Genetic Counseling Service Delivery and Outcomes in Diverse and Underserved Populations
Conditions: Genetic Predisposition
Sponsor: University of Texas Southwestern Medical Center

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Randomized Control Trial Comparing Genetic Counseling Service Models for the Underserved
NCT06212310
10/15/2021

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Randomized Control Trial Comparing Genetic Counseling Service Models for the Underserved
PROTOCOL FORM / RESEARCH DESCRIPTION
If an item does not apply to your research project, indicate that the question is "not applicable” – do not leave sections blank
Click once on the highlighted entry in each box to provide your response. Click the item number/letter or word, if hyperlinked,
for detailed instructions for that question.  If your response requires inserting a table, picture, etc, you may need to first delete the
box that surrounds the answer and then insert your table or other special document.
1. Purpose and objectives.
List the purpose and objectives:
The overarching goal of this pilot prospective randomized controlled study is to compare patient-reported and clinical operations
outcomes between in-person genetic counseling (IPGC – control) and telephone-based genetic counseling (TGC – intervention)
in an indigent English or Spanish-speaking population seeking genetic counseling for hereditary cancer syndromes to create a
framework for effective and efficient genetic service delivery in these populations nationally. General genetic education and
principles will be conveyed through a standard genetic counseling session including a pre-test education video in both the TGC
and IPGC arms. Our primary project objectives are to compare the following outcomes between the IPGC and TGC study arms.
Aim 1: Patient reported outcomes – A. Patient satisfaction with genetic counseling visit; B. Knowledge of basic principles of
cancer genetics and implications of genetic testing for personal healthcare and relatives. Secondary objectives for this aim are: 1.
Patient ability to make informed choice; and 2. Genetic counseling-specific empowerment outcomes. Aim 2: Clinical outcomes –
visit completion rate; Secondary objectives are: 1. Genetic testing completion rate; and 2. Genetic testing cancelation/failure rate.
We hypothesize that patients in the TGC arm will not have significant differences in knowledge, satisfaction, informed choice or
genetic counseling-specific empowerment compared to the IPGC arm. We also expect significantly increased visit completion
rate and lower test completion rate in the TGC arm compared to the IPGC arm, but no significant difference in sample failure
rate.
2.  Background.

Describe past experimental and/or clinical findings leading to the formulation of your study.

For research involving investigational drugs, describe the previously conducted animal and human studies.

For research that involves FDA approved drugs or devices, describe the FDA approved uses of this drug/device in
relation to your protocol.

Attach a copy of the approved labeling as a product package insert or from the Physician’s Desk Reference.
You may reference sponsor’s full protocol or grant application (section number and/or title) or if none, ensure background
includes references.
Please respond to all components of this item, or clearly indicate which components are not applicable.
a.
Background
Similar studies have been performed in primarily non-Hispanic white, above-average income, college-educated, English-
speaking populations1-6 , but to our knowledge, a study comparing outcomes of TGC and IPGC service delivery models
(SDMs) has not been reported in an entirely indigent population with a high volume of Latinx/Spanish-speaking patients.
Indigent Populations. Less access to healthcare and hereditary risk assessment are well documented in indigent populations,
often composed of ethnic/racial minorities, or geographically isolated and economically underserved groups. 7-9 Barriers
include provider paucity, under-recognition of family history risk factors, financial hardship, and other factors. 10- 17 Internet
use via mobile technologies has increased access to healthcare information in indigent populations .18, 19 National surveys
revealed 91% of families living below the poverty level have some type of internet access, and of Americans earning
<$30,000 annually, 701% owned a smart phone. Review of 2019 internal program data revealed 84-88% of safety-net
hospital clinic uninsured/Medicaid patients provided an email address and reported internet connectivity. This access creates
an avenue for genetic counselors to reach underserved populations. Genetic Counseling Service Delivery. Some randomized
trials comparing outcomes of TGC v. IPGC cancer risk assessment sessions in resource-rich populations showed similar
levels of patient satisfaction, knowledge, cancer worry, risk perception, decisional conflict, and motivation to change health-
related behavior with similar data for telegenetics (video) studies. In one study, the majority of participants indicated they
would not have pursued genetic counseling had TGV not been offered. Need for Project. A majority (89%) report already
using a phone for medical discussions. Traditional healthcare infrastructures remain a barrier for indigent patients, and while
the rise in telegenetics companies and platforms in a response to the increasing need for remote genetic counseling to

