Pilot Study to Evaluate a Behavioral Activation Prenatal and Postpartum Intervention for Depressed Pregnant Smokers
Phase: NA
Conditions: Depression, Tobacco Use Disorder
Sponsor: M.D. Anderson Cancer Center

Protocol 2020-0972 
December 28, 2023Page 1 of 48 
Pilot Study to Evaluate a Behavioral Activation Prenatal and Postpartum 
Intervention for Depressed Pregnant 
Smokers 

Protocol 2020-0972 
December 28, 2023Page 2 of 48 
 
Specific Aims 
Primary Aims 
Aim 1 (Stage IA) 
Conduct qualitative group interviews with depressed pregnant smokers and depressed smokers 
within the first 4 months of the postpartum period, to adapt and refine the delivery of behavioral 
activation therapy (BA) and health and wellness education (HW) via smartphone 
videoconferencing, a BA and HW smartphone application (app) including supportive smoking 
cessation messages in the prenatal and postpartum periods.  Participants will be queried on a) 
barriers and supports to completing treatment sessions and study assessments; b) suggestions 
for decreasing barriers and increasing treatment acceptability; c) usefulness of BA, HW and 
smoking cessation counseling treatment materials, and; d) usefulness and acceptability of the 
BA and HW apps.  
Aim 2 (Stage IA) 
Adapt BA and smoking cessation counseling manuals, BA and HW app and content, and 
treatment integrity rating scales for the prenatal and postpartum period  
Aim 3 (Stage IA) 
Pilot test the delivery, via smartphone videoconferencing, of a 10-week treatment course of BA 
and HW and conduct process evaluation of technical issues in the use of smartphones, barriers 
to participation and retention; completion of study assessments, and; adequacy of procedures 
for addressing psychiatric emergencies. 
Aim 4 (Stage IB) 
Conduct a preliminary randomized trial with depressed pregnant smokers comparing BA to HW 
to evaluate: 1) Effect of BA on abstinence at 4 ½ months postpartum; 2) Effect of BA on 
depression at 4 ½ months postpartum; 3) Feasibility of acceptance of the smartphone delivery 
of BA and HW, and assessment components indicated by a) retention; b) completion of prenatal 
and postpartum sessions; c) completion of study assessments, d) strength of therapeutic 
alliance from both the participant and therapist perspective; e) participant and therapist ratings 
on satisfaction questionnaire; 4) Feasibility of study procedures as indicated by a) percentage of 
sessions interrupted by technical difficulties, and; b) percentage of urine cotinine and/or 
anabasine tests received for biochemical verification of self-reported abstinence at 4 ½ months 
postpartum. 
Secondary Aims 
Secondary Aim 1 (Stage IB) 
Evaluate change in hypothesized treatment mechanisms including positive affect, negative 
affect, and cognitive function in relation to treatment effects on smoking and depression. 
Secondary Aim 2 (Stage IB) 
Conduct qualitative interviews with women who completed and did not complete postpartum 
treatment to assess a) barriers to completing treatment sessions; b) usefulness of postpartum 
treatment; c) suggestions for decreasing barriers and improving treatment acceptability, and; d) 
relevant experiences unexpected by participants and researchers. 
BACKGROUND 
Importance of the Problem 
Comorbid depression is associated with continued smoking during pregnancy 
and nicotine dependence  Smoking and depression frequently co-occur in pregnant women, 
especially in women of low-income status.1, 2  Depression is associated with continued smoking 
during pregnancy.  In a recent large epidemiological study, depressed women were twice as 
likely to continue to smoke during pregnancy than nondepressed women (16.3% vs. 7.2%).3  
Using data from the 2008-2014 National Survey on Drug Use and Health, 40% of pregnant 
women experiencing current serious psychological distress, as assessed by the K6 screening 
instrument, reported current smoking compared to 11.7% of women without recent distress.  

Protocol 2020-0972 
December 28, 2023Page 3 of 48 
 
Among women with current serious psychological distress, the prevalence of current prenatal 
smoking had not changed between 2008 to 2014, whereas among women without distress, the 
prevalence of smoking significantly declined.4  Depression in pregnant women who smoke is 
strongly associated with higher levels of nicotine dependence.2, 5  These studies suggest that 
depression is associated with difficulty quitting in pregnant smokers and that they may require 
more tailored approaches to cessation treatment. 
Smoking and depression during pregnancy have independent negative effects on 
birth and infant outcomes  Independently, maternal depression and smoking during the 
prenatal and postnatal periods produce pernicious effects on fetal and child health, suggesting 
there may be additive negative effects when these factors co-occur.6  Smoking during 
pregnancy is responsible for 20% or more of the incidence of low birth weight, a condition that is 
associated with neonatal, perinatal, and infant morbidity and mortality.7, 8  Pregnant women who 
smoke are at increased risk for a number of adverse pregnancy outcomes including placental 
abruption, pre-term birth, stillbirth, sudden infant death syndrome, and spontaneous abortion.9, 10  
Maternal smoking during the postpartum period is associated with infants’ higher risk of 
hospitalization for respiratory tract and other types of infections during the first 12 months of 
life,11–13 slower lung growth and lung function decrements,14, 15 increased school absence,15 and 
sudden infant death syndrome.16, 14   
Clinically significant maternal depressive symptoms during pregnancy are associated 
with preterm birth and low birth weight, especially among low-income women.  This effect is 
independent of smoking, and the magnitude of risk for preterm birth posed by clinically 
significant antenatal depressive symptoms is comparable to the risk of smoking 10 or more 
cigarettes a day.17  The presence of affective disorders and clinically significant depressive 
symptoms during pregnancy have been found to be associated with abnormalities in fetal 
activity, low Apgar scores, poor neurobehavioral functioning, neuroendocrine abnormalities in 
the limbic-hypothalamic-pituitary axis at birth, newborn irritability, and fetal death.18–21  Major 
depressive disorder (MDD) during the prenatal period is associated with poor maternal-fetal 
attachment which has been shown to negatively influence psychosocial child development.22  
Postpartum maternal depression is related to increased risk of injury among infants and 
toddlers,23 decreased breastfeeding duration,24, 25 reduced weight gain during infants’ first 2 
years of life,26, 27 increased infant hospitalization28 and emergency room visits,29 poorer parental 
preventive practices for child safety 30, 31 and increased risk for adjustment problems in 
childhood.32  
 
Scientific Premise 
Brief counseling with pregnant and postpartum smokers is largely ineffective or 
produces low abstinence rates  Psychosocial smoking cessation interventions administered 
during the prenatal period have yielded only modest effects and low abstinence rates of 7.6% in 
control conditions and 13.3% in experimental conditions.33, 34 A more recent review of all 
intervention types in pregnant smokers (e.g., self-help booklets, counseling) found that the 
pooled mean estimate of the proportion of women smoking at end of pregnancy was 87%.35  It 
is important to note that the majority of studies in this review evaluated information booklets and 
brief counseling interventions (15 to 90 minutes).  Interventions that have offered up to 8 hours 
of counseling and/or multiple counseling contacts have been found to be more efficacious in 
pregnant smokers and have produced higher abstinence rates (18% to 39%).36–38 The modest 
abstinence outcomes that most prenatal smoking cessation interventions have produced, 
decline further in the postpartum period, and in most studies, prenatal differences between 
experimental and control conditions are no longer significant at postpartum follow-ups.33, 39  In 
the review of all intervention types, the pooled mean estimate of women smoking at 6 months 
postpartum was 94%.35  A number of studies have evaluated postpartum counseling 

