Pilot RCT of Remote Mental Health and Substance Use Screening, Brief Intervention and Referral to Treatment (SBIRT), Compared to In-Person SBIRT for Peripartum Women
Phase: NA
Conditions: Pregnancy, Substance Use, Depression, Anxiety
Sponsor: Medical University of South Carolina

Version #11 07/29/2024 
 
Study Title: Pilot RCT of Remote Mental Health and Substance Use Screening, Brief Intervention and Referral 
to Treatment (SBIRT), Compared to In-Person SBIRT for Peripartum Women. 
Principal Investigator: Constance Guille, MD, MSCR 
 
1.0 Objectives / Specific Aims 
 
Specific Aim 1 
 
The goal of Specific Aim 1 is to develop an effective remote mental health and substance use Screening, Brief 
Intervention and Referral to Treatment (SBIRT) program for pregnant and postpartum women. The objectives 
of this current application for Specific Aim 1 are to conduct a pilot RCT of a text-message based SBIRT and 
home-based telemedicine services for pregnant and postpartum women – called Listening to Women (LTW), 
compared to treatment as usual (TAU) with the primary objective to provide effect size estimates for a larger 
RCT. 
 
Specific Aim 1: Conduct a pilot, small-scale randomized controlled trial to examine feasibility and preliminary 
efficacy of LTW, compared to TAU. Outcomes related to feasibility include percentage of eligible patients 
recruited, study attrition, study retention, and mental health and substance use treatment appointment 
attendance. Outcomes related to preliminary efficacy will include participation in screening, referral and 
treatment at baseline, compared to TAU. 
 
The central hypotheses for Specific Aim 1 are that the study is feasible and women assigned to LTW will be 
more likely to screen positive and successfully obtain treatment in less time, compared to those that are 
assigned to TAU. 
 
Specific Aim 2 
Upon completion of Specific Aim 1, the goal of Specific Aim 2 is to evaluate the effectiveness of a remote mental 
health and substance use Screening, Brief Intervention and Referral to Treatment (SBIRT) program for pregnant 
and postpartum women. The objectives of this current application for Specific Aim 2 are to conduct an RCT of 
a text-message based SBIRT and home-based telemedicine services for pregnant and postpartum women – 
called Listening to Women (LTW), compared to treatment as usual (TAU) with the primary objective to include 
attendance to treatment at baseline, compared to TAU. 
 
Specific Aim 2: Conduct a randomized controlled trial to examine the effectiveness of LTW, compared to TAU. 
Outcomes related to effectiveness include attendance to treatment at baseline, compared to TAU. 
 
The central hypotheses are that a greater proportion of women assigned to LTW will attend treatment following 
a referral, compared to TAU. 
 
Specific Aim 3 
 
The goal of Specific Aim 3 is to gather data related to maternal and newborn diagnosis codes, health care 
utilization, and costs for our study participants with Medicaid. 
 
Specific Aim 3: We will compare Medicaid data among those assigned to LTW vs. TAU. 

Version #11 07/29/2024 
 
 
The central hypothesis is that those assigned to LTW will have lower health care utilization and costs during 
the postpartum year, compared to TAU. 
 
 
2.0 
Background 
During pregnancy and the year postpartum (perinatal period), mental health problems are common such as 
mood, anxiety and substance use disorders. Perinatal mood and anxiety disorders are the most common 
complication of pregnancy and childbirth affecting at least 1 in 7 perinatal women [1]. Perinatal substance use is 
also common, and the prevalence is increasing. Perinatal opioid use disorder alone has increased 4-fold over 
the past decade [2]. Perinatal mental health and substance use are associated with significant maternal, 
obstetric, infant and child morbidity [3-9], and mortality [10-14]. 
Given the prevalence and impact of perinatal mood, anxiety and substance use disorders, and evidence 
demonstrating mitigation of its effects on maternal and child health through psychotherapy and 
psychopharmacotherapy [16,17], a multitude of professional societies recommend universal screening of 
pregnant and/or postpartum women using validated screening tools and provision of adequate mental health 
treatment and/or treatment referrals [18-22]. Unfortunately, however, the vast majority of women with mood, 
anxiety or substance use problems will remain under-diagnosed and under-treated [23-24]. Less than 50% of 
peripartum women with a mental illness, and less than 20% of women with a substance use problem are 
identified in clinical settings [6]. Among these women, less than 15% receive treatment, fewer than 10% receive 
adequate treatment and less than 5% achieve remission [4]. 
While mental health screening is widely accepted by perinatal women and Ob/Gyn providers [25,26], further 
work is needed to facilitate implementation of screenings in Ob/Gyn practices that translate to treatment 
participation. However, key provider and systems-level barriers to treatment exist and include: 1) lack of 
screening in obstetric settings and lack of provider training in technical aspects of mental health and substance 
use disorder care [26-28] and relevant communication skills [29]; 2) absence of standardized processes and 
procedures for integrated obstetric and mental health and substance use disorder treatment [29,30]; 3) lack of 
mental health providers willing to treat pregnant women [30]; 4) lack of referral networks [29-33]; and, 5) 
inadequate capacity and resources to ensure mental health evaluation, treatment, follow-up, and care 
coordination [29- 35]. 
To address these barriers we designed, implemented and piloted LTW in routine perinatal care in one obstetric 
practice (see 3.0 Intervention to be Studied) as part of a quality improvement project. Our pilot demonstrates 
high rates of participation with 87.78% (273/311) of women approached agreeing to take part in LTW and 
completing the text-message screening. Preliminary data comparing LTW (N=273) to a historical dataset 
extracted from the EHR including peripartum women receiving in-person SBIRT in the same clinic (N=2,988) 
found a significantly greater proportion of women enrolled in LTW screened positive (81.15% vs. 33.33%; 
X2=169.50, p<0.0001), were referred for treatment (76.12% vs. 57.63%; X2=18.03, p<0.0001), and received 
treatment (94.91% vs. 16.04%; X2=245.41, p<0.0001), compared to women receiving in-person SBIRT. 
 