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service under-resources and rural areas, outcomes of TGC in indigent populations have not been well-studied. Over 38
million people in the United States are considered low-income and are more likely to be patients in safety-net hospital
systems, which necessitates optimization of genetic counseling SDMs in these cohorts. TGC, in particular, is critical to study
in indigent populations given patient preference and accessibility to phone service. A UCSF study showed that indigent
patients offered TGC versus video genetic counseling preferred the former and had an increased uptake of genetic
counseling compared to other interventions.
Our study is not amenable to the following pieces of this question: For research involving investigational drugs, describe the
previously conducted animal and human studies.  For research that involves FDA approved drugs or devices, describe the
FDA approved uses of this drug/device in relation to your protocol.   Attach a copy of the approved labeling as a product
package insert or from the Physician’s Desk Reference.
b.
Current practice
n/a
3.  Study Design.
Describe the study design (e.g., single/double blind, parallel, crossover, etc.)  Consider inserting a scheme to visually present the
study design.
This is a two-arm parallel randomized controlled study of IPGC vs. TGC with two enrolling sites.

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4.  Research Plan / Description of the Research Methods:
4.a. Provide a comprehensive narrative describing the research methods.
1) Provide the order in which tests/procedures will be performed,
2) Provide the setting for these events and a description of the methods used to protect privacy during the study.
3) Provide the plan for data analysis (include as applicable the sample size calculation)
Please respond to all components of this item, or clearly indicate which components are not applicable.
Data Tracking and Storage. All survey data will be captured, stored, tracked, and analyzed via Research Electronic Data Capture
(REDCap), a secure, web-based application for research data.
Randomization and Scheduling:
Study coordinator (SC) will monitor referral queue daily
Randomization software (http://abtesting.ideas42.org/randomize/) will be used to randomize patients in the referral queue to each
study arm (in-person genetic counseling or IPGC/ telephone genetic counseling or TGC). Patients who meet the following
exclusion criteria will not be randomized to a study arm. Patients who are excluded from the study will be scheduled for an
appointment as per normal clinic protocol by the clinic schedulers.
SC will monitor number of participants per study arm and adjust recruitment accordingly.
Patients who have been randomized to a study arm will be scheduled for IPGC or TGC by schedulers at John Peter Smith (JPS)
and Parkland Hospital (PHHS). Schedulers will inform patients of their appointment as per normal clinic protocol. Spanish-
speaking patients will be contacted with an interpreter.
Patients who elect alternative service delivery model for genetic counseling than what was assigned after randomization will be
excluded from the study. The genetic counseling appointment type will be modified based on patient preference and patient will
continue with scheduled visit, but not as part of the study.
SC will record the following data for all referred patients in Research Electronic Data Capture (RedCap), a secure, web-based
application for research data: MRN; study arm assigned; genetic counseling appointment date; if patient was excluded from
study, and reason for exclusion. The following demographic data will also be tracked: patient’s age; patient’s sex; patient’s race
and ethnicity; patient’s preferred language; patient’s contact information (phone number and e-mail address)
Study Eligibility Determination and Informed Consent. One week prior to scheduled genetic counseling appointment, SC will call
patient to assess if patient meets study eligibility criteria. Spanish-speaking patients will be contacted with an interpreter.
If SC cannot reach the patient, SC will make second contact attempt the following business day.
Scheduled patients who cannot be reached or do not call back will be excluded from study.
SC will record the following data in RedCap: contact date and outcome; if eligibility criteria were met; if patient was excluded from
study, and reason for exclusion.
If patient qualifies for study, SC will describe study protocol and get verbal consent for study participation using the consent
script. All patients will be sent a hard copy of the consent document for their records (available in English and Spanish)
electronically along with the study surveys via RedCap.
Patients who decline will be excluded from study. Study participation status will be recorded in RedCap (including reason for
declining participation).
Patients who decline to be in the study will be sent an appointment letter and will continue with scheduled genetic counseling
appointment as per normal clinic protocol, not as part of the study.
Pre-Appointment Resources and Survey Completion. Patients who agree to participate in the study will be sent the pre-
appointment survey (Appendix B). A Spanish version of the survey will be sent to Spanish-speaking patients. Surveys will include
a hard copy of the consent document that can be downloaded as desired. Survey links will be sent to patients via email. All
surveys will be available through REDCap.
The pre-appointment survey will consist of the Multi-dimensional Model of Informed Choice (MMIC) assessment and the
Genomics Outcome Scale (GOS).
SC will check pre-appointment survey completion status two business days prior to appointment.
Patients with incomplete pre-appointment surveys will be contacted two business days prior to appointment and will be reminded
to complete survey. Patients will be offered the option to complete survey via telephone with SC. Spanish-speaking patients will
be contacted with an interpreter.