Protocol 2020-0972 
December 28, 2023Page 4 of 48 
 
interventions designed to maintain cessation throughout pregnancy and into the postpartum 
period, or to prevent relapse in women who quit on their own during pregnancy.  The majority of 
these studies have tested low intensity counseling sessions—1 to 4 brief postpartum counseling 
sessions delivered by nurses and trained clinical staff.40–48 Reviews of postpartum interventions 
have found no evidence of statistically significant benefits for these brief interventions.49, 50  
Evidence that an intensive depression-focused intervention is efficacious for 
smoking cessation in depressed pregnant smokers   In a previous randomized trial,51 we 
evaluated the efficacy of an intensive,10-session prenatal smoking cessation intervention that 
included a depression-focused treatment component (cognitive behavioral system of 
psychotherapy [CBASP]), compared to the time and therapist contact health and wellness 
education (HW) control that will be used in the proposed study.  We did not target depressed 
women in our recruitment.  However, 23.3% of women entered the trial with current MDD and 
13.6% were in partial remission of a major depressive episode.  The average CES-D score for 
the sample was above the cut-off for possible depression (18.8).  We hypothesized, a priori, that 
women with the highest depressive symptoms would benefit to a greater extent from CBASP 
compared to HW.  At end of treatment, both treatments produced some of the highest rates of 
abstinence that have been reported at end of prenatal treatment (45.3% for CBASP and 39.2% 
for HW).  At 6 months following end of treatment, which occurred on average at 4½  months 
postpartum, women in the highest quartile of CES-D scores (M = 35.08, SD = 5.07) at study 
entry treated with CBASP were significantly more likely to be abstinent (26% versus 9%) and 
had significantly lower levels of depression through 6 months postpartum compared to women 
in the high depression group treated with HW.   These findings support the premise that 
clinically depressed pregnant women may benefit to a greater extent from an intensive smoking 
cessation intervention that concurrently addresses both depression and smoking than an 
intervention that addresses smoking only.  However, similar to other prenatal smoking cessation 
studies, abstinence significantly declined by 6 months postpartum, and there were no group 
differences at the 6-month postpartum follow-up.   
Extended psychosocial interventions are recommended for pregnant women  The 
proposed study is in line with recent recommendations to study extended treatment approaches 
for pregnant smokers that allow for treatment of women in the prenatal period and postpartum 
periods.52, 53  Such treatments should address factors that are associated with difficulty quitting 
and increased risk of relapse, such as stress, and should focus on providing continued support 
of both abstinent, and nonabstinent women for quitting, preventing relapse, and getting back to 
abstinence as soon as possible following relapse.53  The proposed study focuses on depressed 
pregnant smokers, a group that is likely to experience the highest severity of factors known to 
be associated with relapse risk including poor mental health and stress associated with the 
transition from birth to postpartum.  
Behavioral activation is efficacious for the treatment of depression in pregnant 
women and shows promise as a smoking cessation intervention in smokers with 
elevated depressive symptoms Behavioral activation emphasizes the relationship between 
activity and mood.  It seeks to increase engagement in rewarding and adaptive activities, 
decrease activities such as avoidance and withdrawal that maintain or increase risk for 
depression, and solve problems that limit access to reinforcers.  It has been found to be 
comparable in efficacy to cognitive therapy (CT) and antidepressant medication (ADM) for the 
treatment of current MDD54, 55 and more efficacious than either CT or ADM in more severely 
depressed patients.55  Importantly, BA has been found to be more effective than treatment as 
usual in depressed pregnant women when delivered by trained nurses and master level 
behavioral health counselors in obstetric clinical settings, and was more effective in reducing 
anxiety symptoms and stress.56  In addition, there is evidence for the efficacy of BA plus 

Protocol 2020-0972 
December 28, 2023Page 5 of 48 
 
standard smoking cessation counseling compared to standard smoking cessation counseling 
alone in smokers with elevated depressive symptoms.57 58 
Theoretical model for targeting both depression and smoking   A recently proposed 
theoretical model59 posits that among smokers with comorbid depression, adverse internal 
states of low positive affect (PA), high negative affect (NA) and cognitive impairment function as 
motivational states that predict greater reinforcement value of smoking and elicit an expectation 
of greater reinforcement value.  Explicit goal-directed instrumental knowledge of response 
sequences that yield reinforcement from nicotine is acquired, which drives behavior to achieve 
the desired smoking outcome in specific external contexts.  These incentive learning processes 
serve to promote smoking maintenance and relapse in depressed smokers. The theoretical 
framework is applicable to smokers in general.  However, in those with comorbid depression, 
these internal motivational states are especially effective in driving smoking because depressed 
smokers experience more intense adverse states, thus greater reinforcement; and withdrawal is 
more severe, further intensifying these adverse states as smoking motivators.  The high reward 
value of smoking in these states is particularly motivating during abstinence and is 
conceptualized as the primary trigger for smoking maintenance and relapse. A prediction of this 
model is that treatment should attenuate these states and reverse positive expectancies 
associated with smoking to help depressed smokers achieve cessation. 
We posit that BA, given evidence of its efficacy in addressing depression and anxiety 
symptoms, will be more effective than HW at addressing these states and thus produce higher 
levels of smoking abstinence.  More specifically, we hypothesize that BA will address PA 
through treatment components that increase availability of positive reinforcement and increase 
reward value of potentially pleasant events; NA through treatment components that encourage 
approach behavior in the context of adverse emotional states and encourage a problem-solving 
stance;60, 61 and cognitive deficits resulting from BA’s greater resolution of depressive symptom 
severity.59  We will evaluate PA, NA and cognitive function as mediators of both smoking and 
depression treatment outcomes. 
Smartphone videoconferencing interventions have potential reach and impact in 
low-income populations with psychiatric disorders  Historically intensive treatment 
approaches have been labor intensive, cost prohibitive and unfeasible for populations such as 
pregnant and postpartum women.  However, recent developments in mobile/internet based 
software provide opportunities to deliver psychotherapeutic interventions via 
videoconferencing.62–66  A chief benefit of videoconferencing delivery of mental health 
interventions is the capability of this technology to display visual and auditory information, which 
offers a greater proxy to traditional in-person service delivery than web- or telephone-based 
treatment delivery and may be especially important when delivering more complex, empirically-
validated interventions.  Delivery of empirically-validated psychotherapies by videoconferencing 
has the potential to reduce barriers to treatment delivery and access including overcoming cost 
and motivational barriers when patients must travel great distances to seek treatment.  This may 
be an especially important issue in delivering high quality, empirically-validated treatments to 
low SES populations. Videoconferencing delivery of psychotherapies may also provide greater 
opportunity for low-income populations to access providers who are trained in empirically-
validated therapies and it may allow for more cost-effective delivery of extended treatments 
which, as noted above, have been found to be more efficacious in the treatment of smoking 
than standard courses of treatment.   
Gaps in Scientific Knowledge and Technical Capacity That Will Be Addressed   
  As noted above, in-home videoconferencing delivery of evidence-based 
psychotherapies has been found to be feasible and acceptable when delivered on desktop, 
laptops and tablets.  However, to date there has been less focus on testing video-based 
psychotherapeutic interventions via smaller screen, portable devices such as smartphones. In 

Protocol 2020-0972 
December 28, 2023Page 6 of 48 
 
low-income populations, smartphones may serve as the only or primary access that individuals 
have to access the internet.  Given the importance of the therapeutic alliance in predicting 
symptom reduction in depression treatments,67 it is especially important to evaluate the quality 
of the alliance that can be established when BA is delivered by smartphone.  In addition, it is not 
known whether smartphone video and audio quality are adequate for delivery of psychotherapy.  
Within a research context, it is desirable to conduct screening and study assessments remotely 
by telephone and smartphone to reduce the need for participants to travel to the research 
location.  This would allow for increased ability to recruit and retain participants and opportunity 
to evaluate a completely remote delivery of the intervention.  However, remote assessment 
introduces questions concerning measurement integrity and ability to adequately manage 
psychiatric emergencies. Specific to the targeted population, there are no studies demonstrating 
the acceptability and feasibility of extending behavioral treatments from the prenatal to 
postpartum period in low-income pregnant smokers with high levels of depressive symptoms.  
Women who continue to smoke during pregnancy experience more psychological problems, 
less paternal social support and more stress associated with family problems, finances, job 
strain, and unemployment.19, 68–71 These factors could pose barriers to engaging in treatment 
over long periods of time, especially when treatment is delivered remotely. 
The proposed study will utilize Stage I of the Stage Model of Behavioral Therapies 
Research to address these research gaps. The Stage Model of Behavioral Therapies, which is 
supported by National Institute on Drug Abuse, articulates progressive stages of development 
and evaluation of behavioral interventions.  Stage IA is focused on therapy development and 
manual writing.  Stage IB is focused on pilot testing of a final version of the therapy.72  The 
figure below depicts the stages of the proposed study by the Stage Model.  To increase the 
generalizability of study findings to the population in which smoking rates are highest during 
pregnancy and a population that might be actively screened and referred for treatment in the 
future should the intervention be found to be efficacious, we will recruit participants from 
antenatal clinics that serve predominantly low income pregnant women, and also recruit from 
the community, potentially across Texas, using advertising that may include social media, ads, 
print, or flyers.  We will use master level counselors to deliver the interventions and utilize self-
report questionnaires to assess important variables which could more easily translate to use in 
tobacco treatment services.  Completion of this study will allow for the evaluation of a number of 
aspects of feasibility and acceptability of smartphone real-time video delivery of an evidence-
based behavioral therapy in a population that previously has been recalcitrant to treatment.  
Findings will contribute to overall knowledge of the feasibility of delivering intensive behavioral 
interventions via newly developed technologies and information on BA’s effect size for planning 
of future trials. If BA is found to be efficacious in depressed pregnant smokers in future trials, it 
could be more broadly disseminated through quit lines and other remotely delivered smoking 
cessation specialist services.  
Investigative Team 
 
The PI, Dr. Janice Blalock, has extensive experience conducting studies evaluating 
cognitive behavioral interventions for the treatment of depressive and anxiety disorders and 
comorbid depression and smoking.  During her tenure as a clinical assistant professor at 
University of Texas Medical Branch, she served as a co-investigator and site psychotherapy 
supervisor on a multi-site study evaluating a combined CBASP and antidepressant medication 
intervention versus medication and CBASP alone, in the treatment of chronic major 
depression.73–82 She was co-principal investigator on our previous clinical trial evaluating 
CBASP as a smoking cessation intervention for pregnant smokers during the prenatal period 
(R01 DA14301).  She has published and co-authored numerous articles examining treatment of 
smoking in pregnant women and the impact of depression and other psychological variables on 
smoking-related outcomes in pregnant smokers.83–87, 51, 88, 89 Dr. Blalock was also the PI on a 

Protocol 2020-0972 
December 28, 2023Page 7 of 48 
 
NIMH-funded study (R01 MH076776) and subcontract (1R01MH087692) investigating CBASP 
as a smoking cessation intervention for chronically depressed smokers.   
 