While these preliminary data are exciting, a randomized control trial will be necessary to determine the feasibility 
and efficacy of LTW. The goal of Specific Aim 1 is to examine the feasibility and preliminary efficacy of the 
proposed RCT methodology. Specific Aim 1 will inform Specific Aim 2 to then conduct a larger-scale RCT that 
examines LTW, compared to a control condition. This will allow us to identify and address barriers in recruitment, 
retention, use of LTW, and other procedures essential to successful conduct of the RCT. This approach is 
consistent with expert recommendations to use pilot mechanisms to test the feasibility of doing a full-scale RCT, 
use data yielded by the pilot study to “de-bug” the methodology, and to assess optimal strategies to executing 
the RCT [51- R34]. 
 
3.0 
Intervention to be studied 
LTW is a mobile phone-based program designed to enhance delivery of Screening, Brief Intervention, and 
Referral to Treatment (SBIRT), an evidence-based approach for mental health and substance use screening 

Version #11 07/29/2024 
 
and treatment for perinatal women [36-38]. This program was created as a result of key informant interviews with 
obstetric providers and pregnant and postpartum women with opioid use disorders. Feedback from these groups 
informed the development of LTW. 
 
The program utilizes mobile phone text message-based screenings with immediate automated feedback, 
paired with remote care coordination and, if appropriate, home-based telemedicine mental health and 
substance use disorder treatment services. Women coming into routine prenatal care (see Recruitment) are 
eligible to take part in the study. Those agreeing to take part are sent a text message with routine mental 
health and substance use screening questions (see LTW protocol for screening questions) currently employed 
as part of standard of care. These screening questions are the SBIRT which is a survey with 9 questions 
related to depression, anxiety, substance abuse (alcohol, cigarettes, other drugs including prescription 
medication), and domestic violence (see LTW protocol). However, LTW uses text-message based screening 
with phone based assessment and referral to treatment, and TAU is an in-person screening and referral to 
treatment assessment. The same screening tools are used to assess substance abuse and mental health 
problems in LTW and TAU. Once they complete these screenings via text message, they are provided 
immediate feedback about their scores, and recommendations (see LTW protocol for automated messages). 
Contact information for the study’s care coordinator is also provided along with her availability i.e., Monday – 
Friday 8am-5pm. In addition, while specific questions about suicidal ideation are not asked via the text 
message screening, all participants receive a text message: “If you are ever experiencing a mental health 
emergency, such as a desire to harm yourself or others, please go to your nearest emergency room. If you are 
feeling suicidal you can call the National Suicide Prevention Lifeline 1-800-273-8255 anytime” (see LTW 
protocol for automated messages). 
Information about the screening is stored in a REDCap database. A care coordinator is reviewing this 
information Monday through Friday 8am-5pm and texts or calls any patient that screens positive for mental 
health or substance use that requires further assessment as would be done in-person during routine clinical 
care (see LTW protocol describing branching logic from screens and clinical risk categories). The care 
coordinator contacts the patient and further assesses their mental health and substance use symptoms and 
needs for resources and/or treatment. If the participant would benefit from further mental health and/or 
substance use evaluation and treatment, the care coordinator schedules the patient for a home-based 
telemedicine visit. The care coordinator communicates all screening information in the Electronic Health 
Record (EHR) for all providers to review, and if applicable includes information about the scheduled 
appointment or resources provided. 
4.0 
Study Endpoints 
Specific Aim 1: 
 
Primary pilot efficacy outcome variables include: 
Completion of SBIRT: We will compare the proportion of participants that complete a screen for mental 
health and substance use, the proportion of those screening positive that are referred to treatment, and the 
proportion of those referred to treatment that had at least one mental health and/or substance use disorder 
treatment appointment among those assigned to LTW, compared to TAU. 
Time to Treatment: We will measure the time from completion of screening positive to time of first 
mental health or substance use treatment appointment (if a referral to treatment was appropriate) among those 
assigned to LTW, compared to TAU. 
Reduction in Mental Health Symptoms: Among women referred for treatment, we will compare the 
mean change in the Edinburgh Postnatal Depression Scale (EPDS) among those assigned to LTW, compared 
to TAU. Of note, the suicidal ideation question (item #10) will be omitted from this questionnaire. 
Reduction in Substance Use: Among women referred for treatment, we will compare change in 
substance use frequency and amount as measured by the NIDA-Modified Assist (see LTW protocol) among 
those assigned to LTW, compared to TAU. 
Improved Maternal Functioning: Among women referred for treatment, we will compare the change in 
maternal functioning measured by the Medical Outcomes Study Short Form 36 (SF-36v2) among those 
assigned to LTW, compared to TAU. 

Version #11 07/29/2024 
 
 
Secondary pilot feasibility and acceptability outcome variables include: 
Recruitment: We will determine the proportion of patients who agree to participate as compared to the 
total number solicited to enroll for each recruitment approach. 
Attrition: We will examine the proportion of study participants that prematurely terminate i.e., do not 
complete screenings, or are unable to be contacted for referral and/or treatment. 
Study retention: We will determine the proportion of study participants that complete all assessment 
points associated with the protocol. 
Treatment Attendance: We will collect data from the EHR to determine the proportion of participants 
that attended a mental health or substance use treatment appointment. 
Improved Health-Related Social Needs: Among women referred for treatment, we will compare the 
change in health-related social needs measured by the Accountable Health Communities (AHC) Health- 
Related Social Needs (HRSN) Screening Tool among those assigned to LTW, compared to TAU. 
Voice Biomarkers: Voice analysis will be completed using an online platform SurveyLex (owned by 
NeuroLex, Inc.). Among women referred for treatment, we will analyze voice recordings for characteristics 
(acoustic, linguistic, or meta feature) which may be compared between those assigned to LTW and those 
assigned to TAU, and compared to other measures collected in either LTW or TAU including EPDS, NIDA 
Modified Assist, and/or AHC HRSN. 
 
