design and ensure each site is executing the 
study as prescribed. Site PIs are responsible for hiring and training site staff and will provide 
clinical and research expertise in the design and implementation of study instruments and 
protocols. Site PIs will monitor study enrollment and troubleshoot any recruitment issues as 
needed. They will also assist with chart review for participant delivery outcomes.  
Other Co-investigators 
Additional co-investigators will join the monthly calls and biannual in-person meetings. They will 
support patient recruitment from the obstetric practices at each site and will provide clinical 
input into data analyses and manuscripts for submission to peer-reviewed journals. They will 
also assist with chart review for participant delivery outcomes. 
Project Manager 
The project manager is responsible for the overall operations of the study, including managing 
recruitment and enrollment, guiding IRB submissions, and scheduling and preparing agendas for 
investigator and coordinator meetings. The project manager will monitor project timelines and 
ensure recruitment goals are met and recruitment and data collection are carried out per 
established protocols. The project manager will document any revisions to protocols and 
surveys and acquire IRB approvals as needed. The project manager will also work with the data 
manager/statistical analyst to design and implement study databases. 
Data Manager/Statistical Analyst  
The data manager/statistical analyst is responsible for creating and managing all databases for 
the project, monitoring data quality, and conducting data cleaning and statistical analyses under 
the direction of the statistician co-investigator and PIs.   
Research Coordinators/Interviewers 
The Research Coordinators (RCs) are the primary administrative points of contact for the study. 
They will prepare and submit all materials for IRB approval including the initial application, 
renewals, and all modifications. They will pilot and fine-tune study instruments; screen, consent, 
and interview participants; randomize participants per protocol; abstract medical data from 

PROCEED Study Protocol………………           -7- 
06 January 2016 
 
charts; and distribute participant remuneration. They will be responsible for following the 
guidelines for study operations outlined in this protocol and will email the UCSF project manager 
in the event of any protocol violations (e.g., mis-randomization, erroneous inclusion of subjects 
in the study, breach of confidentiality). They will participate in weekly or biweekly conference 
calls with the project manager and one or more PIs to go over recruitment and data collection 
activities and targets.  
 
STUDY SCHEMA 
 
Purpose: 
 
To assess the effect of the PROCEED Prior Cesarean 
Decision Support app (versus usual care without the app) 
on rates of trial of labor after cesarean (TOLAC) among 
pregnant women with a prior cesarean delivery (CD). 
Design: 
 
This is a two-armed randomized controlled trial (RCT) 
among 1,320 English- or Spanish-speaking pregnant 
women (1:1 randomization sequence for the 
intervention).   
Study 
Population: 
 
Pregnant women receiving prenatal care at a 
participating healthcare facility. Women will be eligible to 
enroll if they meet all of the following criteria. 
Inclusion criteria: 
• 
Between 12 weeks 0 days and 24 weeks 6 days 
gestation at enrollment 
• 
Speak English or Spanish 
• 
Have had one and only one prior CD 
• 
Prior low transverse cesarean 
• 
Unknown scar but TOLAC eligible 
 
Exclusion criteria: 
• 
No prior cesarean delivery, or more than one  
• 
Multiple gestation pregnancy 
• 
Prior vaginal birth after cesarean 
• 
Any contraindications to TOLAC  (prior classical 
cesarean, prior uterine surgery, T-incisions, other 
contraindication) 
• 
Delivering at outside institution 
 
Study Size: 
 
The recruitment goal is 1,320 participants, for a 
recruitment rate of 40 participants per month and a final 
subset of 627 per arm (1254) projecting 5% loss to follow 
up.    

Study 
Intervention: 
 
Participants in the intervention arm will be provided with 
the PROCEED Prior Cesarean Decision app, which includes 
approximately 15 minutes of dynamic web-based 
informational content including potential maternal and 
neonatal complications from vaginal and cesarean 
deliveries, values clarification questions, and 
individualized estimates of likelihood of successful 
TOLAC.   
Study 
Duration: 
 
Data collection start date: January 2016 
Estimated data collection end date:  July 2019  
 
 
Primary 
Hypothesis: 
 
Compared to women who receive usual care only, women 
who are randomized to use the Prior Cesarean Decision 
app will be more likely to undergo TOLAC. 
Secondary 
Hypotheses: 
 
Compared to women who receive usual care only, 
women randomized to use the Prior Cesarean Decision 
app will: 
1. be more likely to have a vaginal birth after cesarean 
(major secondary outcome) 
2. be more knowledgeable about TOLAC and elective 
repeat cesarean delivery (ERCD) and their potential 
outcomes 
3. experience less decisional conflict 
4. report higher levels of shared decision making 
regarding delivery approach 
5. report higher levels of decision self-efficacy  
6. report higher levels of decision satisfaction 
7. experience lower rates of maternal and neonatal 
morbidities 
Study Sites: 
University of California, San Francisco 
Marin Community Clinic 
Massachusetts General Hospital 
Northwestern University Medical Center 
 
 
 

PROCEED Study Protocol………………           -9- 
06 January 2016 
 
 
OVERVIEW OF STUDY DESIGN AND RANDOMIZATION SCHEME 
 
 
 
1.0 
 INTRODUCTION 
1.1. Background and Prior Research 
Public health impact of cesarean rate in the US. Cesarean delivery (CD) is the most common 
inpatient surgery in the US, accounting for nearly one third of births annually. In the last decade, 
the CD rate has increased by approximately 50%, with almost 1.3 million procedures performed 
in 2012.1 Moreover, at $7.8 billion annually, these deliveries account for almost half of 
childbirth-related expenses of hospitalization.2 CDs have been associated with an increase in 
major maternal morbidity,3–5 with corresponding increases in length of inpatient care following 
delivery and frequency of hospital readmission.6 Organizations including Healthy People7, the 
American College of Obstetricians and Gynecologists (ACOG)8, and the American College of 
Nurse Midwives9 have targeted reducing the CD rate as an important public health goal for more 
than a decade; however, identifying interventions to achieve this goal has proven challenging. 
Causes and consequences of the rising rate of repeat cesareans. Repeat CDs are a significant 
contributor to the increased cesarean rate, resulting from the combination of a rising rate of 
primary CD and a decreasing rate of vaginal birth after cesarean, which declined from a high of 
28.3% in 19962 to 9.2% in 2010.10 Why the VBAC rate has decreased so dramatically remains a 
subject of debate. Numerous medical and nonmedical factors have been posited as contributing 
to this decline, including the decreasing number of hospitals willing to provide this option and 
the diminishing number of obstetric providers who offer this approach. In addition, a substantial 
portion of the decrease is related to women foregoing trial of labor after cesarean (TOLAC) even 
though their hospitals and obstetricians provide the opportunity. For example, among hospitals 
in the NICHD Maternal-Fetal Medicine Units network, TOLAC rates declined from 51.8% to 
29.8% (p<.001) from 1999-2002, even though TOLAC continued to be offered at all sites.11 In a 
study of “good TOLAC candidates” at a 14-hospital network where TOLAC was available, the 
average TOLAC rate was only 30%.12 And at Northwestern, one of the clinical sites for our study, 
Pregnant women with 1 
prior cesarean  
N = 1320 
PROCEED App 
(N = 660) 
R 
Usual Care 
(N = 660) 

TOLAC rates decreased by two-thirds from 1995 to 2010 although all providers offer this labor 
approach. 
Importantly, the declining VBAC rate is not primarily due to new and more concerning 
information about the risks of TOLAC; recent epidemiologic studies have demonstrated that the 
core population-level outcomes of TOLAC, such as the chance of VBAC or of uterine rupture if a 
TOLAC is attempted, are no different today than they were three decades ago.2,13–15  Similarly, 
this decline is not primarily due to changes in characteristics of the population that would make 
VBAC less likely if TOLAC is undertaken; these decreases in TOLAC have affected all women, 
regardless of their probability of VBAC or risks of adverse TOLAC outcomes.11 The extent to 
which these changes are 
driven by patient 
preferences is not 
known. Data from 
qualitative studies offer 
some insight, but the 
value of that information 
is limited by the non-
generalizability of the 
study populations and 
the lack of quantitative 
analyses.16–21 
Furthermore, while 
decreased TOLAC rates 
are occurring throughout 
the US, there are 
persistent, unexplained 
racial/ethnic, geographic, and socioeconomic differences in rates of TOLAC and VBAC.22  This 
variation, in the absence of a demonstrated basis in clinical science or patient preferences, 
raises concern about the efficiency, effectiveness, and patient-centeredness of approach to 
delivery after CD.23  
Call to action. An NIH consensus conference statement noted that “the informed consent 
process for TOLAC and ERCD should be evidence-based, minimize bias, and incorporate a strong 
emphasis on the values and preferences of pregnant women,” and recommended 
“interprofessional collaboration to refine, validate, and implement decision-making and risk 
assessment tools” to accomplish that goal.22 Given the broad policy support for shared decision 
making in this context,22,24 the large absolute number of women facing the choice of TOLAC, and 
the short- and long-term consequences of this decision for mothers and babies, an intervention 
aimed at informing patients and helping them articulate their preferences could lead to 
improvements in the decision making process and have a significant impact on the health of 
individuals and the health care system.25,26 Our overarching goal is to create and evaluate a tool 
to help TOLAC-eligible women delivering at hospitals that offer TOLAC consider individualized 
risk assessments, incorporate their values and preferences, and participate in a shared decision 
making process with their providers to make informed decisions about delivery approach. We 
believe this improved informed decision making process will lead to increased TOLAC. 
Our prior studies of decision making. In a recently completed randomized study (R01 
HD049686), PI Kuppermann and colleagues found that women who used a prenatal testing 
decision tool had significantly lower uptake of invasive diagnostic testing, greater knowledge 
TOLAC
ERCD
VBAC
CD
VBAC
CD
TOLAC-eligible 
woman:
1 prior CD, no 
contra-indications 
Delivery approach: 
TOLAC vs. ERCD
Delivery mode: 
VBAC or CD
Figure 1.  Delivery approach versus delivery mode.   For women who are 
eligible for trial of labor after  cesarean (TOLAC), a decision  regarding the 
delivery approach (whether to schedule an elective repeat cesarean 
delivery (ERCD) or to undergo TOLAC) is made. The TOLAC rate is the 
percentage of eligible women who undergo a TOLAC (versus an ERCD). If 
TOLAC is chosen, the ultimate delivery mode  (VBAC or CD) is uncertain. 
Most, but not all, women who plan an ERCD will deliver via CD.

PROCEED Study Protocol………………           -11- 
06 January 2016 
 
about testing and birth defects, and better comprehension of the risks of amniocentesis or 
chorionic villus sampling.27 We believe the PROCEED study also has the potential to generate an 
evidence-based intervention that may lower the overall CD rate among diverse populations of 
women, a critical yet elusive goal in obstetric care. Moreover, because the Prior Cesarean 
Decision app will make explicit the probability of achieving VBAC, it is expected that the group of 
women who undertake TOLAC after using the decision app will be enriched with those who are 
more likely to succeed in their attempt. As over 90% of morbidity occurs in women who 
undertake TOLAC but ultimately have a cesarean during labor28, this app may also lower the rate 
of CD without increasing either maternal or perinatal morbidity. 
2.0 
STUDY HYPOTHESES AND DESIGN 
2.1. Primary Hypothesis 
The primary hypothesis of this study: 
• 
Compared to women who receive usual care only, women who are randomized to use the 
Prior Cesarean Decision app will be more likely to undergo TOLAC. 
2.2. Secondary Hypotheses 
The secondary hypotheses of this study are: 
• 
Compared to women who receive usual care only, women randomized to use the Prior 
Cesarean Decision app will: 
1. be more likely to have a vaginal birth after cesarean (VBAC) (major secondary outcome);  
2. be more knowledgeable about TOLAC and ERCD and their potential outcomes; 
3. experience less decisional conflict; 
4. report higher levels of shared decision making regarding delivery approach;  
5. report higher levels of decision self-efficacy; 
6. report higher levels of decision satisfaction; and 
7. experience lower rates of maternal and neonatal morbidities 
2.3. Study Design 
This is a two-armed RCT to assess the impact of a Prior Cesarean Decision app on the delivery 
outcomes of 1,320 English- or Spanish-speaking women with a prior cesarean delivery (1:1 
randomization sequence for the intervention).  Following is a consort diagram of the study:  
 
 

Figure 2. Consort diagram 
 
 
 
 
 

PROCEED Study Protocol………………           -13- 
06 January 2016 
 
 
2.3.1. Timeline 
 
Randomized 
controlled trial 
(n=1320) 
2016 
2017 
2018 
2019 
2020 
Jan-
Mar 
Apr-
Jun 
Jul-
Sep 
Oct-
Dec 
Jan-
Mar 
Apr-
Jun 
Jul-
Sep 
Oct-
Dec 
Jan-
Mar 
Apr-
Jun 
Jul-
Sep 
Oct-
Dec 
Jan-
Mar 
Apr-
Jun 
Jul-
Sep 
Sep-
Dec 
Jan-
Mar 
Apr-
Jun 
Recruit RCT 
d
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Phone follow-up 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chart reviews 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Create 
databases, enter 
and clean data 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Analyze data and 
prepare 
manuscripts 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2.3.2. Randomization 
Randomization tables will be generated with SAS v9.4 using the RAND function utilizing the 
Mersenne-Twister random number generator. To make treatment assignments difficult to 
anticipate, the program will generate randomly permuted blocks of 8, 10, and 12 in random 
order. Randomization will be stratified by language (English/Spanish) and recruitment site. 
Randomization tables will be uploaded into a randomization module in the study database by 
the data analyst. To protect the integrity of the randomization sequence, RCs will not have 
access to the randomization tables. 
3.0 
STUDY POPULATION 
A total of 1,320 pregnant women between 12 weeks 0 days and 24 weeks 6 days gestation with 
one prior cesarean will be enrolled into the study from three distinct geographic areas of the 
United States. Three sites serve primarily lower income women, with many Spanish speakers. 
The remaining three sites serve primarily English-speaking communities of higher socioeconomic 
status.  
Participants will be randomized to receive the Prior Cesarean Decision app or usual care, 
stratified by site and language. Participants will be selected for the study according to the 
criteria in Sections 3.1 and 3.2. They will be approached, screened, and enrolled as described in 
Sections 5.1.1., 5.1.2., and 5.1.3. Issues related to participant retention and withdrawal from the 
study are described in Sections 3.3 and 3.4, respectively. 
3.1. Inclusion Criteria 
Women who meet all of the following criteria are eligible for inclusion in the study: 
• 
Prior cesarean delivery 
• 
Between 12 weeks 0 days and 24 weeks 6 days gestation at enrollment 
• 
English- or Spanish speaker 
• 
Prior low transverse cesarean 

3.2. Exclusion Criteria 
Women who meet any of the following criteria will be excluded from this study: 
• 
No prior cesarean delivery, or more than one 
• 
Multiple gestation pregnancy 
• 
Unable to speak English or Spanish 
• 
Prior VBAC 
• 
Ineligible for TOLAC (due to prior classical cesarean, prior uterine surgery, T-incision, or 
other contraindication) 
• 
Delivering at outside institution 
3.3. Participant Retention 
Once a participant enrolls in PROCEED, the study site will make every effort to retain her in the 
study for the entire follow-up period in order to minimize possible bias associated with loss to 
follow-up. Components of such procedures may include: 
• 
Thorough explanation of the study interview schedule and procedural requirements 
during the informed consent process. 
• 
Collection of email and/or phone contact information at the study Baseline Screening 
and Enrollment interview.  
• 
Repeated contact attempts to schedule appointments. 
• 
Immediate follow-up for missed appointments. 
• 
In-person approach of patients visiting the site for prenatal care if contact cannot be 
reestablished through email or phone.   
• 
Follow-up with patients delivering at outside institutions to obtain verbal report of the 
delivery outcome and consent for release of medical records.  
3.4. Participant Withdrawal 
Regardless of the participant retention methods used, participants may voluntarily withdraw 
from the study for any reason at any time. The site PI also may withdraw participants from the 
study to protect their safety and/or if they are unwilling or unable to comply with required study 
procedures. Participants may also be withdrawn if the study sponsor, regulatory authorities, or 
site IRB terminate the study prior to its planned end date. 
The study team will evaluate participants withdrawn from the study on a case-by-case basis to 
determine whether delivery outcomes may be collected from the chart and retained in analyses. 
A final determination will be made according to a participant’s stated preference for use of her 
chart data and the data use guidelines set forth in the informed consent form.  
4.0 
 STUDY ARMS 
4.1. Standard of Care 
Standard of care varies across study sites. Following is a description of the procedures in place at 
each site: 
San Francisco Bay Area, California 
University of California San Francisco (UCSF)  
Women who establish prenatal care at UCSF are typically seen between 8 and 12 weeks 
gestation for their first obstetrical visit. The initial intake visit is in person and is conducted by 
various obstetric providers including nurse practitioners (NP), certified nurse midwives (CNM), 