 
 
 
 
RESEARCH DESIGN AND METHODS 
Aims 1-3 Approach 1 (Stage IA) 
 
Design The overall objective of Aims 1, 2 and 3 is to adapt an existing BA treatment 
protocol90 that has been tailored for depressed pregnant women56 for delivery via real-time 
videoconferencing on smartphones during the prenatal and postpartum periods.  As part of Aim 
2, we will adapt these existing BA treatment protocols to create a manual for treatment of 
depression in the prenatal and postpartum period.  We have existing smoking cessation 
counseling manuals for treatment of pregnant smokers in the prenatal period from a previous 
trial,51  which we will extend to the postpartum period.  The focus of BA during the postpartum 
period will be similar to that of the prenatal period—“increasing engagement in rewarding and 
adaptive activities, decreasing engagement in activities that maintain or increase aversive 
control (including avoidance) and solving problems that limit access to reward or maintain or 
increase aversive control.”60 However, there is a need to further develop the smoking cessation 
counseling treatment for the postpartum period which we will accomplish in this phase of the 
study.  
There is a need to evaluate the feasibility of delivering such therapies by smartphone 
videoconferencing given the potential for lack of treatment engagement over a smaller screen, 
use of data plan minutes for extra-treatment activities that deplete minutes available for pending 
treatment sessions and loss of cell phones. Other areas in need of evaluation include technical 
issues associated with equipment, need for technical support and remote management of 

Protocol 2020-0972 
December 28, 2023Page 8 of 48 
 
adverse reactions and psychiatric emergencies.  Among pregnant and postpartum women, 
there may be barriers that impact their ability to participate in numerous therapy sessions over 
an extended period of time, such as lack of child care and unwillingness/inability to be located in 
a private area when treatment sessions are scheduled.  During stage IA of the project, we will 
continuously evaluate the data collected, and if we feel that the data collected has provided the 
information to optimize the treatments and study procedures for AIM 4 (Stage IB), we may begin 
AIM 4 before we finish AIM 3.   .      
Aim 1 (Stage IA) and Secondary Aim 2; Research Design 
Participants In year 1, we will recruit a) depressed pregnant smokers and; b) depressed 
women within 4 months postpartum who smoke to participate in individual interviews or in focus 
groups of up to 12 participants each.  Approximately two thirds of the sample (up to 24 
participants) will be gestational age up to 36 weeks, and approximately one third (up to 12 
participants) will be within 4 months postpartum. Women will be required to meet Stage IA trial 
eligibility criteria and will be recruited in the same manner as women who will participate in the 
Stage IB trial (See Section Eligibility criteria and Recruitment sites). Participants will be provided 
with a smartphone preloaded with an institutionally approved videoconferencing application to 
reduce barriers to participating in the focus group. They will be able to keep the smartphone 
following the completion of the focus group (See Provision of Smartphones and Data Plans).  
 
In the case that Covid-19 prevents us from conducting focus groups, we will conduct one-on-
one interviews with women who meet the eligibility criteria. 
 
Participant Compensation Participants will be compensated by way of a reloadable gift card;  
$25 for the completion of the baseline visit and $50 for the completion of the one-time focus 
group, for a total of $75. 
 
Eligibility Criteria: AIM 1 
 
Inclusion criteria for Aim 1 
1) Pregnant (or within 4 months post-partum for aim 1 only) 
2)  Meets criteria for current Major Depressive Disorder (MDD) as assessed by the Mini 
International Neuropsychiatric Interview (MINI) 7.0.2  OR PHQ score of 10 or greater.   
3)   ≥ 18 years of age 
4)  Have a telephone  
5)  Self report smoking, even a puff, cigarettes, little cigars and/or cigarillos in the past 30 days.  
6)  Approximately two thirds of the sample will be gestational age up to 36 weeks, and 
approximately one third will be within 4 months postpartum 
7)  Able to speak and read English 
8) Subjects must report a current residence in the State of Texas  
Exclusion criteria for Aims 1 
 
1) Rated on the Columbia-Suicide Severity Rating Scale113 at screening as in the past month 
having had active suicidal ideation with some intent to act or active suicidal ideation with 
specific plan and intent (indicated by answering “YES” on both Q3 and Q4, and/or 5) and/or 
endorsing “YES” to having engaged in preparatory acts towards or attempting suicide in the 
past 3 months (as indicated by answering “YES”  to both parts of Q6)   
2) Have a lifetime or current diagnosis of Psychotic Disorder as assessed by specified Mini 
International Neuropsychiatric Interview (MINI) 7.0.2 modules. 

Protocol 2020-0972 
December 28, 2023Page 9 of 48 
 
3) Have a past or current diagnosis of Bipolar Disorder I or II or have a past or current 
diagnosis of Other specified Bipolar and related disorder as assessed by specified MINI 
7.0.2 modules. 
4) Any otherwise not specified medical or psychiatric condition, illness, disorder, or 
concomitant medication that could compromise participant safety or treatment, as 
determined by the Principal Investigator and/or Study Physician. 
5) Participant considered by the investigator as unsuitable candidate for full participation in the 
study. 
 
Refer to sections Participant Recruitment (Aim 1, 3, 4), Pre-Screening Assessment (AIM 
1, 3, 4), Informed Consent Process (AIM 1, 3, 4), Baseline Screening Phone Visit (AIM 1, 3, 
4) for detailed information of the enrollment process.  
 
 
Focus Group Procedures and Data Analysis Objectives of Aim 1 are to collect 
qualitative data on a) barriers and supports to completing treatment sessions and study 
assessments; b) suggestions for decreasing barriers to treatment engagement and increasing 
treatment acceptability; and c) usefulness of BA, HW and smoking cessation counseling 
treatment materials that will include pregnancy specific materials that focus on the prenatal and 
postpartum period (Forever Free…For Baby and Me),91 and; d) usefulness and acceptability of 
the BA app, supportive HW app messages and supportive smoking cessation messages.  
Examples of smoking cessation counseling material specific to the postpartum period include: 
ways that smoking abstinence improves the health of the newborn and risks of second and third 
hand smoke to infants and children, management of stress and negative moods related to birth 
and new motherhood, use of alcohol as a risk-factor in the postpartum period, hormonal 
changes after birth, effect of smoking on breastfeeding and benefits of breastfeeding, lifestyle 
balance as a protection against relapse, and coping with weight gain using non-smoking 
strategies.  Individual interview or focus group participants will also view a sample list of Health 
and Wellness topics and a video sample of BA techniques (refer to study document ‘Ppt HW 
Manual Contents’) 
Given that our focus is on low-income women, we will include specific questions on 
variables frequently noted in low-income women who smoke that may present barriers to 
successful cessation and treatment engagement (refer to study document ‘Focus Group 
Questionnaire’).  Women who continue to smoke during pregnancy are more impoverished, 
more nicotine dependent, have more smokers in their social network, are more likely to 
consume alcohol during pregnancy, to be single and to have an unintended pregnancy than 
those who quit.92, 68, 93, 71, 94  They experience more psychological problems, less paternal social 
support, lower self-efficacy for coping with daily stressors, and more stress associated with 
family problems, finances, job strain, unemployment, and physical and sexual violence.19, 68–71  
Similar smoking and demographic factors are associated with postpartum relapse or smoking.95–
101 We will use findings from these questions to inform the development of the prenatal and 
postpartum smoking cessation materials and the BA treatment protocol. 
Focus groups or individual interviews will be conducted by experienced staff who are 
part of the Assessment, Intervention and Measurement (AIM) Shared Resource at MD 
Anderson Cancer Center, via institutionally approved videoconferencing software.  This shared 
resource provides specialized research support, including collection and analysis of data from 
focus groups.  Dr. Yolanda Villarreal will provide expertise on focus group implementation and 
qualitative data analyses.  For the proposed study, AIM staff and Dr. Blalock will consult with Dr. 
Villarreal in developing focus group semi-structured interview protocols.  AIM personnel, which 

Protocol 2020-0972 
December 28, 2023Page 10 of 48 
 
may include both a facilitator and note-taker, will conduct these focus groups, composed by 
criterion-based network sampling.102  
Focus Group/Individual interview Data Analysis Focus groups or individual interviews will 
be recorded with a digital audio recorder and professionally transcribed.  Recordings and 
transcripts will be stored in REDCap and will be destroyed within 1 year of the end of the study. 
Each transcript will be validated by the staff person who conducted the interview to assure 
accurate and complete transcription.  With Dr. Blalock as cross-reader, Dr. Villarreal will work 
with readers (i.e., AIM staff) to code transcripts for overarching themes, supported by  ATLAS.ti 
qualitative data analysis software, using conventional grounded theory methodology (identifying 
categories that capture the basic aspects of the group’s experience).103 Specifically, data 
analysis will focus on the intervention adaptation content and considerations identified by focus 
group and individual interview participants. Data analysis will consist of the 3 phases of 
“constant comparison”.104,105, 106  In their coding, the readers will consider five established criteria 
recommended by Krueger:107 frequency, specificity of responses, emotions, extensiveness, and 
big picture.  The focus group or individual interview transcript will be read and discussed by the 
team of readers to identify initial ideas for treatment modifications and improvements. The 
transcript will then be coded using the domains identified by the team but also using open 
coding to identify additional details for intervention improvements. Readers will discuss their 
coding to consensus and present results to the PI and co-Investigators. Dr. Villarreal will 
organize identified concepts that emerged from coding into themes with a particular focus on 
improvements for the intervention. A summary of the focus group and individual interviews 
results and a revised manual will be sent to the external auditor, Dr. Angela Stotts, an expert in 
the field of smoking cessation interventions for women in the prenatal and postpartum periods.  
The role of the external auditor is to provide an expert point of view from a professional not 
involved in the study’s data collection or analysis, in a qualitative form of testing reliability and 
convergent validity.108  Dr. Stotts will comment briefly, in writing or audio recording, on the 
consistency of each theme with her knowledge of the area; her comments will be incorporated 
into Dr. Villarreal’s full report on the results which will be used to develop the adapted treatment 
materials.   
Given Drs. Villareal and Stott’s role in analyzing the focus group and individual interview 
data, they may have access to protected health information of focus group participants through 
listening to audio recorded focus group or individual interview sessions that will include voice 
prints.  This has been noted in the consent document for Aim 1 and Secondary Aim 2. 
 