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SC will attempt to contact patients who cannot be reached the following business day.
Patients who do not complete pre-appointment survey will be excluded from study but will continue with scheduled genetic
counseling appointment as standard of care.
Pre-appointment survey completion status and survey completion method will be recorded in RedCap by SC.
Genetic Counseling and Genetic Testing. Patients who are unable to watch the educational video prior to, or during their genetic
counseling visit will be excluded from the study. They will still continue with their appointment, but not through the study. Patients
excluded for this reason will be recorded in RedCap by SC.
Sample failure and test completion status will be recorded in RedCap by SC. Failure to complete testing will not exclude patient
from the study itself.
Post-Appointment Survey and Study Incentive. SC will send post-appointment survey within 24 hours of GC appointment. A
Spanish version of the survey will be sent to Spanish-speaking patients.
The post-appointment survey will consist of the Multi-dimensional Model of Informed Choice (MMIC) assessment, the Genetics
Outcome Scale (GOS) and the Genetic Counseling Satisfaction Scale (GCSS).
SC will monitor survey completion status. Those with incomplete post-appointment surveys will receive reminder two business
days post-appointment and will be offered option to complete the survey via telephone with SC.
If patient is not reached, SC will attempt to contact patient the following day (three business days post-appointment).
Those with incomplete surveys one week after the genetic counseling appointment will be excluded from study. This data will be
recorded in RedCap.
Those who complete study surveys will be sent a $15 gift card electronically.
Location/Setting. For IPGC, patients will be seen within PHHS/JPS clinics. Spanish translation services are provided through
PHHS and JPS for patients in their institutions. TGC patients will not be required to be in a certain environment, but we anticipate
they will be in their homes or workplace in a secure, private location. GCs will either be in a HIPPA compliant setting offsite or
within a UTSW workspace for TGC visits.
Data Analysis. Our primary study outcomes are to compare change in knowledge pre and post visit (through MMIC knowledge
questions), patient satisfaction with GC visit after completion (GCSS) and genetic counseling visit completion rate between IPGC
and TGC. Secondary objectives include comparison of empowerment score (GCOS), informed choice (MMIC scale), genetic
testing completion, and cancelation/failure rates between the arms.
To evaluate intervention effects, we will conduct univariable and multivariable analysis for comparisons of each outcome of
interest between intervention (TGC) and control group (IPGC). For the survey data, we will examine the data from each survey
as well as total score or overall index of multiple questionnaires and compare them between the two study arms. We will perform
linear regression models for continuous outcomes (e.g., total score of questionnaires) and logistic regression models for binary
outcomes that are based on binary response (e.g., visit completion rates, test cancelation/failure and test completion rates). To
compare binary outcomes between arms (such as visit completion rate), we will test by comparing rates of each arm via Chi-
squared analysis and control for potential confounders. Potential covariates under consideration (e.g., age, race, sex, language,
etc.) will be assessed as necessary and adjusted in multivariable models accordingly. We will evaluate whether there is any
evidence of multi-collinearity issues among these variables to be adjusted in the model. Possible effect modifiers of intervention
effects will be also evaluated by testing interactions (e.g., sex) and addressed to develop the final multivariable models, as well
as reporting the intervention effect stratified as an effect modifier. Underlying assumptions of aforementioned regression models
including linearity of associations will be also evaluated. We will examine dropouts or missing data to be able to identify accurate
missing data mechanisms and select the best statistical approach. All analyses will be performed using SAS 9.4 (SAS Institute
Inc, Cary, NC) at a statistical significance level of p=.05.
We anticipate a post-enrollment dropout (failure to complete the surveys) rate of 30% given our work with the underserved
population.55 We plan to enroll 280 patients at a 1:1 ratio per arm (100 individuals enrolled per arm), expecting 200 to complete
measured responses. We will monitor the dropout rate after the initial 50 individual responses are completed and adjust accrual
for study-specific dropout until we have 200 participants’ complete measured responses. With 200 patients we will enroll, we can
detect mean differences of 0.398 standard deviation (SD) between two study arms with 80% power at a significance level of 0.05
(Table 1). For example, assuming SD of 2 for the GCSS, we will be able to detect a minimum difference of 0.8 (=0.398*2)
between two study arms with 100 participants enrolled per arm. For GCOS, assuming SD of 46.58, we will be able to detect a
minimum difference of 18.54 between pre- and post-visit scores. For visit completion as the primary binary outcome variable, we
will be able to detect a minimum difference of 18.6% assuming 63% in the control group, e.g., 81.6% (intervention) vs. 63%
(control) with 80% power at significance level of 0.05. Of note, previously published outcomes and unpublished internal data will
serve as a baseline for the study population.56

