Use of a Novel Decision Aid for Prenatal Aneuploidy Screening
Phase: NA
Conditions: Aneuploidy, Pregnancy Complications
Sponsor: University of North Carolina, Chapel Hill

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PROTOCOL TITLE:  Use of a computerized decision aid for prenatal aneuploidy screening 
Short Title:  
Aneuploidy decision aid 
Lead Investigator: 
Laura Carlson, M.D. 
 University of North Carolina at Chapel 
Version Date: January 3, 2018 
NCT number: 02991729 

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TABLE OF CONTENTS 
Table of Contents ................................................................................................................................. 2 
Abbreviations and Definitions of Terms ........................................................................................... 3 
Protocol Synopsis ................................................................................................................................. 4 
1 
BACKGROUND  AND RATIONALE .......................................................................................... 7 
2 
STUDY OBJECTIVES ................................................................................................................... 9 
3 
INVESTIGATIONAL PLAN ....................................................................................................... 10 
4 
STUDY PROCEDURES .............................................................................................................. 12 
5 
STUDY EVALUATIONS AND MEASUREMENTS ................................................................. 14 
6 
STATISTICAL CONSIDERATIONS .......................................................................................... 15 
10  DATA COLLECTION AND MANAGEMENT .......................................................................... 17 
14 REFERENCES .............................................................................................................................. 18 
 
 
 
 

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ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
MSSKQ 
Maternal serum screening knowledge questionnaire 
cfDNA 
Cell-free DNA screening 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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PROTOCOL SYNOPSIS 
 
Study Title 
Use of a Computerized Decision Aid for Prenatal Aneuploidy Screening 
Funder 
• 
National Center for Advancing Translational Sciences (NCATS), 
NIH, Grant #UL1TR001111 
• 
UNC Department of OBGYN Cefalo-Bowes Grant (internal 
funding) 
Clinical Phase 
Phase II 
Study Rationale 
• 
All women should be offered aneuploidy screening or testing in 
each pregnancy 
• 
Screening and testing options are complex 
• 
Decision aids have been shown to improve knowledge and 
decrease decisional conflict with healthcare decisions, including 
aneuploidy screening 
• 
Prior decision aids which have been evaluated for aneuploidy 
screening did not include the newest screening option of cell-free 
DNA 
Study Objective(s) 
Primary  
• 
To evaluate whether use of the computerized decision aid is 
noninferior than an abbreviated visit with a genetic counselor in 
increasing patient knowledge 
Secondary 
• 
To evaluate whether use of the computerized decision aid is 
noninferior than an abbreviated visit with a genetic counselor in 

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decreasing patient decisional conflict 
• 
To evaluate whether use of the decision aid in addition to genetic 
counseling improves patient knowledge and decisional conflict over 
genetic counseling alone 
• 
To examine test chosen for aneuploidy screening 
 
Test Article(s) 
(If Applicable) 
A computerized decision aid was developed within a tablet-based 
application, available in Spanish and English, at a 10th grade reading level, 
to aid in patient education surrounding aneuploidy screening and testing 
options 
Study Design 
 
Unmasked randomized controlled trial 
Subject Population 
key criteria for Inclusion 
and Exclusion: 
Inclusion Criteria 
• 
English and Spanish-speaking pregnant women 
• 
Undergoing genetic counseling for indication of aneuploidy screening 
• 
Ages 18-50 
Exclusion Criteria 
1. Multiple gestation 
2. Prior aneuploidy screening in current pregnancy 
3. Prior abnormal ultrasound in current pregnancy 
Number Of Subjects  
 
200  
Study Duration 
Each subject’s participation will last for the duration of the study visit 
(approximately 45 minutes). 

