Technology-Based Intervention for Reducing Sexually Transmitted Infections and Substance Use During Pregnancy
Phase: NA
Conditions: Sexually Transmitted Infection, Alcohol Use Complicating the Puerperium, Alcohol Use Complicating Pregnancy, Unspecified Trimester, Drug Use
Sponsor: University of Michigan

 
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Technology-Based Intervention for Reducing Sexually 
Transmitted Infections and Substance Use During Pregnancy 
 
NCT03826342 
 
Date of IRB Approval: November 22, 2024 
 
 

 
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Technology-Based Intervention for Reducing Sexually Transmitted Infections and 
Substance Use During Pregnancy 
 
Principal Investigator: 
Golfo Tzilos Wernette, Ph.D. 
1018 Fuller St. 
Ann Arbor, MI  48104-1213 
Ph:  734-936-5508 
 
Co-Investigators: 
Quyen Ngo, Ph.D. 
Hazelden Betty Ford Foundation 
 
Okeoma Mmeje, MD 
University of Michigan 
 
Caron Zlotnick, Ph.D. 
Brown University 
 
Stanley Kuo, Ph.D. 
University of Michigan 
 
Ananda Sen, Ph.D. 
University of Michigan 
 
Katherine J. Gold, MD 
University of Michigan 
 
Laura Monkman, Ph.D. 
University of Michigan 
 
Analay Perez, Ph.D. 
University of Michigan 
 
Melissa Dejonckheere, Ph.D. 
University of Michigan 
 
Statistician: 
Dongru Chen, MA 
University of Michigan 
 
 
Information Technology Specialist: 
Josh Budde 
University of Michigan 
 
Project Coordinators: 
Kristina Countryman, MPH 
University of Michigan 
 
 
Current protocol submission and version number V.29 10/17/24 Date of previous submission dates and version numbers:  V.1, 
11/14/18; V.2, 2/1/19; V.3, 3/1819, V.4, 5/9/19, V.5 7/10/19, V.6 11/13/19, V.7 2/21/20, V.8 4/27/20, V.9 6/23/20, V.10 6/26/20, V.11 
9/11/20, V.12 2/1/21, V.13 5/24/21, V.14 8/18/21, V.15 9/7/21, V.16 10/12/21, V.17 1/25/22, V.18 3/15/22, V.19 5/10/22, V.20 7/6/22, 
V.21 8/15/22, V.22 2/7/23, V.23 9/8/23, V.28 05/13/24 
 
 
 
 
 
 

 
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Table of Contents: 
 
 
1.0.  Significance ………………………………………………………………………………….4 
 
2.0.  Innovation…………………………………………………………………………………….6 
 
3.0.  Aims…………………………………………………………………………………………..7 
 
4.0.  Approach …………………………………………………………………………………….8 
 
4.1. The Health Check-up for Expectant Moms (HCEM) …………………………….8 
 
4.2. Preliminary data from R21…………………………………………………………..9 
 
4.3. Research Team………………………………………………………….…………...9   
 
5.0.  Research Design and Methods…………………………………………………………..10 
 
5.1. Inclusion/exclusion criteria…………………………………………………………12 
 
5.2. Recruitment………………………………………………………………………….12 
 
5.3. Recruitment and Informed Consent………………………………………………13 
 
5.4. Methods……………………………………………………………………………...14 
 
5.5. Measures…………………………………………………………………………….16 
 
5.5.1 Table 1 study measures………………………………………………….16 
 
5.5.2 Primary outcome measures……………………………………………...16 
 
5.5.3 Secondary outcome measures…………………………………………..17 
 
6.0. Retention…………………………………………………………………………………….19 
 
7.0. Data Analysis………………………………………………………………………………..19 
 
7.1. Procedures for Handling Discordance Between Self-Report and Hair 
       Sample……………………………………………………………………………….20 
 
7.2. Costs…………………………………………………………………………………20 
 
7.3. Missing Data………………………………………………………………………...20 
 
7.4. Power………………………………………………………………………………...20 
 
8.0. Factors Affecting Implementation…………………………………………………………21 
 
9.0. Design Considerations to Enhance Rigor, Reproducibility and Impact……………….21 

 
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10.0. Limitations and Countermeasures………………………………………………………21 
 
11.0. Project Timeline…………………………………………………………………………...22 
 
11.1. Table 2……………………………………………………………………………..22 
 
12.0. Protection of Human Subjects……………………………………………………………22 
 
12.1. Risks to the Human Subjects…………………………………………………….22 
 
12.2. Potential Risks……………………………………………………………………..23 
 
          12.2.1. Breach of confidentiality…………………………………………………………23 
 
          12.2.2. Coercion…………………………………………………..……………………...24 
 
          12.2.3. Discomfort………………………………………………………………………..24 
 
12.3. Protection Against Risk……………………………………………………..…….24 
  
  
12.4. Potential Benefits of the Proposed Research to the Subjects & Others…….25 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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1.0. Research Strategy: Significance  
Statement of the Problem: Sexually transmitted infection (STIs), alcohol, and drug use are 
common and critical interrelated factors that are associated with negative consequences for the 
mother and fetus. There are virtually no empirically supported interventions that are tailored to 
specifically address these growing public health concerns together during pregnancy. Based upon 
our encouraging R21 findings, we now propose to test a brief computer-based intervention to fill 
this critical healthcare gap for a vulnerable, high-risk population.  
 
1.1. STIs are an urgent public health concern for childbearing women STIs are at a record 
high in the United States, and STI risk is an increasingly critical and costly health problem for 
American women, especially for pregnant women who can transmit the infections to their babies. 
STIs among women are associated with significant morbidity and mortality, including premature 
death. The American Congress of Obstetricians and Gynecologists (ACOG) and Centers for 
Disease Control and Prevention (CDC) reported that over the past decade, childbearing women 
have comprised one of the most rapidly expanding group infected by STIs, including HIV, in the 
U.S., and this epidemic is “accelerating in young women” Nearly 25% of pregnant women are 
infected with one of four STIs. Among those who had been treated for an STI in the past 6 
months, 30% tested positive for a current STI during their pregnancy. Critical to this trend is the 
intersection of STIs and alcohol/drug use – both highly prevalent among women. 
 
1.2. STIs and alcohol/drug use during pregnancy lead to significant biomedical risks to 
woman and fetus A pregnant woman carries a risk of transmitting an STI to her infant during 
pregnancy, delivery, or breast-feeding, especially if untreated. STIs such as chlamydia and 
gonorrhea can be transmitted from the mother to her infant during the delivery, what the CDC 
laments as a “tragic systems failure.”  Adverse effects of prenatal STIs can include miscarriage, 
ectopic pregnancy, stillbirth, low birth weight, neurological damage, and neonatal sepsis. Illicit 
drug use also has major health consequences for the pregnant women that can in turn negatively 
affect fetal development, rates of STIs, depression, intimate partner violence, as well as 
significant prenatal and neonatal complications (e.g., neurobehavioral and congenital 
abnormalities). Recent reviews suggest infants whose mothers used marijuana during pregnancy, 
compared to those who did not, were more likely to have lower birth rates and require neonatal 
intensive care. Prenatal alcohol exposure can lead to a wide range of adverse effects, known as 
Fetal Alcohol Spectrum Disorders (FASD) with an estimated 12,000 infants born with FAS each 
year, and up to three times as many have alcohol-related problems.  
 
1.3. The intersection of STI and substance use disorders in the lives of pregnant women  
The Healthy People 2020 objectives include increasing abstinence from alcohol/illicit drug use 
among pregnant women.  Past year prevalence of all illicit drug use was 5.4% for pregnant 
women. There has been a dramatic national five-fold increase in opiate use during pregnancy, 
leading to a surge in the incidence of neonatal abstinence syndrome (NAS) of 383% over the past 
decade. NAS is a postnatal drug withdrawal syndrome and includes central nervous system 
irritability. Marijuana use during pregnancy is also on the rise, increasing by 62% over the past 
decade. Nearly 12% of pregnant women reported using marijuana in the past year, in part due to 
an increased perception of the safety of marijuana use during pregnancy Regarding alcohol use, 
19% of women in their first trimester of pregnancy report using alcohol, and 3% report binge 
drinking (4 or more drinks in a row. Since underreporting during pregnancy can be substantial, the 
actual proportion of women drinking during pregnancy is even higher. The co-occurrence of 
alcohol and substance use and sexual risk taking contribute significantly to STI acquisition, 
particularly in high-risk and vulnerable populations. Regardless of partner status, monogamous 
pregnant women who use alcohol or substances are more likely to engage in sexual risk 
behaviors than their non-pregnant counterparts, and they are five times less likely to use condoms 
than their non-pregnant counterparts. The use of alcohol/drugs increases the probability for sex 
risk behavior through disinhibition and impairment of judgment, making the case for addressing 
these behavior risks together.  
 
1.4 Critical need to address these risks together during pregnancy Despite the escalating 
rates of substance use during pregnancy, and that co-occurrence with sex risk behavior 
contributes significantly to STI acquisition, there are currently no brief interventions that target 
both of these risks simultaneously during pregnancy. The extant literature includes computer-

 
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based interventions with a single focus either on improving sexual health, or reducing alcohol/drug 
use, and very few of these have targeted pregnant women exclusively. A recent brief intervention 
study identified alcohol use as a critical factor in reducing sex risk behaviors, suggesting the 
importance of implementing this target in STI preventive interventions, however, it excluded 
pregnant women.9 A review by the U.S. Preventive Services Task Force concluded that 
“methodologically rigorous trial evidence” is lacking for pregnant women. Ondersma and 
colleagues are currently testing a brief computer-delivered intervention targeting marijuana use 
during pregnancy; however, it does not address sex behavior risk. Existing computer-delivered 
brief motivational interventions for multi-risks (e.g., alcohol/drug use, dating violence, and/or HIV 
risk behavior) have primarily targeted students and male and female patients presenting to the 
emergency department, excluding pregnant women. Recent meta-analysis has indicated the 
superiority of targeting multiple health behaviors rather than just focusing on one behavior. The 
advantage of fewer sessions, if efficacious, increases the potential feasibility of implementation in 
a wide variety of settings – and the overall impact is greater when accessible and disseminable to 
larger populations.  
 
1.5. Pregnancy and postpartum period: a critical time to intervene Given the highly unique 
set of concerns for this subset of women, including 1) a dramatic national increase in the number 
of women misusing opioids during pregnancy, leading to a surge in the incidence of neonatal 
abstinence syndrome (NAS) of 383% over the past decade), 2) marijuana use is on the rise 
during pregnancy, increasing by 62% over the past decade (and low awareness of the associated 
health risks for the developing fetus), 3) low rates of condom use during pregnancy; STIs at 
record high for childbearing women, 4) tremendous health risks and adverse consequences to 
woman, fetus, and newborn, 5) lack of access to child care services, and 6) the challenges of 
social stigma, shame and guilt that can be significant for pregnant women who struggle with their 
substance use, there is a clear need for an intervention tailored to these unique needs of pregnant 
women. Because the majority (97%) of pregnant women receive at least some prenatal care, the 
CDC and ACOG have identified the perinatal period as an urgent time for STI prevention and 
subsequent behavior change, including substance use, to reduce risk for acquiring infection.  
Further, postpartum women are vulnerable to  
increased risk of STIs associated with high-risk sexual behaviors including inconsistent condom 
use and prevalence of alcohol use – with national data suggesting prevalence rates as high as 
30-49% -- and drug use prevalence in the range of 4-9%.  Recently, the NIH issued a strong 
recommendation for physicians to advise pregnant women to avoid marijuana use, with growing 
concerns of its use by women to treat nausea during pregnancy. To optimize postpartum care, the 
ACOG has recommended proactively addressing both risky health behaviors during pregnancy 
given that as many as 46% of women in the U.S. do not receive postpartum care, and only 21% 
receive routine STI screening. There is thus a tremendous opportunity and a clear need to 
advance clinical care in this important area, especially during the antenatal period. 
 