Specific Aim 2: 
Primary Outcome: 
 
Attendance to Treatment: treatment attendance (defined as attending at least 1 or more visits with a 
mental health and/or substance use disorder (SUD) treatment provider during pregnancy and the postpartum 
year) 
Secondary Outcomes 
Reduction in Mental Health Symptoms: Among women referred for treatment, we will compare the 
mean change in the Edinburgh Postnatal Depression Scale (EPDS), GAD-7 Anxiety and CSSRS among those 
assigned to LTW, compared to TAU. Of note, the suicidal ideation question (item #10) will be omitted from the 
EPDS questionnaire. 
Reduction in Substance Use: Among women referred for treatment, we will compare change in 
substance use frequency and amount as measured by the NIDA-Modified Assist (see LTW protocol) and TLFB 
among those assigned to LTW, compared to TAU. 
Improved Maternal Functioning: Among women referred for treatment, we will compare the change in 
maternal functioning measured by the Medical Outcomes Study Short Form 36 (SF-36v2) among those 
assigned to LTW, compared to TAU. 
Improved Health-Related Social Needs: Among women referred for treatment, we will compare the 
change in health-related social needs measured by the Accountable Health Communities (AHC) Health- 
Related Social Needs (HRSN) Screening Tool among those assigned to LTW, compared to TAU. 
For the outcome variables for specific aims 1 and 2 we will collect data from the EHR including SBIRT data, if 
the participant was referred to treatment, where they were referred to treatment, if they attended a mental 
health or substance use treatment appointment and where they attended the appointment, how many 
appointments they attended, and the numbers of days from date of SBIRT completion to date of mental health 
or substance use treatment appointment. 
 
Specific Aim 3: 
The data that will be collected on study participants with Medicaid include: 
Number and costs of prenatal care visits 
Number and costs of postpartum care visits 
Number and costs of hospitalizations during pregnancy and the postpartum year 

Version #11 07/29/2024 
 
Number and costs of ED visits during pregnancy and the postpartum year 
Number and costs of newborn care visits (outpatient, inpatient and ED) in the first year of life 
Maternal diagnosis codes for prenatal care visits, postpartum care visits, hospitalizations and ED visits 
Newborn diagnosis codes for outpatient, inpatient and ED visits 
 
 
 
5.0 
Inclusion and Exclusion Criteria/ Study Population 
Inclusion criteria include: 1) age 18-41; 2) currently pregnant or postpartum; 3) if pregnant, receiving prenatal 
care; 4) English fluency; 5) owner of a cell phone with SMS text-message based capability; 6) access to WIFI 
and a device to allow audio and video teleconferencing; 7) able to provide informed consent. Exclusion criteria: 
None 
 
6.0 
Number of Subjects 
A total of 450 participants will be randomized in Specific Aim 1 (n=100) and Specific Aim 2 (n=350). To 
randomize 450 participants we will need to approach about 1,500 participants in order to get to 450 total 
participants. 
 
7.0 
Setting 
Recruitment will occur remotely, in person and via the EHR. Potential participants will be pregnant women 
receiving prenatal care and postpartum women. 
 
8.0 
Recruitment Methods 
Recruitment will occur remotely, in person and via the EHR. A Research Data Request will be submitted to 
obtain a recruitment report of MUSC patients who potentially meet eligibility criteria. The recruitment report will 
include a search for pregnant and postpartum women. The report will include mrn, age, race, ethnicity, date of 
prenatal care visit, date of postpartum visit, delivery date, ob/gyn provider name, MyChart account (Yes/No), 
cell phone number, email address and current ICD-9 or 10 diagnoses. The purpose of the ICD codes will be to 
ensure we are approaching enough women with substance use disorders, and/or a mood or anxiety disorder 
diagnoses, and therefore likely to screen positive on either an in-person or text-message SBIRT screening. In 
addition, ICD codes will be used for urn stratification at randomization. Any patients who have not opted out of 
being contacted for research will be contacted by phone call or text message and invited to participate. If a cell 
phone number is not available, the message with a link to a RedCap eligibility survey will be sent via email or 
MyChart message. The study team will not cold-contact any patients who have chosen to opt-out of receiving 
contact about research or who have met the maximum number of contact attempts at the time of recruitment. 
Our PI’s clinic policy is to ask all patients if they would like to be contacted for research opportunities and if 
they prefer to be contacted by phone or text message. The vast majority of women prefer to be contacted 
through a text message. Therefore, we believe cold-contacting patients via text is acceptable for this study. 
All other patients will be contacted through their providers to be informed of the study if the provider feels it is 
appropriate. If the potential participant’s provider has agreed to have the study team contact their patient, a 
phone call or text message will be sent to the potential participant inviting them to take part in the study. If a 
cell phone number is not available, the message with a link to a RedCap eligibility survey will be sent via email. 
If the potential participant does not respond to the phone call, text or email, the study team may also notify 
potential participants that a message was sent to them via MyChart. The text message (or email/MyChart 
message) will include a link to a brief RedCap eligibility survey. For those meeting the eligibility screening 
criteria, the RA/RC will schedule a time to verify eligibility criteria and review the informed consent either 
remotely or in-person. 
Another method of recruitment will include Women’s Health Services clinics, where after women are identified 
as pregnant or postpartum by the patient’s nurse or provider, they will be approached by the study team, with 
the provider’s permission, to take part in the study. Additionally, research staff may do a review of Women’s 
Health Services provider schedules and patient charts in EPIC to identify potentially eligible women for 
inclusion. Research staff will approach patients when they arrive for their regularly scheduled appointment. 

Version #11 07/29/2024 
 
We will also recruit from the MUSC antepartum unit and the mother-baby unit. Patients will be approached by 
the study team, with the provider’s permission, to take part in the study. Additionally, research staff may do a 
review of the antepartum and mother-baby unit schedules and patient charts in EPIC to identify potentially 
eligible women for inclusion. Research staff will approach patients while they are staying on the antepartum 
and mother-baby units. If the patient agrees to taking part in the study the RA will consent the participant and 
complete baseline procedures. 
Another way to recruit is the potentially eligible patients in the PI and Co-Is practices will be informed and 
approached about the study as the PI and Co-Is feel is appropriate. Participants will also be recruited via study 
advertisement (e.g., flyers) and online postings (e.g., social media, linkedin). 
 
9.0 Consent Process 
Signed informed consent will be obtained from study participants. The consent process will take place via one 
of the following modalities: 1) Remote or in person electronic consent (e-consent) via REDCap (if remote, e- 
consent will be facilitated with a discussion over the phone or via video), 2) Remote consent via doxy.me 
facilitated with either a discussion over the phone or video connection via doxy.me, 3) Mailed (paper) consent 
facilitated with a discussion over the phone, or 4) in person consent (e.g., in clinic). 
 