PROCEED Study Protocol………………           -15- 
06 January 2016 
 
generalist obstetricians or maternal fetal medicine (MFM) specialists depending on patient 
preference or risk based upon questionnaire by the OB scheduling team.   
A complete medical, surgical and obstetrical history and physical exam, including a 
viability/dating ultrasound, is performed.  Note is made of prior pregnancy histories, including 
gestational age at delivery, pregnancy complications and modes of prior deliveries. If a patient 
gives a history of cesarean delivery (CD), attempts are made to obtain the operative report to 
review indications and hysterotomy type. Discussions regarding candidacy for trial of labor are 
initiated by all levels and type of OB care providers at the first OB visit and revisited in 
subsequent visits with discussions regarding risks/benefits and alternatives.  Calculation and 
discussion of likelihood of successful vaginal birth after CS using the MFMU calculator is 
common but not universal.  The discussions and patient choice are documented in the problem 
list. If the patient was followed by a NP or CNM throughout the pregnancy she is referred at 
least once to an obstetrician or MFM for a discussion regarding the mode of delivery.  At 34-35 
weeks gestation, if patient chooses ERCD, she is scheduled in the birth center OR schedule at 39 
weeks.  If she chooses to undergo TOLAC, a discussion of timing of delivery or induction of labor 
is conducted in the OB clinic with the clinician; otherwise spontaneous labor is 
awaited.  Patients who choose to undergo a TOLAC do not sign written consents at 
UCSF.  Surgical consents are signed by the inpatient OB team with the patient prior to ERCD.   
Marin Community Clinic. At Marin Community Clinics, obstetric patients initiate care with an RN 
whose scope of practice includes intake examinations, patient triage, and initial review of 
laboratory and diagnostic results. At the intake appointment, the obstetric nurse reviews the 
patient’s medical and obstetric history, initiates routine initial laboratory studies, and provides 
the patient with educational material. Most of the patients seen at our site, which is a Federally 
Qualified Health Care Center, are eligible for Medi-Cal, so the obstetric nurse also ensures that 
the patient begins the insurance eligibility process. After this initial intake appointment, patients 
are referred for an initial appointment with an obstetric provider who might be a nurse midwife, 
a family practice physician, or a nurse practitioner. Patients with complicated medical issues are 
referred to the two obstetricians who serve as consultants to the other providers. 
Patients with a prior cesarean section are screened for PROCEED eligibility and participation in 
the study is discussed by the obstetric nurse at the initial intake appointment. Patients are also 
identified and screened during their subsequent visits with obstetric providers. The Site Principal 
Investigator is informed when a patient would like to participate and forwards demographic 
information for these patients to the PROCEED Study Coordinator who contacts the patients for 
interviews. 
All patients who have had a prior cesarean and are eligible for a TOLAC are counseled regarding 
mode of delivery for their current pregnancy.  A significant number of our patients are Spanish 
speaking and are scheduled between 24 and 34 weeks for a monthly group class in Spanish on 
the risks and benefits of TOLAC versus elective repeat cesarean section. The class consists of a 
group session followed by individual appointments with an obstetrician to address patient 
concerns and preference for mode of delivery. Patient who are English-speaking or speak 
another language are scheduled for an individual consultation with an obstetrician. Patients who 
elect trial of labor after cesarean are seen again to review their delivery plan if they have not yet 
delivered after 39 weeks. Patients who elect repeat cesarean are scheduled for an obstetric visit 
at 36 weeks to schedule a repeat cesarean section at 39 weeks.   
 
 

Chicago, Illinois 
Northwestern University Medical Center. Women who establish prenatal care at ambulatory 
practices associated with Northwestern Memorial Hospital are most often seen in the first 
trimester for a first obstetrical visit. An initial intake is conducted at which medical, surgical and 
obstetric histories are taken. Most obstetric providers are physicians, although there are groups 
with midwives as well, and in those groups patients who are eligible for care with either type of 
provider largely self-select into physician vs. certified nurse midwifery care. Providers review 
operative reports for prior cesareans if available.  Discussions about delivery approach typically 
begin on the first prenatal visit and may be revisited throughout the course of the pregnancy.  If 
elective repeat cesarean delivery (ERCD) is preferred, or even considered, a slot on the OR 
schedule is often reserved, at whatever gestational age and date are deemed acceptable and 
appropriate after conversations between the patient and provider.  
Boston, Massachusetts 
Massachusetts General Hospital. Women who establish prenatal care at Massachusetts General 
Hospital are typically seen between 8 and 12 weeks for a first obstetrical visit. An initial intake is 
conducted by a practice nurse at most sites, and often by phone at the largest site. During the 
initial intake, medical, surgical and obstetric histories are collected for new patients and are 
updated for returning patients. Prior pregnancy history is noted, including gestational age, 
pregnancy complications and modes of prior deliveries. Patients largely self-select into physician 
vs. certified nurse midwifery care, though access to physician care may be somewhat restricted 
to those with medical or obstetrical complexities at the three community health centers where 
prenatal care is provided. Operative reports for prior cesareans are reviewed for hysterotomy 
type, with findings documented in the problem list in the electronic medical record; attempts 
are made to obtain outside records for surgeries not performed at MGH or within the Partners 
Healthcare system. Discussions about approach of delivery generally begin as early as at the first 
prenatal visit and are revisited throughout the course of the pregnancy. Risks and benefits of 
trials of labor after cesarean are reviewed in detail and women’s preferences, even if 
provisional, are recorded in their problem lists. Calculation and documentation of the likelihood 
of successful vaginal birth after cesarean using the "MFMU calculator" is common but not 
universal. If elective repeat cesarean delivery (ERCD) is preferred, or even considered, a slot on 
the OR schedule is often reserved, at whatever gestational age and date are deemed acceptable 
and appropriate after conversations between the patient and provider. The primary provider 
will often schedule a time when s/he is available. For patients desiring ERCD who are enrolled in 
midwifery care, a visit with a physician provider is often scheduled prior to the planned delivery 
date. For women considering TOLAC, risks and benefits of induction of labor are reviewed 
should indication (including post-term pregnancy) arise. In the third trimester, women sign 
written informed consent for care on Labor and Delivery, including for repeat cesarean delivery 
or TOLAC where applicable. 
Note: At all study sites, usual care for women with a prior cesarean includes counseling by the 
provider regarding mode of delivery. No formal educational intervention, web tools, or decision 
support is in place at any site. Use of the NICHD VBAC prediction tool is at the discretion of the 
prenatal provider.   
4.2. Intervention  
The Prior Cesarean Decision app (Appendices 1 and 2) includes the following features: 1) 
approximately 15 minutes of web-based content, 2) topic-specific content and graphics, 3) user-
specific risk data presented in a dynamic and interactive environment, and 4) content in both 

PROCEED Study Protocol………………           -17- 
06 January 2016 
 
English and Spanish. The program is organized into segments and sub-segments that are 
interactive and sequenced. To create a satisfying user experience and enhance user interaction, 
some segments include “learn more” buttons to access additional content. Users enter clinical 
information and responses to values clarification exercises, taking advantage of the mHealth 
platform to increase patient engagement while targeting both intuition and deliberation to 
optimize the effectiveness of decision support.29  
The app was developed using a process based on the International Patient Decision Aids 
Standards Collaboration (IPDAS) quality checklist30 to confirm that the content, development 
process, and effectiveness of the Prior Cesarean Decision app conform to the highest standards. 
Published data, as well as our own testing of prior interactive multimedia decision tools, 
provided the foundation for the content and framework for the Prior Cesarean Decision app. 
Focus groups and one-on-one interviews were conducted at all sites prior to initiation of 
enrollment for the RCT. Women of varying literacy levels who were patients of the institution 
and had a prior cesarean section within the past three years were invited to participate in a one-
time 60-90 minute feedback session with study personnel in which they completed a basic 
demographics questionnaire and were shown various versions of the app during the 
development process. The sessions were audio recorded and staff took notes of specific 
feedback to incorporate into the app. The app developers also attended some sessions to hear 
directly from potential future users. Participants were remunerated $60 for their participation. 
 
5.0 
STUDY PROCEDURES 
5.1. Overview 
The RC will perform a preliminary eligibility screening by chart audit of all women seeking 
prenatal services at the site (see section 5.1.1.). Women with one prior cesarean who speak 
English or Spanish and do not appear to have any contraindications to VBAC will be identified 
and approached for in-person eligibility review.  
Women will be approached in the clinic waiting area before a prenatal appointment, informed 
of their potential eligibility for the study, and asked to complete and return a printed copy of the 
opt-in form (see section 5.1.2,). If time permits and the woman is eligible and interested in 
participating, screening, enrollment, and randomization will take place same-day and 
immediately after the opt-in form is completed.  
All study instruments will be administered in the language preferred by the participant, English 
or Spanish. A baseline screening form will be completed to verify the woman’s eligibility, then 
written informed consent obtained from those eligible and interested in participating. 
Participant sociodemographic characteristics, expected due date, and current preference as to 
delivery approach will be collected using a baseline questionnaire. The participant will then be 
randomized to app (intervention) or no app (control). Participants randomized to app will be 
provided an iPad tablet pre-loaded with the app to view at their own pace (see sections 4.2 and 
5.1.3. for more information). A short health literacy assessment will be administered after the 
app. Apart from the app, the intervention arm will receive usual care. A woman randomized to 
no app will complete the baseline questionnaire including the health literacy assessment, and 
will not view the app.  
Patient-reported secondary outcomes will be assessed at 34 weeks 0 days to 37 weeks 6 days 
gestation through a phone follow-up interview administered by an interviewer blinded to the 

randomization group of the participant (see section 5.1.4.). After delivery, chart review will be 
performed by a blinded co-investigator to ascertain the primary outcome of delivery approach 
(TOLAC or ERCD), the secondary outcome of delivery mode (vaginal or cesarean) and any 
contraindications to TOLAC that developed post-randomization (see section 5.1.5.). Research 
assistants will also review the chart to collect other clinical data from the delivery encounter 
including the secondary maternal and neonatal morbidity outcomes.  
Participants will receive $40 in remuneration for participating in the baseline screening and 
enrollment interview and $40 for participating in the phone follow-up interview. Participants 
who deliver at an outside institution will be contacted by telephone to collect self-reported 
delivery outcome and other pregnancy and delivery information as well as permission for 
release of the medical record (see section 5.1.6.). 
5.1.1. Chart audit (<25 weeks gestation) 
The medical charts of women who will be <25 weeks gestation at the next prenatal visit to the 
site will be reviewed for eligibility by a RC or provider at the site. Women with one prior 
cesarean who speak English or Spanish and have no contraindications to VBAC will be flagged 
for further in-person eligibility review.  
5.1.2. Opt-in form (<25 weeks gestation) 
Women flagged for follow-up according to the chart audit will be approached in the clinic 
waiting area before the prenatal appointment or told about the study by the provider during an 
OB visit. Women interested in participating will be asked to complete and return a printed copy 
of the opt-in form (Appendices 3 and 4). If the woman meets gestational age criteria for baseline 
screening (see section 5.1.3) and has enough time to complete the baseline screening and 
enrollment interview (approximately 15 minutes), the screening questionnaire can be 
administered on the same day (see section 5.1.3.). Otherwise, she will be contacted by the RC to 
schedule the screening in conjunction with an upcoming prenatal visit. A record of every woman 
approached will be kept in a REDCap database. 
5.1.3. Baseline screening and enrollment interview (12 weeks 0 days to 24 weeks 6 days gestation) 
Screening Questionnaire. In-person screening for eligibility will be administered by tablet when 
the woman is between 12 weeks 0 days and 24 weeks 6 days gestation, usually immediately 
after the opt-in form is collected. Eligibility will be assessed using a seven-question screening 
questionnaire (Appendices 5 and 6). A woman will be confirmed eligible if she self-reports all of 
the following: (1) a due date corresponding to a gestational age of 12 weeks 0 days to 24 weeks 
6 days at time of interview, (2) carrying a singleton pregnancy, (3) a single prior cesarean 
section, (4) a cesarean section at her most recent delivery, (5) the cesarean section was not 
‘classical’, i.e., the cut on the uterus does not run up and down, (6) does not recall any other 
uterine surgeries that would make her ineligible for a cesarean section, e.g. a myomectomy for 
removal of uterine fibroids, (7) planning to deliver at the current institution. Responses to the 
screening questionnaire will be collected in a REDCap database.  
Consent. After the screening, printed informed consent and permission for release of medical 
records will be obtained from eligible participants using the consent and HIPAA forms 
(Appendices 7-10; see sections 8.2 and 8.3 for more information).  
Baseline Questionnaire. The baseline questionnaire (Appendices 11 and 12) will be administered 
by tablet after consent. This form collects participant age, race/ethnicity, education, income, 
form of health insurance, estimated due date, and current preference for delivery approach. A 

PROCEED Study Protocol………………           -19- 
06 January 2016 
 
print copy of the questionnaire will be offered to the participant to follow along as questions are 
read aloud (Appendix 13). The RC will keep track of the time at the start and end of the 
interview and note if there is an interruption to the interview lasting more than 5 minutes. The 
RC will also record if anyone is with the participant during the interview. Questionnaire data will 
be collected in a REDCap database. 
Randomization and intervention. Treatment group will be assigned according to a randomization 
table in REDCap generated by the statistician co-investigator. If randomized to app, the 
participant will be given a tablet to view the app at her own pace (Appendices 1 and 2). The app 
will provide information on potential maternal and neonatal complications from vaginal and 
cesarean deliveries, values clarification questions, and an individualized estimate of the 
likelihood of a successful TOLAC. After viewing the app, a printed summary sheet with her 
answers to the values clarification questions and probability of successful TOLAC will be 
provided to each participant to take home (Appendices 14 and 15). More information about the 
app is provided in section 4.2. A participant randomized to the control arm will not view the 
app. If she inquires about the intervention, she will be told it consists of standardized 
information about the benefits and risks of trial of labor and elective cesarean. 
Health Literacy Assessment. The interview will conclude with a short health literacy assessment 
(Appendices 11 and 12) which evaluates a woman’s ability to interpret a nutritional label. The 
assessment will be completed by both treatment arms.  
Remuneration and follow-up reminder. Women who complete the baseline interview will 
receive $40 in remuneration in the form of a gift card (Appendices 16 and 17) or check.   
5.1.4. Phone follow-up interview (34- to 37 weeks gestation) 
The Phone Follow-up interview will be completed with participants in both arms of the study 
between 34- and 37 weeks 6 days gestation. The goal of this interview is to collect data on the 
secondary study endpoints of knowledge about TOLAC and ERCD; decisional conflict; shared 
decision-making regarding delivery approach; decision self-efficacy; and decisional satisfaction.   
Chart audit. Before contacting a participant, the RC will review her chart to establish whether 
she is still pregnant, has already delivered, or has experienced pregnancy loss before 22 weeks.  
Phone interview. If the participant has not yet delivered, she will be contacted by the RC at 33 
weeks gestation to schedule a time for the phone follow-up interview. A copy of the phone 
follow-up questionnaire (Appendices 18 and 19) will be offered to the participant by email or 
mail so she may follow along as questions are read aloud. The questionnaire will be 
administered by a different interviewer and collected in a separate REDCap database than the 
baseline questionnaire to ensure the interviewer remains blinded to the participant’s 
randomization assignment. 
The phone follow-up interview will consist of: (1) a six-item short form of the Spielberger State-
Trait Anxiety Inventory, which assesses the woman’s general anxiety level31, (2) eight questions 
to assess the woman’s knowledge of TOLAC and ERCD adapted from a published questionnaire 
32, (3) a 16-item Decisional Conflict Scale33, (4) an 11-item Decisional Self-Efficacy scale34, (5) a 
single-item assessment of the woman’s preferred role in the decision-making concerning her 
delivery approach35, (5) a 9-item shared decision making questionnaire (adapted from the SDM-
Q-936), and (6) a six-item Satisfaction with Decision Scale37. More information about these 
survey instruments can be found in section 7.1.2. 