1.6. Use of a computer-based, brief motivational intervention is ideally suited for target 
population 
A computer-delivered brief intervention is a self-directed, low cost intervention that has several 
notable strengths for working with women in the perinatal period. The use of computer-assisted 
self-interview in disclosure of STI/HIV risk has been empirically supported in terms of encouraging 
the disclosure of sexual risk-taking and additional STI testing without increasing the rate of STI 
diagnosis, and very few studies have assessed computer-based STI prevention interventions 
exclusively in women. In computer-delivered intervention trials using the software we propose 
here, perinatal participants and participants in general have found receiving the MI intervention 
acceptable and highly likeable, suggesting that a high proportion will engage with the intervention 
and return for follow up assessments. Over the past decade, interactive technology for alcohol 
and other substance use disorders have been available and supported by clinical trials. In the 
extant literature, technology-based interventions for substance use demonstrate that while the 
effect of these interventions are again mild-moderate in size, there are positive aggregate effects 
in meta-analyses that can have meaningful public health impact given their overall low cost and 
potential reach. Further the reach and impact is magnified, as there is potential to aid both the 
participant and the fetus. 
 
1.7. Role of economic data to inform clinical and policy decisions on resource allocation 

 
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Economic data plays a key role in understanding the relative value of costs and benefits 
associated with a new health intervention and is critical for future dissemination and 
implementation. Many preventive interventions do not save money, but require a net investment in 
health resources to yield additional benefits. Implementation decisions will typically consider 
disease burden, intervention safety and efficacy, resource use, cost-effectiveness, as well as 
related factors such as feasibility. The pace of health spending has continued to increase as 
health reform efforts are aimed at slowing the growth in health expenditures. It is critical that data 
be available to evaluate the costs and benefits of any new interventions such as the proposed 
HCEM, Health Check-up for Expectant Moms, an innovative computer-delivered screening and 
brief intervention (SBI) program tailored for high-risk, non-treatment seeking pregnant women.  
Economic evaluations can provide information to clinical and policy decision makers on 
prioritization. Evaluation of resource utilization and costs can also inform feasibility and scale-up 
considerations for the implementation of HCEM. 
 
Summary of scientific premise: In summary, there are several converging lines of data that 
support the scientific premise of this proposal. STIs as well as alcohol and drug use are common 
and critical interrelated factors that are associated with negative consequences for the mother, 
fetus, and infant. Despite the clear risks of STIs among pregnant adult women, very few STI-
focused interventions have specifically targeted this group of women and there are currently no 
brief interventions that target both of these risks simultaneously to address the unique needs of 
pregnant women, including health risks to their unborn children. The proposed project will test an 
innovative, high-reach, easily implementable, low-cost computer-delivered intervention, HCEM, 
which is theoretically driven and will address known barriers in early intervention with at-risk 
women throughout pregnancy and will extend to the postpartum period. A fully powered trial of the 
HCEM optimized to extend impact to the postpartum period is necessary to determine efficacy. 
Given that these risks peak during childbearing years and extend into postpartum period, if this 
promising intervention of high public health significance is found efficacious, it can be readily 
integrated into prenatal health care settings and thus reduce the risk for adverse outcomes for 
very large numbers of vulnerable women and infants. 
 
Importance of the Knowledge to be Gained 
STI risk and alcohol/drug use are highly prevalent problems in the lives of pregnant women, in 
particular. Both are associated with physical, psychological and emotional impairment for the 
woman, serious negative consequences for the developing fetus, and have been shown to 
increase the cost of health care during pregnancy. Despite the serious morbidity associated with 
these health concerns, few women are being screened for both STIs and alcohol/drug use during 
pregnancy: only one third of women are assessed for alcohol use during prenatal care visits. 
Further, there are few interventions that address either of these critical issues during pregnancy, 
and virtually none that target both STI risk and alcohol/drug use during pregnancy simultaneously. 
The information gained through this research will help us to develop and empirically evaluate the 
efficacy of an intervention for this population. If our intervention proves to be efficacious, this 
would enable professionals in primary and prenatal care or other settings to have a meaningful 
impact on STI risk and alcohol/drug use within their setting. Further, there is promising evidence 
that the application of brief interventions to women in the prenatal period offers substantial 
benefits to both the woman and her unborn child. The paucity of research targeting both of these 
health risks together during pregnancy, and the potential success of implementing a computer-
based brief intervention in this population invites the proposed research investigation.  
 
2.0. Innovation The theoretical, methodological and clinical innovation of HCEM improves upon 
current literature in significant ways, specifically: 1) HCEM is innovative because we are targeting 
the unique needs of pregnant women early in pregnancy who endorse both risk for unsafe sex 
and alcohol/drug use – common, problematic, dual concern for pregnant women that has not 
typically been addressed concurrently; 2) HCEM is brief and it includes booster sessions that are 
specifically designed for a high-risk study population who are likely to benefit from additional 
contact as the literature suggests increases in efficacy and promotion of gains with behavioral 
interventions when boosters are provided, 3) HCEM targets STI risk reduction for the postpartum 
period as well as during pregnancy, extending and sustaining the impact of intervention; and, 4) 
we include assessment of key birth outcomes that are affected by STIs and alcohol/drug use. 
 

 
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3.0. Specific Aims 
 Sexually transmitted infections (STIs) are at a record high in the United States, and STI risk is an 
increasingly critical and costly public health concern for American childbearing women. STIs and 
alcohol/drug use are interrelated and common morbidities that have significant direct and indirect 
relationships with health and functioning over the longer term for mother and fetus. Undetected 
and untreated STIs can lead to serious long-term consequences for childbearing women including 
infertility; for pregnant women, STIs can lead to a number of serious health risks including 
premature birth, low birth weight, increased need for neonatal care, and fetal death. Similarly, 
there has been a dramatic national increase in substance use during pregnancy, particularly 
opiate and marijuana use, leading to complications during pregnancy and poorer birth outcomes. 
Nearly one quarter of pregnant women are infected with an STI, and over 15% report some form 
of risky alcohol or drug use. Women who abuse substances are disproportionately more likely to 
engage in risky sexual behaviors that can result in STIs. Because of this intersection between 
substance use and STIs and because both are clearly associated with poor health outcomes, the 
ACOG and CDC strongly recommend targeting both risks during pregnancy.  
Many challenges prevent the implementation of behavioral treatment programs in prenatal 
settings, and many women fail to engage in treatment even when it is readily available. These 
same women, however, may be willing to engage with brief, technology-delivered interventions 
that are tailored to their unique needs, and these approaches may be more applicable to be 
disseminated within overwhelmed prenatal care practices. Our team has successfully tested an 
innovative computer-delivered screening and brief intervention (SBI) program tailored for high-
risk, non-treatment seeking pregnant women. Our preliminary results (n = 50) indicate that the 
Health Check-up for Expectant Moms (HCEM) is acceptable and feasible, and is associated with 
significant reduction in the key outcomes of alcohol or drug use (OR = 0.15, p = 0.015), with a 
trend toward significance in the reduction of unprotected sex (OR = 0.17, p = 0.12) during 
pregnancy.  
The objective of this proposed study is to build upon these promising R21 findings by 
testing whether HCEM, a computer-delivered SBI that simultaneously targets STI risk and 
alcohol/drug use during pregnancy, reduces antenatal and postpartum risk more than an 
attention, time, and information matched control condition among pregnant women seeking 
prenatal care. To meet this objective, we propose a two-group, randomized controlled trial in 
which a racially diverse sample of 250 pregnant women at risk for STIs and alcohol/drug use are 
recruited from high-volume prenatal care clinics or through telephone and online methods, and 
are assigned to either (a) a computer-delivered, single-session brief intervention plus two booster 
sessions; HCEM); or (b) a computer-delivered control condition. Computer and/or phone-
delivered follow-up assessments will occur at 2 and 6 months, and extending to 6-weeks 
postpartum. Our biometric objective measures include STI incidence (e.g., chlamydia, gonorrhea) 
and birth outcomes. We propose the following Specific Aims: 
 
Aim 1 (Primary outcomes): To test the hypothesis that HCEM, compared to an attention, time 
and information matched control condition, will reduce risk of STIs and alcohol/drug use among 
at-risk pregnant women during pregnancy at 2 and 6-months follow-up.  
   (a) 
HCEM, as compared to control, will result in fewer unprotected sexual occasions;  
   (b) 
HCEM, as compared to control, will result in lower alcohol use and illicit drug use, and 
fewer heavy episodic drinking days.  
Aim 2 (Secondary outcomes): To test the hypothesis that HCEM will be associated with key 
secondary outcomes:  
  (a) 
HCEM, as compared to control, will result in fewer STIs (re-infection and/or new infections) 
during pregnancy and at 6-weeks postpartum; 
  (b) 
HCEM, as compared to control, will result in fewer unprotected sexual occasions and 
lower alcohol use and illicit drug use at 6-weeks postpartum; 
  (c) 
HCEM, as compared to control, will result in better birth outcomes (e.g., low birth weight); 
  (d) 
To collect and measure resource utilization and costs of HCEM to provide preliminary data 
to assess feasibility for future implementation and dissemination and to inform practice guidelines. 
Aim 3 (Mediation): To explore direct and indirect effects in the above hypotheses: 
  (a) 
To explore the effect of HCEM on the intermediate outcomes of pregnancy-specific 
knowledge and risk perceptions, autonomous motivation and self-efficacy during pregnancy; 
  (b) To test these theory-based mediators of HCEM primary effects hypothesized above. 
 

 
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Impact: This project will fill a critical gap and provide much-needed data on the efficacy and utility 
of a practical computer-delivered, brief motivational intervention tailored to reach high-risk women 
during pregnancy and extending impact to postpartum. If this promising intervention is found 
efficacious, it can be readily integrated into prenatal health care settings and thus reduce the risk 
for adverse outcomes for very large numbers of vulnerable women and infants. 
 
4.0. Approach  
The proposed study is a two-group, randomized, controlled design with an initial session 
(conducted close to the first prenatal visit), plus two booster sessions within one month later (at 2 
and 4 weeks). There will be follow up assessments at 8 and 24 weeks, and at 6 weeks 
postpartum, conducted by computer and delivered by RA either at the clinic, or remotely over the 
telephone, or at participants’ home. Birth outcome data will be available by postpartum medical 
records. We will focus on testing the efficacy and utility of the theoretically driven HCEM to target 
STI risk during pregnancy and postpartum, integrating alcohol and drug use given the well-
supported relationship between these risks. The proposed study will use a sophisticated 
intervention development tool, the Computerized Intervention Authoring Software (CIAS). A 
technology-delivered intervention approach promotes scientific rigor and greatly facilitates 
replicability in the community. 
 