Aim 2 (Stage IA) Research Design 
Treatment Manual Development In year 1, our BA expert consultant Dr. Hubley will draft an 
initial version of the prenatal and postpartum BA treatment manual (Appendix BA Participant 
Manual.  The BA Counselor Manual (Appendix Counslor BA Manual) is a comprehensive 
Behavioral Activation treatment guide developed by investigators at the University of Colorado 
Boulder. The original manual was designed to lead eight (8), 60-minute counseling sessions 
with the target population.  The protocol delivery in AIM 3 is for ten (10), 45-minute counseling 
sessions.  The protocol delivery in AIM 4 is for ten (10) prenatal, four (4) postpartum 45-minute 
counseling sessions. This treatment manual is organized into meetings designed to coincide 
with the treatment sessions.  The sections were designed for a discussion of the material, not 
merely didactic instruction. The structure of each meeting is somewhat loose so that the level of 
emphasis on each component can be tailored to the needs of the individual. Meeting topics can 
be re-visited in any session as the need arises. Sessions that extend beyond those mentioned 
in the manual will follow a similar outline and content. Dr. Blalock and the study therapists will 
modify an existing prepartum version of HW (from a previous study with pregnant smokers51) 

Protocol 2020-0972 
December 28, 2023Page 11 of 48 
 
and draft an initial version of a postpartum HW control condition (Appendix . HW Participant 
Manual).  To ensure that the HW condition focuses exclusively on health-related 
psychoeducation and prohibits discussion of affective-related materials, modifications to the HW 
manual will include removal of all affective focused materials (e.g., depression, stress) and 
replacement with health-related materials. Dr. Blalock and the therapists will also modify an 
existing version of a smoking cessation counseling treatment manual and draft an initial version 
of the postpartum smoking cessation treatment manual.  We will draw from health-related and 
postpartum smoking cessation material currently under development for a service project that is 
focused on low-income pregnant smokers in Northeast Texas (CPRIT PP180077, PI: Blalock).  
We will utilize feedback from the focus group/individual interview data analysis to further modify 
treatment materials to increase acceptability and applicability of the BA and HW treatments.  Dr. 
Hubley will adapt the existing Quality of Behavioral Activation Scale, the BA fidelity tool 
developed at the University of Colorado for use in clinical trials. This may be used in the 
certification of the therapists in AIM 2 (Stage IA). Dr. Hubley will adapt the Review of Alma 
Mentoring for Peers (RAMP) form, the BA fidelity tool developed at the University of Colorado 
for use in clinical trials to be used in AIMs 3 and 4. Dr. Blalock and the study therapists will 
modify existing HW and smoking cessation scales used in our previous study with pregnant 
smokers, to reflect changes in treatment protocols.  These scales will be used to monitor 
therapist adherence and competence during the preliminary pilot AIM 3 (Stage IA) work and the 
AIM 4 (Stage IB) trial.  Dr. Hubley will train Dr. Blalock in the use of the BA fidelity rating forms.    
 
 
Aim 3 (Stage IA) Research Design 
 
Participants  In years 1 and 2, we will recruit up to 16 participants (half  assigned to BA 
and half assigned to HW who meet the study eligibility criteria (see section Eligibility Criteria ), 
with the exception that we will attempt to recruit women who are between 12 to 34 weeks in 
gestational age.. This will allow us to pilot test a 10-week course of treatment for BA and HW 
that may extend into the postpartum period for some women depending on their gestational age 
at the time of study entry. The participants will be seen during years 1 and 2.  Women who 
participated in focus groups or individual interviews who meet the gestational age eligibility 
criterion will be offered the opportunity to participate. To encourage completion of screening and 
treatment sessions, which will allow for more complete collection of pilot data from this limited 
number of participants, we will compensate women for completing all required questionnaires 
and applicable samples at each visit.  Compensation is as follows:  $25 for screening visit, $30 
for Visit 1, and $20 for V2-V10, for a possible total of $235. 
Therapist Training In an effort to ensure cultural competence of therapists, study 
therapists will be required to take a cultural competence course as part of their training.  During 
year 1, Dr. Blalock and the therapists will complete a virtual in-person training conducted by Dr. 
Hubley.  This training will include didactic sessions, readings, familiarization with treatment and 
fidelity rating forms and role playing of BA skills.  The therapists will be master level counselors.  
Dr. Hubley will work with Dr. Blalock to develop an ongoing training and supervision plan.  Using 
this plan and under the guidance of Dr. Hubley, Drs. Blalock and Hubley or Dr. Blalock will meet 
with the study therapists on a regular basis for supervision, during Aim 3 treatment delivery and 
Aim 4 randomized trial treatment delivery.    A licensed psychologist or a PI designee will 
oversee training in HW.  Following the BA virtual in-person training and initial pre-certification, 
and HW training, Dr. Blalock will deliver the abbreviated 10-session BA protocol to one Stage IA 
pilot participant. The therapists will deliver both BA and HW 10-session protocols to Stage IA 
pilot participants.  Each session will be videotaped. Dr. Hubley will provide fidelity ratings on Dr. 
Blalock’s case and will also provide ratings and feedback on the therapist cases.  Dr. Blalock 

Protocol 2020-0972 
December 28, 2023Page 12 of 48 
 
and Dr. Hubley will complete ratings of BA fidelity, and Dr. Hubley will provide further guidance 
to Dr. Blalock on these ratings. A licensed psychologist or a PI designee will complete ratings of 
Smoking Cessation behavioral counseling and HW treatment and adherence. Regular 
supervisory feedback to the study therapists will be based on Drs. Hubley and the PI designees 
viewing of taped sessions and their ratings on the fidelity scales.  Supervisory feedback during 
the Stage IB trial will be based on ratings of videotaped sessions in both conditions. Dr. Hubley 
will continue to provide guidance to Dr. Blalock and study therapists throughout the Stage IB 
trial. 
Therapist Certification The modified BA, HW and smoking cessation prenatal/ postpartum 
treatment rating scales will be utilized to certify Dr. Blalock’s and therapists’ adherence and 
competence following delivery of treatment during mock sessions in AIM 2 (Stage IA)  and to 
monitor therapist adherence and competence during the Stage IA preliminary  pilot and Stage 
IB trial.  The exact rating form to be used will be determined by the rater and the PI.  Additional 
minor changes may be made to the form in the future based on ongoing discussions between 
the PI and the raters. If substantive changes are made, the updated form will be re-submitted for 
IRB review (See Appendix.  BA Rating Form for a sample rating form). Fidelity to the BA 
intervention will be assessed based on Dr. Hubley’s ratings of 2 randomly selected sessions of 
AIM 2, Stage IA cases to certify therapists who meet standards in the delivery of BA 
(operationalized as a mean score of 3 on the rating scale).    Similarly, for the HW intervention, 
a PI designee will rate 2 sessions of the AIM 2 (Stage IA) mock cases to certify therapists’ who 
meet standards in the delivery of HW (operationalized as a mean score of 3 on the HW rating 
scale).  
 
Preliminary Pilot Testing Procedures The objectives of Aim 3 are to pilot test delivery, 
via smartphone videoconferencing, of a 10-week treatment course of smartphone delivery of BA 
and HW and to conduct process evaluation of technical issues in use of smartphones, barriers 
to participation and retention; assessment burden, and adequacy of procedures for addressing 
psychiatric emergencies.   To provide preliminary assessment of smartphone and data plans in 
these participants, we will include assessment of these variables during this phase of the study. 
 
Participants may be provided with headphones, if they want them, to ensure privacy of 
therapy session discussions with the therapist.  Women will be allowed to keep the 
headphones.  During years 1-2, up to 16 participants (half  each assigned to BA and HW) will be 
screened and enrolled in the study, according to procedures listed in the Eligibility Criteria  We 
will abbreviate therapist manuals and treatment materials to a 10-session protocol that may 
span both prenatal and postpartum periods, depending on the participant’s gestational age at 
the time of study entry.  This will allow us to conduct preliminary testing of treatment delivery 
within the time constraints of a 3-year study.  The BA and HW treatments will be delivered by 
Dr. Blalock and the study therapists.  During years1-2, the investigative team (Drs. Blalock, 
Hubley, and Villarreal) will meet regularly with the study therapists to discuss results of process 
measures from the participants and overall impressions of needed changes in study treatment 
and procedures.  Prior to running the randomized trial, we will modify these changes in addition 
to any technical and study procedures, study materials and biochemical verification strategies.  
 