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Table 1. Summary of instrumentation with objectives, measures and distribution plan. Summary of data analysis plan per
primary and secondary objectives. Minimum detectable difference between two study arms with 80% power at 2-sided
significant level of 0.05 (n=100 per arm)
Aims
Objective
Type
Instrumentation
Outcome
Measure
Distribution
Minimum Detectable Effect Size
at 80% power
Aim 1: Patient
Satisfaction
Primary
GCSS
Whole scale
score
Post
+/-0.8 points, assuming SD = 21
Aim 1:
Knowledge
Primary
MMIC (8
knowledge
questions)
Measure score
difference from
pre/post
Pre and Post
+/-2 points, assuming SD = 5.03
Aim 1: Informed
Decision Making
Second
MMIC (entire
measure)
Measure score
difference from
pre/post
Pre and Post
n/a
Aim 1: GC-
specific
empowerment
Second
GOS
Measure score
difference
pre/post
Pre and Post
+/-18.54 points, assuming SD =
46.5850
Aim 2: GC visit
completion
Primary
Database query
Proportion of
visits scheduled
and completed
n/a
18.6%, assuming 63% in control
group57
Aim 2: Genetic
test completion
Second
Database query
Proportion of
genetic tests
completed w/n
60d of visit
n/a
19.4%, assuming 77.4% in control
group57
Aim 2: Genetic
test
cancelation/failure
Second
Database query
Proportion of
genetic tests
initiated
compared to
tests
canceled/failure
n/a
15%, assuming 9% in control
group57

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4.b. List of the study intervention(s) being tested or evaluated under this protocol
N/A - this study does not test or evaluate an intervention.
Skip to item 4.d.
#
Study intervention(s) being tested or evaluated under the protocol
Add or delete rows as needed
Affiliate
Place a check next to
institution(s) where the
intervention will be
performed
Local Standard
Practice?
Indicate whether the
intervention is
considered
acceptable practice
locally for applicable
institutions
1
Insert study intervention 1 here
☐UTSW
☐Yes
☐PHHS
☐Yes
☐CMC
☐Yes
☐THR
☐Yes
☐TSRH
☐Yes
☐Other:
☐Yes
2
Insert study intervention 2 here
☐UTSW
☐Yes
☐PHHS
☐Yes
☐CMC
☐Yes
☐THR
☐Yes
☐TSRH
☐Yes
☐Other:
☐Yes
4.c.  Risk:Benefit Analysis of study interventions being tested or evaluated under this protocol
For each study intervention identified in section 6b above, complete a risk:benefit analysis table.
(Two tables are provided, copy & paste additional tables as needed or delete both tables if this study does not test an
intervention)