4.1. The Health Check-up for Expectant Moms (HCEM) is a brief intervention (one session plus 
two booster sessions) that is theory-driven and derived from empirical support (see Figure 2, 
below). Motivational interviewing (MI) has been found to be effective for STI/HIV risk reduction. MI 
is an intervention approach with wide dissemination and demonstrated efficacy.  Consistent with 
the Self Determination Theory (SDT), MI is a client-centered counseling style that facilitates 
internal motivation to change through alignment of behavior change with deeply held beliefs, 
values, and goals. MI utilizes evolving 
readiness and self-efficacy to change. 
Moreover, the MI model appears to 
be generalizable to different 
populations, including low-income 
urban women. The components of 
the STI and alcohol/drug use risk 
reduction to be used in HCEM are 
formulated to be highly specific to 
the perinatal setting and entail 
increasing knowledge and targeting risk perceptions about STI transmission and prevention 
during pregnancy (which includes education about alcohol/drug use, for example the health risks 
associated with marijuana use on the developing fetus), increasing intrinsic motivation to act 
during pregnancy based on that knowledge, and ensuring sufficient behavioral skills (self-efficacy) 
to change behavior (e.g., increase in condom use, decrease in substance use) during pregnancy, 
as self-efficacy can be a strong predictor of condom use in women. In previous studies, MI has 
led to greater changes in the perception of risks of substance use, suggesting it may be an 
important mediator. In their comprehensive review of the literature evaluating HIV risk reduction 
interventions, Fisher et al. concluded that effective risk reduction involves separate factors. First, 
risk reduction entails increasing one’s knowledge about STI/HIV transmission and prevention. 
Second, one’s motivation to reduce risk must be enhanced. Third, effective risk reduction requires 
adequate behavioral skills. In their Information-Motivation-Behavior (IMB) model, the authors 
argue that information and motivation activate one’s behavioral skills, which in turn lead to risk 
reduction. In the area of STI/HIV risk reduction, the IMB model is a well-established model, and 
the intervention, HIV-RBI based on this model has garnered strong empirical support, especially 
among low-income urban women. In general, motivationally-enhanced interventions yielded larger 
effect sizes (d = 0.56) than traditional skills-based interventions (ds = 0.32 to 0.43). These IMB 
components were selected as mediators of HCEM on both theoretical and empirical grounds and 
tailored for the pregnancy setting. For example, knowledge and risk perception are pregnancy-
specific. The other two mediator measures are specifically worded to direct women to respond 
only about the duration of their pregnancy. Each mediator is either modifiable or could form a 
basis for tailoring, which will inform future interventions. Such an MI-based, STI risk reduction 
intervention, may be of particular value for pregnant women at risk for alcohol/drug use in 
reducing STI risk, because MI identifies these women’ strengths and builds upon their successes 
Figure 1. Conceptual Model of HCEM Effects and 
Mechanisms 

 
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(i.e., other changes they have made during pregnancy), thereby countering experiences and 
perceptions that may make them vulnerable for substance use. Additionally, MI with its 
collaborative and non-confrontational approach and its emphasis on increasing awareness to 
successful steps towards their well-being is consistent with recommendations for brief 
interventions in substance use, including increasing self-efficacy and relapse prevention skill sets 
to extend into postpartum.  
 
4.2. Preliminary data from R21 Along with two members of this research team, the PI conducted 
a RCT pilot study of 50 high-risk pregnant women attending prenatal care in a large urban clinic in 
Providence, RI, with comparable patient demographics to the clinical sites proposed in the current 
study. The intervention received very high mean ratings of satisfaction (6.3 out of 7), and the 
computer software was rated highly by both control and the intervention participants (4.6 out of 5). 
Feedback from the exit interview was positive with participants consistently reporting that they found 
the intervention educational, interesting, and realistic. The RCT was feasible in terms of recruitment 
and enrollment of participants. A total of 401 
women were screened over the course of nine 
months, with 34% meeting eligibility criteria. 
Overall, of the 50 women enrolled for the 
randomized trial, all 50 completed the intervention session. Forty-nine women (98%) completed the 
booster session and assessment 4 months later, demonstrating feasibility and uptake of these 
sessions. Participants in the HCEM condition demonstrated a significantly larger reduction in any 
self-reported 
marijuana 
or 
alcohol 
use 
compared to control condition (time-by-group 
interaction p = 0.015). There was a higher 
reduction of unprotected sex at follow-up in 
the intervention arm than control (27% vs. 
5%); the direction and magnitude of this effect 
was very promising and would be of clinical 
significance, however, was not significant with 
this small sample size ((OR = 0.17, p = 0.12); 
see Fig 3, right). These encouraging findings 
strongly support the current application. The 
lack of significance regarding unprotected sex 
reduction may also indicate that additional 
contact may be needed for our high-risk group 
of pregnant women, supporting a second 
booster session in the proposed trial.  
      Evidence of high acceptability of 
computerized intervention The HCEM is MI-
consistent, incorporating the general principles, including expression of empathy and support of 
client’s self-efficacy (Miller & Moyers). Results from our pilot testing found that 100% (50 out of 
50) of the women reported feeling respected, and not judged, by HCEM. Further, previous studies 
using CIAS-based SBIRT packages with thousands of perinatal women have consistently yielded 
extremely high ratings for acceptability and ease of use.11,53,83  
      Incomplete mediation by alcohol factors supports need for multiple-targeting. Our recent 
mediation analysis of a computer-delivered brief intervention to reduce alcohol and sexual risk 
behavior among 372 patients in the ER determined that only 23% of the intervention effect on 
condomless sex was mediated by reduced heavy drinking This suggests that meaningful 
reductions in sex risk likely require active promotion of safer sexual behaviors such as condom 
use skills, in addition to focusing upon alcohol use per se.  
 
4.3. Research Team Our study team is experienced and capable of conducting the proposed 
study and includes a strong team of investigators with long experience in designing and 
conducting computer-based brief motivational interventions to address high-risk behaviors among 
vulnerable women. We have tremendous experience in the recruitment and retention of high-risk 
samples, including perinatal women in these clinical settings as evidenced by a number of 
successful NIH trials. The PI and Mmeje (Co-I) are affiliated with the proposed clinic sites, which 
will facilitate conducting the study (see Letters of Support). 
Figure 2. Reductions in Main Outcomes of R21 Study 

 
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      Drs. Tzilos (PI), Zlotnick (Co-I) have conducted a number of brief motivational intervention 
trials using the same CIAS-based software to be used in the proposed study. The PI adapted and 
tailored a brief, computer-based intervention for pregnant women at risk for alcohol use. She 
screened 490 pregnant women from an urban prenatal clinic and randomized 50 women at-risk 
for alcohol use during pregnancy to complete either a single-session, computer-based brief 
intervention or a time and attention-matched control condition; both groups completed a one-
month follow up assessment. Dr. Zlotnick is a Professor in the Departments of Psychiatry and 
Human Behavior, and Obstetrics and Gynecology at Brown University. She has extensive 
experience in testing interventions to meet the unique needs of challenging high-risk perinatal 
populations within clinical settings (e.g., perinatal women with intimate partner violence, low-
income women at risk for postpartum depression) and other high-risk women (e.g., incarcerated 
women with interpersonal violence and HIV/STI risk behaviors), with very high retention rates. 
Further, she, the PI, adapted a computer-based SBIRT approach for pregnant women at risk for 
STIs/HIV primarily, integrating alcohol/drug use given the relationship between these risks during 
pregnancy (R21 HD075658).  
      Dr. Ngo (Co-I) is the Research Director at the Hazelden Betty Ford Foundation. She is a fully-
licensed Clinical Psychologist with expertise in substance use, violence and trauma, 
contemplative practice, and technology-assisted psychological interventions. Dr. Kuo (Co-I) is an 
Assistant Research Scientist in the Department of Internal Medicine at Michigan Medicine. His 
area of expertise includes clinical economics and decision analysis. Dr. Sen (Co-I) is Professor in 
the Departments of Family Medicine and Biostatistics at the University of Michigan. He has 
considerable experience as biostatistician on large clinical trials involving behavioral interventions 
and his primary role on this study will be supervisory. Dongru Chen, a statistician in the 
department, will work directly under his supervision and will assist him with statistical analysis, 
report generation and manuscript preparation. Dr. Sen and the PI have collaborated on the R21 
study. Dr. Mmeje is a staff physician at the Von Voigtlander OB clinic and an Assistant Professor 
in the Department of Obstetrics and Gynecology. Her area of expertise is reproductive infections 
diseases and HIV/STI risk among pregnant women. Dr. Katherine Gold (Co-I) is a family 
physician, obstetrics and mental health researcher, and an associate professor in the University of 
Michigan Departments of Family Medicine and Obstetrics & Gynecology. Our team has 
demonstrated excellent retention rates with high-risk perinatal samples ranging from 87% for up to 
one-year postpartum and 94% for a 9 months follow-up period.  
 
In summary, our research team and preliminary studies demonstrate strong support that 
we can successfully: 1) recruit and retain the target population 2) optimize and deliver the planned 
technology-delivered intervention, and 3) demonstrate significant behavior change. 
 
5.0. Research Design and Methods 
Program and procedure modifications: We will optimize the intervention program based on results 
of the R21 study, including updates to the tailored content of the intervention and the addition of a 
second booster session. We will include an additional booster session because 1) our sample will 
be a high-risk group and likely to benefit from additional contact, 2) boosters will target the 
prevention or reduction of the behavioral risks during postpartum, and 3) the literature suggests 
increases in efficacy and promotion of gains with behavioral interventions when boosters are 
provided. Our proposed Michigan clinical sites are comparable to the Rhode Island clinic site 
where we conducted the pilot study, with respect to patient volume, clinic setup and flow, and 
serving pregnant women on public assistance. These procedures will enhance study feasibility by 
ensuring that procedures are in place to interview participants on schedule, that recruitment 
procedures are culturally sensitive, that our assessments do not place undue burden on 
participants, measures are feasible and acceptable, and that dropout rates are minimized. HCEM 
is specifically tailored, innovative and relevant to diverse pregnant women in a number of ways. 
First, the images/content will be culturally sensitive and appropriate for a racially/ethnically diverse 
group of women (e.g., including pictures and video testimonials of women from racially/ethnically 
diverse backgrounds). Second, we will carefully coordinate appointments with prenatal visits to 
facilitate travel and increase likelihood of greater follow up rates. The software is highly interactive 
and individualized, has been found in previous research including our own to be well-understood 
and liked by low-income, pregnant and postpartum women, relies heavily on realistic interactions 
with a narrator to mimic the conversational, empathic nature of person-delivered brief 
interventions. Our team has the expertise and well-established programmer training methods to 

 
12
work with research staff to complete the programming of the HCEM and assessment materials in 
a timely manner. We have successfully adapted five previous trials without any delays.  
      Overview: The 60-minute intervention is focused on reducing STI risk behaviors including 
alcohol/drug use during pregnancy. It will begin with an introduction to the intervention structure 
and will provide a tutorial guided by the narrator, which interacts in a collaborative, MI-consistent 
style with the ability to use emotionally expressive statements and empathic reflection. The 
Information component, which is consistent with the FRAMES approach and will follow 
recommended guidelines for brief interventions, will be delivered using the MI-consistent elicit-
provide-elicit framework, including open-ended questions and reflections in providing facts about 
STI transmission and prevention; testing and behaviors that can be utilized to reduce risk during 
pregnancy; associated risks of alcohol and drug use for both woman and fetus and will highlight 
the bidirectional relationships among these risk factors, especially how alcohol/drug use increases 
risk for STIs. In order to facilitate condom desensitization and skills, information about various 
forms of condoms, lubricants and dental dams, as well as their application, will be delivered by the 
software in video format, to increase interest and engagement. Moreover, HCEM includes short 
video testimonials of women who share their challenges/successes with respect to changes in 
their alcohol/drug use during pregnancy, as well as women who had an STI, how it affected them 
during pregnancy, and how they sought support. In our pilot study, participants rated these 
components of HCEM as highly acceptable, “interesting and real” and found them to be relevant 
to their own relationships.  
        Motivational strategies such as collaborative, reflective listening, exploring goals and values 
are utilized to elicit change talk and enhance participants’ autonomous motivation. The narrator 
will elicit behavior change by asking open-ended questions, reviewing change rulers (importance, 
readiness, and confidence rulers (1 to 10)) to support participants’ self-efficacy and autonomous 
motivation (e.g., “On a scale of 1-10, how important is it to you to change your marijuana use 
during pregnancy?”). The intervention will encourage participants to explore and resolve 
ambivalence. For example, the narrator will ask for the good things about changing/not changing 
their selected substance and provide a checklist in which they endorse as many pros as they 
would like (e.g., marijuana use helps my nausea). The narrator will reflect back to them the 
specific reasons that they selected, and will note that feeling two ways about one’s marijuana use 
is quite normal. The intervention is designed to explicitly and directly target and enhance 
autonomous motivation to change STI risk behaviors, including alcohol/drug use (while marijuana 
use was the primary drug endorsed in the pilot study, the participant will have the option to 
choose which specific drug(s) she would like to focus on for the duration of the intervention), and 
provides opportunity for the participant to select and practice behavioral skills necessary to reduce 
risk (e.g., negotiating communication of their intentions to their partners) during pregnancy. The 
software tailors the intervention content to include key MI components regarding STI risk (e.g. 
personalized feedback on STI risk, and optional goal-setting addressing STI risk behaviors). After 
summarizing personal concerns as identified by the participant (e.g., “I want to cut down on my 
alcohol use”), the software elicits from participants steps that can be taken to reduce STI risk. In 
order to enhance behavioral skills and utilization of resources for STI risk reduction, participants 
are taught male and female condom application with anatomical models as well as strategies to 
negotiate condom use to respond more assertively within a sexual context during pregnancy. The 
literature suggests that skill-building interventions improve self-efficacy in condom use among 
high-risk females.96 In our pilot testing, participants found these skills as educational and helpful, 
and several women reported a general lack of knowledge about how to use female condoms and 
expressed interest to use them. Supporting participants’ efficacy for behavior change is a key 
concept of MI.  
          