All participants will be provided with a hard copy and/or an electronic copy of the consent form. Participants will 
be informed that participation in this research is strictly voluntary. Informed consent will include a detailed 
description of the purpose and the procedures of the study emphasizing our policy regarding privacy and 
confidentiality and an opportunity for the individual to ask any questions or voice concerns. Signatures on the 
consent form may be obtained with paper and pen OR electronically via REDCap or doxy.me. Participants who 
do not have access to the required technology to complete consent remotely via REDCap or doxy.me will be 
given the option to complete consent via mail facilitated with a discussion over the phone. 
10.0 
Study Design / Methods 
 
Specific aim 1: A two arm pilot RCT (N=100) with 2:1 allocation will examine feasibility and preliminary efficacy 
of LTW, compared to TAU. Specific aim 2: A RCT (N=350) with 2:1 allocation will examine effectiveness of 
LTW, compared to TAU. As of the approval of amendment #12 the allocation will switch to 1(LTW):2(TAU) for 
specific aim 2. Recruitment will primarily occur proactively and remotely via the EHR. We will conduct a weekly 
EHR search via a recruitment report for all new pregnant and postpartum patients in the past week. The report 
will include mrn, age, race, ethnicity, date of prenatal care visit, date of postpartum visit, delivery date, ob/gyn 
provider name, MyChart account (Yes/No), cell phone number, email address and current ICD-9 or 10 
diagnoses. Any patients who have not opted out of being contacted for research will be contacted and invited 
to participate. The study team will not cold-contact any patients who have chosen to opt-out of receiving 
contact about research or who have met the maximum number of contact attempts at the time of recruitment. If 
the potential participant has not opted out of being contacted, or the potential participant’s provider has agreed 
to have the study team contact their patient, a phone call will be made or message will be sent via text, email 
or MyChart message to the potential participant inviting them to take part in the study. This invitation will 
include clear opt out procedures should the patient not wish to be contacted in the future for the purpose of this 
study. If interested, participants will complete a screening online via REDCap to determine study eligibility (see 
above for inclusion criteria). After completing preliminary determination of eligibility, if eligible and interested in 
participating in the study, participants will be scheduled for a time to complete informed consent (see 9.0 
Consent Process). 
 
Following consent, all participants will subsequently be text messaged and/or emailed a REDCap link, 
accessible via smartphone, tablet, or computer to complete study assessments. Assessments that need to be 
completed by interview will be scheduled with study staff and completed via doxy.me or telephone. For specific 
aim 1 participants only, participants will also complete voice analysis through Surveylex. Participants will be 
presented with a questionnaire consisting of one task to complete through the Surveylex online form. One task 
to be answered and entered as text, and three tasks involving voice recordings in response to prompts. The 
tasks in the online form include the following: Text question (one task): 1) What is your participant ID?; Voice 
recording (three tasks): During voice recording tasks, the participant will be reminded that there is no right or 

Version #11 07/29/2024 
 
wrong answer for these tasks and that they may choose to skip the question or stop their answer at any time 1) 
Please repeat this phrase: “The quick brown fox jumped over the lazy dogs.” (10 seconds) 2) Please describe 
yesterday from start to finish (30 seconds) and 3) Please describe what brings you happiness (30 seconds). 
Assessments will occur at baseline (following consent). Participants will be randomized to LTW or TAU, 
respectively. 
Survey assessments are estimated to take 30 minutes to complete and will be administered remotely via 
REDCap through our established procedures and via doxy.me or telephone for interview assessments. Voice 
analysis for specific aim 1 participants only takes less than 10 minutes to complete and can be completed 
remotely. Participants will be compensated via electronic gift cards which will be emailed or texted to 
participants. Participants will receive $25 for completion of the baseline assessments. To encourage 
participants to complete all 3 surveys, participants will be paid an additional $20 if they complete all 3 surveys 
(baseline). 
Assessments include 
 
Measures 
Baseline 
Consent 
X 
Randomization 
X 
Demographics 
Questionnaire 
X 
EPDS Survey 
X 
NIDA Modified Assist 
X 
Accountable Health 
Communities (AHC) 
Health-Related Social 
Needs (HRSN) 
Screening Tool 
X 
The Medical Outcomes 
Study Short Form Survey 
36 (SF-36v2) 
X 
*Voice Biomarkers 
X 
**GAD-7 Anxiety 
X 
+**Columbia Suicide 
Severity Rating Scale 
(CSSRS) 
X 
+**Timeline Follow-Back 
(TLFB) 
X 
***Usability Scale Survey 
X 
*Only the 100 participants in specific aim 1 complete voice biomarkers 
**Only participants in specific aim 2 complete the GAD-7, CSSRS and TLFB 
***Only participants assigned to LTW will complete the usability scale 
+ As of the approval of amendment 10 newly enrolled participants will not complete CSSRS and TLFB. 
Participants consented prior to the approval of amendment 10 will complete CSSRS and TLFB at baseline. 
 
Specific aim 3: We will gather healthcare utilization data on our study participants who have Medicaid 
insurance. The MUSC study team will extract the maternal Medicaid IDs from our study participants with 
Medicaid insurance from the EHR. We will share a list of these maternal Medicaid IDs with Medicaid, and they 
will return data related to maternal and newborn diagnosis codes, health care utilization and costs for these 
participants i.e., prenatal care visits, postpartum care visits, hospitalizations and ED visits during pregnancy 
and the postpartum year. The MUSC study team will send the maternal Medicaid ID’s of study participants to 
Medicaid in a password protected spreadsheet. Medicaid will send the MUSC study team a password 
protected spreadsheet of data. The spreadsheet of data Medicaid will send back to MUSC will be coded since 

Version #11 07/29/2024 
 
it will contain the Medicaid ID's of participants. 
 
The Medicaid ID is the only link to subjects in the study. The document linking Medicaid ID’s and our study 
participants will be stored on a University secure network drive or in MUSC BOX. The linking document will be 
stored separately from the study data and only trained study personnel will have access to the linking 
document. 
 
Study data will be stored on a University secure network drive or in MUSC BOX. The spreadsheet of data that 
Medicaid will send the MUSC study team will be password protected. Only trained study personnel will have 
access to the password protected data spreadsheet. 
 
The MUSC study team will have access to the Medicaid ID’s as well as Medicaid. 
 