Given Dr. Hubley’s and other PI designees role in training and supervising the study 
therapists through viewing of videotaped counseling sessions, as external collaborators they will 
have access to participants’ protected health information.  This has been noted in the consent 
document for this aim. 
 
 

Protocol 2020-0972 
December 28, 2023Page 13 of 48 
 
Visit Windows  We will aim to schedule Visit 1 randomization approximately 1  
week following baselines, but may be delayed due to various reasons including 
but not limited to the following:  a) medical findings that may be significant but not 
exclusionary, b) participant-related events (e.g., travel, work schedules), or c) 
study related factors (e.g., full clinic schedule).  
In these cases where a visit is delayed past 30 days, a re-review of any eligibility 
criteria will be determined on a case by case basis. If there are no significant 
changes, participants will be allowed to continue to randomization as described 
above. If there are significant changes, the baseline and psychiatric screening 
process will be conducted again as deemed appropriate by PI. 
 Starting at V2 through V10, there will be a +5 calendar days window.  Given that women 
coming in at later gestational ages will give birth during their time in treatment, flexibility in 
scheduling will be allowed without having to log deviations.  If the woman gives birth during the 
treatment visits, we will allow their next visit window to be extended an additional 5 calendar 
days in order to reschedule the visit, for a total of + 10 calendar days.  
 
Eligibility Criteria: AIM 3 
 
Inclusion criteria for Aims 3  
1) Meets criteria for current Major Depressive Disorder (MDD) as assessed by the Mini 
International Neuropsychiatric Interview (MINI) 7.0.2  OR PHQ score of 10 or greater.   
2)   ≥ 18 years of age 
3)  Have an address and telephone number where they may be reached  
4)  Self report smoking, even a puff, cigarettes, little cigars and/or cigarillos in the past 30 days.  
5)  Gestational age between 12 to 34 weeks 
6)  Able to speak and follow verbal and written instructions in English 
7) Subjects must report a current residence in the State of Texas and must not have plans to 
move out of the state in the next 2.5 months 
8) Subjects referred directly from UT Health providers, the provider or designee will confirm 
pregnancy status through their electronic health record prior to the referral. Subjects referred by 
any other means will confirm positive pregnancy status through an at-home test.  
9) Willing to refrain from the use of other nicotine/tobacco products for the duration of the study  
10) Agree to be treated via telehealth (live audio-video conference and phone) and to be 
contacted via text and/or email  
11) Provide informed consent and agree to all assessments and study procedures  
 
Exclusion criteria for Aim 3 
1) Currently participating in individual psychotherapy 
2) Currently participating in other smoking cessation treatments and refuses to refrain from use 
for the duration of the study 
3) Rated on the Columbia-Suicide Severity Rating Scale113 at screening as in the past month 
having had active suicidal ideation with some intent to act or active suicidal ideation with 
specific plan and intent (indicated by answering “YES” on both Q3 and Q4, and/or 5) and/or 
endorsing “YES” to having engaged in preparatory acts towards or attempting suicide in the 
past 3 months (as indicated by answering “YES”  to both parts of Q6)   

Protocol 2020-0972 
December 28, 2023Page 14 of 48 
 
4)  Have a lifetime or current diagnosis of Psychotic Disorder as assessed by specified Mini 
International Neuropsychiatric Interview (MINI) 7.0.2 modules. 
5) Have a past or current diagnosis of Bipolar Disorder I or II or have a past or current 
diagnosis of Other specified Bipolar and related disorder as assessed by specified MINI 
7.0.2 modules. 
6)Any otherwise not specified medical or psychiatric condition, illness, disorder, or concomitant 
medication that could compromise participant safety or treatment, as determined by the 
Principal Investigator and/or Study Physician. 
7) Participant considered by the investigator as unsuitable candidate for full participation in the 
study. 
 
 
 
Refer to Table 1 & Table 2 (Prenatal & Postpartum) for the full schedule of assessments, 
and more details in section AIM 3 and AIM 4 Assessments. 
 
Refer to sections Participant Recruitment (Aim 1, 3, 4), Pre-Screening Assessment (AIM 
1, 3, 4), Informed Consent Process (AIM 1, 3, 4), Baseline Screening Phone Visit (AIM 1, 3, 
4) for detailed information of the enrollment process.  
 
 
Aim 4 Approach (Stage IB)   
Design The objective of Aim 4 is to conduct a preliminary randomized trial to evaluate 
the effect of BA on abstinence and depression at 4 ½ months postpartum; to demonstrate the 
feasibility of the smartphone-delivered BA intervention for depressed pregnant smokers during 
prenatal and through 2 ½ months postpartum, and feasibility of study procedures.  We will 
recruit pregnant smokers in the same manner as AIM 3 (Stage IA). We will employ a 
randomized, controlled between groups design in which depressed pregnant smokers will be 
randomly assigned, using a form of adaptive randomization called minimization,112 to either BA 
or HW.  We will stratify treatment assignment by baseline depression, smoking rate and 
gestational age.  The data that are collected will be used to support feasibility of delivering a 
prenatal and postpartum intervention to depressed pregnant smokers via smartphone and to 
provide estimates of effect size for planning future fully-powered trials.  
Participants We will recruit up to  50 depressed pregnant smokers who are between 18 to 32 
weeks gestational age in their pregnancies. 
 
Compensation AIM 4 
 We will pay women in the Stage IB randomized trial up to $25 for completion of the 
baseline screening visit, $65 for completion of the end of prenatal treatment assessment, end of 
postpartum treatment assessment (2 ½ months) If the participant is lost to follow-up in either the 
prenatal or postpartum period or did not complete all visits during those timeframes, they will be 
compensated for the final visit that was completed. Given the variability in timing for each 
individual participant, if this scenario occurs payment may be delayed until the final visit is 
verified)) and the 4 ½ months postpartum assessment, with the possibility of $220 in total 
compensation.   
Feasibility of Recruitment As indicated in Dr. Refuerzo’’s letter of support, the UT 
OB/GYN faculty provide clinical care at multiple clinics that will serve as recruitment sites for this 
study.  A total of approximately 4,574 births per year to predominantly low-income women are 
under UT faculty care.  Based on a study that was recently conducted in a UT clinic that is 
similar to clinics from which we will be recruiting, 14% of women identified as smokers.89  A 

Protocol 2020-0972 
December 28, 2023Page 15 of 48 
 
study using a nationally representative survey found that among women who smoked cigarettes 
during pregnancy, 12.4% met criteria for a mood disorder and 37.3% of women with nicotine 
dependence had a mood disorder.  Using the estimate of 14% smoking from the UT clinic study 
and national findings on percent of women with depressive disorders, we conservatively 
estimate that 25% of the 640 women who smoke will meet our depression criteria of scoring ≥ 
10 on the Patient History Questionnaire 9 (PHQ-9) each year.  Using these percentages, we 
estimate that 160 women would meet our criteria per year and that 50% would meet all eligibility 
criteria and consent to participate, providing around 80 women per year who would be eligible.  
Thus, we feel confident that we will be able to recruit up to 21 women who meet our eligibility 
criteria for Stage IA focus groups during year 1; up to 16 women for Stage IA pilot work during 
year 1 and early year 2, and; up to -50 women for Stage IB work during year 3.  
  
 
Eligibility Criteria: AIM 4 
 
Inclusion criteria for AIM 4  
1) Meets criteria for current Major Depressive Disorder (MDD) as assessed by the Mini 
International Neuropsychiatric Interview (MINI) 7.0.2  OR PHQ score of 10 or greater.   
2) ≥ 18 years of age 
3) Have an address and telephone number where they may be reached  
4) Self report smoking, even a puff, cigarettes, little cigars and/or cigarillos in the past 30 days.  
5) Gestational age between 18to 32 weeks  
6) Able to speak and follow verbal and written instructions in English 
7) Subjects must report a current residence in the State of Texas and must not have plans to 
move out of the state in the next 7-8 months 
8) Subjects will confirm positive pregnancy status through study provided pregnancy test or 
provide paperwork verifying pregnancy status if the pregnancy test is inconclusive 
9)  Willing to refrain from the use of other nicotine/tobacco products for the duration of the 
study  
10) Agree to be treated via telehealth (live audio-video conference and phone) and to be 
contacted via text and/or email  
11) Provide informed consent and agree to all assessments and study procedures 
12) Interested in treatment that might change smoking behavior or help them quit smoking 
13) Be the only participant in their household currently receiving treatment on this protocol 
 
 
 
Exclusion criteria for Aim 4 
 
1) Currently participating in individual psychotherapy 
2) Currently participating in other smoking cessation treatments and refuses to refrain from use 
for the duration of the study 
3) Rated on the Columbia-Suicide Severity Rating Scale113 at screening as in the past month 
having had active suicidal ideation with some intent to act or active suicidal ideation with 
specific plan and intent (indicated by answering “YES” on both Q3 and Q4, and/or 5) and/or 
endorsing “YES” to having engaged in preparatory acts towards or attempting suicide in the 
past 3 months (as indicated by answering “YES”  to both parts of Q6)   
4)  Have a lifetime or current diagnosis of Psychotic Disorder as assessed by specified Mini 
International Neuropsychiatric Interview (MINI) 7.0.2 modules. 