The software includes an optional personalized plan which is designed to increase 
awareness of risk factors for STI and alcohol/drug use in the woman’s life, including partner 
substance use - which may increase these risks for the woman during pregnancy - and offers 
personalized advice for decision-making that maximizes the woman’s sexual safety. The narrator 
will elicit participants’ willingness to change and an emphasis is placed on eliciting change talk. 
For example, the narrator will ask if she would like to set a change goal during her pregnancy. If 
she does not wish to do so, the narrator reflects, in a non-judgmental manner, her lack of 
readiness at this time and elicits information regarding what signs would tell the participant that 
she did need to change. If the participant wishes to set a change goal, the program will guide her 
through a brief change plan process. Participants will be provided a menu of choices for when, 
why, and how she would like to make a change/setting a goal (e.g., a commitment to use 

 
13
condoms every time she has sex for the remainder of her pregnancy). The plan will extend 
decision-making to the postpartum period, including change goals that address alcohol/drug use 
and condom use after her baby is born, and will be reinforced in the booster sessions.  
 
Web-based booster sessions: Within one month of completing the intervention, participants in 
both conditions will complete two, 15-20-minute booster sessions delivered remotely. For 
participants in the control condition, the booster content will be similar to the baseline content. For 
participants in the HCEM condition, the booster sessions will review their own personalized plan 
and identifying any challenges or barriers to increasing safety behaviors (i.e., intention to increase 
condom use and/or reduction of the substance that they selected). Review of change plan will 
include: reduction in STI risk 
behavior, including alcohol/drug use, 
identification of triggers for unsafe 
sex. Booster sessions explicitly target 
the prevention or reduction of STI 
risk behaviors including alcohol/drug 
use during the postpartum period, 
when prevalence of these risk 
behaviors increase, and address 
health risks associated with 
postpartum substance use (e.g., risks 
of substance use while 
breastfeeding). Sessions will 
emphasize principles of MI (e.g., 
fostering autonomous motivation), 
reviewing and reinforcing aspects of 
their change plan that are also 
relevant to the postpartum period (e.g., generating options and goal-setting), and accessible at 
home for ease of completion using a computer or mobile device – an improvement to the R21 
study (see Fig 3, above; study homepage). Recent research demonstrates that low-income 
childbearing women, including women of color and perinatal women, frequently use and show 
strong interest in technology in general and for acquiring health information. Research of low-
income single childbearing women found 78% had a smartphone. Our own research with high-risk 
perinatal women found that all participants had smartphones and were active users. The booster 
sessions reinforce and sustain the effects of the brief intervention. The addition of a second 
booster bolsters the preventive effects for the postpartum period.  
 
5.1. Inclusion/exclusion criteria: Participants will be 250 pregnant women (as close as possible 
to first prenatal visit), age 18 or older, and will follow similar recruitment to the R21 study given 
feasibility and acceptability rates. Specifically, the study will include pregnant women who 
endorse: 1) at least one unprotected vaginal (or anal) sex occasion (USO) in the past 30 days 
(supported by the literature for our “high risk” sample, identified as such based on childbearing 
age, urban, ethnically diverse, and reporting co-morbid recent history of substance use), and 2) 
having more than one male partner in the last 6 months and/or having uncertainty about current 
sexual partner’s monogamy, and 3) current alcohol/drug use risk, 4) currently resides in the state 
of Michigan. Exclusion criteria include: 1) inability to provide informed consent (e.g., clear 
cognitive impairment), or 2) inability to understand English. 
 
5.2. Recruitment: We successfully completed the R21 study in a prenatal clinic in Providence, 
Rhode Island. We will implement similar methods to recruit for the proposed study. Past year 
public health data reports increases in STI cases reported in Washtenaw County (Michigan). 
Recruitment will take place in a number of ways, including in-person at clinical sites within 
Michigan Medicine, other Michigan based clinics, or remotely. Remote recruitment for Michigan 
Medicine patients will happen by a member of the research team conducting a chart review 
(MiChart) and contacting prenatal patients over the phone, via physical mail, or through email 
messages. The research team will also recruit online by advertising on the University of Michigan 
Health Research website (https://umhealthresearch.org) or through social media platforms (e.g. 
Facebook, Instagram). Online/remote recruitment will not be limited to Michigan Medicine 
patients, however; pregnant women residing in the state of Michigan who are patients of outside 
Figure 3. Study Website 

 
14
institutions (including, but not limited to The Luke Clinic) will also be eligible to participate if they 
meet the study inclusion criteria. We chose Michigan Medicine clinics and clinics in the state of 
Michigan because of the high-volume access to a socioeconomically, racial/ethnically, culturally 
diverse pregnant population relative to the prenatal clinic in Rhode Island (there are higher rates 
of African American women, who, compared to white women, are disproportionately affected by 
STIs). Also, Washtenaw County is in the top third of counties in the U.S. for Chlamydia rate. 
Further, the CDC reports that STI rates in Michigan surpass those in Rhode Island, where the 
R21 study was completed, further supporting the clinic selection for the proposed study.1 Overall, 
these rates and supporting data reflect a high-risk sample of pregnant women at these two clinics.  
        In sum, based on these reasons and the prevailing literature (see above sections), we 
anticipate conservatively that 80% of the women who will meet inclusion criteria for alcohol or 
drug use (20% of those screened) will also meet criteria for STI risk in the past year, yielding an 
overall inclusion rate of 16%. Based on the feasibility data of the R21 study, we anticipate that to 
enroll approximately 250 women (see Power Analysis section, below), we anticipate screening 
1,540 women, which will take roughly 48 months (a rate of approximately 32 participants/month). 
Based on rates determined in the pilot study, as well as estimates of rates for risk behaviors at 
Michigan Medicine clinic sites (generated from past-year medical records data and supplemented 
with data reported at the county level as well as the CDC for STI risks in specific counties), we 
expect that rates of eligibility and enrollment will yield a rate of 5-6 participants completing 
baseline per month between the clinic sites, yielding a total of 250 participants over the course of 
Yrs. 1 – 4. Follow up assessments for all 250 participants will be completed by the 5th month of 
Year 5. The research team has had high follow-up rates (6-14% attrition) in intervention trials 
involving high-risk pregnant women in prenatal sites,104-106 and with other challenging populations, 
including women using substances.107,108 Moreover, we have had high retention rates (85%) in 
intervention trials including adults endorsing risky alcohol use who receive care in the proposed 
(Michigan Medicine) health system.41 
 
Recruitment for the implementation phase: research staff will contact each clinic and provide the 
study information. The clinic director, clinic manager, or responsible party will direct us as to the 
best method for dispersing the information to the clinic staff (e.g., sending an email with additional 
information). Interested staff members will then contact the research team to schedule an 
interview. We anticipate interviews will take anywhere from 30-45 minutes. In addition to 
recruitment of clinic staff, we plan to recruit and enroll 5-30 participants who have already 
completed the study to tell us about their thoughts and opinions around the HCEM program. We 
will use a 2-page addendum as the consent form to enroll these participants since they have 
already completed the study. These will be participants who agreed to be contacted by us for 
future research. We will contact these participants via email, phone, and text to see if they are 
interested in completing the interview which will be conducted virtually (through Zoom). We 
anticipate these interviews will last 30 minutes or less and participants will receive a $50 Amazon 
gift card or check. 
 
Recruitment site: The clinical trial recruitment will be conducted at Michigan Medicine clinics, 
and with non-Michigan Medicine OB clinics. We chose these clinics because they provide access 
to socioeconomically, racial/ethnically, culturally diverse pregnant patient population. Due to the 
COVID-19 pandemic, recruitment from these clinics will also take place remotely over the 
telephone, via physical mail, or through email messages. The research team will also recruit 
online by advertising on the University of Michigan Health Research website 
(https://umhealthresearch.org) or through social media platforms (e.g. Facebook, Instagram). 
The Michigan Medicine team will also work in partnership with the Luke Clinic sites in Detroit and 
Flint in order to recruit from their patient population.  
 
 
5.3. Recruitment and Informed Consent 
Women from Michigan Medicine will be recruited in one of several ways, including: being 
approached in the waiting room, being approached by the research assistant or a member of the 
health care team while waiting for their physician in the examination room (with permission given 
to introduce the study); through their physician giving them a study flyer or verbally telling them 
about the study, through a member of the research team conducting a chart review (MiChart) and 
contacting prenatal patients over the telephone (and text message), via physical mail, or through 

 
15
email messages; or through study flyers posted in Michigan Medicine clinics/hospitals and 
throughout the University of Michigan Campus. Non-Michigan Medicine patients will be recruited 
in one of several ways: through flyers posted in non-Michigan Medicine clinics/hospitals and in 
offices at the Michigan Department of Health and Human Services, through flyers posted in 
community/public spaces such as bus stations, libraries, churches, childcare centers, local pre-k 
through 12 schools, food pantries/grocery stores, laundromats, and similar spaces; through social 
media (i.e. Facebook, Instagram); through the UM Health Research website, and similar 
recruitment strategies. Patients from Luke Clinic will be recruited in one of two ways: 1) they will 
be informed of the study by clinic staff and will complete a contact information sheet if they are 
interested in being contacted by a member of the study team (remote screening), or 2) they will be 
approached by study staff in-person and asked if they would like to complete the eligibility 
screener on a study iPad.  In addition to the $5 gift card for completing the screener, patients who 
fill out the contact sheet or take the screener in-person will receive a small gift bag (containing lip 
balm, hand lotion, etc.) to show our appreciation for their time. For patients that screen eligible, 
steps will be taken for enrollment and permission to access their Luke Clinic’s Electronic Medical 
Record system, allowing for patient contact and data access.  
In a Michigan Medicine clinic setting, those who express tentative interest in the screening 
survey will be directed to speak with the study RA to complete the short (10-15 minutes) 
computer-delivered health survey including questions to determine eligibility. Before completing 
the screening survey, they are given a copy of the screener consent, to which they must verbally 
agree to before proceeding. The computerized screening will use software delivered on an easy 
to use iPad iOS. The research team has used this procedure successfully to recruit this target 
population. In a remote setting, potential participants will complete the same screener online using 
their home computer, tablet or smart phone. The screener will include well-validated and 
recommended measures for this population. Women who score eligible on the screener in a clinic 
setting, will be informed by the RA about the clinical trial, and interested women will fill out a 
contact sheet and make an appointment for the baseline session. Before conducting the baseline 
session, the RA will explain the informed consent process as well as the study procedures, and 
ask comprehension questions before obtaining consent. Both the informed consent process and 
the baseline session will be conducted in a private room in the clinic (or a private room at the 
Department of Family Medicine office), providing a confidential and comfortable environment for 
the participant.  
In a remote setting, the screener consent will be directly before the screener (on Qualtrics) 
questions. A woman hitting the “next” button and continuing on to the screener questions means 
that they agree to the consent. This is similar to how the screener consent works in-person, as we 
provide women with a paper consent and they verbally agree to take the screener. Women who 
take the screener online will automatically be informed of their eligibility upon completion. If they 
screen eligible, we will either call them directly to give them more information about the study and 
to collect additional contact information, or we will send a secure REDCap (or Qualtrics) survey 
link, where they can enter in their contact information. We employ these methods to allow the 
screening survey to remain anonymous should a woman decide not to participate in the larger 
study. For women recruited from social media, they will first see an ad for the study, and if 
interested, click on it for more information. This will bring them to a brief pre-screener survey on 
Qualtrics, which will ask them to confirm that they are pregnant and plan on delivering in the state 
of Michigan. If they are found eligible on the pre-screener survey, they are invited to enter their 
name and phone number so that the research team can contact them to answer some additional 
pregnancy related questions. If the participant is able to answer these pregnancy questions, then 
the RA will invite them to take the screening survey and ask for their email address (screening 
survey is sent via email). The reason we employ a pre-screener and telephone call is to avoid the 
possible fraud that can occur with social media recruitment (i.e. participant misrepresentation of 
their pregnancy status, spammers, and internet bots). Furthermore, if the participant passes the 
pre-screener survey and phone call and goes on to take the study screener but answers that they 
are not pregnant or indicate a different gestational age, then we will assume it’s a fraudulent 
screener and we will not pay out the $5 gift card. The pre-screener survey and phone call will not 
be necessary for Michigan Medicine recruits as we can verify their pregnancy status on MiChart. 
Participants’ contact information (e.g. phone number) and the contact information of up to 
three other individuals (e.g., family/friends) will be collected after screening eligible for the study, 
for the purposes of scheduling the baseline and follow-up assessments; this information will also 
be stored on the HIPAA-compliant database REDCap, which is administered and managed 