11.0 
Data Management 
 
Data Management 
 
Regarding questionnaire data, data will be obtained for research purposes only. All data will be collected, 
stored, and managed via REDCap, which is a secure, web-based application designed exclusively to support 
data capture for research studies. REDCap provides secure, web-based flexible applications, including real 
time validation rules with automated data type and range checks at the time of entry. The underlying database 
is hosted in a secure data center at MUSC, a secure environment for data systems and servers on campus, 
and includes redundancy, failover capability, backups and extensive security checks. The system has several 
layers of protection including user/group account management, "Data Access Groups" which allow data to be 
entered by multiple groups in one database with segmented user rights for entered data, audit trails for all 
changes, queries and reports, and Secure Sockets Layer (SSL) encryption. The recruitment report project will 
be housed in RedCap and will only be accessible to the research team. The research team will only have 
access to the RedCap recruitment project while actively enrolling for the study. The recruitment report will be 
stored in a separate RedCap project from the project containing our research data. 
Name and relevant contact information will be obtained to provide compensation and every effort will be made 
to maintain subject confidentiality, in accordance with HIPAA. All data will be identified only by code numbers 
(participant IDs). Participant IDs will be linked to participants’ names in a password-protected file that is 
accessible only to the PI and trained research staff. Voice sample data gathered through SurveyLex for the 
participants in specific aim 1 only, is stored by default on NeuroLex’s HIPAA compliant Microsoft Azure servers 
managed by NeuroLex. Access to this data is limited to research staff by a single unique username and 
password. Voice features collected through Surveylex will be download and stored on an MUSC Box account, 
accessible only to study staff. 
 
For specific aim 3, the Medicaid ID is the only link to subjects in the study. The document linking Medicaid ID’s 
and our study participants will be stored on a University secure network drive or in MUSC BOX. The linking 
document will be stored separately from the study data and only trained study personnel will have access to 
the linking document. Study data will be stored on a University secure network drive or in MUSC BOX. The 
spreadsheet of data that Medicaid will send the MUSC study team will be password protected. Only trained 
study personnel will have access to the password protected data spreadsheet. The MUSC study team will 
have access to the Medicaid ID’s as well as Medicaid. 
 
 
12.0 
Provisions to Monitor the Data to Ensure the Safety of Subjects (if applicable) 
This plan is based on the recommendations in NIDA’s “Guidelines for Developing a Data and Safety 
Monitoring 
Plan” 
(https://www.drugabuse.gov/funding/clinical-research/guidelines-developing-data-safety- 
monitoring-plan). 

Version #11 07/29/2024 
 
Summary of the Protocol 
The goal of this work is to develop an effective remote mental health and substance use Screening, Brief 
Intervention and Referral to Treatment (SBIRT) program for pregnant and postpartum women. The objectives 
of this current application are 1.) to conduct a pilot RCT of a text-message based SBIRT and home-based 
telemedicine services for pregnant and postpartum women – called Listening to Women (LTW), compared to 
treatment as usual (TAU) with the primary objective to provide effect size estimates for a larger RCT and 2.) to 
conduct a larger scale RCT to examine the effectiveness of LTW, compared to TAU. 
Trial Management 
The study will be managed from the Women’s Reproductive Behavioral Health Division within the Department 
of Psychiatry and Behavioral Sciences at the Medical University of South Carolina (MUSC). Recruitment, data 
collection, data management, and treatment provision will be coordinated and centrally managed at our research 
lab at MUSC and will be implemented within local MUSC clinics. 
Data Management and Analysis 
Participants will enter data in REDCap, a secure, web-based application designed exclusively to support data 
capture for research studies. REDCap provides: 1) an intuitive interface for data entry (with data validation); 2) 
audit trails for tracking data manipulation and export procedures; 3) automated export procedures for seamless 
data downloads to common statistical packages (SPSS, SAS, Stata, R); 4) procedures for importing data from 
external sources; and 5) advanced features, such as branching logic and calculated fields. These procedures 
are effective in minimizing data entry errors (e.g., missing or errant data). The data analysis plan is outlined 
above. 
 
Quality Assurance 
Accuracy and completeness of the data collected will be ensured by weekly review. The REDCap system does 
not accept outliers, illogical response patterns, etc. The PI and research assistants will have weekly meetings to 
discuss any qualitative comments received during data collection and any problems in data collection. The PI 
will examine the database for potential irregularities monthly. Initial data analyses will examine distributions of 
variable scores and comparability of baseline characteristics across conditions in case analyses need to be 
adjusted for these. Confidentiality procedures are outlined above. 
Regulatory Issues 
All serious AEs will be reported to the MUSC Committee on Human Research within 48 hrs. Follow-up of all 
unexpected and serious AEs will also be reported. All AEs will be reviewed weekly by the PI and yearly by the 
IRB. Any significant actions taken by the local IRB, and protocol changes will be relayed to the funding agency. 
We estimate the significant AE rate to be 5% or less. Potential conflicts of interest (COI) will be reported using 
the SRNT rules for disclosure as well as the rules of MUSC’s COI committee. 
 
Trial Safety 
Process of AE/SAE collection, assessing by PI and/or medical monitor and reporting 
AEs and SAEs occurring during the course of the study will be collected, documented, and reported in 
accordance with protocol and IRB reporting requirements. All research staff involved with adverse event 
reporting will receive general and protocol specific AE/SAE training including identification, assessment and 
evaluation, and documentation and reporting training. The PI and study team will identify any potential AEs 
during the course of the study from subject self-report. This information will be provided to the PI, who will be 
responsible for AE/SAE assessment and evaluation including a determination of seriousness and study 
relatedness. 
Definition of AE and SAE 
Adverse events are defined as any untoward medical occurrence that may present itself during treatment or 
administration of an intervention, and which may or may not have a causal relationship with the treatment. 
Serious adverse events are defined as any medical occurrence that: 
1. 
Results in death, 
2. 
Is life-threatening, 

Version #11 07/29/2024 
 
3. 
Requires inpatient hospitalization or prolongation of existing hospitalization, 
4. 
Results in persistent or significant disability/incapacity, 
5. 
Is a congenital anomaly/birth defect. 
OR 
6. 
Requires intervention to prevent one of the above outcomes 
 