Protocol 2020-0972 
December 28, 2023Page 16 of 48 
 
5) Have a past or current diagnosis of Bipolar Disorder I or II or have a past or current 
diagnosis of Other specified Bipolar and related disorder as assessed by specified MINI 
7.0.2 modules. 
6) Any otherwise not specified medical or psychiatric condition, illness, disorder, or 
concomitant medication that could compromise participant safety or treatment, as 
determined by the Principal Investigator and/or Study Physician. 
7) Participant considered by the investigator as unsuitable candidate for full participation in the 
study. 
 
Inclusion criterion for Secondary Aim 2, Stage IB 
Women enrolled in the study who dropped out of the study during the first month of the 
postpartum treatment phase or women who completed at least 3 of the 4 postpartum treatment 
sessions 
Because study therapists will be asked to complete the WAI and acceptability of 
treatment ratings as part of Aim 4 work, they will be considered study participants and will 
provide verbal consent to complete these measures.   
 Inclusion criterion for Study Therapists 
1. Masters degree in psychology, social work, or other counseling degree 
2. Training in the delivery of psychotherapy and counseling interventions 
 
Participant Recruitment (Aim 1, 3, 4)  
We have established a subcontract with The University of Texas Health Science Center at 
Houston (UTHSC) to assist us with recruitment. The PI, Dr. Jerrie Refuerzo, is an Associate 
Professor in the Department of Obstetrics, Gynecology and Reproductive Sciences, McGovern 
Medical School—UT Health (see Letter of Support).   
 
Designated staff will conduct a pre-screen of women who may be identified as potentially 
eligible. This pool of candidates are women being seen in multiple large clinics staffed by UT 
OB/GYN faculty for depression and smoking eligibility(see Feasibility of Recruitment and Pre-
Screen Assessment Script), and also self-referrals from community advertising, which may 
include but not limited to social media, radio, digital and print ads.  We may also utilize mailing 
lists that target our audience to send IRB approved post-cards.    
 
Study participants will be individuals residing in the State of Texas. Recruitment efforts may 
include direct mail from registries, mailing flyers, public service announcements, media 
interviews, and advertisements on online social media, radio, television, digital media and 
recruitment companies, and newspaper outlets. Institutional channels may be used to aid study 
recruitment, including, but not limited to, patient database data mining (e.g., EPIC, TRTP 
database) for potentially eligible patients and other internal recruitment methods (e.g., MyChart 
to send messages, newsletters, inside MD Anderson television channels). The Tobacco 
Research and Treatment Program’s web screener database for tobacco users, outlined in IRB-
approved PA18-0423, also may be used as a recruitment source for this study. This database 
houses data collected from an internet-based screening questionnaire to recruit tobacco users 
from the Houston area, as well as across Texas more broadly, who may be interested in 
participating in tobacco use and cessation studies at MD Anderson Cancer Center. PA18-0423 
allows the sharing of data with IRB-approved MD Anderson protocols. We will rotate through 
various venues throughout the recruitment period. We have many years of experience using 
these venues for quitting and nonquitting tobacco clinical trials recruitment. The MD Anderson 
Marketing and Communications departments may also assist in arranging interviews, public 
service announcements, and social media communications to assist in study recruitment. 

Protocol 2020-0972 
December 28, 2023Page 17 of 48 
 
Additionally, we may engage the services of external clinical trials recruitment services to obtain 
contact information of prospective study participants.  
 
 
Pre-Screening Assessment (AIM 1, 3, 4) All participants across Aims 1,3 and 4 will be 
prescreened by telephone or in person for basic eligibility requirements (refer to study document 
Appendix Pre-Screen Assessment). The pre-screening assessment will be performed by a 
delegated and trained collaborator from The University of Texas Health Science Center or a 
staff member from MD Anderson. This may be done over the phone or in-person. An initial 
description of the study design will be provided, and demographic data will be collected, as well 
as concomitant medications, current smoking and other nicotine/tobacco use, current/recent 
treatments for tobacco use, pregnancy status, and current psychotherapy involvement. Data 
collected will be in a shared database between UT Health and MD Anderson.  Responses to the 
phone screen questions will be used to determine initial eligibility.  
 
All participants who remain eligible after pre-screening will then be scheduled to meet with a 
clinician for their Baseline screening telephone visit where the study requirements will be 
explained in more detail and the Informed Consent Document reviewed and signed (see 
Informed Consent Process for details). A set of questionnaires will be sent to the participant 
approximately 5 days prior to the scheduled visit and they will be asked to complete the 
assessments prior to the telephone baseline screening visit. Since the questionnaires contain 
information required to determine eligibility, staff may send extra prompts via text, email or 
phone call to the participant to complete the assessments prior to the visit. As a last resort, 
participants will be informed that this screening visit may be rescheduled if they are unable to 
complete the assessments prior to the visit. 
 
Informed Consent Process (AIM 1, 3, 4) Separate consent documents have been developed 
for Aims 1, 3 and 4. Participants may receive a copy of the Informed Consent Document 
electronically prior to their baseline screening phone visit which they may review prior to their 
scheduled visit and prepare questions. If the participant does not have a valid email address, we 
will not send the consent document. At the baseline screening phone visit a trained staff 
member will verbally review the consent document with the participant. Participants will have the 
opportunity to ask questions about the consent document or other study-related assessments 
and procedures prior to consenting to continue screening. If the participant agrees to participate 
in the screening process and the study: 
Aim 1: the participant will give their verbal agreement to proceed. The study staff will 
then sign the verbal consent document and document the consenting process in RedCap. A 
verbal consent is used in this aim because it may not be practical (feasible) to obtain signed 
authorization from these participants as our interactions with them are restricted to video 
conferenced focus groups and requiring a process to obtain a signature would create a barrier 
to recruitment; it may bias the sample that is recruited for the study if a signature is required, 
given that this may include a low income population that is likely to be burdened by child care 
needs, financial stressors, etc. A written consent may lead to women who are not experiencing 
these burdens to volunteer. Participants will be registered in the institutional database (CORe) 
within two business days of providing verbal consent to engage in Baseline Screening 
procedures. 
Aim 3: The consent process will be a two-stage consent process. The participant will 
give their verbal agreement to proceed. The study staff will then sign the verbal consent 
document and document the consenting process in the study database. A verbal screening 

Protocol 2020-0972 
December 28, 2023Page 18 of 48 
 
consent is used because it may not be practical (feasible) to obtain signed authorization from 
these participants as our interactions with them at the screening visit are restricted to telephone.  
Requiring a process to obtain a signature would create a barrier to recruitment; it may bias the 
sample that is recruited for the study if a signature is required, given that this may include a low 
income population that is likely to be burdened by child care needs, financial stressors, etc. 
Participants will be registered in the institutional database (OnCORE) within two business days 
of providing verbal consent to engage in Baseline Screening procedures. 
At V1, the main treatment informed consent document will be sent to the participant via a 
link, which will be pushed through DocuSign, via text and/or email. They will be asked to 
electronically sign the document before proceeding. Following the participant signature, study 
staff will then sign the consenting document and document the consenting process in the study 
database.  Participants will be registered and assigned to treatment in the institutional database 
(OnCORE) within two business days of signing consent.    
The verbal consents for all Aims will cover the eligibility screening assessments, 
including the review of the pre-screening assessment and information provided in the 
questionnaires, and will make clear that by consenting to proceed does not mean they are 
eligible to participate in the study. The Consent documents will also cover the details of study 
participation specific to each Aim. 
 
Aim 4:  At the baseline screening visit, the informed consent document will be sent to the 
participant via a link, which will be pushed through DocuSign, via text and/or email. They will be 
asked to electronically sign the document before proceeding. Following the participant 
signature, study staff will then sign the consenting document and document the consenting 
process in the study database.  Participants will be registered in the institutional database 
(OnCORE) within two business days of signing consent.    
The consent for Aim 4 will cover the eligibility screening assessments, including the 
review of the pre-screening assessment and information provided in the questionnaires, and will 
make clear that by consenting to proceed does not mean they are eligible to participate in the 
study. The Consent documents will also cover the details of study participation specific to each 
Aim. 
 