 
16
through the Michigan Institute for Clinical and Health Research (MICHR) at the University of 
Michigan. This database will only be accessible by the Study Coordinator and research staff. Any 
information about a participant will never be released to outsiders without their explicit consent, 
except in the event of abuse of children/elderly/handicapped (report to the Michigan State) or a 
medical emergency, when pertinent medical information will be given to the medical personnel 
caring for the individual. Participants will also be informed about the risk of loss of confidentiality 
due to STI testing and drug screens.  
To obtain study consent remotely, potential participants will be emailed the study consent 
document and asked to read it before a scheduled phone call with the RA. During this call, the RA 
will review all sections of the consent document with the woman, answer any questions she may 
have, and then ask comprehension questions just as is done during in-person informed consent. If 
the woman agrees to be part of the study, she will give her consent verbally over the phone, 
rather than signing a paper copy. The remote baseline session itself will be conducted both over 
the phone and online, using the CIAS study software.  
 
5.4. Methods: We will implement the same study procedures as in our previous studies with 
pregnant women (see above). Women who express tentative interest in the screening survey will 
be directed to speak with the study RA to complete the short (10-15 minutes) computer-delivered 
health survey including questions to determine eligibility. In a remote setting, women will take the 
screening survey online, and if eligible, provide their contact information for the RA to follow-up 
with them. The computerized screening will use the CIAS software delivered on an easy to use 
iPad iOS (in-person), or on the participant’s own Internet connected device (remote). The 
screener will include well-validated and recommended measures for this population. The research 
team has used this procedure successfully to recruit this target population.  
        Women who score eligible on the screener will be informed by the RA about the 
clinical trial and will explain the informed consent process as well as the study procedures (see 
Fig 4, below). For in-person study visits, the baseline session will be conducted in a private room 
in the clinic (Michigan Medicine), providing a confidential and comfortable environment for the 
participant. Given the current COVID-19 pandemic and associated research restrictions, the 
baseline session will be conducted remotely (August 2020 to present time, February 2023), both 
over the phone and online, using the CIAS software. Upon completion of the baseline session 
(whether it is conducted in-person or remotely), and following previous studies with similar design, 
women in both conditions will receive appropriate referrals for: (1) testing and treatment for STIs, 
and (2) brochures specifically designed to facilitate reductions in drinking and drug use during 
pregnancy (note: we will use publications from the National Institutes of Health and/or the Centers 
for Disease Control and Prevention). Women in both conditions will also receive a comprehensive 
list of local (Washtenaw County) and online resources for relevant topics such as substance use 
help, mental health counseling, STI testing centers, food pantries, etc. Additionally, all participants 
in this study will receive care as usual from their medical team; no screening, referral, or 
counseling will be withheld in any way at any time. Such a design—involving a treatment as usual 
control, supplemented by additional referrals and materials—is typical of clinical trials of 
behavioral interventions for substance abuse and STI/HIV risk interventions. Participants 
randomized to the intervention arm are offered a “safe sex kit,” which includes male and female 
condoms, dental dams, and lubrication. If the participant is completing the intervention remotely, 
the research team will obtain permission for this kit to be mailed to their place of residence. 
Booster sessions can be completed by the participant in their home and accessed through 
our secure, HIPAA-compliant study website using either a computer or mobile device (see Fig. 3, 
above). The use of computer technology for gathering self-report data further enhances overall 
protection. This software utilizes SSL technology for encrypting of communications between 
remote computers and the server itself, is HIPAA-compliant, and is currently used in a number of 
major NIH-funded research studies, including those of the PI. Data will be encrypted in transit 
between user and server. Importantly, no identifying information will be entered into the CIAS 
software. Given the sensitive nature of this research, the computer software will simply generate a 
code number for each participant. Additionally, all forms with participant information will be 
marked with a code number and not with the participants’ name. The link between the participant 
code number and name will be securely stored on the HIPAA-compliant database REDCap. This 
database will only be accessible by the Study Coordinator and Research Assistants.  
 
In-person follow-up assessments will be completed at the clinic (Michigan Medicine) and 
scheduled with prenatal visits when possible. Given the current COVID-19 pandemic and 

 
17
associated research restrictions, the follow-up assessments will be conducted remotely (August 
2020 to present time, February 2023), both over the phone and online, using the CIAS software. 
The postpartum assessment will be conducted by the RA at a private and confidential location 
convenient to the participant (e.g., clinic, home, or remotely), coordinated with the timing of the 
postpartum medical visit, maximizing likelihood of completion.  
 
For the assessment timepoints that require urine sample collection for STI testing, 
Michigan Medicine participants have the option to complete STI testing at any Michigan Medicine 
lab site. For both Michigan Medicine and non-Michigan Medicine participants, they have the 
option to receive an at-home STI testing kit. The study team will be responsible for mailing the kit 
to the study participant and covering the cost of returning the kit. Drug testing will no longer be 
required for study participants (as of November 2022). Instead, the study team will collect the 
results of already existing drug tests in the patient’s chart completed during the duration of their 
study participation. This will include patients at Luke Clinic, for whom the research team will have 
guest access to the clinic’s Electronic Health Record System, allowing for the collection of patient 
medical information.  
 
Should an already enrolled participant choose to leave the study or not follow through with 
appointments for some reason, we will ask them for their feedback through an anonymous and 
voluntary survey that asks what the research team can do to more easily facilitate women’s 
participation in the study. 
 
 
 
 
 
 
Information-matched control condition: We will use the same, well-validated, attention, time 
and information-matched control used successfully in our five previous studies with pregnant 
women, including in the pilot R21 (ratings of acceptability were equally high among intervention 
and control group participants). The content will consist of a series of questions regarding 
television show preferences and viewing a brief series of videos of popular entertainers/shows, 
with subsequent requests for ratings of subjective preference, and will also help to limit 
inadvertent therapeutic effects that plague control groups in brief intervention research. We will 
include facts about alcohol/drug use and risky sex during pregnancy, along with informational 
brochures from NIAAA/CDC that provide face validity. 
 
5.5. Measures: Participants meeting inclusion criteria will complete an assessment session on 
the iPad iOS. The battery is designed to minimize assessment with the control group in order to 
take in to account growing concerns regarding the motivational properties of assessment, leading 
to substantial Type II error in brief alcohol intervention studies. All of the self-report measures 
included in this study have good psychometric properties (see Table 1, below).  
 
Screener items (embedded with general health questions): 
1. Questions for history of STI sexual risk (i.e., number of occasions of condomless vaginal (and 
anal) sex in the past 30 days);  
2. T-ACE (four questions)  is a screen for risk drinking developed for use in OB/GYN settings;  
3. Substance Use Risk-Profile Pregnancy Scale (SURP-P) (three questions) this screening is 
specifically designed to quickly identify obstetrical patients at risk for alcohol or illicit drug use.  
 
Table 1. Study Measures 
 
Antenatal 
Postpartum 
Self-report measures 
Baseline 
19-28 
weeks 
36-39 
weeks 
6 weeks 
  Demographic Information 
X 
 
 
 
  Marlowe-Crowne Social Desirability – Short Form  
X 
 
 
 
Figure 4. Study Timeline 

 
18
 
*In-person, Michigan Medicine visits only. 
**A urine sample may be collected in place of a hair sample in the event that a hair sample cannot 
be collected.  
 
The following assessment measures will be administered at the baseline assessment: 
1. Demographic information, including age, race, ethnicity, marital/partner status, parity, 
employment, socioeconomic status.  
2. Marlowe-Crowne Social Desirability Scale-Short,114 includes 13 items sensitive to social 
desirability bias. 
 
5.5.2 Primary Outcome Measure: 
 
1. Unprotected sexual occasions (USOs) at the 8-week follow-up assessment. 
 
USOs will be obtained from the Timeline Follow-Back (TLFB) to assess sex-risk behaviors 
at baseline and follow up assessments. The TLFB is a calendar assisted structured interview 
that provides a way to cue memory so that accurate recall is enhanced for event-level data; it 
has been used to assess sexual risk-taking. USOs will be assessed in the 90 days prior to 
the baseline, as well as the 8-week follow-up assessments.  
 
5.5.3 Secondary Outcome Measures: 
 
1. Alcohol use and Illicit drug use: Self-reported days of alcohol and illicit drug use at 8-week 
assessment. 
 
 
The TLFB will be used to measure alcohol use by using the variable of percent 
days abstinent. Illicit drug use will also be collected from the TLFB, and measured by using 
the “yes/no” variable for each day. Both variables will be assessed in the 90 days prior to the 
baseline, as well as the 8-week follow-up assessments.  
 
 
Other Outcomes: 
 
A. Alcohol use: In addition to the percent days abstinent variable, the TLFB will be used to 
measure drinks per drinking day and heavy episodic drinking episodes.  
 
B. Illicit drug use: While not a primary outcome measure, the study has collected objective hair 
measures at various points through the duration of the research study (1.5-inch samples) 
providing up to a 90-day window (by Psychemedics, Inc.) to corroborate self-reported drug use at 
follow-up assessments (see Data Analysis section, below), as well as urinalysis. Our team has 
experience from our pilot study with feasibility of obtaining hair samples from pregnant women; we 
   Timeline Follow-back, sex, alcohol, drug use 
X 
X 
X 
X 
    Condom Use Self-Efficacy 
X 
X 
X 
X 
   Treatment Self-Regulation Questionnaire 
X 
X 
X 
X 
   HIV/STI Knowledge Questionnaire 
X 
X 
X 
X 
   Risk Perceptions Items (STI) 
X 
X 
X 
X 
   Importance, Readiness, and Confidence Rulers  
X 
X 
X 
X 
   Condom Attitude Scale 
X 
X 
X 
X 
  Perceived Competence Scale 
X 
X 
X 
X 
 COVID-19 Family Stress Screener  
X 
X 
X 
X 
Objective biometric measures 
 
 
 
 
 
   Urine or Vaginal Swab Collection: STI Testing 
X* 
X 
X 
X 
   Birth Outcomes 
 
 
 
X 
   Hair Sample Testing (suspended 11/2022) 
X** 
 
X** 
 
Economic and implementation measures 
 
 
 
 
   Costs Analysis 
X 
X 
X 
X 
   Clinic staff surveys 
X 
 
 
 

 
19
improved upon our ability to collect hair samples as the study progressed (e.g., reducing refusal 
rates by 45% and obtaining samples from 85% of participants). In the case that a hair sample was 
not obtained, the team attempted to collect a urine sample instead. The urine samples were 
collected by a trained RA, which corroborated the self-report of drug use in the prior 30 days. 
Results were read by the RA after 5 minutes, and then the sample discarded. Results, reported by 
study ID, will be transferred by secure, encrypted electronic file and downloaded to a secure 
Michigan Medicine server. The study team has discontinued this measure (participants enrolled in 
November 2022 and on), as collecting hair samples has become increasingly difficult due to the 
COVID-19 pandemic and the expanding locations of our participant population. These challenges 
have made meeting participants in-person for sample collection challenging.  
 