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4.c.
Study Intervention #1
Insert name used in 4.b.
List each group exposed to this
intervention on a separate line.
(e.g., experimental, control, Arm A, Arm B,
etc)
Or state All Groups/Subjects
For each group, list the benefits of this intervention. (Benefits can be directly from
the intervention or from a monitoring procedure likely to contribute to the subject’s
well being).  If there are no benefits, state “none”.
If you are requesting a Waiver of Informed Consent, complete the table below.
If you have a consent form, list the reasonably foreseeable risks in the consent form (and do not complete this section).
List the risks according to the probability (likely, less likely or rare) and magnitude (serious or not serious).
(include: 1) expected adverse events; 2) rare and serious adverse events; 3) all other psychological, social, legal harms)
Do not delete frequency. Frequency must be estimated because it will assist you with determining which adverse events will require
prompt reporting.
Not serious
Serious
Likely
These risks are expected to occur in
more than 20 out of 100 subjects.


Not serious
Serious
Less likely
These risks are expected to occur in 5-
20 subjects or less out of 100 subjects.


Serious
Rare
These risks are expected to occur in
less than 5 subjects out of 100


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4.c.
Study Intervention #1
Insert name used in 4.b.
List each group exposed to this
intervention on a separate line.
(e.g., experimental, control, Arm A, Arm B,
etc)
Or state All Groups/Subjects
For each group, list the benefits of this intervention.  (Benefits can be directly from
the intervention or from a monitoring procedure likely to contribute to the subject’s
well being).  If there are no benefits, state “none”.
If you are requesting a Waiver of Informed Consent, complete the table below.
If you have a consent form, list the reasonably foreseeable risks in the consent form (and do not complete this section).
List the risks according to the probability (likely, less likely or rare) and magnitude (serious or not serious).
(include: 1) expected adverse events; 2) rare and serious adverse events; 3) all other psychological, social, legal harms)
Do not delete frequency. Frequency must be estimated because it will assist you with determining which adverse events will require
prompt reporting.
Not serious
Serious
Likely
These risks are expected to occur in
more than 20 out of 100 subjects.


Not serious
Serious
Less likely
These risks are expected to occur in 5-
20 subjects or less out of 100 subjects.


Serious
Rare
These risks are expected to occur in
less than 5 subjects out of 100


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4.d. List ALL other research procedures or components not listed in table 4.b.
The combination of Tables 4b and 4d should account for all of the research
procedures that will take place during this study.
Consider grouping similar procedures under a single component (e.g., blood work, CT = safety
assessments)
#
Research component

individual
procedures
example:
Eligibility Assessments

History and
physical

Questionnaire

Laboratory tests
Add or delete rows as needed
Column A
Local Standard
Practice Indicate the
number of times each
procedure will be
performed as stipulated
in the research plan that
would be performed if
the participant were not
participating in the
study.
Column B
Research Only
Indicate the number of times
each procedure will be
performed solely for research
purposes (meaning that the
participant would not undergo
the same number of
procedures or would not
undergo the procedure(s) at
the same frequency if they
were not participating in the
study)
Column D
Risks
If you are requesting a Waiver of Informed
Consent, complete the table below.
List the reasonably expected risks for each procedure
or group of procedures under the following categories
as appropriate:
Serious and likely;
Serious and less likely;
Serious and rare;
Not serious and likely;
Not serious and less likely
1
Eligibility Assessments
Review inclusion/exclusion
criteria
1
Not serious and less likely
2
Questionnaires
Pre-visit: MMIC/GOS
1
Not serious and less likely
Post-visit: MMIC/GOS/GCSS
1
Not serious and less likely
3
Video education viewing
Educational video sent to
telephone GC patients for
viewing prior/during visit
1
Not serious and less likely
Educational video for in-
person GC patients viewed in
session
1
Not serious and less likely
4

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5.  Safety Precautions. (Describe safeguards to address the serious risks listed above.)
a. Describe the procedures for protecting against or minimizing any potential risks for each of the more than minimal risk
research procedures listed above.
n/a
b. Where appropriate, discuss provisions for ensuring necessary medical or professional intervention in the event of adverse
events, or unanticipated problems involving subjects.
In the event of a research-related injury or if you experience an adverse reaction, we advise in the consent for to immediately
contact the study coordinator. We advise the participant to see the section “Contact Information” for phone numbers and
additional information in the consent form. Risks related to this study are not above standard clinical care.
c. Will the safeguards be different between/among groups?
Yes
No
n/a