Documentation and Reporting 
AEs/SAEs are documented and reported as per protocol and IRB requirements. Research staff will identify 
adverse events and obtain all available information to assess severity, seriousness, study relatedness, 
expectedness, outcome and the need for change or discontinuation in the study intervention. Adverse events 
are generally documented on AE Logs and AE Case Report Forms (CRFs). Additional relevant AE information, 
if available, will be documented in a progress note in the research record as appropriate to allow monitoring and 
evaluation of the AE. If the AE meets the definition for serious, appropriate SAE protocol specific reporting forms 
are completed and disseminated to the appropriate persons and within the designated timeframes. For each 
AE/SAE recorded, the research staff will follow the AE/SAE until resolution, stabilization or until the subject is no 
longer in the study as stated in the protocol. 
When a reportable SAE is identified, the research coordinator will initiate an SAE form, and the following 
individuals will be notified by facsimile transmission within 24 hours of the site’s initial notification of the SAE: 
i. The PI will provide oversight, consultation, assessment and documentation as appropriate of the 
SAE. 
ii. The PI will notify the MUSC institutional review board (IRB) and complete the AE 
report form in conjunction with the study coordinator. The MUSC IRB meets monthly and 
communication with the IRB is through email, memos, official IRB forms, and online 
reporting. 
iii. The NIDA program officer. Any adverse event will be reported to NIDA in an individual 
adverse event report. 
iv. The data safety monitoring board members 
If complete information is not available when the initial 24-hour SAE report is disseminated, follow-up 
information will be gathered to enable a complete assessment and outcome of the event. This information may 
include hospital discharge records, autopsy reports, clinic records, etc. The research coordinator will attach 
copies of source documents to the SAE report for review by the PI and for forward to the NIH program officer as 
appropriate within 2 weeks of the initial SAE report. In addition, the PI will provide a signed, dated SAE summary 
report, which will be sent to the NIDA Medical Safety Officer within two weeks of the initial SAE report. 
We will report adverse events to the MUSC IRB online as soon as possible, but no later than 10 working 
days after the PI first learns of the event. The MUSC IRB AE reporting requirements are as follows: All deaths 
that occur during the study or 30 days post termination from the study are required to be reported as adverse 
events even if they are expected or unrelated. Other adverse events are reportable to the MUSC IRB if the AE 
is unexpected AND related or possibly related AND serious or more prevalent than expected. All three criteria 
must be met for an AE to be reported to the MUSC IRB. The IRB definition of unexpected is that the AE is not 
identified in nature, severity or frequency in the current protocol, informed consent, investigator brochure or with 
other current risk information. The definition of related is that there is a reasonable possibility that the adverse 
event may have been caused by the drug, device or intervention. Reportable AEs are reviewed by the IRB Chair 
and reported to the IRB Board at the next meeting. 
AE/SAE follow up plan 
All unexpected AE and SAEs will be monitored until resolved. A detailed summary of all AEs will be prepared 
weekly by the research coordinator. The candidate and the mentorship/consultation team will evaluate the 
progress of the study at biweekly study team meetings, including periodic assessments of data quality and 
timeliness, participant recruitment and retention, participant risk versus benefit, and other factors that can affect 
study outcome. We will also consider factors external to the study, such as scientific or therapeutic developments 
that may have an impact on the safety of participants or the ethics of the study. All AEs are reviewed annually 
by the Data Safety Monitoring Board (DSMB) and yearly by the IRB. Any significant actions taken by the local 
IRB and protocol changes will be relayed to NIDA. 

Version #11 07/29/2024 
 
Data and Safety Monitoring Plan Administration 
The PI will be responsible for monitoring the trial. The PI will examine monthly the outcomes database for missing 
data, unexpected distributions or responses, and outliers. The PI will check weekly with the research assistant 
about any AEs/SAEs. A DSM report will be filed with the IRB and funding agency on a yearly basis, unless 
greater than expected problems occur. The report will include participant characteristics, retention and 
disposition of study participants, quality assurance issues and reports of AEs, significant/unexpected AEs and 
serious AEs. We will report efficacy at the end of the trial. 
13.0 
Risks to Subjects 
 
This is considered a minimal risk study. Minimal risk means the probability and magnitude of harm or discomfort 
anticipated in the research are not greater in and of themselves other than those ordinarily encountered in daily 
life or during performance of routine physical or psychological examinations or tests. The LTW screening tool is 
the same tool that is used in clinical practice, the only difference is in its delivery. The potential risks in this study 
include those related to: a) confidentiality; b) frustration; and c) emotional distress. 
 
a) Confidentiality: Participants will be made aware of limits to confidentiality at the beginning of screening 
and when reviewing study procedures/during informed consent which include report of suicidal or 
homicidal intent or report of abuse or neglect. If the participant reports substance use during pregnancy 
or suicidal or homicidal intent or abuse/neglect, Dr. Guille will take appropriate action by completing a 
psychiatric assessment and facilitating appropriate treatment. Additional appropriate actions as outlined 
by the MUSC IRB, NIH, and the State of South Carolina, may also include contacting the department of 
social services, authorities and/or pursuing involuntary commitment at a mental health or substance use 
disorder treatment facility. If participants present no imminent danger but also need more extensive 
treatment of mental health or substance use concerns, appropriate care will be facilitated. 
b) Frustration: Participants may become frustrated while completing study assessments. Participants will 
be informed that they may refuse to answer any question(s) that they do not wish to answer and that they 
may discontinue study participation at any time. 
c) Emotional Distress: Participants will be asked questions that may be sensitive in nature. Participants 
may find the questions distressing or find the questions make them feel uncomfortable. Participants will 
be informed that they may refuse to answer any question(s) that they do not wish to answer and that they 
may discontinue study participation at any time. 
 
Since patients will all currently be receiving prenatal care or will be currently postpartum, there are no additional 
risks associated with participation in this study. 
Adequacy of Protection Against Risks 
 
Recruitment and Informed Consent 
Study participants will be recruited from local MUSC clinics. Pregnant and postpartum patients identified via the 
EMR through a recruitment report (research data request) will be sent a message inviting them to participate in 
a research study. Interested patients will complete determination of eligibility via MUSC’s REDCap system, a 
secure, HIPAA-compliant data management system. All participants will review consent documents and will 
provide informed consent consistent with procedures outlined above. Participants will be given the opportunity 
to ask questions about their participation throughout the course of the study. A copy of the informed consent will 
be kept centrally at our study office within locked filing cabinets, and a copy will be given to each study participant 
as well. Participants will be given a study phone number and e-mail address to contact for questions. 
 