C. STI Testing: STI testing for Michigan Medicine patients will be handled in one of two ways: 
onsite at the Michigan Medicine clinic laboratories (MLabs) by providing a urine sample, or 
through at-home STI test kits (vaginal swab). Specific infections assessed will include three STIs 
most common among sexually active childbearing women: 1) Trichomoniasis; 2) Chlamydia 
trachomatis; 3) Neisseria gonorrhea. For patients outside of Michigan Medicine, no urine sample 
will be collected, instead, the at-home STI testing kit (testing for the aforementioned STIs) will be 
mailed to them free of charge. After self-swab collection, participants will mail this kit (with pre-
paid postage) directly to the Johns Hopkins University School of Medicine laboratory for analysis 
(see more detailed information in section 12.1 below). Sensitive nucleic acid amplification tests 
make it possible to accurately diagnose STIs from urine samples. Vaginal swab tests are run on 
the Hologic Panther using the Aptima Combo 2 Assay to accurately detect STIs. Clinical 
outcomes include any incident STI and recurrent STI. These three specific diseases were 
selected as microbiologic outcomes because they encompass the most common infections seen 
in sexually active childbearing women that can result in adverse reproductive outcomes, can be 
unequivocally measured, and are immediately treatable. Women who test positive at any time 
during the study will be linked to comprehensive STI care at Michigan Medicine. Dr. Mmeje (Co-I), 
study physician, will facilitate treatment or will refer patients to another Michigan Medicine 
physician (for Michigan Medicine patients) who will provide treatment and counseling free-of-
charge to the participant. For non-Michigan Medicine participants who test positive, Dr. Mmeje will 
write a prescription for the appropriate treatment which will be available at a Michigan Medicine 
Pharmacy. Should they prefer to seek treatment elsewhere, research staff will do their best to 
help facilitate this process, and any cost of treatment outside of Michigan Medicine will be the 
responsibility of the participant. Research staff will also follow-up with non-Michigan Medicine 
participants to confirm that treatment was received and/or to help identify any obstacles to 
treatment (e.g., if patient needs additional treatment referrals, etc.). If the STI is reportable, it will 
be reported to the Health Department as required by law. It will be outlined in the consent form 
that if participants are noted to be STI positive, their health care provider will be notified to 
coordinate care and management. When baseline and follow-up assessments are delivered 
remotely, we will delay the collection of all biological specimens (urine screens at lab) for STI 
testing until they have a prenatal visit at the clinic. In this case, the study team will resume (pre-
pandemic) study procedures of ordering an STI urine screening on MiChart and direct the 
participant to go to the clinic lab after their prenatal visit with their provider, which will require no 
research staff contact. Regardless of this testing, we still plan to obtain consent to access STI 
results from the participant’s prenatal visits with their provider, by checking their medical chart on 
MiChart. These results will correspond with the participant’s prenatal/postpartum medical visits 
where testing occurred.  
 
D. Birth and maternal health outcomes: Will be collected electronically by the PI and study team 
through mother and baby’s hospital medical records (Von Voigtlander Hospital is the home to the 
majority of births in Washtenaw County, where participants from all Michigan Medicine study clinic 
sites give birth). Birth outcomes of interest will include: birth weight, head circumference, preterm 
birth, NICU admission and length, gestational age, APGAR scores (at 1-minute, 5-minutes, 10-
minutes), birth length, fetal distress, neonatal withdrawal (neonatal abstinence syndrome), 
meconium testing results, vaginal or cesarean birth, and breastfeeding at discharge. We will also 
be collecting maternal health outcomes. These include antepartum outcomes that are associated 
with substance use and/or high-risk pregnancies, including: diagnosis of chorioamnionitis and/or 
endometritis, admission for preterm labor, shortened cervix, vaginal or IM progesterone 
administration, antenatal steroid therapy, intrauterine growth restriction. We will also review the 

 
20
participant’s medical chart for any provider STI testing, diagnosis, and treatment completed during 
the pregnancy and postpartum period. If a participant delivers outside of the Michigan Medicine 
healthcare system, we will ask them to sign a request for outside records authorization form, so 
that we can request these birth and maternal health outcomes be sent to us from the delivering 
institution/birth center. Our study team will also have access to Luke Clinic’s Electronic Health 
Record System, allowing for the collection of patient medical information directly by the study 
team.  
 
E. Unprotected sexual occasions (USOs): A partner-by-partner assessment of sexual behaviors 
and condom use will be made for each of the participant’s sexual partners. USOs will be 
measured, as will partner type (casual, main). 
 
F. Pregnancy-Specific Intermediate Outcomes and Mediators 
 
 
Importance, confidence, and readiness rulers modified for the pregnancy context: 
Questions to determine readiness to change, importance for change (e.g., “How important is it 
that women quit marijuana use while pregnant?”), and confidence in ability to change substance 
use during pregnancy.  
 
1. Condom Use Self-Efficacy (CUSES) questionnaire. We will administer the subscale including 
items about individual’s perceived ability to use condoms during pregnancy. 
2. HIV/STI Knowledge Questionnaire: Measure of HIV/STI related knowledge adapted for 
pregnancy. 
3. Risk Perception. We will include items previously tested in pregnant samples to assess 
perception of risk of alcohol, marijuana, and sexual risks during pregnancy (e.g., “To what 
extent do you see your marijuana use as a problem?”). 
4. Treatment Self-Regulation Questionnaire (TSRQ; adapted version): Based on previous 
validated research, we will assess subscales of autonomous and controlled motivation for 
condom use, alcohol and drug use using adapted items from the TSRQ (e.g., “I want to make 
a change in my drinking because”: I personally believe it is the best thing for my health 
(autonomous) vs. Others would be upset with me if I drank (controlled)). 
 
G. Intervention Costs 
 
This study will be to measure the total costs of HCEM from both the provider and the participant 
perspectives. Unmeasured time costs for either staff or for participants can be a key barrier to the 
implementation and long-term viability of a new preventive intervention since preventive and 
screening recommendations can compete for implementation time from staff. We will address this 
potential barrier by measuring all relevant costs associated with the study interventions through 
primary data collection. We will derive estimates of resource requirements for the two study arms 
(HCEM, control) from process data collected during the RCT, including measuring material costs 
of hardware (tablet computers, maintenance to computers), expenses of CIAS software, materials 
costs (e.g., condoms, etc.), as well as managerial time required for screening participants. Costs 
for personnel will be based on salaries of program staff. In the cost analyses, we will calculate the 
costs of implementing HCEM. All costs will be adjusted to US 2015 dollars using the Gross 
Domestic Product Price Index. Control costs will be adjusted to reflect the proportion of time study 
participants reported spending on the STI-related material, not including the assigned general TV 
viewing time.  Questions on time allocation across activities will be included in the follow-up 
assessment. Net costs (savings) will be calculated by subtracting mean costs per participant in 
the control condition from mean costs per participant for HCEM condition. Change in treatment 
gains will be measured as the difference in STI incidence compared to the control condition. The 
outcome for the cost analysis will be expressed in dollars per STI averted. Given typical 
skewness, we will report means, medians, standard errors, minimum, maximum, and quantiles to 
provide information on cost distribution. Tests will be employed to assess distributions of the cost 
and identify appropriate methods for generating confidence intervals, such as non-parametric 
bootstrapping. 
 
H. COVID-19 Family Stress Screener  
 
 

 
21
The current coronavirus (COVID-19) outbreak is causing extra stress for many people, including 
families with children of all ages. We would like to know how this outbreak is impacting their 
health, safety and security. The COVID-19 Family Stress Screener will be embedded into CIAS 
and completed as a part of the baseline and each follow-up visit.  
 
6.0. Retention: The research team has had retention rates (an average of 90%) in large 
treatment trials involving high-risk, low-income pregnant and postpartum populations. The current 
study will employ several approaches that we have found helpful in achieving these low attrition 
rates, including study staff’s strong relationships with participants, efforts to value and appreciate 
the women’s participation in the study, and frequent personal contact with the women for the 
duration of the study. Booster sessions will be web-based and accessible for participants to 
complete at home. RAs call women to remind them of their assessment appointments and 
maintain a list of two other people who will always know where the participant resides. Transport 
and childcare are provided as deemed necessary to complete assessments, particularly during 
the postpartum assessment. Compensation for participants’ time helps facilitate retention.  
 
A. Special circumstances affecting study retention 
 
Because study eligibility includes being pregnant, and the HCEM is specifically tailored for 
pregnant women, in the event that an enrolled participant experiences a miscarriage, they will no 
longer be eligible for the study per the study research protocol. If study staff learns of miscarriage, 
study staff will call (or email if that is the preferred method of contact for the participant) the 
participant to follow up and offer Michigan Medicine resources for pregnancy loss, as well as 
notifying them of their new eligibility status.  
 
7.0. Data Analysis: Descriptive statistics will be calculated to summarize baseline characteristics 
for the full cohort and by intervention arm. Quality inspection will be carried out periodically to 
screen for missing-ness and data anomalies, and entry error. T-tests and chi-square-tests will be 
used to compare study arms with respect to demographic characteristics and baseline measures 
of unprotected sex and alcohol/drug use. Any identified confounders with p ≤ 0.10 will be included 
in all subsequent analyses. Using the TLFB, we estimate the frequency of number of days in the 
90-day period that the participant is engaged in a risky behavior. This will be carried out 
separately for each of the outcomes, namely, unprotected sex, illicit drug use and alcohol use, 
and heavy episodic drinking days (Hypothesis 1 and 2). The outcomes will be analyzed under a 
clustered count regression framework (Poisson or Negative Binomial) with frequency as outcome, 
and time (baseline, 2 months, 6 months), group (HCEM, control) and time-by-group interaction as 
the primary covariates. A generalized linear mixed models (GLIMMIX) approach will be adopted 
assigning a random subject intercept to account for the clustering within each participant. The 
regression model will be further controlled for potential confounders such as demographic 
characteristics, social desirability, and other variables that are identified to be significantly 
associated with outcome in the univariate analyses. We will adjust analyses for baseline 
pregnancy stage and assessment timing, as well as delivery status (delivered/not delivered) at 
follow up assessments in our data analysis, and pregnancy loss during course of study (e.g., 
miscarriage or stillbirth). Changes over time within each group will be estimated post-hoc by sliced 
effects derived from the regression model. In additional analysis, reduction in proportion of 
participants engaged in the risky behavior on ≥ 1 days within the 90-day period will be analyzed 
using a clustered logistic regression with a dichotomous outcome at the subject level indicating 
the status of the engagement, and with time (baseline, 2 months, 6 months), group (HCEM, 
control), time-by-group interaction as the primary factors. As before, a random subject intercept 
will account for the clustering and the model will be controlled for the same ensemble of 
covariates as in the case of the count regression models. Similar analyses will be conducted in 
the secondary aims for the outcomes that will be measured postpartum. To test hypothesis 3a 
and 3b, we will use structural equation modeling (SEM) approach. These include pregnancy-
specific measures of autonomous motivation, self-efficacy, knowledge and risk perceptions (see 
Table 1). These measures are all continuous and will be measured at all three time points. All 
relevant direct and indirect effects will be evaluated. Significance of the indirect effect of the 
mediators will be tested using bootstrap method which appears to have good power in small 
samples. Birth outcome data will be available to the team by accessing patient medical records 
postpartum (Hypothesis 2c). 

 
22
 
7.1. Procedures for Handling Discordance Between Self-Report and Hair Sample: We will 
conduct sensitivity analysis to assess hair sample testing and to evaluate the concordance 
between hair sample results and self-reported drug use on the TLFB at follow up assessments. In 
the case of discordance between self-report data and hair sample, following standards in the 
literature supporting the use of hair sample as a secondary measure in clinical trials, we will use 
hair testing in combination with self-report to confirm reported abstinence (e.g., we will change 
self-report abstinence to non-abstinence if objective data indicates illicit drug use). Because of the 
difficulties in collecting samples for drug testing due to COVID-19, we suspended all collection of 
biological samples for drug testing for participants enrolled November 2022 and on. 
  