 
Baseline Screening Phone Visit (AIM 1, 3, 4) At the baseline screening phone visit (V0), 
which will ideally occur within 30 days of the pre-screen visit, study participants may be asked to 
verify information provided at the pre-screening assessment to verify that there have not been 
any changes since completion. A trained staff member will then complete the consenting 
process (described above). Once the participant has provided their consent, a Master’s level 
counselor will then administer the remaining screening psychiatric assessments, the Mini 
International Neuropsychiatric Interview (MINI) 7.0.2, the Columbia-Suicide Severity Rating 
Scale (C-SSRS)113  and the Patient Health Questionnaire (PHQ-9). In AIM 4, the PHQ will be 
administered through Qualtrics, except for Question 9 pertaining to suicidal ideation, which will 
be asked by the clinician during the visit.  Aims 3 and 4 will have additional screening measures, 
including but not limited to a brief relevant medical history (Appendix Medical History), 
medication use (Appendix. CCMs & Other Smoking Cessation Medications_Treatments & Other 
Psychotherapy Form) ,  smoking history (Appendix. Baseline Demographic & Smoking History), 
current nicotine/tobacco use (Appendix. TFBI), measure to assess anxiety (Appendix. GAD-7), 
childhood trauma (Appendix. Childhood Trauma Questionnaire), dependence on tobacco 

Protocol 2020-0972 
December 28, 2023Page 19 of 48 
 
(Appendix. FTND), positive and negative affect (Appendix. PANAS), and cognitive function 
(Appendix. PROMIS)  (See Table 1 & Table 2 (Prenatal & Postpartum). Screening 
Assessment Schedule). If a participant reports severe depressive and/or anxiety symptoms or 
suicidal ideation on the PHQ-9 and/or C-SSRS, a designated senior clinician, clinical 
psychologist, and/or the study physician/medical team will be consulted for further assessment, 
evaluation, intervention, or referral to treatment as clinically appropriate per standard of care. 
Additionally, participants whose depressive disorders or other psychiatric symptoms/disorders 
place them at high risk for self-harm will be excluded from the study. The PI or her designee 
may review these symptoms with the participant to determine the need for outside community 
referral and/or a referral back to Dr. Refuerzo and team if they were the referring provider, who 
will handle any moderate to severe psychological and/or pregnancy symptoms of concern, as 
deemed necessary by the delegated mental health practitioners (MHPs).  
 
 
Participants who remain eligible following the completion of the baseline screening assessments 
will be: 
 
AIM 1:  enrolled or randomized into the study and mailed a smartphone, headphone set, and 
reloadable gift card.  The participant will be scheduled for an equipment check call (to test their 
study phone and the videoconferencing platform to work out any technical issues) prior to the 
individual interview or focus group session (Aim 1).    
 
AIMs 3:  mailed a welcome study kit including a smartphone, headphone set if the ppt wishes to 
have them, a reloadable gift card, welcome letter, compensation scheme, staff contacts list, 
zoom instructions, and if applicable, a pregnancy collection kit.  The participant will be 
scheduled for an equipment check call to test their study phone and the videoconferencing 
platform to work out any technical issues prior to their first treatment visit.   After signing the 
main treatment consent at visit 1, the participant will be enrolled into the study.  The participant 
will be mailed a second kit containing urine cotinine collection kits and instructions, a smoking 
cessation participant manual, and their assigned participant treatment manual and additional 
resources.    
 
The study-specific supplies will be shipped to eligible participants and tracked through 
eShipGlobal or a comparable system within two business days of completion of the Baseline 
Screening visit.  
 
If a person is deemed ineligible, she will be notified and may be referred to her physician for 
local medical/psychiatric care for follow-up, if applicable. Resource information may be provided 
to a participant if deemed appropriate (Appendices: Texas FQHC list, Texas Mental Health 
Resources, Texas Sheriff’s Departments, Texas Domestic Violence Resources, Smoking 
Cessation Resources). These resources are intended to be living documents and may be 
updated in real time if we learn that some of the resources are outdated, or new resources are 
identified, etc.  
 
 
AIM 4:  mailed a welcome study kit including a smartphone, headphones if the ppt requests 
them, a reloadable gift card, welcome letter, compensation scheme, staff contacts list, zoom 
instructions, and a pregnancy collection kit.  The participant will be scheduled for an equipment 
check call to test their study phone and the videoconferencing platform to work out any technical 
issues prior to their first treatment visit.   At Visit 1, after a review of information for final 
eligibility, if participant remains eligible, she will be randomized into the study.  The participant 

Protocol 2020-0972 
December 28, 2023Page 20 of 48 
 
will be mailed a second kit containing urine collection kits and instructions, a smoking cessation 
participant manual, their assigned participant treatment materials and additional resources.    
 
The study-specific supplies will be shipped to eligible participants and tracked through 
eShipGlobal or a comparable system within two business days of completion of the Baseline 
Screening visit and Visit 1.  
 
If a person is deemed ineligible, she will be notified and may be referred to her physician for 
local medical/psychiatric care for follow-up, if applicable. Resource information may be provided 
to a participant if deemed appropriate (Appendices: Texas FQHC list, Texas Mental Health 
Resources, Texas Sheriff’s Departments, Texas Domestic Violence Resources, Smoking 
Cessation Resources). These resources are intended to be living documents and may be 
updated in real time if we learn that some of the resources are outdated, or new resources are 
identified, etc.  
 
 
 

Protocol 2020-0972 
December 28, 2023Page 21 of 48 
 
AIM 1 & 3:  Table 1 
 
 
 
 
 

Protocol 2020-0972 
December 28, 2023Page 22 of 48 
 
AIM 4: Table 2. Prenatal: 
 
 
 

Protocol 2020-0972 
December 28, 2023Page 23 of 48 
 
AIM 4: Table 2. Postpartum 
 
 
 
 

Protocol 2020-0972 
December 28, 2023Page 24 of 48 
 
Request for Waiver of Written Consent We are requesting a waiver of written consent on Aim 
1 focus groups, Aims 3 baseline screening visits, Secondary Aim 2 focus groups and study 
therapist completion of questionnaires and satisfactions ratings.  The justification for this waiver 
request is a) because the research or data collection on each of these study components does 
not involve procedures for which a written consent is required; b) the verbal scripts contain all of 
the required elements of a consent and; c) the research conducted during these study 
components presents no more than minimal risk.  For the focus group components, the 
participants are not MD Anderson patients.  The focus group discussion will be conducted 
virtually with all participants providing verbal consent and completing a screening visit prior to 
joining the session.   
 
 
Request for Waiver of Witness to Consent We will request a waiver of witness to consent for 
all aims involving participants (Aims 1, 3 and 4). All Aims will be conducted virtually; as such, 
most participants may be in their own homes and may not have another person available to 
witness the consent. We feel this would place an undue burden on the participant to have to 
identify and coordinate with a non-study team member as a witness and may prove to be a 
barrier to participation in the project.  
Additionally, this project is looking at soliciting feedback from the target population to assist in 
the development of counseling treatment manuals; the manuals, in turn, will be used in a small 
randomized trial to evaluate a depression-focused smoking cessation treatment for pregnant 
women experiencing depressive symptomatology as assessed by our screening 
measures. Participants will not be given medications to assist with smoking cessation or mood 
disorders.  Only behavioral interventions will be used, and therefore the project could be 
considered low-risk.  
Provision of Smartphones and Data Plans  While the majority of low-income young women 
own smartphones, only 56% have access to home broadband.115  To address this potential 
barrier to data access, we will provide smartphones and unlimited high speed data plans to 
each of the participants.  At this early stage of treatment development, this will allow us to 
evaluate the feasibility, acceptability and preliminary efficacy of providing BA via 
videoconferencing.  We have negotiated a minimal cost of $25 per month, with free phones 
provided with this plan. The plans also come with unlimited talk, text and email.  Women will be 
allowed to use the smartphones for personal use.  The provision of email addresses and text 
through the plans will provide another means by which to contact participants.  Smartphones will 
be provided to participants of Aims 1, 3, and 4. For all participants, information regarding the 
use of video conferencing and completion of questionnaires on the smartphones will be 
provided at the Pre-Screen assessment visit. Participants will also receive an instruction guide 
on how to join the zoom video sessions (Appendix. Zoom Participant Instructions). Enrolled 
Participants in Aims 1, 3, and 4 will be allowed to keep the smartphones and headphones (if 
they were provided).  
Replacement of equipment.  Reports of damaged or lost smartphones, and headphones 
will be reviewed by study staff and a decision made regarding replacements. All efforts will be 
made to replace equipment one time, with additional requests reviewed by the project 
supervisor.  
 
Treatment Similar to our previous trial, when women enter the trial later in the gestational age 
range or miss sessions, we will attempt to schedule two sessions per week and make-up 
sessions to ensure that women have an opportunity to attend all of the scheduled prenatal and 
postnatal sessions.  Participants will be provided with headphones, if they request them, which 

Protocol 2020-0972 
December 28, 2023Page 25 of 48 
 
they may choose to use to ensure privacy of therapy session discussions with the therapist. 
Missed sessions are to be expected and therefore deviations will not be logged. 
 
Participant Withdrawal. A withdrawal occurs when an enrolled participant actively withdraws 
consent for further participation in the study, prior to completion of the protocol. Participants may 
withdraw consent from the trial at any time at their own request, or they may be withdrawn at 
any time at the discretion of the investigator for safety reasons. All attempts will be made to 
conduct all evaluations required by the protocol. 
 
Addressing Negative Birth Outcomes. Preterm and negative birth outcomes are common 
in low income women, especially those with depression who smoke. We will handle these 
events in the following manner. Women who do not deliver live births will be allowed to continue 
postpartum treatment if they wish.  We will remove them from the sample and replace them with 
a new participant.  For women who experience preterm birth, we will consider providing 
additional sessions in the postpartum period to ensure a full treatment dose in these individuals.  
For women who experience other negative birth outcomes which interfere with participation in 
the postpartum period, we will attempt to make up for missed sessions by increasing the 
frequency of sessions within the postpartum treatment timeframe.  Should negative birth 
outcomes cause an imbalance in treatment delivery across treatment conditions, this should be 
detected in our initial analyses of group differences, which will allow us to treat number of 
treatment sessions as a confounder if such differences are found to be correlated with 
outcomes (See Statistical Design and Power, Baysesian Modeling Strategy). 
Prenatal.   
During the prenatal period, participants of 18-22 weeks gestational age will receive 10 
individual sessions of BA or HW.  The prenatal HW treatment will be similar to the treatment that 
was utilized in our previous trial.51  These women will have 16 weeks to complete their 10 
individual sessions.   
During the prenatal period, participants of 23-32 weeks gestational age will receive 10 
individual sessions of BA or HW.  The prenatal HW treatment will be similar to the treatment that 
was utilized in our previous trial.51  These women will have 12 weeks to complete their 10 
individual sessions.   
We may do additional check in calls or text communications with participants to maintain 
engagement between prenatal and postpartum treatment sessions.   
 