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The entire study is expected to last 12 months. 
Study Phases 
Screening 
Study Treatment 
Follow-Up   
 (1) Screening: Women scheduled for genetic counseling for indication of 
aneuploidy screening will be approached regarding eligibility and 
willingness to participate prior to their scheduled appointment.  
(2) Intervention: Participants will be randomized either to use the above-
described decision aid prior to genetic counseling or to genetic counseling 
alone. 
(3) Follow-up: None after study visit 
Efficacy Evaluations 
(1) Knowledge: A 12 question modification of the MSSKQ 
questionnaire will be used to assess knowledge 
(2) Decisional conflict: A validated low-literacy decisional conflict 
scale will be used to assess decisional conflict  
Pharmacokinetic 
Evaluations 
N/A 
Safety Evaluations 
N/A 
Statistical And Analytic 
Plan 
(1) Primary outcome: Noninferiority of knowledge will be assessed 
graphically and with Wilcoxon Rank-Sum 
(2) Secondary outcomes: knowledge and decisional conflict scores 
will be assessed with Wilcoxon Rank-Sum 
 
DATA AND SAFETY 
MONITORING PLAN 
Participants were provided with contact information for the PI should they 
have any concerns. No safety concerns are anticipated. 
 
 

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1 
BACKGROUND AND RATIONALE 
Many different aneuploidy screening and diagnostic testing options are available to patients based on gestational age, all 
with different risks and benefits. Cell-free DNA screening has improved sensitivity and specificity for common 
aneuploidies1 but likely reduced detection of other chromosomal abnormalities.2 However, traditional screening such as 
first trimester screening, which have poorer detection characteristics for common aneuploidies, may be more likely to 
identify pregnancies other, less common, chromosomal abnormalities.2 Diagnostic testing choices include chorionic villus 
sampling and amniocentesis, both of which carry a low risk of pregnancy loss of approximately 1 in 455 to 1 in 900 
respectively.3 Counseling on screening and testing options is recommended by the American College of Obstetrics and 
Gynecology for all women, ideally at the first prenatal visit.4 Additionally, recommendations by the American College of 
Medical Genetics emphasize the importance of appropriate pretest counseling for patients undergoing prenatal screening 
with cell-free DNA.5 
This increasing number of screening modalities complicates prenatal counseling for prenatal care providers and can be 
difficult for patients to understand, especially patients with low health literacy.6 While many patients may be aware of 
trisomy 21, many have never heard of other aneuploidies and may be unfamiliar with the basic principles of genetic 
screening and prenatal aneuploidy detection. 
Because low health literacy affects many women of reproductive age and because most obstetric providers have limited 
time in an initial prenatal visit to explain the rapidly expanding choice of tests, our aim was to develop a decision aid for 
aneuploidy screening and testing that could easily be used in various clinics and settings.  Decision aids have been shown 
to improve patients’ knowledge and decrease decisional conflict with health care decisions in healthcare settings,6 and in 
the field of obstetrics and gynecology.6,7 This is particularly true when decisions are complex and involve patient value 
assessment.6 A decision aid has been previously developed and tested to address aneuploidy screening,8 though an 
important new screening modality in cell-free DNA has become available since the development of this tool. We 
hypothesize that a computerized decision aid to review available aneuploidy screening and testing options would not be 
inferior to a counseling visit with a genetic counselor in increasing patient knowledge. The combination of the decision 
aid followed by a genetic counseling appointment would also be expected to decrease decisional conflict.  
1.1 
Description of Intervention  

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A decision aid incorporating all aneuploidy screening and diagnostic testing options available at the time of the study 
was developed with input from maternal fetal medicine physicians, a geneticist, and genetic counselors.  This was 
designed within a tablet-based application. The decision aid was also translated into Spanish by a single translator and 
the translation reviewed by a second native Spanish speaker. The language was simplified to a 10th grade reading level 
on the Flesch-Kincaid scale.  Completion of the decision aid takes approximately 20 minutes. Information surrounding 
patient age and gestational age are incorporated to guide the study participant toward available options. 
 
 
 

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2 
STUDY OBJECTIVE  
2.1 
Primary Objective 
The primary hypothesis of this study was that knowledge scores of women in group 2 following completion of 
the decision aid only would not be inferior to knowledge scores of women in group 1 following genetic 
counseling. A noninferiority limit of 1 question different on a 12 point questionnaire was selected as a clinically 
relevant difference. 
2.2 
Secondary Objective 
Secondary outcomes included decisional conflict following decision aid completion, decisional conflict 
following decision aid completion and genetic counseling, change in knowledge score after genetic counseling 
in women who used the decision aid, choice of testing, and pursuit of invasive testing with high risk results. 
 