During the phone follow-up interview, the woman will be asked where she plans to deliver. If at 
an outside institution, the RC will request the participant’s consent to be contacted again for the 
post-delivery questionnaire and to have a copy of her delivery record forwarded to the study 
team (see section 5.1.6.).  
If the participant is no longer pregnant at the time of the phone follow-up interview, the RC will 
administer an abbreviated form of the phone follow-up questionnaire documenting where the 
woman delivered, date of delivery, delivery approach, and method of delivery. Women who had 
a loss before 22 weeks will not be contacted for a phone follow-up interview.  
Remuneration. Women who complete the telephone interview will receive $40 in remuneration 
in the form of a gift card or check.  
5.1.5. Chart audits (after delivery) 
Participant charts will be reviewed after delivery to abstract delivery approach, delivery mode, 
and other clinical data (Appendices 20 and 21). Abstraction of delivery outcome data and any 
contraindications to TOLAC before delivery will be performed by a PI, co-investigator or research 
coordinator who is blinded to the randomization assignment. Other data from the delivery 
encounter, including maternal and neonatal morbidities and findings from the cervical exam at 
time of admission, will be abstracted by the RC. Data will be collected in REDCap. A comments 
box on the data collection form will allow RCs to document challenges interpreting the chart, 
which can also be raised at a coordinator call or addressed to a co-investigator or PI if necessary.  
Investigator review. For investigator review of outcomes, the delivery note may provide clarity; 
in other cases, review of both the labor and delivery and prenatal record will be necessary. 
Whether the patient developed an absolute contraindication to TOLAC before her delivery 
admission may be obtained from the op note. Breech, Previa, or any congenital anomaly not 
compatible with vaginal delivery should be documented. To establish planned approach for the 
current delivery, the investigator will use the following definitions: 
• 
Participant planned ERCD if:  
o Delivered by scheduled ERCD at 39 weeks prior to labor for no reason other 
than desired RCD rather than TOLAC 
o Presented in labor prior to scheduled cesarean, and opted to proceed with 
cesarean for primary reason that desired RCD rather than TOLAC 
o Presented with indication for delivery prior to scheduled cesarean 
(preeclampsia, IUGR, NRFT) and opted to proceed with cesarean for primary 
reason that desired RCD rather than TOLAC 
 
Note: If there are two indications for RCD in the chart, including a 
nonelective indication for timing of delivery less than 39 weeks, the 
investigator will code the first as the "nonelective" indication and the 
second as ERCD. 
 
• 
Participant considered TOLAC if: 
o Underwent TOLAC 
o Planned TOLAC if labor prior to certain gestational age, but reached that 
gestational age limit and underwent ERCD 
o Planned TOLAC if spontaneous labor, but then developed an indication for 
induction and underwent ERCD 

PROCEED Study Protocol………………           -21- 
06 January 2016 
 
5.1.6. Post-delivery phone interview for outside deliveries (after due date) 
If a participant’s due date has elapsed by more than three weeks and there is no record of the 
delivery at the site, she has likely delivered at an outside institution. In such cases, the RC will 
contact the participant by phone or email to set up a time for the post-delivery phone interview. 
During the interview, the participant will be queried for self-report of the date of delivery, 
delivery approach and mode, and other pertinent information such as whether the outside 
facility offers TOLAC, whether the woman experienced contractions or rupture of membranes, 
use of pitocin for labor augmentation, use of forceps or vacuum to assist with delivery, baby’s 
birthweight, maternal weight gain during pregnancy, and other information. In addition, the RC 
will request the name of the outside institution where the woman delivered and her permission 
to contact the institution for release of her delivery record. Responses will be collected using the 
post-delivery questionnaire (Appendices 22 and 23) and stored in a REDCap database (Appendix 
24).  
6.0 
SAFETY MONITORING AND ADVERSE EVENT REPORTING 
6.1. Safety Monitoring and Clinical Data Review 
A multi-tiered safety review process will be followed for the duration of this study. Close 
cooperation between the principal investigator, site principal investigators and other co-
investigators, project manager, study coordinators, study statistician, and other study team 
members will be necessary to monitor participant safety and to respond to concerns in a timely 
manner. The investigative team will have monthly conference calls during the period of study 
implementation and additional ad hoc calls will be convened as needed. 
RCs will report all participant complaints to the investigative team.  These will be discussed 
during weekly/biweekly RC calls and monthly investigator calls. 
Each study site is responsible for continuous close monitoring and management of adverse 
events (AE) in accordance with the protocol for AE reporting at their home institution 
(Appendices 27-30). The study site PIs are responsible for the initial evaluation and reporting of 
safety information and for alerting the investigative team if unexpected concerns arise.  
6.2. Reporting Requirements for this Study 
The site PI or RC will report an adverse event to the local IRB if study staff determines it may 
qualify as an Unanticipated Problem or Adverse Event because the event meets all three criteria 
listed below: 
• 
Unanticipated in severity or frequency  AND 
• 
At least possibly related to the study intervention AND   
• 
Is Serious OR not serious but suggests placing subjects or others at greater risk 
In addition, all SAEs will be reported to the study team within 72 hours of recognition by study 
staff. 
7.0 
STATISTICAL CONSIDERATIONS 
7.1. Endpoints 
7.1.1. Primary Endpoint 
Consistent with the primary study hypothesis that women who are randomized to use the Prior 
Cesarean Decision app will be more likely to undergo TOLAC compared to women who receive 
only usual care, the following endpoint will be assessed in the medical record for the delivery: 

• 
Proportion of women who elect TOLAC 
7.1.2.  Secondary Endpoints 
Consistent with the secondary study hypothesis that women who are randomized to use the 
Prior Cesarean Decision app will be more likely to have a VBAC compared to women who 
receive only usual care, the following endpoint will be assessed in the medical record for the 
delivery:  
• 
Proportion of women who have a VBAC 
Consistent with the secondary study hypothesis that women who are randomized to use the 
Prior Cesarean Decision app will be more knowledgeable about TOLAC and ERCD and their 
potential outcomes compared to women who receive only usual care, the following endpoint 
will be assessed at weeks 34- to 37 gestation:  
• 
Knowledge about TOLAC and ERCD and their potential outcomes, as assessed with a  
modified version of a published questionnaire.32 
Consistent with the secondary study hypothesis that women who are randomized to use the 
Prior Cesarean Decision app will experience less decisional conflict compared to women who 
receive only usual care, the following endpoint will be assessed at weeks 34- to 37 gestation:  
• 
Decisional conflict regarding delivery approach, as measured based on the participant’s 
score on a well-validated Decisional Conflict Scale33 recommended for the assessment of 
decision quality by the IPDAS.38 This measure generates an overall conflict score and 5 
subscale scores and has been used extensively to evaluate patient-centered decision 
tools in a wide range of clinical contexts.39  
Consistent with the secondary study hypothesis that women who are randomized to use the 
Prior Cesarean Decision app will report higher levels of shared decision making regarding 
delivery approach compared to women who receive only usual care, the following endpoint will 
be assessed at weeks 34- to 37 gestation:  
• 
Shared decision making, as measured using the SDM-Q-9, a psychometrically evaluated 
self-assessment tool.36  
Consistent with the secondary study hypothesis that women who are randomized to use the 
Prior Cesarean Decision app will experience greater decision self-efficacy compared to women 
who receive only usual care, the following endpoint will be assessed at weeks 34- to 37 
gestation:  
• 
Decision self-efficacy, as measured using a validated 11-item Decisional Self-efficacy 
Scale.34   
Consistent with the secondary study hypothesis that women who are randomized to use the 
Prior Cesarean Decision app will report higher levels of decision satisfaction compared to 
women who receive only usual care, the following endpoint will be assessed at weeks 34- to 37 
gestation:  
• 
Decisional satisfaction, as measured using the Satisfaction with Decision Scale, a 6-item 
scale designed to measure global satisfaction with a decision and to differentiate this 
from related aspects of satisfaction.37   
Consistent with the secondary study hypothesis that women who are randomized to use the 
Prior Cesarean Decision app will experience lower rates of maternal and neonatal morbidity 

PROCEED Study Protocol………………           -23- 
06 January 2016 
 
compared to women who receive only usual care, the following endpoints will be assessed in 
the medical record for the delivery:  
• 
Maternal major morbidity, defined as any of: uterine rupture, hysterectomy, surgical 
injury (bowel, bladder/ureter, or other), maternal death.    
• 
Maternal minor morbidity, defined as any of: blood transfusion, postpartum febrile 
morbidity (endometritis, cellulitis, urinary tract infection, or other infection)     
• 
3rd or 4th degree lacerations 
• 
Neonatal death or HIE, defined as any of: stillbirth/fetal demise (antepartum or 
intrapartum), neonatal death, HIE     
• 
Neonatal respiratory morbidity, defined as any of: respiratory morbidity requiring CPAP 
or intubation     
• 
Neonatal intensive care unit (NICU) admission 
 
7.2. Sample Size 
Table 1 shows the minimum difference in TOLAC due to the Prior Cesarean Decision app that has 
80% power. For a recruitment goal of 1,320 participants (1:1 per intervention arm) and 
assuming 5% loss to follow-up and a baseline rate of 33% in the control group, we will have at 
least 80% power to detect an 8% absolute increase in TOLAC due to the app.  
Table 1: Minimum detectable effects for randomization α=.05, two-sided, power = 80%. 
LTFU = lost to follow-up rate. 
Outcome 
Assumptions 
Effect 
Measure 
N=1,200 
N=1,320 
N=1,440 
N=1,660 
TOLAC  
Baseline rate 
(33%)  
LTFU (5%) 
Absolute 
increase 
(%) 
8% 
. 
8% 
 
7% 
 
7% 
 
7.3. 
Blinding 
Assessors of the primary and secondary outcomes will remain blinded to the randomization 
assignment throughout the study. The study participant and the RC who administers the 
baseline screening and enrollment interview will be aware of the participant’s randomization 
assignment. Phone follow-up questionnaires and chart audits will be administered by a different 
interviewer and collected in a separate database than the baseline questionnaire to ensure the 
interviewer remains blinded to the participant’s randomization assignment during collection of 
study endpoints. 
7.4. Data Analysis 
We will present sample characteristics by treatment assignment in the form of n’s and %’s for 
categorical variables and means/standard deviations or medians and interquartile ranges for 
continuous variables. 
For our primary outcome TOLAC and major secondary outcome VBAC, we will calculate the 
proportion with the outcome by treatment arm and test for differences between treatment 
arms using a Poisson regression model which has been adjusted for recruitment site and 

language of interview and includes robust standard errors. Comparisons will be presented in the 
form of relative risks and 95% confidence intervals. Differences between treatment arms for the 
maternal and neonatal morbidity outcomes will be evaluated in the same manner. For 
continuous outcomes (e.g., decisional conflict, shared decision making regarding delivery 
approach, decision self-efficacy, and decisional satisfaction), we will calculate the mean score by 
treatment arm and test for differences using linear regression models adjusted for recruitment 
site and language of interview. 
For our primary outcome TOLAC and major secondary outcome VBAC, we will examine 
interactions of treatment arm by the a priori defined factors of site, race/ethnicity, and 
language. For each interaction, differences will be evaluated using a Poisson regression model 
with an interaction term for treatment arm by subgroup. 
Analyses will exclude women who had a pregnancy loss before 22 weeks gestation. We will also 
perform a sensitivity analysis of TOLAC and VBAC rates and differences in TOLAC and VBAC 
between treatment arms after excluding women who develop placenta previa or breech 
presentation. 
8.0   HUMAN SUBJECTS CONSIDERATIONS 
8.1. Ethical Review  
Informed consent forms will pass through review and approval by the local IRB. as will 
participant education and recruitment materials, any other documents requested by the IRB, 
and any subsequent modifications to a document after approval. Review will be with respect to 
scientific content and compliance with applicable research and human subjects regulations.  
IRB review of the study protocol will occur at least annually. The Site PI or RC will provide safety 
and progress reports to the IRBs at least annually and within three months of study termination 
or completion. These reports will include the total number of participants enrolled in the study, 
the number of participants who completed the study, all changes in the research activity, and all 
unanticipated problems involving risks to human subjects or others.  
8.2. Informed Consent 
Written informed consent will be obtained from each study participant prior to enrollment using 
an informed consent form approved by the local IRB in accordance with all applicable 
regulations. A copy of her signed informed consent form will be offered to the participant 
(Appendices 7 and 8). 
8.3. HIPAA 
Permission for release of medical records for ascertainment of clinical endpoints will be 
obtained from participants with the Health Insurance Portability and Accountability (HIPAA) 
form, which documents the personal health information that may be released, to whom it may 
be released, how it may be used, when permission for its release expires, and under what terms 
permission may be cancelled (Appendices 9 and 10). 
8.4. Risks 
Breach of confidentiality. Although study sites will make every effort to protect participant 
privacy and confidentiality, it is possible that participants' involvement in the study could 
become known to others. We are evaluating a mobile health intervention linked to a cloud 
platform and there is the possibility that study participation could become known to others 
despite the use of firewalls, password protection, and other security measures.  

PROCEED Study Protocol………………           -25- 
06 January 2016 
 
8.5. Benefits 
Participation in the intervention arm of this study may lead to improved rates of TOLAC and 
other beneficial outcomes as posited in sections 2.1 and 2.1 of this manual. There may be no 
direct benefits to participants in the control arm of this study; however, they and others may 
benefit in the future from information learned from this study. 
8.6. Incentives 
Participants will be compensated for their time and effort in this study through remuneration of 
$40 following participation in the baseline interview and $40 following participation in the 
phone follow-up questionnaire.  Remuneration will be the in the form of a gift card (Appendices 
16 and 17) or check.  
8.7. Confidentiality 
All study-related information will be stored securely at the study site in locked file cabinets or on 
password-protected databases managed in accordance with section 9.1.3. of this study protocol. 
Participant study information will not be released without the written permission of the 
participant except as necessary for monitoring by the NIH and/or the site IRB.  
9.0 ADMINISTRATIVE PROCEDURES 
9.1. Study Coordination 
Study implementation will be directed by this study protocol. Study case report forms and other 
study instruments are attached as Appendices 1-30. Protocols for training and study team 
communication are covered in sections 9.1.1. and 9.1.2. Section 9.1.3 reviews database 
management and data quality monitoring plans. Use of information is described in Section 9.1.4. 
9.1.1.  Trainings 
The project manager at UCSF will train the RCs and other project staff at each of the sites.  
Topics covered will include:  
• 
Study background, justification & aims 
• 
Inclusion & exclusion criteria, eligibility screening 
• 
Participant tracking in REDCap 
• 
Appointment scheduling 
• 
Approaching potentially eligible participants 
 
Etiquette for in-person approach in the clinic waiting bay 
 
Opt-in/opt-out forms 
• 
Informed consent 
• 
Randomization protocol 
• 
Questionnaires 
 
Baseline face-to-face questionnaire 
 
Phone follow-up questionnaire 
• 
Equipment 
 
iPads 
 
Portable Wi-Fi-enabled color printers 

• 
Chart review 
• 
Remuneration 
9.1.2. Study Communication 
Calls and in-person meetings will be scheduled throughout the study period to ensure clear 
communication, collegial collaboration, and rapid response to any challenges that may arise. 
Investigator Calls. 
The PI will lead monthly conference calls with the site PIs, co-investigators, project manager, 
and data manager. Topics to be discussed will include: 
• 
Project timelines 
• 
Recruitment plans 
• 
Enrollment and retention reports 
• 
Study design and implementation 
• 
Questionnaire revisions (as necessary) 
• 
Data analysis plans, progress and results 
• 
Manuscript and abstract plans and progress 
• 
Review of draft manuscripts and abstracts 
• 
IRB renewals and modifications 
• 
Budgets and contracts 
• 
Other study management issues as needed 
Research Coordinator Calls. 
The project manager at UCSF will hold weekly 30-minute phone calls with the research 
coordinators for the first six months of the project. After six months, they will switch to a bi-
weekly conference call schedule. The PI or a site PI will participate as needed. Coordinator calls 
will cover the following topics: 
• 
Current totals interested, scheduled for enrollment, enrolled, scheduled for phone 
follow-up, followed-up, charts reviewed, by site 
• 
Successes, challenges, and new ideas for: 
o Screening and approaching patients 
o Reaching recruitment targets 
o Utilizing technology (iPads, printers, Wi-Fi) 
o Administering questionnaires 
o Interfacing with the app  
o Scheduling and coordinating follow-up interviews and chart reviews 
o Carrying out follow-up interviews and chart reviews 
o IRB modifications 
o Other issues as needed 

PROCEED Study Protocol………………           -27- 
06 January 2016 
 
Annual Meetings. 
Each year, the PI will host an annual in-person meeting of one- to two days with the site PIs, co-
investigators, project manager, data manager, and RCs. Topics covered will be similar to the 
monthly calls but with time for lengthier discussion. Parallel break-out sessions for investigators 
and staff may be held to cover topics relevant to each group. A meeting of the PI and site PIs 
may also take place to discuss confidential matters and critical leadership/management 
decisions. A second annual meeting for broader visioning of scientific goals and dissemination 
plans will be held in-person among study members attending the annual Society for Maternal 
Fetal Medicine conference.   
9.1.3.  Database Management and Data Quality Monitoring 
Randomization assignment, survey responses, and chart audit data for all sites will be collected 
and stored in REDCap databases hosted centrally at UCSF. Data will be behind an institutional 
firewall and accessible through a web portal via login credentials known only to qualified study 
staff. Randomization assignment will be collected in a separate database than the phone follow-
up questionnaire and chart audits to ensure staff remain blinded to treatment group while 
gathering outcome data. Sites will maintain their own tracking and recruitment logs in local 
REDCap databases (Appendix 24). Protected health information, such as patient names, medical 
record number, estimated due date, clinic visit schedule, telephone number and email address 
will be collected on the tracking and recruitment log to aid with scheduling and participant 
follow-up. A unique study identifier will be generated for each participant to link records across 
databases. 
Data from the app will be collected through a secure, password-protected online portal linked to 
a PostGRE SQL database on a Heroku cloud platform, which provides best-in-class server 
security, including firewalls, physical security, and regular compliance auditing.  
Clinical, survey and app data will be transferred to SAS statistical software for cleaning, 
reporting and analysis. Quality control reports and queries will be generated and distributed to 
the study sites on a routine schedule for verification and resolution.    
9.2. Use of Information and Publications 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov. Presentation 
and publication of the results of this study will be governed by guidelines determined by the 
study team and as necessary and appropriate by their associated institutions policies. Any 
presentation, abstract, or manuscript will be approved by the protocol chair prior to submission.  
 