7.2. Costs: Summary statistics for total HCEM-specific costs will be reported. Additional 
component cost outcomes will be reported including implementation time, and patient time. Net 
costs (savings) will be calculated by subtracting mean costs per participant in the control arm from 
mean costs per participant for HCEM. Change in treatment gains will be measured as the 
difference in STI status for HCEM compared to the control arm. The outcome for the cost analysis 
will be expressed in dollars per STI positive event averted (Hypothesis 2d).  
 
7.3. Missing Data: The missing values at the subject-level will be imputed using multiple 
imputation (MI) methods. This will use the chained equation method that allows both categorical 
and continuous variables to be imputed together without making any multivariate joint 
distributional assumption. We will combine the results from 10 imputed datasets using Rubin’s 
formula.131 The MI approach is valid for `Missing at Random’ scenario, i.e in cases, where the 
missing-ness mechanism is independent of the outcome after adjusting for covariates. Refusal to 
provide hair sample is perhaps one variable for which such an assumption may not be 
appropriate. Thus, for the models we use the information on hair sample, we will equate refusal 
with substance use. Based on our improved methodology for hair collection in the R21, we expect 
to yield ≤15% refusal. Given that refusal is likely to be low, impact on results is likely to be small. If 
refusal exceeds 15%, we will conduct imputation strategies that make various assumptions about 
missingness and the odds that it represents. Our inability to collect hair and urine samples at 
remote visits for drug testing (during the COVID-19 pandemic, which began in March 2020 and is 
currently ongoing as of February, 2023) will result in increased missing data. Because of the 
difficulties in collecting samples for drug testing due to COVID-19, we suspended all collection of 
biological samples for drug testing for participants enrolled November 2022 and on. 
 
7.4. Power: We estimated power based on our R21 study and calculated it using extensive 
simulation. For the count outcomes, power was obtained under a Poisson regression framework 
with time, group, and time-by-group interaction as covariates. Data was simulated 1000 times 
from models characterized by time and group specific means as well as the variance of the 
random effects estimated from the pilot data. Power was assessed for the interaction term as well 
as the main effects empirically by the proportion of times the corresponding coefficient was 
deemed statistically significant at 5% level.  
      For all the outcomes, our proposed sample of 250 should be adequate for detecting small to 
moderate effect sizes. Even assuming the worst-case scenario of up to 20% drop-out in both 
arms, we plan to recruit 125 participants per arm. In our data, we observed reduction in risky 
behavior in both study arms; however, the reduction in the intervention arm was significantly 
larger. For example, for unprotected sex, the baseline average number of days of unprotected sex 
was 36 based on the pilot data. Assuming that the average number of days of unprotected sex 
drops to 32 and 29 in the control and HCEM groups, respectively, (similar to that obtained in the 
pilot data) at any of the follow up points, using 100 subjects per arm the difference in the reduction 
in the groups will be deemed as statistically significant with more than 90% power. We assume a 
difference of 10 days between the intervention and the control groups in the change from baseline 
to be clinically significant. The differences for alcohol use and drug use were more prominent in 
our R21 data and we anticipate to be well powered for these aims. Similar effects were obtained 
when the dichotomous counter-parts were simulated using a clustered logistic regression model. 
In our data, more than 95% of the participants at baseline were engaged in risky sexual behavior. 
In the proposed study, we estimate a drop by 50% in the HCEM arm, which would be statistically 
significant using the above sample size. Outcomes of binary alcohol/drug use also yield power 
above 80% for scenarios similar to those obtained in the pilot data.  

 
23
 
8.0. Factors Affecting Implementation: We will explore factors that affect integration of HCEM 
into primary care. We will interview up to 30 staff stakeholders (e.g., clinical staff will be some 
combination of physicians, nurses, social worker, MA’s, PA’s, etc.) across each site including 
Michigan Medicine sites where we recruited for the study (West Ann Arbor, East Ann Arbor, 
Ypsilanti Health Center, etc.) and clinics outside Michigan Medicine, including Packard Health, to 
assess perceived barriers and facilitators, workflow impact, and fit with patient and site needs. In-
depth interviews will be conducted remotely using Zoom. We will ask specific questions (see 
Interview Guide) relevant to implementation of the HCEM. Additionally, we will include quantitative 
measurement via a Likert Scale (1-5), for example, providers will be asked questions about the 
feasibility and clinical utility of HCEM (e.g., “Will HCEM improve the overall quality of perinatal 
care? “What is the likelihood of incorporating HCEM into your prenatal program?”). We will also 
include open-ended questions about how HCEM could be improved to be of greater clinical utility 
to the health care provider and their patients. In addition to interviewing clinic staff, we will also 
recruit a subset of our study participants (approximately up to 10) to assess patients’ 
recommendations for HCEM modification (e.g. length of HCEM, readability). Additionally, we will 
be able to describe the program costs that would be needed to implement in a new setting. The 
interviews over Zoom will be recorded with the permission of the participants and the recordings 
will be stored on secure password protected computers and will only be accessible by the Study 
Coordinator and research staff. Recordings will either be transcribed using Zoom, or a third-party 
company like Lingperfect (audio files only), a HIPAA compliant transcription service. 
  
9.0. Design Considerations to Enhance Rigor, Reproducibility and Impact: A number of our 
methodological design decisions were determined by our pilot R21 findings. A limitation of many 
studies on STI risk reduction interventions for women is the imbalance in intensity of sessions 
between the experimental intervention and control group, which makes it difficult to determine if 
intervention differences are attributable to differences in attention between the conditions or to the 
“active ingredients” of the intervention. Our control condition will be matched for time, attention, 
and information, and will provide a rigorous test of the effect of HCEM. Follow-up assessments 
will be administered by RAs who are blinded to treatment assignment (and not by the same RAs 
who administers the intervention). Our study sites reflect considerable socioeconomic and 
ethnic/racial diversity, and higher rates of STIs and substance use, which will allow for 
generalizability of the results beyond one study site.  
 
10.0. Limitations and Countermeasures: Limitations of the current study include: potential 
issues related to disclosure of sensitive information, the use of self-report, assessment reactivity 
and effect on measured outcomes, the inclusion of only English-speaking participants, and 
generalizability of study results to other populations. To address these study limitations: 1) We will 
use technology to minimize socially desirable responses, particularly with stigmatizing behaviors, 
2) we will directly assess and adjust for social desirability bias, 3) the baseline computerized 
assessment will occur prior to randomization to minimize bias; 4) loss to follow-up will be limited 
by computer-based assessment and home visits during postpartum assessment, and by our 
experience with long-term follow-up of high risk, vulnerable samples of women; 5) the information-
matched control condition has been found acceptable and engaging in at least 4 behavioral 
studies that we know of including our own previous trials, and 6) based on data available at the 
clinic sites, there is only a small percent of women who are Spanish-speaking only. While 
participants will be recruited as close to first prenatal visit as possible, we will also include eligible 
high-risk women who are at later stages of pregnancy; we will adjust analyses for baseline 
pregnancy stage and assessment timing, as well as delivery status (delivered/not delivered) at 
follow up assessments in our data analysis, and pregnancy loss during course of study (e.g., 
miscarriage or stillbirth). We include monogamous pregnant women because STI risk is 
significantly elevated when substance abuse is present, regardless of partner status. Moreover, in 
our R21 study, 86% of the sample was monogamous, and yet intervention reduced condomless 
sex and substance abuse. We decided not to include genital herpes as an STI outcome as this is 
not in the clinical guidelines for STI screening set forth by the CDC. Dr. Mmeje will determine on a 
case-by-case basis for consideration of serological testing of genital herpes based on clinical 
presentation (e.g., active lesion) or partner history.  
 

 
24
11.0. Project Timeline: We include a timeline detailing the proposed study activities (see Table 2, 
below). 
 
11.1. Table 2. Planned Study Timeline  
 
Year 1 
Year 2 
Year 3 
Year 4 
Year 5 
 
1 
2 
3 
4 
1 
2 
3 
4 
1 
2 
3 
4 
1 
2 
3 
4 
1 
2 
3 
4 
HCEM Refinement, IRB, Hiring/Training Staff 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Recruitment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline / Follow-ups, Barriers Assessment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data Analysis/Publications 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12.0. PROTECTION OF HUMAN SUBJECTS 
This Human Subjects Research meets the definition of Clinical Research and of a Phase I clinical 
trial. It also meets the criteria of the OHRP for permitted research involving pregnant women (45 
CRF, Subpart B, Part 46.204). 
 
12.1. Risks to the Human Subjects 
Human Subjects Involvement and Characteristics 
Participants will include a total of 250 women in the prenatal period and their infants 
(details in proceeding section). Participants will be recruited from either Michigan Medicine or non-
Michigan Medicine clinics. The inclusion criteria will be pregnant women (as contemporaneous as 
possible to first prenatal visit), age 18 or older, and will follow similar recruitment to the R21 study 
given feasibility and acceptability rates. Specifically, the study will include pregnant women who 
endorse 1) at least one unprotected vaginal (or anal) sex occasion (USO) in the past 30 days 
(supported by the literature for our “high risk” sample, identified as such based on childbearing 
age, urban, ethnically diverse, and reporting co-morbid recent history of substance use), and 2) 
having more than one male partner in the last 6 months and/or having uncertainty about current 
sexual partner’s monogamy, and 3) current alcohol/drug use risk, and 4) is receiving medical care 
in the state of Michigan. Exclusion criteria include: 1) inability to provide informed consent (e.g., 
clear cognitive impairment), or 2) inability to understand English (understand the consent form 
when read aloud and assessments that are narrated by computer). No women will be excluded 
from recruitment on the basis of race or handicap. The inability to understand English will be 
determined by the inclusion of a subject comprehension assessment that will consist of a brief 
(five-question) true/false ‘quiz’ at the end of the consent form. These questions will relate back to 
key issues covered in the consent (e.g., “I can quit the study once I have started?” True_ False_) 
and will be modeled after the recommendations made by the NIH/U.S. Department of Health and 
Human Services. Incorrect answers will be reviewed with the participant and determination will be 
made regarding ability to understand English. For clinic-based or remote-based assessments, the 
women will receive cash, check, and/or gift cards (total equivalent to $270) for their participation 
($5 gift card for taking the eligibility screener, $60 for baseline session, $20 for the first booster 
session, $20 for the second booster session, $15 for the first STI test, $30 for completing the first 
follow-up assessment, $15 dollars for the second STI test, $30 for completing the second follow-
up assessment, $60 for completing the final follow-up assessment, and $15 for the final STI test 
during postpartum). For remote-based assessments, the women will receive the same 
compensation amount for each session, but payments will be delivered in the form of electronic 
gift cards or check. Women in the prenatal period were selected for two primary reasons: (a) 
interventions at this juncture may take advantage of a particularly salient point in a woman’s life, 
in which she may be more open to considering behavior change; and (b) any positive change 
made has the possibility of a dual impact, on the woman’s life as well as that of her infant. Of 
these 250 women, 125 women will be randomized to an intervention condition (Health Check-up 
for Expectant Moms, a brief motivational computer-delivered intervention) and 125 to a time, 
attention and information-matched control condition.  
 