 
 
 
 
 
 
 
 
 
 

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3 
INVESTIGATIONAL PLAN  
3.1 
Study Design 
This is an unblended randomized controlled trial. 
Women randomized to group 1 will meet with the genetic counselor as scheduled, then complete the knowledge and 
decisional conflict assessments. Women randomized to group 2 will self-administer the decision aid within the app, then 
complete the knowledge and decisional conflict assessments. Following this, they will met with the genetic counselor as 
scheduled; following this appointment, they will again complete the same assessment. Additionally, prior to and following 
meeting with the genetic counselor, women in group 2 will be asked whether they would or did find it helpful to meet 
with a genetic counselor.  
Genetic counselors will be educated prior to study initiation that their counseling should not be modified based on group 
assignment; generally, women < 35 years old received abbreviated counseling on aneuploidy screening and testing 
options and those ≥ 35 years old received more extensive counseling. Within ACMG guidelines, all screening tests are 
available to all women; cost information and insurance coverage information on available tests will also be provided prior 
to final decision making. Women will then undergo their screening or testing modality of choice. All study participation 
and completion of initial screening will be completed within the single encounter. 
3.2 
Allocation to Treatment Groups and Blinding (if applicable) 
Via a coin-flip algorithm within the decision aid application, women will be randomly assigned to group 1 (control group) 
or group 2 (decision aid group) 
3.3 
Study Duration, Enrollment and Number of Subjects 
Study duration for each participant is limited to the single study visit during which patients are enrolled, complete 
questionnaires, and complete genetic counseling. 200 participants will be enrolled. This is anticipated to take 
approximately 12 months. 
3.4 
Study Population 
English and Spanish-speaking women with a singleton gestation at less than 22 weeks who are scheduled to meet with a 
genetic counselor at one of three prenatal diagnosis clinics for a discussion of aneuploidy screening and testing options are 
eligible for participation.  

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Exclusion criteria include: multiple gestations, prior abnormal ultrasound in the current pregnancy, or prior aneuploidy 
screening in the current pregnancy. 
 
 

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4 
STUDY PROCEDURES  
4.1 
Screening procedure 
For the randomized trial, charts of women scheduled to see a genetic counselor for a discussion of aneuploidy screening 
or testing were screened for eligibility and eligible women were contacted within a week before their visit by telephone by 
trained study personnel. Women who indicated in the medical record that they preferred Spanish were contacted by 
Spanish-speaking study personnel. Those who agreed to participate were asked to arrive early for their appointment to be 
enrolled in the study. 
4.2 
Intervention 
Following informed consent, the app was accessed and a study ID assigned. Via a coin-flip algorithm within the app, 
women were randomly assigned to group 1 (control group) or group 2 (decision aid group). As it was not pragmatic for 
this study, randomization assignment was not blinded. Investigators were not involved in developing the randomization 
scheme within the app. All women completed an initial demographic and knowledge questionnaire immediately following 
randomization via self-administered assessments within the app.  
Study flow is described in the below figure. Women randomized to group 1 met with the genetic counselor as scheduled, 
then completed the knowledge and decisional conflict assessments. Women randomized to group 2 self-administered the 
decision aid within the app, then completed the knowledge and decisional conflict assessments. Following this, they met 
with the genetic counselor as scheduled; following this appointment, they again completed the same assessment. 
Additionally, prior to and following meeting with the genetic counselor, women in group 2 were asked whether they 
would or did find it helpful to meet with a genetic counselor.  

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4.3 
Subject Completion/ Withdrawal procedures 
Participants are instructed to inform their enrolling research study personnel should they desire to withdraw and 
participation could be terminated at that time. 
 