 

 
10.0 REFERENCES 
1. 
Hamilton, B. E., Martin, J. A. & Ventura, S. J. Births: preliminary data for 2012. Natl. Vital 
Stat. Rep. Cent. Dis. Control Prev. Natl. Cent. Health Stat. Natl. Vital Stat. Syst. 62, 1–20 (2013). 
2. 
Guise, J.-M. et al. Vaginal Birth After Cesarean: New Insights. (Agency for Healthcare 
Research and Quality (US), 2010). 
3. 
Silver, R. M. Delivery after previous cesarean: long-term maternal outcomes. Semin. 
Perinatol. 34, 258–266 (2010). 
4. 
Silver, R. M. et al. Maternal morbidity associated with multiple repeat cesarean 
deliveries. Obstet. Gynecol. 107, 1226–1232 (2006). 
5. 
Clark, E. A. S. & Silver, R. M. Long-term maternal morbidity associated with repeat 
cesarean delivery. Am. J. Obstet. Gynecol. 205, S2-10 (2011). 
6. 
Lydon-Rochelle, M., Holt, V. L., Martin, D. P. & Easterling, T. R. Association between 
method of delivery and maternal rehospitalization. JAMA 283, 2411–2416 (2000). 
7. 
Healthy People - HP2010 Final Review. Available at: 
https://www.cdc.gov/nchs/healthy_people/hp2010/hp2010_final_review.htm. (Accessed: 22nd 
September 2017) 
8. 
American College of Obstetricians and Gynecologists. Task Force on Cesarean Delivery 
Rates. Evaluation of cesarean delivery. Available at: 
https://pdfs.semanticscholar.org/7a74/0973f8fe4d2834ee29f0a59fc96458c8d38a.pdf 
(Accessed: 22nd August 2018) 
9. 
American College of Nurse-Midwives Responds to ACOG's 2010 VBAC 
Recommendations. Available at: 
http://www.midwife.org/acnm/files/ccLibraryFiles/Filename/000000000075/ACNMResponseto
VBACBulletin_082610FINAL.pdf (Accessed: 22nd September 2017) 
10. 
Hamilton, B. E., Martin, J. A. & Ventura, S. Births: Preliminary data for 2010. 60, (2011). 
11. 
Grobman, W. A. et al. The change in the rate of vaginal birth after caesarean section. 
Paediatr. Perinat. Epidemiol. 25, 37–43 (2011). 
12. 
Metz, T. D. et al. How do good candidates for trial of labor after cesarean (TOLAC) who 
undergo elective repeat cesarean differ from those who choose TOLAC? Am. J. Obstet. Gynecol. 
208, 458.e1-6 (2013). 
13. 
Macones, G. A. et al. Maternal complications with vaginal birth after cesarean delivery: 
a multicenter study. Am. J. Obstet. Gynecol. 193, 1656–1662 (2005). 
14. 
Lavin, J. P., Stephens, R. J., Miodovnik, M. & Barden, T. P. Vaginal delivery in patients 
with a prior cesarean section. Obstet. Gynecol. 59, 135–148 (1982). 

PROCEED Study Protocol………………           -29- 
06 January 2016 
 
15. 
Landon, M. B. et al. Maternal and perinatal outcomes associated with a trial of labor 
after prior cesarean delivery. N. Engl. J. Med. 351, 2581–2589 (2004). 
16. 
McClain, C. S. The making of a medical tradition: vaginal birth after cesarean. Soc. Sci. 
Med. 1982 31, 203–210 (1990). 
17. 
Emmett, C. L., Shaw, A. R. G., Montgomery, A. A., Murphy, D. J. & DiAMOND study 
group. Women’s experience of decision making about mode of delivery after a previous 
caesarean section: the role of health professionals and information about health risks. BJOG Int. 
J. Obstet. Gynaecol. 113, 1438–1445 (2006). 
18. 
Kirk, E. P., Doyle, K. A., Leigh, J. & Garrard, M. L. Vaginal birth after cesarean or repeat 
cesarean section: medical risks or social realities? Am. J. Obstet. Gynecol. 162, 1398-1403; 
discussion 403–405 (1990). 
19. 
Moffat, M. A. et al. Decision making about mode of delivery among pregnant women 
who have previously had a caesarean section: A qualitative study. BJOG Int. J. Obstet. Gynaecol. 
114, 86–93 (2007). 
20. 
McClain, C. S. Patient decision making: the case of delivery method after a previous 
cesarean section. Cult. Med. Psychiatry 11, 495–508 (1987). 
21. 
McClain, C. S. Why women choose trial of labor or repeat cesarean section. J. Fam. 
Pract. 21, 210–216 (1985). 
22. 
National Institutes of Health. National Institutes of Health Consensus Development 
Conference Statement vaginal birth after cesarean: new insights March 8-10, 2010. Semin. 
Perinatol. 34, 351–365 (2010). 
23. 
Wennberg, J. E. Time to tackle unwarranted variations in practice. BMJ 342, d1513 
(2011). 
24. 
Oshima Lee, E. & Emanuel, E. J. Shared decision making to improve care and reduce 
costs. N. Engl. J. Med. 368, 6–8 (2013). 
25. 
Grobman, W. A. et al. Development of a nomogram for prediction of vaginal birth after 
cesarean delivery. Obstet. Gynecol. 109, 806–812 (2007). 
26. 
Gilbert, S. A. et al. Elective repeat cesarean delivery compared with spontaneous trial of 
labor after a prior cesarean delivery: a propensity score analysis. Am. J. Obstet. Gynecol. 206, 
311.e1-9 (2012). 
27. 
Kuppermann, M. et al. Randomized trial of an informed free choice approach to 
prenatal testing among women of varying literacy levels [abstract]. Med Dec Making (2013). 
28. 
McMahon, M. J., Luther, E. R., Bowes, W. A. & Olshan, A. F. Comparison of a trial of 
labor with an elective second cesarean section. N. Engl. J. Med. 335, 689–695 (1996). 

29. 
Martin, J. N. et al. Vaginal delivery following previous cesarean birth. Am. J. Obstet. 
Gynecol. 146, 255–263 (1983). 
30. 
Guise, J.-M. et al. Safety of vaginal birth after cesarean: a systematic review. Obstet. 
Gynecol. 103, 420–429 (2004). 
31. 
Marteau, T. M. & Bekker, H. The development of a six-item short-form of the state scale 
of the Spielberger State-Trait Anxiety Inventory (STAI). Br. J. Clin. Psychol. 31 ( Pt 3), 301–306 
(1992). 
32. 
Bernstein, S. N., Matalon-Grazi, S. & Rosenn, B. M. Trial of labor versus repeat cesarean: 
are patients making an informed decision? Am. J. Obstet. Gynecol. 207, 204.e1-6 (2012). 
33. 
O’Connor, A. M. Validation of a decisional conflict scale. Med. Decis. Mak. Int. J. Soc. 
Med. Decis. Mak. 15, 25–30 (1995). 
34. 
UM_Decision_SelfEfficacy.pdf. Available at: 
https://decisionaid.ohri.ca/docs/develop/User_Manuals/UM_Decision_SelfEfficacy.pdf 
(Accessed: 27th September 2017) 
35. 
Deber, R. B., Kraetschmer, N. & Irvine, J. What role do patients wish to play in treatment 
decision making? Arch. Intern. Med. 156, 1414–1420 (1996). 
36. 
Kriston, L. et al. The 9-item Shared Decision Making Questionnaire (SDM-Q-9). 
Development and psychometric properties in a primary care sample. Patient Educ. Couns. 80, 
94–99 (2010). 
37. 
Holmes-Rovner, M. et al. Patient satisfaction with health care decisions: the satisfaction 
with decision scale. Med. Decis. Mak. Int. J. Soc. Med. Decis. Mak. 16, 58–64 (1996). 
38. 
IPDAS-Chapter-L.pdf. Available at: http://ipdas.ohri.ca/IPDAS-Chapter-L.pdf (Accessed: 
26th September 2017) 
39. 
O’Connor, A. M. et al. Decision aids for people facing health treatment or screening 
decisions. Cochrane Database Syst. Rev. CD001431 (2009). 
doi:10.1002/14651858.CD001431.pub2 
 
 

PROCEED Study Protocol………………           -31- 
06 January 2016 
 
11.0 APPENDICES 
Appendix 
Name of Document 
Version Date 
1 
App PDF-English 
112015 
2 
App PDF-Spanish 
112015 
3 
Opt-in form-English 
111615 
4 
Opt-in form-Spanish 
112015 
5 
Screening questions-English 
111615 
6 
Screening questions-Spanish 
112015 
7 
UCSF Consent-English 
111615 
8 
UCSF Consent-Spanish 
112015 
9 
UCSF HIPAA-English 
111615 
10 
UCSF HIPAA-Spanish 
112015 
11 
Baseline Questionnaire-English 
111615 
12 
Baseline Questionnaire-Spanish 
112015 
14 
App summary sheet-English 
111615 
15 
App summary sheet-Spanish 
112015 
16 
UCSF Gift Card Receipt-English 
111615 
17 
UCSF Gift Card Receipt-Spanish 
112015 
18 
Phone Follow-up Questionnaire-English 
111615 
19 
Phone Follow-up Questionnaire-Spanish 
112015 
20 
Chart Review tool (investigator) 
111615 
21 
Chart Review tool (RC) 
111615 
22 
Post Delivery Phone Questionnaire for 
Outside Deliveries-English 
111615 
23 
Post Delivery Phone Questionnaire for 
Outside Deliveries-Spanish 
112015 
24 
RedCap tracking & recruitment log data 
dictionary 
010416 
25 
IRB/CHR Approval Letter-UCSF 
121415 
26 
IRB Approval Letter-Massachusetts General 
121815 
27 
28 
29 
30 
IRB Approval Letter-Northwestern 
IRB Adverse Event Reporting-Northwestern 
IRB Adverse Event Reporting-Mass. General 
IRB Adverse Event Reporting-UCSF 
121015 
111315 
111315 
111315 
 
 

 
PROCEED Study Protocol………………           -1- 
28 September 2018 
 
Note:  The only protocol change we instituted on this protocol was the addition of a site in 
San Francisco (California Pacific Medical Center, St. Luke’s Campus). Because of this 
addition, we added new study team members to the protocol and we included a description 
of usual care at that site. No changes were made to the statistical analysis plan.  
 
Effect of a Patient-Centered Decision App on 
TOLAC: An RCT 
 
 
 
The PRiOr CEsarEan Decision App (PROCEED) Study 
 
 
 
Sponsored by: 
US National Institute of Health 
Grant #1R01HD078748 
 
IRB Approvals 
UCSF/Marin Community Clinic: CHR #13-11707 
Massachusetts General Hospital: IRB #2015P002284 
Northwestern University Medical Center: IRB #STU00104496 
St. Luke’s Campus, California Pacific Medical Center: IRB #2017.096EXP 
 
 
Principal Investigator: Miriam Kuppermann, PhD, MPH 
Professor and Vice Chair for Clinical Research 
Department of Obstetrics, Gynecology & Reproductive Sciences 
School of Medicine 
University of California, San Francisco 
 

 
PROCEED Study Protocol………………           -2- 
28 September 2018 
 
 
Version Date: 28 September 2018 
v2 
The PRiOr CEsarEan Decision App (PROCEED) Study 
 
TABLE OF CONTENTS 
 
STUDY TEAM ROSTER .................................................................................................................................... 4 
PERSONNEL AND DUTIES .............................................................................................................................. 5 
STUDY SCHEMA ............................................................................................................................................. 6 
OVERVIEW OF STUDY DESIGN AND RANDOMIZATION SCHEME .................................................................. 8 
1.0 
INTRODUCTION ................................................................................................................................. 8 
1.1. 
Background and Prior Research ................................................................................................... 8 
2.0 
STUDY HYPOTHESES AND DESIGN .................................................................................................. 10 
2.1. 
Primary Hypothesis ..................................................................................................................... 10 
2.2. 
Secondary Hypotheses ............................................................................................................... 10 
2.3. 
Study Design ............................................................................................................................... 10 
2.3.1. 
Timeline ...................................................................................................................................... 12 
2.3.2. 
Randomization ............................................................................................................................ 12 
3.0 
STUDY POPULATION ....................................................................................................................... 12 
3.1. 
Inclusion Criteria ......................................................................................................................... 12 
3.2. 
Exclusion Criteria ........................................................................................................................ 13 
3.3. 
Participant Retention .................................................................................................................. 13 
3.4. 
Participant Withdrawal ............................................................................................................... 13 
4.0 
STUDY ARMS ................................................................................................................................... 13 
4.1. 
Standard of Care ......................................................................................................................... 13 
4.2. 
Intervention ................................................................................................................................ 16 
5.0 
STUDY PROCEDURES ....................................................................................................................... 16 
5.1. 
Overview ..................................................................................................................................... 16 
5.1.1. 
Chart audit (<25 weeks gestation) .............................................................................................. 17 
5.1.2. 
Opt-in form (<25 weeks gestation) ............................................................................................. 17 
5.1.3. 
Baseline Screening and Enrollment interview  (12 weeks 0 days-24 weeks 6 days gestation) .. 17 
5.1.4. 
Phone Follow-up interview (34- to 37 weeks gestation) ............................................................ 18 
5.1.5. 
Chart audits (after due date) ...................................................................................................... 19 
5.1.6. 
Post-delivery Phone interview for outside deliveries (after due date) ...................................... 20 
6.0 
SAFETY MONITORING AND ADVERSE EVENT REPORTING .............................................................. 20 
6.1. 
Safety Monitoring and Clinical Data Review .............................................................................. 20 
6.2. 
Reporting Requirements for this Study ...................................................................................... 21 
7.0 
STATISTICAL CONSIDERATIONS ....................................................................................................... 21 
7.1. 
Endpoints .................................................................................................................................... 21 
7.1.1. 
Primary Endpoint ........................................................................................................................ 21 
7.1.2. 
Secondary Endpoints .................................................................................................................. 21 
7.2. 
Sample Size ................................................................................................................................. 22 
7.3. 
Blinding ....................................................................................................................................... 23 
7.4. 
Data Analysis ............................................................................................................................... 23 
 
 

 
PROCEED Study Protocol………………           -3- 
28 September 2018 
 
8.0 
HUMAN SUBJECTS CONSIDERATIONS ............................................................................................. 23 
8.1. 
Ethical Review ............................................................................................................................. 23 
8.2. 
Informed Consent ....................................................................................................................... 24 
8.3. 
HIPAA .......................................................................................................................................... 24 
8.4. 
Risks ............................................................................................................................................ 24 
8.5. 
Benefits ....................................................................................................................................... 24 
8.6. 
Incentives .................................................................................................................................... 24 
8.7. 
Confidentiality ............................................................................................................................ 24 
9.0 
ADMINISTRATIVE PROCEDURES ...................................................................................................... 24 
9.1. 
Study Coordination ..................................................................................................................... 24 
9.1.1. 
Trainings ..................................................................................................................................... 24 
9.1.2. 
Study Communication ................................................................................................................ 25 
9.1.3. 
Database Management and Data Quality Monitoring ............................................................... 26 
9.2. 
Use of Information and Publications .......................................................................................... 27 
10.0 
REFERENCES .................................................................................................................................... 27 
11.0 
APPENDIX ........................................................................................................................................ 30 
 