Because pregnant women are a special population, we will have a DSMB (see below). 
During baseline and follow-up assessments, urine samples or at-home vaginal swabs will be 
collected so sensitive nucleic acid amplification tests can be conducted to diagnose STIs of 
interest (i.e., chlamydia trachomatis, neisseria gonorrhea). When baseline and follow-up 
assessments are delivered remotely, the study team will direct Michigan Medicine participants to 
go to the clinic lab when they have scheduled prenatal visits with their provider, which requires no 

 
25
physical contact with research staff. Regardless of this testing, we still plan to obtain consent to 
access STI results from the participant’s prenatal and postpartum visits with their provider, by 
checking their medical chart on MiChart. The at-home STI testing kits are provided and analyzed 
by The Center for Innovative Diagnostics for Infectious Diseases at the Johns Hopkins University 
School of Medicine. They run an online outreach screening program for sexually transmitted 
infections (STIs) that was initiated in 2004. A kit is mailed to participants’ homes with the materials 
needed to collect urogenital (vaginal) specimens for STI testing. Each kit includes the dry swabs 
needed for specimen collection, sample collection instructions, a biohazard bag for returning the 
specimens, a contact form, and a cardboard mailer for the specimen return (with prepaid 
postage). Upon return of the specimens by participants, JHU personnel log in the returned 
specimens, prepare them for testing, conduct the laboratory tests, verify results, and report results 
to the contracting organization (our research group) or directly to participants as requested. All 
samples obtained in the study will be used for research purposes only and will be discarded 
immediately upon completion of data entry and quality control procedures. While this STI testing 
will be performed primarily for research purposes, all results will be provided to study participants. 
Participants who test positive for any of the three STIs or with a recurrent STI will be referred for 
comprehensive STI care to their treating physician or health care provider at Michigan Medicine (if 
participant is a Michigan Medicine patient) to receive treatment to ensure cure. For Michigan 
Medicine patients, Dr. Mmeje (Co-I), study physician, will facilitate treatment or will refer patient to 
another Michigan Medicine physician who will provide treatment and counseling free-of-charge to 
the participant. For participants who test positive and are not Michigan Medicine patients, Dr. 
Mmeje will write a prescription for the appropriate treatment which will be available at a Michigan 
Medicine Pharmacy. Should they prefer to seek treatment elsewhere, research staff will do their 
best to help facilitate this process, and any cost of treatment outside of Michigan Medicine will be 
the responsibility of the participant. At the participants request, research staff will also 
confidentially communicate STI results to the participant’s health care physician, asking the 
participant to sign a medical release of information for this purpose. Research staff will also 
follow-up with non-Michigan Medicine participants to confirm that treatment was receive and/or to 
help identify any obstacles to treatment (e.g., if patient needs additional treatment referrals, etc.). 
Because both chlamydia and gonorrhea are reportable to the Michigan Health Department, they 
will be reported to the Health Department as required by law. We will not include genital herpes as 
this is not standard of care and not in the clinical guidelines for STI screening set forth by the 
Centers for Disease Control and Prevention (CDC). Dr. Mmeje will determine on a case-by-case 
basis for consideration of HSV serologic tests based on clinical presentation (e.g., active lesion) 
or partner history.  
Hair samples will also be obtained at specific follow-up assessments (see Table 1). In the 
case that a hair sample cannot be collected, we will attempt to collect a urine sample for drug 
testing in its place. The hair samples will be obtained by a trained RA and will corroborate self-
report of drug use in the prior 3 months. The samples will be collected from cosmetically 
undetectable areas on the scalp. Samples will be labeled with the study ID only, sealed, and 
stored into a locked cabinet in the locked research offices. They will be sent monthly by tracked 
mail to the Psychemedics laboratory in Culver City, CA for analysis. Urine samples are collected 
by a trained RA at specific study visits, and will corroborate self-report of drug use in the prior 30 
days. Results are read by the RA after 5 minutes, and then the sample is discarded. Results, 
reported by study ID, will be transferred by secure, encrypted electronic file and downloaded to a 
secure Michigan Medicine server. Participants enrolled after August 2022 will no longer submit 
hair samples.  
Participants in this study are pregnant women; as such, are a federally protected 
population in research studies. Since the goal of this research is to develop effective interventions 
for pregnant women who use are at risk for STIs and substance use during pregnancy, research 
with pregnant women is necessary. This research meets all conditions for research involving 
pregnant women (45 CFR, Subpart B, Part 46.204). 
 
Sources of Research Materials 
Research materials obtained from the participants in this study will include self-report 
measures gathered by use of the iPad iOS (or online for remote visits), STI and hair sample 
testing. 
 
12.2. Potential Risks 

 
26
There is the potential for low risks to participants associated with this research project: 
 
12.2.1.Breach of confidentiality: Assessment procedures could reveal sensitive information 
about participants’ medical history and history of alcohol/drug use. Risk of breach of confidentiality 
is possible, though highly unlikely. Specifically, if a participant tells research staff that she is 
planning to harm herself or her children, the research staff will report this information to the 
appropriate agency, as required by law. Other than the need to report those incidents that are 
regulated by mandatory reporting laws (the reportable STIs in Michigan are Chlamydia and 
Gonorrhea), we feel that there is minimal risk to participants with regard to other breaches in their 
confidentiality.  
12.2.2 Coercion: Coercion occurs when potential participants feel compelled to participate in 
research for reasons such as perceived demand or the availability of large sums of 
reimbursement. This can be particularly true when there is little benefit to the individual for their 
participant (not an issue in this study). In the present study, the inclusion of a protected population 
and protection from coercion is of the utmost importance.  
12.2.3 Discomfort: Participation in the study may lead to psychological distress due to the 
sensitive nature of questions regarding disclosure of STI and/or alcohol/drug use during 
pregnancy the related negative social and psychological consequences. There are no physical 
risks conferred by urine testing for the sensitive nucleic acid amplification tests to be conducted to 
diagnose the STIs of interest. However, testing for any sexually transmitted disease can involve 
the psychological burden of finding out one has an infection that needs treatment or having a false 
positive test result.  
Adequacy of Protection Against Risks 
At each point of contact in the study, participants will be reminded of the alternative of not 
participating in the study (or once enrolled, to discontinue participation), and will be informed that 
their care at Michigan Medicine clinics, or any care within Michigan Medicine and in any other 
follow-up medical care at the clinics and/or Michigan Medicine will in no way be affected by their 
decision to participate or not to participate in the study. Moreover, we will provide referral 
information to all participants at each point of contact. Further procedures to minimize each of 
these risks are described below.  
 
12.3. Protection Against Risk 
We will take the following steps to protect against risks associated with this research 
project: 
 
We will minimize the risk of breach of confidentiality. A Certificate of Confidentiality will be 
obtained from the National Institutes of Health prior to the commencement of research. The 
purpose of this certificate is to protect the identity of research subjects participating in studies that 
collect sensitive information. Potential participants will be informed that a Certificate of 
Confidentiality has been obtained for this project and that this certificate will protect the 
investigators from being forced to release any research data in which participants can be 
identified, even under court order or subpoena, although this protection is not absolute. Potential 
participants will be informed of the situations in which they may not be protected under the 
Certificate of Confidentiality. No information about participants will be released without their 
permission or where required by law. This approach has been successfully carried out by Drs. 
Tzilos Wernette and Zlotnick in previous studies involving women in the perinatal period. 
Risk of social or legal consequences as a result of disclosure of STIs and/or alcohol/drug 
use during pregnancy will be dealt with in several ways. We will minimize the potential risks due to 
loss of confidentiality by strictly adhering to the guidelines for research outlined by the University 
of Michigan IRB, Michigan state law and the DHHS Federal Policy for the Protection of Human 
Subjects (45 CFR Part 46 Subpart D). As described in the previous section, there will be full 
informed consent prior to participation in the study (a two-part consent process). Participant data 
will be encrypted in transit between user and server. No identifying information will be entered into 
the CIAS software; the software will designate a unique participant code for each participant. 
Additionally, all forms with participant information will be marked with a code number and not with 
the participant’s name. The link between the participant code number and name will be securely 
stored on the HIPAA-compliant database REDCap, which is administered and managed through 
the Michigan Institute for Clinical Research (MICHR) at the University of Michigan. This database 
will only be accessible by the Study Coordinator and study staff. Lastly, potential participants will 

 
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be informed of the situations in which they may not be protected under the Certificate of 
Confidentiality. Participants will also be informed about the risk of loss of confidentiality due to the 
STIs screens. No information about participants will be released without their permission or where 
required by law. Further, we have confirmed with Child Protective Services (CPS) of the Michigan 
Department of Health and Human Services, that they do not respond to reports of substance use 
during pregnancy unless the report is of a newborn infant with alcohol/drug in its system. Further, 
per the Michigan Department of Health and Human Services guidelines, there is no mandatory 
reporting of the disclosure of alcohol or drug use during the postpartum assessments.  
Possible distress due to sensitive items will be noted clearly in the informed consent 
information sheet (for screening) and in the written informed consent form (for participants). All 
participants will be told that they can skip any question, test, or quit at any time if they become 
uncomfortable. To further address possible distress due to sensitive items, participants will be 
asked by the computer program if anything the computer has asked or done is making them feel 
upset right now. The computer program will notify the research team at completion of study if any 
participant answers yes to this question, in addition to notifying the research team if the participant 
has endorsed any items indicative of possible need/desire for further assistance. (Note that the 
computer program will not provide details regarding any answers, only that there is a need to 
follow-up with the participant verbally to evaluate the need for assistance). At a minimum, all 
participants indicating some distress will be given a list of referral options that will include 
information on how to contact a Michigan Medicine social worker. We will minimize the 
psychological burden associated with STI tests (i.e., trichomoniasis, chlamydia trachomatis, and 
neisseria gonorrhea).  
Participants face the risk of increased psychological distress due to the research 
procedure of STI testing and distress due to a positive test for one of the selected STIs or having 
a false positive test result. All women will be informed that they do not need to be tested for the 
selected STIs, if it poses too much distress for them. They will be reminded that they can 
discontinue participation at any time. Moreover, as mentioned in the section above, clinical 
backup will be provided during all assessments and during the intervention phase of the study by 
a licensed clinician to help facilitate the stabilization and referral process for participants who 
decompensate during assessment procedures.  
At any phase of the study (i.e., during the follow up assessments), participants who test 
positive for any of the three STIs or with a recurrent STI will be referred for comprehensive STI 
care to their treating physician or health care provider at Michigan Medicine (if participant is a 
Michigan Medicine patient). For Michigan Medicine patients, Dr. Mmeje (Co-I), study physician, 
will facilitate treatment according to the 2015 CDC STD Treatment Guidelines or will refer patient 
to another physician who will provide treatment and counseling free-of-charge to the participant. If 
the STI is reportable, it will be reported to the Health Department as required by law. Results of 
STI testing and any subsequent treatment or referrals will also be confidentially communicated to 
the participant’s health care physician, if the participant requests this transfer of information. 
Participants will be asked to sign a medical release of information for this purpose. The study will 
arrange and cover transport costs for participants without transport who need these follow–up 
appointments for STI treatment. Research staff will assist participants in addressing any barriers 
to accessing treatment and will follow-up with participants to confirm that treatment was received. 
For participants who test positive and are not Michigan Medicine patients, Dr. Mmeje will write a 
prescription for the appropriate treatment which will be available at a Michigan Medicine 
Pharmacy. Should they prefer to seek treatment elsewhere, research staff will do their best to 
help facilitate this process, and any cost of treatment outside of Michigan Medicine will be the 
responsibility of the participant. At the participants request, research staff will also confidentially 
communicate STI results to the participant’s health care physician, asking the participant to sign a 
medical release of information for this purpose. Research staff will also follow-up with non-
Michigan Medicine participants to confirm that treatment was received and/or to help identify any 
obstacles to treatment (e.g., if patient needs additional treatment referrals, etc.). 
 
12.4. Potential Benefits of the Proposed Research to the Subjects and Others 
The potential risks associated with participation in this study appear to be mild to 
moderate. Although there is a risk for distress, the procedures proposed for monitoring distress 
should ensure that participants who require a higher level of care receive it. The potential benefits 
of study participation are great, and include STI testing and referral for treatment for STIs. Other 
benefits to women participating in this study include close monitoring of participants’ STI risk, 

 
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alcohol/drug use, as well as participants’ increased awareness of resources for STI and treatment 
providers for women with alcohol/drug difficulties. We will follow standard clinical practice as 
declared in the state of Michigan, and all women in both conditions will receive (1) a brochure 
specifically designed to facilitate reductions in drinking/drug use during pregnancy, and (2) a list of 
referrals, including sites for free STI testing and treatment as well as treatment for alcohol and 
drug use. Half of the participants will receive a brief intervention designed to increase the 
likelihood of self-change and/or obtaining resources for STI and alcohol/drug use. Moreover, 
participants are helping other childbearing women with STI risk through providing information that 
will improve STI risk prevention interventions for this population of women. Such an intervention, 
then, could potentially be presented to unprecedented numbers of persons (within primary care or 
other settings) in a way that is financially and logistically feasible, potentially leading to beneficial 
effects for large numbers of women as well as their infants. Thus, the potential benefits outweigh 
the potential risks of the study.