Protections Against Loss of Confidentiality 
All screening information will be kept in a password protected REDCap database. Only key study personnel will 
have access to the database. If an individual is not eligible to participate based on her answers to the eligibility 
survey, her screener will not include her name or contact information. Only people who meet eligibility criteria 
based on the answers to the eligibility survey will be asked if they would like to be contacted about participation 
in the study and for their name and contact information. Eligible participants’ full name, telephone number and 

Version #11 07/29/2024 
 
e-mail address will be recorded in the study enrollment log located on a secure MUSC drive or in MUSC Box. 
The REDCap database and the study enrollment log are the only places where participants’ names and subject 
identification numbers appear together. Eligible participants will be assigned a subject number, will complete 
informed consent, will be randomized, will complete baseline assessments, and subsequently will receive their 
randomized intervention. 
 
Upon completing eligibility screening, if study eligible, individuals will be provided with an overview of the study, 
asked to review study procedures via a consent form, and asked to provide signed consent. Participants will be 
informed of limitations of confidentiality (i.e., abuse or neglect, intention to harm self or someone else) both 
verbally and/or in writing during the informed consent process. The consent form will include the participant’s 
name, but not his/her subject number. Consent forms will be provided in English. 
Regarding questionnaire data, data will be obtained for research purposes only. All data will be collected, stored, 
and managed via REDCap, which is a secure, web-based application designed exclusively to support data 
capture for research studies. REDCap provides secure, web-based flexible applications, including real time 
validation rules with automated data type and range checks at the time of entry. The underlying database is 
hosted in a secure data center at MUSC, a secure environment for data systems and servers on campus, and 
includes redundancy, failover capability, backups and extensive security checks. The system has several layers 
of protection including user/group account management, "Data Access Groups" which allow data to be entered 
by multiple groups in one database with segmented user rights for entered data, audit trails for all changes, 
queries and reports, and Secure Sockets Layer (SSL) encryption. Name and relevant contact information will be 
obtained to provide compensation and every effort will be made to maintain subject confidentiality, in accordance 
with HIPAA. All data will be identified only by code numbers (participant IDs). Participant IDs will be linked to 
participants’ names in a password-protected file that is accessible only to the PI and trained research staff. Voice 
sample data gathered through Surveylex for specific aim 1 participants only, will be stored on HIPAA compliant 
Microsoft Azure servers managed by NeuroLex. MUSC has a BAA in place with Neurolex. MUSC currently pays 
NeuroLex $100/month for access to their software. MUSC may collect 5000 surveys per month. The data will 
consist of data tables containing the coded participant ID, date of the recording, voice features, and separates 
raw voice recording files. Data tables of voice features extracted from the recordings will have only the subject’s 
coded participant ID, and no other identifying information. Access to the SurveyLex account will be limited to 
research study staff. Staff at NeuroLex will not access this data. 
Voice features collected through SurveyLex will be downloaded and stored on an MUSC Box account, accessible 
only to study staff. 
 
14.0 
Potential Benefits to Subjects or Others 
There is no direct benefit for subjects from participating in the study. 
 
15.0 
Sharing of Results with Subjects 
 
Study enrollment and study outcomes will not be shared with medical staff, including the participant’s 
physician. 
 
References 
 
1. Luca DL, Margiotta C, Staatz C, Garlow E, Christensen A, Zivin K. Financial Toll of Untreated Perinatal 
Mood and Anxiety Disorders Among 2017 Births in the United States. Am J Public Health. 2020;110(6):888- 
896. 
2. Haight SC, Ko JY, Tong VT, Bohm MK, Callaghan WM. Opioid Use Disorder Documented at Delivery 
Hospitalization - United States, 1999-2014. MMWR Morb Mortal Wkly Rep. 2018;67(31):845-849. Published 
2018 Aug 10. 

Version #11 07/29/2024 
 
3. Weissman MM. Postpartum Depression and Its Long-term Impact on Children: Many New Questions. JAMA 
Psychiatry. 2018;75(3):227-228. 
4. Gentile S. Untreated depression during pregnancy: Short- and long-term effects in offspring. A systematic 
review. Neuroscience. 2017;342:154-166. 
 
5. Grote NK, Bridge JA, Gavin AR, Melville JL, Iyengar S, Katon WJ. A meta-analysis of depression during 
pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch Gen 
Psychiatry. 2010;67(10):1012-1024. 
6. Vesga-López O, Blanco C, Keyes K, Olfson M, Grant BF, Hasin DS. Psychiatric disorders in pregnant and 
postpartum women in the United States. Arch Gen Psychiatry. 2008;65(7):805-815. 
 
7. Britton HL, Gronwaldt V, Britton JR. Maternal postpartum behaviors and mother-infant relationship during 
the first year of life. J Pediatr. 2001;138(6):905-909. 
 
8. Deave T, Heron J, Evans J, Emond A. The impact of maternal depression in pregnancy on early child 
development. BJOG. 2008;115(8):1043-1051. 
 
9. Paulson JF, Keefe HA, Leiferman JA. Early parental depression and child language development. J Child 
Psychol Psychiatry. 2009;50(3):254-262. 
10. Goldman-Mellor S, Margerison CE. Maternal drug-related death and suicide are leading causes of 
postpartum death in California. Am J Obstet Gynecol. 2019;221(5):489.e1-489.e9. 
11. Mangla K, Hoffman MC, Trumpff C, O'Grady S, Monk C. Maternal self-harm deaths: An unrecognized and 
preventable outcome. Am J Obstet Gynecol. 2019; 221(4):295-303. 
 