 

 
PROCEED Study Protocol………………           -4- 
28 September 2018 
 
 
STUDY TEAM ROSTER 
University of California, San Francisco 
Miriam Kuppermann, PhD, 
MPH 
Principal Investigator 
miriam.kuppermann@ucsf.edu 
Peter Bacchetti, PhD 
Statistician/Co-investigator 
peter.bacchetti@ucsf.edu 
Juan Gonzalez, MD, PhD 
Co-investigator 
juan.gonzalez@ucsf.edu 
Mari-Paule Thiet, MD 
Co-investigator 
mari-paule.thiet@ucsf.edu 
Allie O’Leary, MPH 
Project manager 
allison.o’leary@ucsf.edu 
Cinthia Blat, MPH 
Data manager/statistical 
analyst 
cinthia.blat@ucsf.edu 
Priscila Valdez Lopez 
Research coordinator 
priscila.valdezlopez@ucsf.edu 
Marin Community Clinic 
Yamilee Bermingham, MD 
Co-investigator 
ybermingham@marinclinic.org 
St. Luke’s Campus, California Pacific Medical Center 
Anna Altshuler, MD, MPH 
Co-investigator 
altshual@sutterhealth.org 
Carla Bello 
Research coordinator 
belloc@sutterhealth.org 
Massachusetts General Hospital 
Anjali Kaimal, MD, MAS 
Site PI/Co-investigator 
akaimal@mgh.harvard.edu 
Allison Bryant, MD, MPH 
Co-investigator 
abryant@partners.org 
Gaby Villaran 
Research coordinator 
gvillaran@mgh.harvard.edu 
Northwestern University Medical Center 
William Grobman, MD, MBA 
Site PI/Co-investigator 
w-grobman@northwestern.edu 
Brittney Williams, MPH 
Research coordinator 
brittney.williams@northwestern.edu 
 
 

 
PROCEED Study Protocol………………           -5- 
28 September 2018 
 
PERSONNEL AND DUTIES 
Principal Investigator (PI) 
The PI is experienced in all aspects of the design, conduct and oversight of randomized 
controlled trials and prospective studies at multiple clinical sites and is an expert in the fields of 
medical decision-making, preference (utility) measurement, and decision-assisting tool creation 
and evaluation. The PI will take a lead role in all aspects of the proposed project, working with 
the site PIs, other co-investigators, and staff members to ensure timely and accurate completion 
of the project. The PI will direct day-to-day activities and provide overall governance and 
scientific leadership to the study. 
Statistician Co-investigator 
The statistician co-investigator will direct analysis strategy for study design and manuscript 
preparation. The statistician will also oversee data analysis by the analyst and advise the PI and 
other co-investigators on methodological issues. 
Site Principal Investigator (site PIs) 
The site PIs will meet monthly by phone and biannually in person (along with the other co-
investigators) to contribute to the overall study design and ensure each site is executing the 
study as prescribed. Site PIs are responsible for hiring and training site staff and will provide 
clinical and research expertise in the design and implementation of study instruments and 
protocols. Site PIs will monitor study enrollment and troubleshoot any recruitment issues as 
needed. They will also assist with chart review for participant delivery outcomes.  
Other Co-investigators 
Additional co-investigators will join the monthly calls and biannual in-person meetings. They will 
support patient recruitment from the obstetric practices at each site and will provide clinical 
input into data analyses and manuscripts for submission to peer-reviewed journals. They will 
also assist with chart review for participant delivery outcomes. 
Project Manager 
The project manager is responsible for the overall operations of the study, including managing 
recruitment and enrollment, guiding IRB submissions, and scheduling and preparing agendas for 
investigator and coordinator meetings. The project manager will monitor project timelines and 
ensure recruitment goals are met and recruitment and data collection are carried out per 
established protocols. The project manager will document any revisions to protocols and 
surveys and acquire IRB approvals as needed. The project manager will also work with the data 
manager/statistical analyst to design and implement study databases. 
Data Manager/Statistical Analyst  
The data manager/statistical analyst is responsible for creating and managing all databases for 
the project, monitoring data quality, and conducting data cleaning and statistical analyses under 
the direction of the statistician co-investigator and PIs.   
Research Coordinators/Interviewers 
The Research Coordinators (RCs) are the primary administrative points of contact for the study. 
They will prepare and submit all materials for IRB approval including the initial application, 
renewals, and all modifications. They will pilot and fine-tune study instruments; screen, consent, 
and interview participants; randomize participants per protocol; abstract medical data from 

 
PROCEED Study Protocol………………           -6- 
28 September 2018 
 
charts; and distribute participant remuneration. They will be responsible for following the 
guidelines for study operations outlined in this protocol and will email the UCSF project manager 
in the event of any protocol violations (e.g., mis-randomization, erroneous inclusion of subjects 
in the study, breach of confidentiality). They will participate in weekly or biweekly conference 
calls with the project manager and one or more PIs to go over recruitment and data collection 
activities and targets.  
 
STUDY SCHEMA 
 
Purpose: 
 
To assess the effect of the PROCEED Prior Cesarean 
Decision Support app (versus usual care without the app) 
on rates of trial of labor after cesarean (TOLAC) among 
pregnant women with a prior cesarean delivery (CD). 
Design: 
 
This is a two-armed randomized controlled trial (RCT) 
among 1,320 English- or Spanish-speaking pregnant 
women (1:1 randomization sequence for the 
intervention).   
Study 
Population: 
 
Pregnant women receiving prenatal care at a 
participating healthcare facility. Women will be eligible to 
enroll if they meet all of the following criteria. 
Inclusion criteria: 
• 
Between 12 weeks 0 days and 24 weeks 6 days 
gestation at enrollment 
• 
Speak English or Spanish 
• 
Have had one and only one prior CD 
• 
Prior low transverse cesarean 
 
Exclusion criteria: 
• 
No prior cesarean delivery, or more than one  
• 
Multiple gestation pregnancy 
• 
Prior vaginal birth after cesarean 
• 
Any contraindications to TOLAC  (prior classical 
cesarean, prior uterine surgery, T-incisions, other 
contraindication) 
• 
Delivering at outside institution 
 
Study Size: 
 
The recruitment goal is 1,320 participants, for a 
recruitment rate of 40 participants per month and a final 
subset of 627 per arm (1254) projecting 5% loss to follow 
up.    

 
PROCEED Study Protocol………………           -7- 
28 September 2018 
 
Study 
Intervention: 
 
Participants in the intervention arm will be provided with 
the PROCEED Prior Cesarean Decision app, which includes 
approximately 15 minutes of dynamic web-based 
informational content including potential maternal and 
neonatal complications from vaginal and cesarean 
deliveries, values clarification questions, and 
individualized estimates of likelihood of successful 
TOLAC.   
Study 
Duration: 
 
Data collection start date: January 2016 
Estimated data collection end date:  July 2019  
 
 
Primary 
Hypothesis: 
 
Compared to women who receive usual care only, women 
who are randomized to use the Prior Cesarean Decision 
app will be more likely to undergo TOLAC. 
Secondary 
Hypotheses: 
 
Compared to women who receive usual care only, 
women randomized to use the Prior Cesarean Decision 
app will: 
1. be more likely to have a vaginal birth after cesarean 
(major secondary outcome) 
2. be more knowledgeable about TOLAC and elective 
repeat cesarean delivery (ERCD) and their potential 
outcomes 
3. experience less decisional conflict 
4. report higher levels of shared decision making 
regarding delivery approach 
5. report higher levels of decision self-efficacy  
6. report higher levels of decision satisfaction 
7. experience lower rates of maternal and neonatal 
morbidities 
Study Sites: 
University of California, San Francisco 
Marin Community Clinic 
California Pacific Medical Center, St. Luke’s Campus 
Massachusetts General Hospital 
Northwestern University Medical Center 
 
 
 

 
PROCEED Study Protocol………………           -8- 
28 September 2018 
 
 
OVERVIEW OF STUDY DESIGN AND RANDOMIZATION SCHEME 
 
 
 
12.0  INTRODUCTION 
12.1. Background and Prior Research 
Public health impact of cesarean rate in the US. Cesarean delivery (CD) is the most common 
inpatient surgery in the US, accounting for nearly one third of births annually. In the last decade, 
the CD rate has increased by approximately 50%, with almost 1.3 million procedures performed 
in 2012.1 Moreover, at $7.8 billion annually, these deliveries account for almost half of 
childbirth-related expenses of hospitalization.2 CDs have been associated with an increase in 
major maternal morbidity,3–5 with corresponding increases in length of inpatient care following 
delivery and frequency of hospital readmission.6 Organizations including Healthy People7, the 
American College of Obstetricians and Gynecologists (ACOG)8, and the American College of 
Nurse Midwives9 have targeted reducing the CD rate as an important public health goal for more 
than a decade; however, identifying interventions to achieve this goal has proven challenging. 
Causes and consequences of the rising rate of repeat cesareans. Repeat CDs are a significant 
contributor to the increased cesarean rate, resulting from the combination of a rising rate of 
primary CD and a decreasing rate of vaginal birth after cesarean, which declined from a high of 
28.3% in 19962 to 9.2% in 2010.10 Why the VBAC rate has decreased so dramatically remains a 
subject of debate. Numerous medical and nonmedical factors have been posited as contributing 
to this decline, including the decreasing number of hospitals willing to provide this option and 
the diminishing number of obstetric providers who offer this approach. In addition, a substantial 
portion of the decrease is related to women foregoing trial of labor after cesarean (TOLAC) even 
though their hospitals and obstetricians provide the opportunity. For example, among hospitals 
in the NICHD Maternal-Fetal Medicine Units network, TOLAC rates declined from 51.8% to 
29.8% (p<.001) from 1999-2002, even though TOLAC continued to be offered at all sites.11 In a 
study of “good TOLAC candidates” at a 14-hospital network where TOLAC was available, the 
average TOLAC rate was only 30%.12 And at Northwestern, one of the clinical sites for our study, 
Pregnant women with 1 
prior cesarean  
N = 1320 
PROCEED App 
(N = 660) 
R 
Usual Care 
(N = 660) 

 
PROCEED Study Protocol………………           -9- 
28 September 2018 
 
TOLAC rates decreased by two-thirds from 1995 to 2010 although all providers offer this labor 
approach. 
Importantly, the declining VBAC rate is not primarily due to new and more concerning 
information about the risks of TOLAC; recent epidemiologic studies have demonstrated that the 
core population-level outcomes of TOLAC, such as the chance of VBAC or of uterine rupture if a 
TOLAC is attempted, are no different today than they were three decades ago.2,13–15  Similarly, 
this decline is not primarily due to changes in characteristics of the population that would make 
VBAC less likely if TOLAC is undertaken; these decreases in TOLAC have affected all women, 
regardless of their probability of VBAC or risks of adverse TOLAC outcomes.11 The extent to 
which these changes are 
driven by patient 
preferences is not 
known. Data from 
qualitative studies offer 
some insight, but the 
value of that information 
is limited by the non-
generalizability of the 
study populations and 
the lack of quantitative 
analyses.16–21 
Furthermore, while 
decreased TOLAC rates 
are occurring throughout 
the US, there are 
persistent, unexplained 
racial/ethnic, geographic, and socioeconomic differences in rates of TOLAC and VBAC.22  This 
variation, in the absence of a demonstrated basis in clinical science or patient preferences, 
raises concern about the efficiency, effectiveness, and patient-centeredness of approach to 
delivery after CD.23  
Call to action. An NIH consensus conference statement noted that “the informed consent 
process for TOLAC and ERCD should be evidence-based, minimize bias, and incorporate a strong 
emphasis on the values and preferences of pregnant women,” and recommended 
“interprofessional collaboration to refine, validate, and implement decision-making and risk 
assessment tools” to accomplish that goal.22 Given the broad policy support for shared decision 
making in this context,22,24 the large absolute number of women facing the choice of TOLAC, and 
the short- and long-term consequences of this decision for mothers and babies, an intervention 
aimed at informing patients and helping them articulate their preferences could lead to 
improvements in the decision making process and have a significant impact on the health of 
individuals and the health care system.25,26 Our overarching goal is to create and evaluate a tool 
to help TOLAC-eligible women delivering at hospitals that offer TOLAC consider individualized 
risk assessments, incorporate their values and preferences, and participate in a shared decision 
making process with their providers to make informed decisions about delivery approach. We 
believe this improved informed decision making process will lead to increased TOLAC. 
Our prior studies of decision making. In a recently completed randomized study (R01 
HD049686), PI Kuppermann and colleagues found that women who used a prenatal testing 
decision tool had significantly lower uptake of invasive diagnostic testing, greater knowledge 
TOLAC
ERCD
VBAC
CD
VBAC
CD
TOLAC-eligible 
woman:
1 prior CD, no 
contra-indications 
Delivery approach: 
TOLAC vs. ERCD
Delivery mode: 
VBAC or CD
Figure 1.  Delivery approach versus delivery mode.   For women who are 
eligible for trial of labor after  cesarean (TOLAC), a decision  regarding the 
delivery approach (whether to schedule an elective repeat cesarean 
delivery (ERCD) or to undergo TOLAC) is made. The TOLAC rate is the 
percentage of eligible women who undergo a TOLAC (versus an ERCD). If 
TOLAC is chosen, the ultimate delivery mode  (VBAC or CD) is uncertain. 
Most, but not all, women who plan an ERCD will deliver via CD.

 
PROCEED Study Protocol………………           -10- 
28 September 2018 
 
about testing and birth defects, and better comprehension of the risks of amniocentesis or 
chorionic villus sampling.27 We believe the PROCEED study also has the potential to generate an 
evidence-based intervention that may lower the overall CD rate among diverse populations of 
women, a critical yet elusive goal in obstetric care. Moreover, because the Prior Cesarean 
Decision app will make explicit the probability of achieving VBAC, it is expected that the group of 
women who undertake TOLAC after using the decision app will be enriched with those who are 
more likely to succeed in their attempt. As over 90% of morbidity occurs in women who 
undertake TOLAC but ultimately have a cesarean during labor28, this app may also lower the rate 
of CD without increasing either maternal or perinatal morbidity. 
13.0 STUDY HYPOTHESES AND DESIGN 
13.1. Primary Hypothesis 
The primary hypothesis of this study: 
• 
Compared to women who receive usual care only, women who are randomized to use the 
Prior Cesarean Decision app will be more likely to undergo TOLAC. 
13.2. Secondary Hypotheses 
The secondary hypotheses of this study are: 
• 
Compared to women who receive usual care only, women randomized to use the Prior 
Cesarean Decision app will: 
8. be more likely to have a vaginal birth after cesarean (VBAC) (major secondary outcome);  
9. be more knowledgeable about TOLAC and ERCD and their potential outcomes; 
10. experience less decisional conflict; 
11. report higher levels of shared decision making regarding delivery approach;  
12. report higher levels of decision self-efficacy; 
13. report higher levels of decision satisfaction; and 
14. experience lower rates of maternal and neonatal morbidities 
13.3. Study Design 
This is a two-armed RCT to assess the impact of a Prior Cesarean Decision app on the delivery 
outcomes of 1,320 English- or Spanish-speaking women with a prior cesarean delivery (1:1 
randomization sequence for the intervention).  Following is a consort diagram of the study:  
 
 

 
PROCEED Study Protocol………………           -11- 
28 September 2018 
 
Figure 2. Consort diagram 
 
 
 