 
 

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STUDY EVALUATIONS AND MEASUREMENTS (how measurements will be made)   
- 
Demographic characteristics will be abstracted from questionnaires and medical chart 
o Age 
o Race/ethnicity 
o Preferred language 
o Parity 
o Gestational age 
o Site of enrollment 
o Insurance status 
o Employment status 
o Education level 
o History of genetic counseling in prior pregnancy 
- 
Baseline knowledge assessment 
o This will be assessed via the previously described modified MSSKQ questionnaire prior to 
intervention 
- 
Knowledge and decisional conflict scores as described will be collected via self-administered questionnaires 
embedded within the application 
 
 

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6 
STATISTICAL CONSIDERATION    
6.1 
Sample size calculation 
An initial power calculation was performed using historical data from the maternal serum screening questionnaire 
assuming a standard deviation of 3 questions; to achieve 80% power with a 2-tailed alpha of 0.05, 92 women would be 
needed in each arm. Assuming a 7.5% fall-out rate from women with nonviable pregnancies, 100 patients were required in 
each arm for a total enrollment of 200 women. 
6.2 Statistical Methods 
Baseline demographics 
• 
Mean age - Wilcoxon rank sum 
• 
AMA as categorical variable - chi2 
• 
Race/ethnicity - Fisher exact 
• 
Mean GA - Wilcoxon rank sum 
• 
GA<14 wks as categorical - chi2 
• 
Insurance status - Fisher exact 
• 
Employed yes/no - chi2 
• 
Education level - fisher exact 
• 
Religion - Fisher exact 
• 
Prior GC - chi2 
• 
Planning invasive testing - Fishers exact 
• 
Mean knowledge score on enrollment - Wilcoxon rank sum 
 
Results 
1. Compare control group following genetic counseling to intervention group following decision aid 
o 
Mean knowledge - Wilcoxon rank sum 
o 
Mean decisional conflict - Wilcoxon rank sum 
o 
Planned test - Fisher exact 

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2. Compare control group following genetic counseling to intervention group following decision aid and genetic 
counseling 
o 
Mean knowledge - Wilcoxon rank sum 
1. Represented in figure 
o 
Decisional conflict - Wilcoxon rank sum 
1. Represented in figure 
o 
Planned test - Fisher exact 
3. Compare intervention group following decision aid to intervention group following both decision aid and genetic 
counseling 
o 
Mean knowledge - Wilcoxon signed rank 
1. Represented in figure 
o 
Decisional conflict - Wilcoxon signed rank 
1. Represented in figure 
o 
Planned test - descriptive (% changed) 
No interim analyses are planned. 
 
 
 
 

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DATA COLLECTION AND MANAGMENT  
Results to questionnaires are stored within the study application and will be downloaded onto a secure server by study 
personnel following each study visit. These files will be encrypted and password protected. This data will then be 
transferred into REDCap data management system for storage and access for statistical analysis by the primary 
investigator. 
 
 

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REFERENCES  
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screening for aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol. 2017. 
2. 
Norton ME, Baer RJ, Wapner RJ, Kuppermann M, Jelliffe-Pawlowski LL, Currier RJ. Cell-free DNA vs 
sequential screening for the detection of fetal chromosomal abnormalities. Am J Obstet Gynecol. 2016;214(6):727 e721-
726. 
3. 
Akolekar R, Beta J, Picciarelli G, Ogilvie C, D'Antonio F. Procedure-related risk of miscarriage following 
amniocentesis and chorionic villus sampling: a systematic review and meta-analysis. Ultrasound Obstet Gynecol. 
2015;45(1):16-26. 
4. 
Practice Bulletin No. 163: Screening for Fetal Aneuploidy. Obstet Gynecol. 2016;127(5):e123-137. 
5. 
Gregg AR, Gross SJ, Best RG, et al. ACMG statement on noninvasive prenatal screening for fetal aneuploidy. 
Genet Med. 2013;15(5):395-398. 
6. 
Stacey D, Legare F, Col NF, et al. Decision aids for people facing health treatment or screening decisions. 
Cochrane Database Syst Rev. 2014;1:CD001431. 
7. 
Dugas M, Shorten A, Dube E, Wassef M, Bujold E, Chaillet N. Decision aid tools to support women's decision 
making in pregnancy and birth: a systematic review and meta-analysis. Soc Sci Med. 2012;74(12):1968-1978.