12. Mehta PK, Bachhuber MA, Hoffman R, Srinivas SK. Deaths from unintentional injury, homicide, and suicide 
during or within 1 year of pregnancy in Philadelphia. Am J Public Health. 2016; 106(12):2208-2210. Accessed 
11 June 2020. 
13. Metz TD, Rovner P, Hoffman MC, Allshouse AA, Beckwith KM, Binswanger IA. Maternal deaths from 
suicide and overdose in Colorado, 2004-2012. Obstet Gynecol. 2016; 128(6):1233-1240. Accessed 11 June 
2020 
 
14. Wallace ME, Hoyert D, Williams C, Mendola P. Pregnancy-associated homicide and suicide in 37 US 
states with enhanced pregnancy surveillance. Am J Obstet Gynecol. 2016; 215(3): 364.e1-364.e10. 
15. Weissman MM, Pilowsky DJ, Wickramaratne PJ, et al. Remissions in maternal depression and child 
psychopathology: a STAR*D-child report [published correction appears in JAMA. 2006 Sep 13;296(10):1234]. 
JAMA. 2006;295(12):1389-1398. 
 
16. Beeber LS, Holditch-Davis D, Perreira K, Schwartz TA, Lewis V, Blanchard H, et al. Short-term in-home 
intervention reduces depressive symptoms in early head start Latina mothers of infants and toddlers. Res Nurs 
Health. 2010;33(1):60–76. 
17. American College of Obstetricians and Gynecologists The American College of Obstetricians and 
Gynecologists Committee Opinion no. 630. Screening for perinatal depression. Obstetrics and gynecology. 
2015;125(5):1268–1271. 
 
18. Kendig S, Keats JP, Hoffman MC, et al. Consensus Bundle on Maternal Mental Health: Perinatal 
Depression and Anxiety [published correction appears in Obstet Gynecol. 2019 Jun;133(6):1287]. Obstet 
Gynecol. 2017;129(3):422-430. 

Version #11 07/29/2024 
 
 
19. O’Connor E, Rossom RC, Henniger M, Groom HC, Burda BU. Primary care screening for and treatment of 
depression in pregnant and postpartum women: evidence report and systematic review for the US Preventive 
Services Task Force. JAMA 2016; 315:388–406. 
20. A Report from the California Task Force on the Status of Maternal Mental Health Care. April 2017; 1-66. 
 
21. Report of the Task Force to Study Maternal Mental Health, Maryland Senate Bill 74/Chapter 6 (2015). 
December 2016; 1-78. 
22. Smith MV, Shao L, Howell H, Wang H, Poschman K, Yonkers KA. Success of mental health referral among 
pregnant and postpartum women with psychiatric distress. Gen Hosp Psychiatry. 2009;31(2):155–162. 
 
23. Byatt N, Levin LL, Ziedonis D, Moore Simas TA, Allison J. Enhancing participation in depression Care in 
Outpatient Perinatal Care Settings: a systematic review. Obstet Gynecol. 2015;126(5):1048–1058. 
 
24. Bauman BL, Ko JY, Cox S, et al. Vital Signs: Postpartum Depressive Symptoms and Provider Discussions 
About Perinatal Depression - United States, 2018. MMWR Morb Mortal Wkly Rep. 2020;69(19):575-581. 
Published 2020 May 15. 
25. LaRocco-Cockburn A, Melville J, Bell M, Katon W. Depression screening attitudes and practices among 
obstetrician-gynecologists. Obstet Gynecol. 2003;101(5 Pt 1):892-898. 
 
26. Byatt N, Simas TA, Lundquist RS, Johnson JV, Ziedonis DM. Strategies for improving perinatal depression 
treatment in north American outpatient obstetric settings. J Psychosom Obstet Gynaecol. 2012;33(4):143–161. 
27. Byatt N, Biebel K, Friedman L, Debordes-Jackson G, Ziedonis D, Pbert L. Patient's views on depression 
care in obstetric settings: how do they compare to the views of perinatal health care professionals? Gen Hosp 
Psychiatry. 2013;35(6):598–604. 
28. Byatt N, Biebel K, Lundquist R, Moore Simas T, Debourdes-Jackson G, Ziedonis D. Patient, provider and 
system-level barriers and facilitators to addressing perinatal depression. J Reprod. Infant Psychol. 
2012;30(5):436–439. 
29. Edge D. Falling through the net - black and minority ethnic women and perinatal mental healthcare: health 
professionals' views. Gen Hosp Psychiatry. 2010;32(1):17-25. 
30. Palladino CL, Fedock GL, Forman JH, Davis MM, Henshaw E, Flynn HA. OB CARES--the obstetric clinics 
and resources study: providers' perceptions of addressing perinatal depression--a qualitative study. Gen Hosp 
Psychiatry. 2011;33(3):267–278. 
31. Price SK, Corder-Mabe J, Austin K. Perinatal depression screening and intervention: enhancing health 
provider involvement. J Women's Health (Larchmt) 2012;21(4):447–455. 
 
32. Kim JJ, La Porte LM, Adams MG, Gordon TE, Kuendig JM, Silver RK. Obstetric care provider engagement 
in a perinatal depression screening program. Arch Womens Ment Health. 2009;12(3):167–172. 
33. Mancini F, Carlson C, Albers L. Use of the postpartum depression screening scale in a collaborative 
obstetric practice. J Midwifery Womens Health. 2007;52(5):429–434. 
34. Byatt N, Biebel K, Debordes-Jackson G, et al. Community mental health provider reluctance to provide 
pharmacotherapy may be a barrier to addressing perinatal depression: a preliminary study. Psychiatr Q. 
2013;84(2):169-174. 

Version #11 07/29/2024 
 
35. Gjerdingen DK, Yawn BP. Postpartum depression screening: importance, methods, barriers, and 
recommendations for practice. J Am Board Fam Med. 2007;20(3):280-288. 
36. Substance Abuse and Mental Health Services Administration (SAMHSA). Screening, brief intervention and 
referral to treatment (SBIRT) in behavioral healthcare. 2011:1-30. 
 
37. Committee on Obstetric Practice. Committee opinion no. 711: Opioid use and opioid use disorder in 
pregnancy. Obstet Gynecol. 2017; 130(2):e81‐e94. 
38. National Council for Behavioral Health. Center of Excellence for Integrated Health Solutions Web site. 
https://www.thenationalcouncil.org/integrated-health-coe/. Updated 2020. Accessed June 10, 2020. 
39. Sim J, Lewis M. The size of a pilot study for a clinical trial should be calculated in relation to considerations 
of precision and efficiency. J Clin Epidemiol. 2012;65(3):301-308.