 
PROCEED Study Protocol………………           -12- 
28 September 2018 
 
13.3.1. Timeline 
 
Randomized 
controlled trial 
(n=1320) 
2016 
2017 
2018 
2019 
2020 
Jan-
Mar 
Apr-
Jun 
Jul-
Sep 
Oct-
Dec 
Jan-
Mar 
Apr-
Jun 
Jul-
Sep 
Oct-
Dec 
Jan-
Mar 
Apr-
Jun 
Jul-
Sep 
Oct-
Dec 
Jan-
Mar 
Apr-
Jun 
Jul-
Sep 
Sep-
Dec 
Jan-
Mar 
Apr-
Jun 
Recruit RCT 
d
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Phone follow-up 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chart reviews 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Create 
databases, enter 
and clean data 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Analyze data and 
prepare 
manuscripts 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
13.3.2. Randomization 
Randomization tables will be generated with SAS v9.4 using the RAND function utilizing the 
Mersenne-Twister random number generator. To make treatment assignments difficult to 
anticipate, the program will generate randomly permuted blocks of 8, 10, and 12 in random 
order. Randomization will be stratified by language (English/Spanish) and recruitment site. 
Randomization tables will be uploaded into a randomization module in the study database by 
the data analyst. To protect the integrity of the randomization sequence, RCs will not have 
access to the randomization tables. 
14.0 STUDY POPULATION 
A total of 1,320 pregnant women between 12 weeks 0 days and 24 weeks 6 days gestation with 
one prior cesarean will be enrolled into the study from three distinct geographic areas of the 
United States. Three sites serve primarily lower income women, with many Spanish speakers. 
The remaining three sites serve primarily English-speaking communities of higher socioeconomic 
status.  
Participants will be randomized to receive the Prior Cesarean Decision app or usual care, 
stratified by site and language. Participants will be selected for the study according to the 
criteria in Sections 3.1 and 3.2. They will be approached, screened, and enrolled as described in 
Sections 5.1.1., 5.1.2., and 5.1.3. Issues related to participant retention and withdrawal from the 
study are described in Sections 3.3 and 3.4, respectively. 
14.1. Inclusion Criteria 
Women who meet all of the following criteria are eligible for inclusion in the study: 
• 
Prior cesarean delivery 
• 
Between 12 weeks 0 days and 24 weeks 6 days gestation at enrollment 
• 
English- or Spanish speaker 
• 
Prior low transverse cesarean 
• 
Unknown scar but TOLAC eligible 

 
PROCEED Study Protocol………………           -13- 
28 September 2018 
 
14.2. Exclusion Criteria 
Women who meet any of the following criteria will be excluded from this study: 
• 
No prior cesarean delivery, or more than one 
• 
Multiple gestation pregnancy 
• 
Unable to speak English or Spanish 
• 
Prior VBAC 
• 
Ineligible for TOLAC (due to prior classical cesarean, prior uterine surgery, T-incision, or 
other contraindication) 
• 
Delivering at outside institution 
14.3. Participant Retention 
Once a participant enrolls in PROCEED, the study site will make every effort to retain her in the 
study for the entire follow-up period in order to minimize possible bias associated with loss to 
follow-up. Components of such procedures may include: 
• 
Thorough explanation of the study interview schedule and procedural requirements 
during the informed consent process. 
• 
Collection of email and/or phone contact information at the study Baseline Screening 
and Enrollment interview.  
• 
Repeated contact attempts to schedule appointments. 
• 
Immediate follow-up for missed appointments. 
• 
In-person approach of patients visiting the site for prenatal care if contact cannot be 
reestablished through email or phone.   
• 
Follow-up with patients delivering at outside institutions to obtain verbal report of the 
delivery outcome and consent for release of medical records.  
14.4. Participant Withdrawal 
Regardless of the participant retention methods used, participants may voluntarily withdraw 
from the study for any reason at any time. The site PI also may withdraw participants from the 
study to protect their safety and/or if they are unwilling or unable to comply with required study 
procedures. Participants may also be withdrawn if the study sponsor, regulatory authorities, or 
site IRB terminate the study prior to its planned end date. 
The study team will evaluate participants withdrawn from the study on a case-by-case basis to 
determine whether delivery outcomes may be collected from the chart and retained in analyses. 
A final determination will be made according to a participant’s stated preference for use of her 
chart data and the data use guidelines set forth in the informed consent form.  
15.0  STUDY ARMS 
15.1. Standard of Care 
Standard of care varies across study sites. Following is a description of the procedures in place at 
each site: 
San Francisco Bay Area, California 
University of California San Francisco (UCSF) and Zuckerberg San Francisco General Hospital 
(ZSFG) 
Women who establish prenatal care at UCSF are typically seen between 8 and 12 weeks 
gestation for their first obstetrical visit. The initial intake visit is in person and is conducted by 

 
PROCEED Study Protocol………………           -14- 
28 September 2018 
 
various obstetric providers including nurse practitioners (NP), certified nurse midwives (CNM), 
generalist obstetricians or maternal fetal medicine (MFM) specialists depending on patient 
preference or risk based upon questionnaire by the OB scheduling team.   
A complete medical, surgical and obstetrical history and physical exam, including a 
viability/dating ultrasound, is performed.  Note is made of prior pregnancy histories, including 
gestational age at delivery, pregnancy complications and modes of prior deliveries. If a patient 
gives a history of cesarean delivery (CD), attempts are made to obtain the operative report to 
review indications and hysterotomy type. Discussions regarding candidacy for trial of labor are 
initiated by all levels and type of OB care providers at the first OB visit and revisited in 
subsequent visits with discussions regarding risks/benefits and alternatives.  Calculation and 
discussion of likelihood of successful vaginal birth after CS using the MFMU calculator is 
common but not universal.  The discussions and patient choice are documented in the problem 
list. If the patient was followed by a NP or CNM throughout the pregnancy she is referred at 
least once to an obstetrician or MFM for a discussion regarding the mode of delivery.  At 34-35 
weeks gestation, if patient chooses ERCD, she is scheduled in the birth center OR schedule at 39 
weeks.  If she chooses to undergo TOLAC, a discussion of timing of delivery or induction of labor 
is conducted in the OB clinic with the clinician; otherwise spontaneous labor is 
awaited.  Patients who choose to undergo a TOLAC do not sign written consents at 
UCSF.  Surgical consents are signed by the inpatient OB team with the patient prior to ERCD.   
California Pacific Medical Center, St. Luke’s Campus. Pregnant women establish prenatal care 
typically in the first trimester with a midwife. The midwife collects a pregnancy history, including 
mode of delivery for any prior pregnancies. Subsequent prenatal care visits may be with an 
obstetrician or a midwife depending on patient’s preferences and co-morbidities. Those who 
have had a prior cesarean meet with an obstetrician late in the second trimester or early third 
trimester to discuss delivery approach. Women who are eligible for TOLAC describe the 
circumstances of their previous cesarean to determine if the indication for cesarean may recur. 
Operative reports from prior surgery are requested when possible. The risks and benefits of 
TOLAC vs scheduled cesarean are reviewed as well as St. Luke’s protocol for TOLAC (needs IV, 
clear liquid diet, continuous fetal monitoring, etc). To gauge preferences, contingency plans are 
discussed— what may happen if an induction is recommended or she remains pregnant beyond 
39 weeks, 40 weeks, etc. Women do not need to commit to TOLAC or ERCD but are encouraged 
to think it over if undecided. If a patient has any interest in TOLAC, she is given a handout 
describing risks and benefits and a TOLAC consent form to review and bring back to a future visit 
(ideally with one of the obstetricians). If she is certain about pursuing TOLAC, she can sign the 
consent form that day. 
Marin Community Clinic. At Marin Community Clinics, obstetric patients initiate care with an RN 
whose scope of practice includes intake examinations, patient triage, and initial review of 
laboratory and diagnostic results. At the intake appointment, the obstetric nurse reviews the 
patient’s medical and obstetric history, initiates routine initial laboratory studies, and provides 
the patient with educational material. Most of the patients seen at our site, which is a Federally 
Qualified Health Care Center, are eligible for Medi-Cal, so the obstetric nurse also ensures that 
the patient begins the insurance eligibility process. After this initial intake appointment, patients 
are referred for an initial appointment with an obstetric provider who might be a nurse midwife, 
a family practice physician, or a nurse practitioner. Patients with complicated medical issues are 
referred to the two obstetricians who serve as consultants to the other providers. 

 
PROCEED Study Protocol………………           -15- 
28 September 2018 
 
Patients with a prior cesarean section are screened for PROCEED eligibility and participation in 
the study is discussed by the obstetric nurse at the initial intake appointment. Patients are also 
identified and screened during their subsequent visits with obstetric providers. The Site Principal 
Investigator is informed when a patient would like to participate and forwards demographic 
information for these patients to the PROCEED Study Coordinator who contacts the patients for 
interviews. 
All patients who have had a prior cesarean and are eligible for a TOLAC are counseled regarding 
mode of delivery for their current pregnancy.  A significant number of our patients are Spanish 
speaking and are scheduled between 24 and 34 weeks for a monthly group class in Spanish on 
the risks and benefits of TOLAC versus elective repeat cesarean section. The class consists of a 
group session followed by individual appointments with an obstetrician to address patient 
concerns and preference for mode of delivery. Patient who are English-speaking or speak 
another language are scheduled for an individual consultation with an obstetrician. Patients who 
elect trial of labor after cesarean are seen again to review their delivery plan if they have not yet 
delivered after 39 weeks. Patients who elect repeat cesarean are scheduled for an obstetric visit 
at 36 weeks to schedule a repeat cesarean section at 39 weeks.   
Chicago, Illinois 
Northwestern University Medical Center. Women who establish prenatal care at ambulatory 
practices associated with Northwestern Memorial Hospital are most often seen in the first 
trimester for a first obstetrical visit. An initial intake is conducted at which medical, surgical and 
obstetric histories are taken. Most obstetric providers are physicians, although there are groups 
with midwives as well, and in those groups patients who are eligible for care with either type of 
provider largely self-select into physician vs. certified nurse midwifery care. Providers review 
operative reports for prior cesareans if available.  Discussions about delivery approach typically 
begin on the first prenatal visit and may be revisited throughout the course of the pregnancy.  If 
elective repeat cesarean delivery (ERCD) is preferred, or even considered, a slot on the OR 
schedule is often reserved, at whatever gestational age and date are deemed acceptable and 
appropriate after conversations between the patient and provider.  
Boston, Massachusetts 
Massachusetts General Hospital. Women who establish prenatal care at Massachusetts General 
Hospital are typically seen between 8 and 12 weeks for a first obstetrical visit. An initial intake is 
conducted by a practice nurse at most sites, and often by phone at the largest site. During the 
initial intake, medical, surgical and obstetric histories are collected for new patients and are 
updated for returning patients. Prior pregnancy history is noted, including gestational age, 
pregnancy complications and modes of prior deliveries. Patients largely self-select into physician 
vs. certified nurse midwifery care, though access to physician care may be somewhat restricted 
to those with medical or obstetrical complexities at the three community health centers where 
prenatal care is provided. Operative reports for prior cesareans are reviewed for hysterotomy 
type, with findings documented in the problem list in the electronic medical record; attempts 
are made to obtain outside records for surgeries not performed at MGH or within the Partners 
Healthcare system. Discussions about approach of delivery generally begin as early as at the first 
prenatal visit and are revisited throughout the course of the pregnancy. Risks and benefits of 
trials of labor after cesarean are reviewed in detail and women’s preferences, even if 
provisional, are recorded in their problem lists. Calculation and documentation of the likelihood 
of successful vaginal birth after cesarean using the "MFMU calculator" is common but not 
universal. If elective repeat cesarean delivery (ERCD) is preferred, or even considered, a slot on 

 
PROCEED Study Protocol………………           -16- 
28 September 2018 
 
the OR schedule is often reserved, at whatever gestational age and date are deemed acceptable 
and appropriate after conversations between the patient and provider. The primary provider 
will often schedule a time when s/he is available. For patients desiring ERCD who are enrolled in 
midwifery care, a visit with a physician provider is often scheduled prior to the planned delivery 
date. For women considering TOLAC, risks and benefits of induction of labor are reviewed 
should indication (including post-term pregnancy) arise. In the third trimester, women sign 
written informed consent for care on Labor and Delivery, including for repeat cesarean delivery 
or TOLAC where applicable. 
Note: At all study sites, usual care for women with a prior cesarean includes counseling by the 
provider regarding mode of delivery. No formal educational intervention, web tools, or decision 
support is in place at any site. Use of the NICHD VBAC prediction tool is at the discretion of the 
prenatal provider.   
15.2. Intervention  
The Prior Cesarean Decision app (Appendices 1 and 2) includes the following features: 1) 
approximately 15 minutes of web-based content, 2) topic-specific content and graphics, 3) user-
specific risk data presented in a dynamic and interactive environment, and 4) content in both 
English and Spanish. The program is organized into segments and sub-segments that are 
interactive and sequenced. To create a satisfying user experience and enhance user interaction, 
some segments include “learn more” buttons to access additional content. Users enter clinical 
information and responses to values clarification exercises, taking advantage of the mHealth 
platform to increase patient engagement while targeting both intuition and deliberation to 
optimize the effectiveness of decision support.29  
The app was developed using a process based on the International Patient Decision Aids 
Standards Collaboration (IPDAS) quality checklist30 to confirm that the content, development 
process, and effectiveness of the Prior Cesarean Decision app conform to the highest standards. 
Published data, as well as our own testing of prior interactive multimedia decision tools, 
provided the foundation for the content and framework for the Prior Cesarean Decision app. 
Focus groups and one-on-one interviews were conducted at all sites prior to initiation of 
enrollment for the RCT. Women of varying literacy levels who were patients of the institution 
and had a prior cesarean section within the past three years were invited to participate in a one-
time 60-90 minute feedback session with study personnel in which they completed a basic 
demographics questionnaire and were shown various versions of the app during the 
development process. The sessions were audio recorded and staff took notes of specific 
feedback to incorporate into the app. The app developers also attended some sessions to hear 
directly from potential future users. Participants were remunerated $60 for their participation. 
 
16.0 STUDY PROCEDURES 
16.1. Overview 
The RC will perform a preliminary eligibility screening by chart audit of all women seeking 
prenatal services at the site (see section 5.1.1.). Women with one prior cesarean who speak 
English or Spanish and do not appear to have any contraindications to VBAC will be identified 
and approached for in-person eligibility review.  
Women will be approached in the clinic waiting area before a prenatal appointment, informed 
of their potential eligibility for the study, and asked to complete and return a printed copy of the 

 
PROCEED Study Protocol………………           -17- 
28 September 2018 
 
opt-in form (see section 5.1.2,). If time permits and the woman is eligible and interested in 
participating, screening, enrollment, and randomization will take place same-day and 
immediately after the opt-in form is completed.  
All study instruments will be administered in the language preferred by the participant, English 
or Spanish. A baseline screening form will be completed to verify the woman’s eligibility, then 
written informed consent obtained from those eligible and interested in participating. 
Participant sociodemographic characteristics, expected due date, and current preference as to 
delivery approach will be collected using a baseline questionnaire. The participant will then be 
randomized to app (intervention) or no app (control). Participants randomized to app will be 
provided an iPad tablet pre-loaded with the app to view at their own pace (see sections 4.2 and 
5.1.3. for more information). A short health literacy assessment will be administered after the 
app. Apart from the app, the intervention arm will receive usual care. A woman randomized to 
no app will complete the baseline questionnaire including the health literacy assessment, and 
will not view the app.  
Patient-reported secondary outcomes will be assessed at 34 weeks 0 days to 37 weeks 6 days 
gestation through a phone follow-up interview administered by an interviewer blinded to the 
randomization group of the participant (see section 5.1.4.). After delivery, chart review will be 
performed by a blinded co-investigator to ascertain the primary outcome of delivery approach 
(TOLAC or ERCD), the secondary outcome of delivery mode (vaginal or cesarean) and any 
contraindications to TOLAC that developed post-randomization (see section 5.1.5.). Research 
assistants will also review the chart to collect other clinical data from the delivery encounter 
including the secondary maternal and neonatal morbidity outcomes.  
Participants will receive $40 in remuneration for participating in the baseline screening and 
enrollment interview and $40 for participating in the phone follow-up interview. Participants 
who deliver at an outside institution will be contacted by telephone to collect self-reported 
delivery outcome and other pregnancy and delivery information as well as permission for 
release of the medical record (see section 5.1.6.). 
16.1.1. Chart audit (<25 weeks gestation) 
The medical charts of women who will be <25 weeks gestation at the next prenatal visit to the 
site will be reviewed for eligibility by a RC or provider at the site. Women with one prior 
cesarean who speak English or Spanish and have no contraindications to VBAC will be flagged 
for further in-person eligibility review.  
16.1.2. Opt-in form (<25 weeks gestation) 
Women flagged for follow-up according to the chart audit will be approached in the clinic 
waiting area before the prenatal appointment or told about the study by the provider during an 
OB visit. Women interested in participating will be asked to complete and return a printed copy 
of the opt-in form (Appendices 3 and 4). If the woman meets gestational age criteria for baseline 
screening (see section 5.1.3) and has enough time to complete the baseline screening and 
enrollment interview (approximately 15 minutes), the screening questionnaire can be 
administered on the same day (see section 5.1.3.). Otherwise, she will be contacted by the RC to 
schedule the screening in conjunction with an upcoming prenatal visit. A record of every woman 
approached will be kept in a REDCap database. 
16.1.3. Baseline screening and enrollment interview (12 weeks 0 days to 24 weeks 6 days gestation) 

 
PROCEED Study Protocol………………           -18- 
28 September 2018 
 
Screening Questionnaire. In-person screening for eligibility will be administered by tablet when 
the woman is between 12 weeks 0 days and 24 weeks 6 days gestation, usually immediately 
after the opt-in form is collected. Eligibility will be assessed using a seven-question screening 
questionnaire (Appendices 5 and 6). A woman will be confirmed eligible if she self-reports all of 
the following: (1) a due date corresponding to a gestational age of 12 weeks 0 days to 24 weeks 
6 days at time of interview, (2) carrying a singleton pregnancy, (3) a single prior cesarean 
section, (4) a cesarean section at her most recent delivery, (5) the cesarean section was not 
‘classical’, i.e., the cut on the uterus does not run up and down, (6) does not recall any other 
uterine surgeries that would make her ineligible for a cesarean section, e.g. a myomectomy for 
removal of uterine fibroids, (7) planning to deliver at the current institution. Responses to the 
screening questionnaire will be collected in a REDCap database.  
Consent. After the screening, printed informed consent and permission for release of medical 
records will be obtained from eligible participants using the consent and HIPAA forms 
(Appendices 7-10; see sections 8.2 and 8.3 for more information).  
Baseline Questionnaire. The baseline questionnaire (Appendices 11 and 12) will be administered 
by tablet after consent. This form collects participant age, race/ethnicity, education, income, 
form of health insurance, estimated due date, and current preference for delivery approach. A 
print copy of the questionnaire will be offered to the participant to follow along as questions are 
read aloud (Appendix 13). The RC will keep track of the time at the start and end of the 
interview and note if there is an interruption to the interview lasting more than 5 minutes. The 
RC will also record if anyone is with the participant during the interview. Questionnaire data will 
be collected in a REDCap database. 
Randomization and intervention. Treatment group will be assigned according to a randomization 
table in REDCap generated by the statistician co-investigator. If randomized to app, the 
participant will be given a tablet to view the app at her own pace (Appendices 1 and 2). The app 
will provide information on potential maternal and neonatal complications from vaginal and 
cesarean deliveries, values clarification questions, and an individualized estimate of the 
likelihood of a successful TOLAC. After viewing the app, a printed summary sheet with her 
answers to the values clarification questions and probability of successful TOLAC will be 
provided to each participant to take home (Appendices 14 and 15). More information about the 
app is provided in section 4.2. A participant randomized to the control arm will not view the 
app. If she inquires about the intervention, she will be told it consists of standardized 
information about the benefits and risks of trial of labor and elective cesarean. 
Health Literacy Assessment. The interview will conclude with a short health literacy assessment 
(Appendices 11 and 12) which evaluates a woman’s ability to interpret a nutritional label. The 
assessment will be completed by both treatment arms.  
Remuneration and follow-up reminder. Women who complete the baseline interview will 
receive $40 in remuneration in the form of a gift card (Appendices 16 and 17) or check.   
16.1.4. Phone follow-up interview (34- to 37 weeks gestation) 
The Phone Follow-up interview will be completed with participants in both arms of the study 
between 34- and 37 weeks 6 days gestation. The goal of this interview is to collect data on the 
secondary study endpoints of knowledge about TOLAC and ERCD; decisional conflict; shared 
decision-making regarding delivery approach; decision self-efficacy; and decisional satisfaction.   
Chart audit. Before contacting a participant, the RC will review her chart to establish whether 
she is still pregnant, has already delivered, or has experienced pregnancy loss before 22 weeks.  

 
PROCEED Study Protocol………………           -19- 
28 September 2018 
 
Phone interview. If the participant has not yet delivered, she will be contacted by the RC at 33 
weeks gestation to schedule a time for the phone follow-up interview. A copy of the phone 
follow-up questionnaire (Appendices 18 and 19) will be offered to the participant by email or 
mail so she may follow along as questions are read aloud. The questionnaire will be 
administered by a different interviewer and collected in a separate REDCap database than the 
baseline questionnaire to ensure the interviewer remains blinded to the participant’s 
randomization assignment (Appendix 24). 
The phone follow-up interview will consist of: (1) a six-item short form of the Spielberger State-
Trait Anxiety Inventory, which assesses the woman’s general anxiety level31, (2) eight questions 
to assess the woman’s knowledge of TOLAC and ERCD adapted from a published questionnaire 
32, (3) a 16-item Decisional Conflict Scale33, (4) an 11-item Decisional Self-Efficacy scale34, (5) a 
single-item assessment of the woman’s preferred role in the decision-making concerning her 
delivery approach35, (5) a 9-item shared decision making questionnaire (adapted from the SDM-
Q-936), and (6) a six-item Satisfaction with Decision Scale37. More information about these 
survey instruments can be found in section 7.1.2. 
During the phone follow-up interview, the woman will be asked where she plans to deliver. If at 
an outside institution, the RC will request the participant’s consent to be contacted again for the 
post-delivery questionnaire and to have a copy of her delivery record forwarded to the study 
team (see section 5.1.6.).  
If the participant is no longer pregnant at the time of the phone follow-up interview, the RC will 
administer an abbreviated form of the phone follow-up questionnaire documenting where the 
woman delivered, date of delivery, delivery approach, and method of delivery. Women who had 
a loss before 22 weeks will not be contacted for a phone follow-up interview.  
Remuneration. Women who complete the telephone interview will receive $40 in remuneration 
in the form of a gift card or check.  
16.1.5. Chart audits (after delivery) 
Participant charts will be reviewed after delivery to abstract delivery approach, delivery mode, 
and other clinical data (Appendices 20 and 21). Abstraction of delivery outcome data and any 
contraindications to TOLAC before delivery will be performed by a PI, co-investigator or research 
coordinator who is blinded to the randomization assignment. Other data from the delivery 
encounter, including maternal and neonatal morbidities and findings from the cervical exam at 
time of admission, will be abstracted by the RC. Data will be collected in REDCap. A comments 
box on the data collection form will allow RCs to document challenges interpreting the chart, 
which can also be raised at a coordinator call or addressed to a co-investigator or PI if necessary.  
Investigator review. For investigator review of outcomes, the delivery note may provide clarity; 
in other cases, review of both the labor and delivery and prenatal record will be necessary. 
Whether the patient developed an absolute contraindication to TOLAC before her delivery 
admission may be obtained from the op note. Breech, Previa, or any congenital anomaly not 
compatible with vaginal delivery should be documented. To establish planned approach for the 
current delivery, the investigator will use the following definitions: 
• 
Participant planned ERCD if:  
o Delivered by scheduled ERCD at 39 weeks prior to labor for no reason other 
than desired RCD rather than TOLAC 
o Presented in labor prior to scheduled cesarean, and opted to proceed with 
cesarean for primary reason that desired RCD rather than TOLAC 

 
PROCEED Study Protocol………………           -20- 
28 September 2018 
 
o Presented with indication for delivery prior to scheduled cesarean 
(preeclampsia, IUGR, NRFT) and opted to proceed with cesarean for primary 
reason that desired RCD rather than TOLAC 
 
Note: If there are two indications for RCD in the chart, including a 
nonelective indication for timing of delivery less than 39 weeks, the 
investigator will code the first as the "nonelective" indication and the 
second as ERCD. 
 
• 
Participant considered TOLAC if: 
o Underwent TOLAC 
o Planned TOLAC if labor prior to certain gestational age, but reached that 
gestational age limit and underwent ERCD 
o Planned TOLAC if spontaneous labor, but then developed an indication for 
induction and underwent ERCD 
16.1.6. Post-delivery phone interview for outside deliveries (after due date) 
If a participant’s due date has elapsed by more than three weeks and there is no record of the 
delivery at the site, she has likely delivered at an outside institution. In such cases, the RC will 
contact the participant by phone or email to set up a time for the post-delivery phone interview. 
During the interview, the participant will be queried for self-report of the date of delivery, 
delivery approach and mode, and other pertinent information such as whether the outside 
facility offers TOLAC, whether the woman experienced contractions or rupture of membranes, 
use of pitocin for labor augmentation, use of forceps or vacuum to assist with delivery, baby’s 
birthweight, maternal weight gain during pregnancy, and other information. In addition, the RC 
will request the name of the outside institution where the woman delivered and her permission 
to contact the institution for release of her delivery record. Responses will be collected using the 
post-delivery questionnaire (Appendices 22 and 23) and stored in a REDCap database (Appendix 
24).  
17.0 SAFETY MONITORING AND ADVERSE EVENT REPORTING 
17.1. Safety Monitoring and Clinical Data Review 
A multi-tiered safety review process will be followed for the duration of this study. Close 
cooperation between the principal investigator, site principal investigators and other co-
investigators, project manager, study coordinators, study statistician, and other study team 
members will be necessary to monitor participant safety and to respond to concerns in a timely 
manner. The investigative team will have monthly conference calls during the period of study 
implementation and additional ad hoc calls will be convened as needed. 
RCs will report all participant complaints to the investigative team.  These will be discussed 
during weekly/biweekly RC calls and monthly investigator calls. 
Each study site is responsible for continuous close monitoring and management of adverse 
events (AE) in accordance with the protocol for AE reporting at their home institution 
(Appendices 28-30). The study site PIs are responsible for the initial evaluation and reporting of 
safety information and for alerting the investigative team if unexpected concerns arise.  
 
 

 
PROCEED Study Protocol………………           -21- 
28 September 2018 
 
17.2. Reporting Requirements for this Study 
The site PI or RC will report an adverse event to the local IRB if study staff determines it may 
qualify as an Unanticipated Problem or Adverse Event because the event meets all three criteria 
listed below: 
• 
Unanticipated in severity or frequency  AND 
• 
At least possibly related to the study intervention AND   
• 
Is Serious OR not serious but suggests placing subjects or others at greater risk 
In addition, all SAEs will be reported to the study team within 72 hours of recognition by study 
staff. 
18.0 STATISTICAL CONSIDERATIONS 
18.1. Endpoints 
18.1.1. Primary Endpoint 
Consistent with the primary study hypothesis that women who are randomized to use the Prior 
Cesarean Decision app will be more likely to undergo TOLAC compared to women who receive 
only usual care, the following endpoint will be assessed in the medical record for the delivery: 
• 
Proportion of women who elect TOLAC 
18.1.2. Secondary Endpoints 
Consistent with the secondary study hypothesis that women who are randomized to use the 
Prior Cesarean Decision app will be more likely to have a VBAC compared to women who 
receive only usual care, the following endpoint will be assessed in the medical record for the 
delivery:  
• 
Proportion of women who have a VBAC 
Consistent with the secondary study hypothesis that women who are randomized to use the 
Prior Cesarean Decision app will be more knowledgeable about TOLAC and ERCD and their 
potential outcomes compared to women who receive only usual care, the following endpoint 
will be assessed at weeks 34- to 37 gestation:  
• 
Knowledge about TOLAC and ERCD and their potential outcomes, as assessed with a  
modified version of a published questionnaire.32 
Consistent with the secondary study hypothesis that women who are randomized to use the 
Prior Cesarean Decision app will experience less decisional conflict compared to women who 
receive only usual care, the following endpoint will be assessed at weeks 34- to 37 gestation:  
• 
Decisional conflict regarding delivery approach, as measured based on the participant’s 
score on a well-validated Decisional Conflict Scale33 recommended for the assessment of 
decision quality by the IPDAS.38 This measure generates an overall conflict score and 5 
subscale scores and has been used extensively to evaluate patient-centered decision 
tools in a wide range of clinical contexts.39  
Consistent with the secondary study hypothesis that women who are randomized to use the 
Prior Cesarean Decision app will report higher levels of shared decision making regarding 
delivery approach compared to women who receive only usual care, the following endpoint will 
be assessed at weeks 34- to 37 gestation:  

 
PROCEED Study Protocol………………           -22- 
28 September 2018 
 
• 
Shared decision making, as measured using the SDM-Q-9, a psychometrically evaluated 
self-assessment tool.36  
Consistent with the secondary study hypothesis that women who are randomized to use the 
Prior Cesarean Decision app will experience greater decision self-efficacy compared to women 
who receive only usual care, the following endpoint will be assessed at weeks 34- to 37 
gestation:  
• 
Decision self-efficacy, as measured using a validated 11-item Decisional Self-efficacy 
Scale.34   
Consistent with the secondary study hypothesis that women who are randomized to use the 
Prior Cesarean Decision app will report higher levels of decision satisfaction compared to 
women who receive only usual care, the following endpoint will be assessed at weeks 34- to 37 
gestation:  
• 
Decisional satisfaction, as measured using the Satisfaction with Decision Scale, a 6-item 
scale designed to measure global satisfaction with a decision and to differentiate this 
from related aspects of satisfaction.37   
Consistent with the secondary study hypothesis that women who are randomized to use the 
Prior Cesarean Decision app will experience lower rates of maternal and neonatal morbidity 
compared to women who receive only usual care, the following endpoints will be assessed in 
the medical record for the delivery:  
• 
Maternal major morbidity, defined as any of: uterine rupture, hysterectomy, surgical 
injury (bowel, bladder/ureter, or other), maternal death.    
• 
Maternal minor morbidity, defined as any of: blood transfusion, postpartum febrile 
morbidity (endometritis, cellulitis, urinary tract infection, or other infection)     
• 
3rd or 4th degree lacerations 
• 
Neonatal death or HIE, defined as any of: stillbirth/fetal demise (antepartum or 
intrapartum), neonatal death, HIE     
• 
Neonatal respiratory morbidity, defined as any of: respiratory morbidity requiring CPAP 
or intubation     
• 
Neonatal intensive care unit (NICU) admission 
18.2. Sample Size 
Table 1 shows the minimum difference in TOLAC due to the Prior Cesarean Decision app that has 
80% power. For a recruitment goal of 1,320 participants (1:1 per intervention arm) and 
assuming 5% loss to follow-up and a baseline rate of 33% in the control group, we will have at 
least 80% power to detect an 8% absolute increase in TOLAC due to the app.  
Table 1: Minimum detectable effects for randomization α=.05, two-sided, power = 80%. 
LTFU = lost to follow-up rate. 
Outcome 
Assumptions 
Effect 
Measure 
N=1,200 
N=1,320 
N=1,440 
N=1,660 
TOLAC 
Baseline rate 
(33%) 
 LTFU (5%) 
 
Absolute 
increase 
(%) 
8% 
8% 
7% 
7% 

 
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28 September 2018 
 
 
 
18.3. 
Blinding 
Assessors of the primary and secondary outcomes will remain blinded to the randomization 
assignment throughout the study. The study participant and the RC who administers the 
baseline screening and enrollment interview will be aware of the participant’s randomization 
assignment. Phone follow-up questionnaires and chart audits will be administered by a different 
interviewer and collected in a separate database than the baseline questionnaire to ensure the 
interviewer remains blinded to the participant’s randomization assignment during collection of 
study endpoints. 
18.4. Data Analysis 
We will present sample characteristics by treatment assignment in the form of n’s and %’s for 
categorical variables and means/standard deviations or medians and interquartile ranges for 
continuous variables. 
For our primary outcome TOLAC and major secondary outcome VBAC, we will calculate the 
proportion with the outcome by treatment arm and test for differences between treatment 
arms using a Poisson regression model which has been adjusted for recruitment site and 
language of interview and includes robust standard errors. Comparisons will be presented in the 
form of relative risks and 95% confidence intervals. Differences between treatment arms for the 
maternal and neonatal morbidity outcomes will be evaluated in the same manner. For 
continuous outcomes (e.g., decisional conflict, shared decision making regarding delivery 
approach, decision self-efficacy, and decisional satisfaction), we will calculate the mean score by 
treatment arm and test for differences using linear regression models adjusted for recruitment 
site and language of interview. 
For our primary outcome TOLAC and major secondary outcome VBAC, we will examine 
interactions of treatment arm by the a priori defined factors of site, race/ethnicity, and 
language. For each interaction, differences will be evaluated using a Poisson regression model 
with an interaction term for treatment arm by subgroup. 
Analyses will exclude women who had a pregnancy loss before 22 weeks gestation. We will also 
perform a sensitivity analysis of TOLAC and VBAC rates and differences in TOLAC and VBAC 
between treatment arms after excluding women who develop placenta previa or breech 
presentation. 
19.0    
HUMAN SUBJECTS CONSIDERATIONS 
19.1. Ethical Review  
Informed consent forms will pass through review and approval by the local IRB. as will 
participant education and recruitment materials, any other documents requested by the IRB, 
and any subsequent modifications to a document after approval. Review will be with respect to 
scientific content and compliance with applicable research and human subjects regulations.  
IRB review of the study protocol will occur at least annually. The Site PI or RC will provide safety 
and progress reports to the IRBs at least annually and within three months of study termination 
or completion. These reports will include the total number of participants enrolled in the study, 
the number of participants who completed the study, all changes in the research activity, and all 
unanticipated problems involving risks to human subjects or others.  

 
PROCEED Study Protocol………………           -24- 
28 September 2018 
 
19.2. Informed Consent 
Written informed consent will be obtained from each study participant prior to enrollment using 
an informed consent form approved by the local IRB in accordance with all applicable 
regulations. A copy of her signed informed consent form will be offered to the participant 
(Appendices 7 and 8). 
19.3. HIPAA 
Permission for release of medical records for ascertainment of clinical endpoints will be 
obtained from participants with the Health Insurance Portability and Accountability (HIPAA) 
form, which documents the personal health information that may be released, to whom it may 
be released, how it may be used, when permission for its release expires, and under what terms 
permission may be cancelled (Appendices 9 and 10). 
19.4. Risks 
Breach of confidentiality. Although study sites will make every effort to protect participant 
privacy and confidentiality, it is possible that participants' involvement in the study could 
become known to others. We are evaluating a mobile health intervention linked to a cloud 
platform and there is the possibility that study participation could become known to others 
despite the use of firewalls, password protection, and other security measures.  
19.5. Benefits 
Participation in the intervention arm of this study may lead to improved rates of TOLAC and 
other beneficial outcomes as posited in sections 2.1 and 2.1 of this manual. There may be no 
direct benefits to participants in the control arm of this study; however, they and others may 
benefit in the future from information learned from this study. 
19.6. Incentives 
Participants will be compensated for their time and effort in this study through remuneration of 
$40 following participation in the baseline interview and $40 following participation in the 
phone follow-up questionnaire.  Remuneration will be the in the form of a gift card (Appendices 
16 and 17) or check.  
19.7. Confidentiality 
All study-related information will be stored securely at the study site in locked file cabinets or on 
password-protected databases managed in accordance with section 9.1.3. of this study protocol. 
Participant study information will not be released without the written permission of the 
participant except as necessary for monitoring by the NIH and/or the site IRB.  
20.0  ADMINISTRATIVE PROCEDURES 
20.1. Study Coordination 
Study implementation will be directed by this study protocol. Study case report forms and other 
study instruments are attached as Appendices 1-32. Protocols for training and study team 
communication are covered in sections 9.1.1. and 9.1.2. Section 9.1.3 reviews database 
management and data quality monitoring plans. Use of information is described in Section 9.1.4. 
20.1.1. Trainings 
The project manager at UCSF will train the RCs and other project staff at each of the sites.  
Topics covered will include:  

 
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28 September 2018 
 
• 
Study background, justification & aims 
• 
Inclusion & exclusion criteria, eligibility screening 
• 
Participant tracking in REDCap 
• 
Appointment scheduling 
• 
Approaching potentially eligible participants 
 
Etiquette for in-person approach in the clinic waiting bay 
 
Opt-in/opt-out forms 
• 
Informed consent 
• 
Randomization protocol 
• 
Questionnaires 
 
Baseline face-to-face questionnaire 
 
Phone follow-up questionnaire 
• 
Equipment 
 
iPads 
 
Portable Wi-Fi-enabled color printers 
• 
Chart review 
• 
Remuneration 
20.1.2. Study Communication 
Calls and in-person meetings will be scheduled throughout the study period to ensure clear 
communication, collegial collaboration, and rapid response to any challenges that may arise. 
Investigator Calls. 
The PI will lead monthly conference calls with the site PIs, co-investigators, project manager, 
and data manager. Topics to be discussed will include: 
• 
Project timelines 
• 
Recruitment plans 
• 
Enrollment and retention reports 
• 
Study design and implementation 
• 
Questionnaire revisions (as necessary) 
• 
Data analysis plans, progress and results 
• 
Manuscript and abstract plans and progress 
• 
Review of draft manuscripts and abstracts 
• 
IRB renewals and modifications 
• 
Budgets and contracts 
• 
Other study management issues as needed 
Research Coordinator Calls. 

 
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28 September 2018 
 
The project manager at UCSF will hold weekly 30-minute phone calls with the research 
coordinators for the first six months of the project. After six months, they will switch to a bi-
weekly conference call schedule. The PI or a site PI will participate as needed. Coordinator calls 
will cover the following topics: 
• 
Current totals interested, scheduled for enrollment, enrolled, scheduled for phone 
follow-up, followed-up, charts reviewed, by site 
• 
Successes, challenges, and new ideas for: 
o Screening and approaching patients 
o Reaching recruitment targets 
o Utilizing technology (iPads, printers, Wi-Fi) 
o Administering questionnaires 
o Interfacing with the app  
o Scheduling and coordinating follow-up interviews and chart reviews 
o Carrying out follow-up interviews and chart reviews 
o IRB modifications 
o Other issues as needed 
Annual Meetings. 
Each year, the PI will host an annual in-person meeting of one- to two days with the site PIs, co-
investigators, project manager, data manager, and RCs. Topics covered will be similar to the 
monthly calls but with time for lengthier discussion. Parallel break-out sessions for investigators 
and staff may be held to cover topics relevant to each group. A meeting of the PI and site PIs 
may also take place to discuss confidential matters and critical leadership/management 
decisions. A second annual meeting for broader visioning of scientific goals and dissemination 
plans will be held in-person among study members attending the annual Society for Maternal 
Fetal Medicine conference.   
20.1.3. Database Management and Data Quality Monitoring 
Randomization assignment, survey responses, and chart audit data for all sites will be collected 
and stored in REDCap databases hosted centrally at UCSF. Data will be behind an institutional 
firewall and accessible through a web portal via login credentials known only to qualified study 
staff. Randomization assignment will be collected in a separate database than the phone follow-
up questionnaire and chart audits to ensure staff remain blinded to treatment group while 
gathering outcome data. Sites will maintain their own tracking and recruitment logs in local 
REDCap databases (Appendix 24). Protected health information, such as patient names, medical 
record number, estimated due date, clinic visit schedule, telephone number and email address 
will be collected on the tracking and recruitment log to aid with scheduling and participant 
follow-up. A unique study identifier will be generated for each participant to link records across 
databases. 
Data from the app will be collected through a secure, password-protected online portal linked to 
a PostGRE SQL database on a Heroku cloud platform, which provides best-in-class server 
security, including firewalls, physical security, and regular compliance auditing.  

 
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Clinical, survey and app data will be transferred to SAS statistical software for cleaning, 
reporting and analysis. Quality control reports and queries will be generated and distributed to 
the study sites on a routine schedule for verification and resolution.    
20.2. Use of Information and Publications 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov. Presentation 
and publication of the results of this study will be governed by guidelines determined by the 
study team and as necessary and appropriate by their associated institutions policies. Any 
presentation, abstract, or manuscript will be approved by the protocol chair prior to submission.  
21.0 REFERENCES 
1. 
Hamilton, B. E., Martin, J. A. & Ventura, S. J. Births: preliminary data for 2012. Natl. Vital 
Stat. Rep. Cent. Dis. Control Prev. Natl. Cent. Health Stat. Natl. Vital Stat. Syst. 62, 1–20 (2013). 
2. 
Guise, J.-M. et al. Vaginal Birth After Cesarean: New Insights. (Agency for Healthcare 
Research and Quality (US), 2010). 
3. 
Silver, R. M. Delivery after previous cesarean: long-term maternal outcomes. Semin. 
Perinatol. 34, 258–266 (2010). 
4. 
Silver, R. M. et al. Maternal morbidity associated with multiple repeat cesarean 
deliveries. Obstet. Gynecol. 107, 1226–1232 (2006). 
5. 
Clark, E. A. S. & Silver, R. M. Long-term maternal morbidity associated with repeat 
cesarean delivery. Am. J. Obstet. Gynecol. 205, S2-10 (2011). 
6. 
Lydon-Rochelle, M., Holt, V. L., Martin, D. P. & Easterling, T. R. Association between 
method of delivery and maternal rehospitalization. JAMA 283, 2411–2416 (2000). 
7. 
Healthy People - HP2010 Final Review. Available at: 
https://www.cdc.gov/nchs/healthy_people/hp2010/hp2010_final_review.htm. (Accessed: 22nd 
September 2017) 
8. 
American College of Obstetricians and Gynecologists. Task Force on Cesarean Delivery 
Rates. Evaluation of cesarean delivery. Available at: 
https://pdfs.semanticscholar.org/7a74/0973f8fe4d2834ee29f0a59fc96458c8d38a.pdf 
(Accessed: 22nd August 2018) 
9. 
American College of Nurse-Midwives Responds to ACOG's 2010 VBAC 
Recommendations. Available at: 
http://www.midwife.org/acnm/files/ccLibraryFiles/Filename/000000000075/ACNMResponseto
VBACBulletin_082610FINAL.pdf (Accessed: 22nd September 2017) 
10. 
Hamilton, B. E., Martin, J. A. & Ventura, S. Births: Preliminary data for 2010. 60, (2011). 
11. 
Grobman, W. A. et al. The change in the rate of vaginal birth after caesarean section. 
Paediatr. Perinat. Epidemiol. 25, 37–43 (2011). 

 
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12. 
Metz, T. D. et al. How do good candidates for trial of labor after cesarean (TOLAC) who 
undergo elective repeat cesarean differ from those who choose TOLAC? Am. J. Obstet. Gynecol. 
208, 458.e1-6 (2013). 
13. 
Macones, G. A. et al. Maternal complications with vaginal birth after cesarean delivery: 
a multicenter study. Am. J. Obstet. Gynecol. 193, 1656–1662 (2005). 
14. 
Lavin, J. P., Stephens, R. J., Miodovnik, M. & Barden, T. P. Vaginal delivery in patients 
with a prior cesarean section. Obstet. Gynecol. 59, 135–148 (1982). 
15. 
Landon, M. B. et al. Maternal and perinatal outcomes associated with a trial of labor 
after prior cesarean delivery. N. Engl. J. Med. 351, 2581–2589 (2004). 
16. 
McClain, C. S. The making of a medical tradition: vaginal birth after cesarean. Soc. Sci. 
Med. 1982 31, 203–210 (1990). 
17. 
Emmett, C. L., Shaw, A. R. G., Montgomery, A. A., Murphy, D. J. & DiAMOND study 
group. Women’s experience of decision making about mode of delivery after a previous 
caesarean section: the role of health professionals and information about health risks. BJOG Int. 
J. Obstet. Gynaecol. 113, 1438–1445 (2006). 
18. 
Kirk, E. P., Doyle, K. A., Leigh, J. & Garrard, M. L. Vaginal birth after cesarean or repeat 
cesarean section: medical risks or social realities? Am. J. Obstet. Gynecol. 162, 1398-1403; 
discussion 403–405 (1990). 
19. 
Moffat, M. A. et al. Decision making about mode of delivery among pregnant women 
who have previously had a caesarean section: A qualitative study. BJOG Int. J. Obstet. Gynaecol. 
114, 86–93 (2007). 
20. 
McClain, C. S. Patient decision making: the case of delivery method after a previous 
cesarean section. Cult. Med. Psychiatry 11, 495–508 (1987). 
21. 
McClain, C. S. Why women choose trial of labor or repeat cesarean section. J. Fam. 
Pract. 21, 210–216 (1985). 
22. 
National Institutes of Health. National Institutes of Health Consensus Development 
Conference Statement vaginal birth after cesarean: new insights March 8-10, 2010. Semin. 
Perinatol. 34, 351–365 (2010). 
23. 
Wennberg, J. E. Time to tackle unwarranted variations in practice. BMJ 342, d1513 
(2011). 
24. 
Oshima Lee, E. & Emanuel, E. J. Shared decision making to improve care and reduce 
costs. N. Engl. J. Med. 368, 6–8 (2013). 
25. 
Grobman, W. A. et al. Development of a nomogram for prediction of vaginal birth after 
cesarean delivery. Obstet. Gynecol. 109, 806–812 (2007). 

 
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26. 
Gilbert, S. A. et al. Elective repeat cesarean delivery compared with spontaneous trial of 
labor after a prior cesarean delivery: a propensity score analysis. Am. J. Obstet. Gynecol. 206, 
311.e1-9 (2012). 
27. 
Kuppermann, M. et al. Randomized trial of an informed free choice approach to 
prenatal testing among women of varying literacy levels [abstract]. Med Dec Making (2013). 
28. 
McMahon, M. J., Luther, E. R., Bowes, W. A. & Olshan, A. F. Comparison of a trial of 
labor with an elective second cesarean section. N. Engl. J. Med. 335, 689–695 (1996). 
29. 
Martin, J. N. et al. Vaginal delivery following previous cesarean birth. Am. J. Obstet. 
Gynecol. 146, 255–263 (1983). 
30. 
Guise, J.-M. et al. Safety of vaginal birth after cesarean: a systematic review. Obstet. 
Gynecol. 103, 420–429 (2004). 
31. 
Marteau, T. M. & Bekker, H. The development of a six-item short-form of the state scale 
of the Spielberger State-Trait Anxiety Inventory (STAI). Br. J. Clin. Psychol. 31 ( Pt 3), 301–306 
(1992). 
32. 
Bernstein, S. N., Matalon-Grazi, S. & Rosenn, B. M. Trial of labor versus repeat cesarean: 
are patients making an informed decision? Am. J. Obstet. Gynecol. 207, 204.e1-6 (2012). 
33. 
O’Connor, A. M. Validation of a decisional conflict scale. Med. Decis. Mak. Int. J. Soc. 
Med. Decis. Mak. 15, 25–30 (1995). 
34. 
UM_Decision_SelfEfficacy.pdf. Available at: 
https://decisionaid.ohri.ca/docs/develop/User_Manuals/UM_Decision_SelfEfficacy.pdf 
(Accessed: 27th September 2017) 
35. 
Deber, R. B., Kraetschmer, N. & Irvine, J. What role do patients wish to play in treatment 
decision making? Arch. Intern. Med. 156, 1414–1420 (1996). 
36. 
Kriston, L. et al. The 9-item Shared Decision Making Questionnaire (SDM-Q-9). 
Development and psychometric properties in a primary care sample. Patient Educ. Couns. 80, 
94–99 (2010). 
37. 
Holmes-Rovner, M. et al. Patient satisfaction with health care decisions: the satisfaction 
with decision scale. Med. Decis. Mak. Int. J. Soc. Med. Decis. Mak. 16, 58–64 (1996). 
38. 
IPDAS-Chapter-L.pdf. Available at: http://ipdas.ohri.ca/IPDAS-Chapter-L.pdf (Accessed: 
26th September 2017) 
39. 
O’Connor, A. M. et al. Decision aids for people facing health treatment or screening 
decisions. Cochrane Database Syst. Rev. CD001431 (2009). 
doi:10.1002/14651858.CD001431.pub2 
 
 

 
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22.0 APPENDICES 
 
Document 
Version 
Date 
1 
App PDF-English 
112015 
2 
App PDF-Spanish 
112015 
3 
Opt-in form-English 
111615 
4 
Opt-in form-Spanish 
112015 
5 
Screening questions-English 
111615 
6 
Screening questions-Spanish 
112015 
7 
UCSF Consent-English 
111615 
8 
UCSF Consent-Spanish 
112015 
9 
UCSF HIPAA-English 
111615 
10 
UCSF HIPAA-Spanish 
112015 
11 
Baseline Questionnaire-English 
111615 
12 
Baseline Questionnaire-Spanish 
112015 
14 
App summary sheet-English 
111615 
15 
App summary sheet-Spanish 
112015 
16 
UCSF Gift Card Receipt-English 
111615 
17 
UCSF Gift Card Receipt-Spanish 
112015 
18 
Phone Follow-up Questionnaire-English 
111615 
19 
Phone Follow-up Questionnaire-Spanish 
112015 
20 
Chart Review tool (investigator) 
111615 
21 
Chart Review tool (RC) 
111615 
22 
Post Delivery Phone Questionnaire for Outside Deliveries-English 
111615 
23 
Post Delivery Phone Questionnaire for Outside Deliveries-Spanish 
112015 
24 
RedCap tracking & recruitment log data dictionary 
010416 
25 
IRB/CHR Approval Letter-UCSF 
121415 
26 
IRB Approval Letter-California Pacific Medical Center 
091718 
27 
IRB Approval Letter-Massachusetts General 
121815 
28 
29 
30 
31 
IRB Approval Letter-Northwestern 
IRB Adverse Event Reporting-Northwestern 
IRB Adverse Event Reporting-Mass. General 
IRB Adverse Event Reporting-UCSF 
121015 
111315 
111315 
111315