Postpartum.  Following birth, women may have up to a month break before resuming 
individual sessions, though have the option to resume earlier if preferred.  Women will receive 
an additional 4counseling sessions in postpartum over 6 weeks.  The participants will complete 
1 follow up visit that occurs 4 ½ months postpartum.     
   
Smoking cessation counseling. Smoking cessation counseling will be delivered during 
the first 15 minutes of the session in both the BA and HW conditions, and will generally follow 
the Clinical Practice Guideline,33 providing specific cessation tips and limited social support and 
problem solving exercises, that will be supplemented with pregnancy focused material relevant 
to smoking-related topics in the prenatal and postpartum periods. During the postnatal period, 
smoking cessation counseling will focus on cessation or relapse prevention, depending on the 
participant’s smoking status.  All participants will be provided with printed evidence-based 
pregnancy-specific cessation materials (Forever Free…For Baby and Me)91 that will serve as an 
outline during smoking cessation counseling discussions (See Section Aims 1-3 Approach 1 

Protocol 2020-0972 
December 28, 2023Page 26 of 48 
 
(Stage 1A),  Focus Group Procedures and Data Analysis for description of postpartum 
intervention topics.)  
BA.  Following the 15-minute smoking cessation counseling component, the 45-minute 
BA component will focus on increasing engagement in rewarding and adaptive activities, 
decreasing activities such as avoidance and withdrawal that maintain or increase risk for 
depression, and solving problems that limit access to reinforcers.  Behavioral activation 
strategies include self-monitoring, scheduling daily activities, rating pleasure and 
accomplishment, exploring alternative behaviors to achieve goals, and role-playing to address 
behavioral deficits.  Postpartum treatment components may be modified depending on the 
outcome of Aim 2.    
HW.  Women assigned to HW will receive 45 minutes of didactic health education 
counseling.  They will be told the primary goal of the HW treatment is to educate them on ways 
to take care of themselves physically during their pregnancies and the postpartum period. The 
purpose of this condition is to provide a time and attention matched control for BA that is 
pregnancy and postpartum relevant but instructional in nature. Participants will be allowed to 
choose from a list of discussion topics including pregnancy symptoms, postpartum hormonal 
changes, sleep, exercise, breastfeeding, yoga, relaxation training, time management and 
parenting tips. During the HW sessions, the therapist will review (read and paraphrase) the 
content contained in the standardized handouts that addressed the chosen topic, noting the 
connection between the HW topics and smoking, where appropriate. The therapist will be 
allowed to provide reflective and supportive listening regarding participants’ comments on the 
HW topics and regarding general events raised by participants during the session. The therapist 
will be prohibited from conducting solution-focused exercises related to HW topics or other 
problems that participants raise, assigning homework, or initiating discussions of progress made 
between treatment sessions concerning any of the HW topics that are discussed.  
 
All sessions will be conducted remotely via interactive video conferencing on smartphone 
devices.  All treatment sessions will be videotaped for use in treatment supervision and 
treatment adherence rating, using an institutionally approved virtual platform (eg. Zoom).     
Given Dr. Hubley’s and other PI designees possible role in supervising the study therapists 
through viewing of videotaped counseling sessions, as external collaborators they may have 
access to participants’ protected health information during this phase of the study.  This has 
been noted in the consent document for this aim. 
At each session, the participant will be asked about any changes to demographics, estimated 
delivery date, medications, other smoking cessation treatment, other counseling treatment, and 
health since their last visit (see Appendix:  Assessment of Changes since last visit).    
Stage IB, Secondary Aim 2 Focus Group Procedures and Data Analysis 
 
 
During year 3, we will recruit a) women who dropped out of the study during the first 
month of the postpartum treatment phase, and; b) women who completed at least 3 of the 
4postpartum treatment sessions, to participate in 2 focus groups of 6 to 7 women who dropped 
out and 2 groups of 6 to 7 women who completed treatment.  Focus groups will be conducted 
by teleconference, using participants’ study smartphones and teleconference facilities at MD 
Anderson.  Participants will be compensated $75 for completing the focus group sessions. 
Objectives of Secondary Aim 2 are to collect qualitative data on a) barriers to completing 
treatment sessions; b) usefulness of postpartum treatment; c) suggestions for decreasing 
barriers and improving treatment acceptability, and; d) relevant experiences unexpected by 
participants and researchers.  We will use the same procedures to conduct focus groups and 

Protocol 2020-0972 
December 28, 2023Page 27 of 48 
 
analyze data as described in section Aim 1 (Stage IA).  These data will be used to inform further 
revision of the intervention for evaluation in future trials. 
, In the event there are conflicts for participant availability that prevents scheduling a 
focus group, we will conduct one-on-one interviews with women who meet the eligibility criteria 
rather than risk losing participants. 
 
 
 
Assessment 
  
Remote Assessment Procedures Participants will be assessed for depression, 
psychiatric disorders, and other measures at baseline, selected measures at each of the 
prenatal and/or postnatal treatment sessions, and at 4 ½ months postpartum.  With the 
exception of the screening telephone calls prior to enrollment, which will be assessed by 
telephone or at prenatal clinic visits, data will be directly entered by participants on the 
smartphone, including daily diaries assessing smoking. Participants will receive SMS or e-mail 
prompts containing a link at the time assessments are scheduled.  Participants who fail to 
complete assessments as scheduled will receive additional SMS or e-mail prompts and, if 
necessary, phone call reminders.  
 
 
 
Measures 
 
Process Measures and Analysis: AIM 3 
Technical issues We will systematically track and assess technical problems with 
smartphone videoconferencing delivery of treatment, assessment and video recording of 
treatment sessions.  These data will be used to develop items for a measure of frequency and 
quality of technical difficulties and impact on the treatment session and assessment completion, 
which will be used in the Stage IB trial (Aim 4).  We will also gather information on the 
effectiveness of contingency plans for completing sessions when interrupted by technical 
difficulties; and on the level of technical assistance needed to support the videoconferencing 
and assessment procedures.   
Barriers to participation   Participants who fail to complete the final treatment session, 
staff will reach out to participants by phone and/or text to attempt to conduct a telephone 
interview  to assess the degree to which various factors interfered with completion of the 
treatment and to list reasons they were unable to complete treatment.  To encourage 
completion of these interviews, women will be paid $20.  Examples of potential barriers that 
participants will be asked to rate include lack of childcare, difficulties using the smartphone to 
complete treatment sessions and assessments, inability to schedule time to complete treatment 
sessions and assessments, and inability to find locations where sessions could be completed 
uninterrupted by members of household.  We will also administer this interview at the end-of-
treatment session (EOT; session 10) to participants who complete treatment and to the study 
therapists. Participants who complete the EOT session will not receive an additional $20 for this 
interview as it will be given as a required questionnaire at EOT.   Frequencies of each barrier 
type will be calculated.  Eligible participants who decline participation will be asked to provide 
reasons for declining and frequencies of reasons for declining will be calculated.  Based on 
these data, the investigators will consider whether additional exclusion criteria are needed or 
whether barriers can be addressed by changing study procedures. 
Assessment burden Completion of study measures will be calculated as the percentage 
of scheduled assessments completed per visit and percentage of scheduled assessments 

Protocol 2020-0972 
December 28, 2023Page 28 of 48 
 
completed per measure.  Participants will be asked to provide feedback regarding their ability to 
complete the assessments.   
Timeline Follow-back Interview (TFBI)111 Self-reports of smoking will be collected from 
participants at baseline using the TFBI. Starting at study entry, self-reported smoking will be 
collected daily with the Ecological Momentary Assessment (EMA) questionnaire(s) sent to the 
patients phone through the Qualtrics platform, an MD Anderson-approved secure platform for 
data collection.   
Biochemical verification of pregnancy.  If the participant is referred directly from UT 
Health providers, the provider or designee will confirm pregnancy status through their electronic 
health record prior to the referral. Participants referred by any other means will confirm positive 
pregnancy status through an at-home test.  
Biochemical verification of self-reported abstinence  All participants will be asked to 
complete a urine cotinine test and send a picture of the results to study staff  at each visit 
(beginning with visit 2) when self-reporting abstinence (Aims 3).  To provide preliminary 
evaluation of the feasibility of collecting these data, we will calculate the ratio of received test 
results to number of participants who completed sessions 2 through 10.  We will use a urine 
cotinine test that measures nicotine at 100 ng/mL, with a negative result to verify 
abstinence.  We will calculate rate of deception based on the ratio of measures meeting this 
criterion to self-report of abstinence.  Point-prevalence abstinence at the end of treatment will be 
defined as both a self-report of not smoking during the previous 7 days and a negative result.    
 
Adequacy of participant safety procedures We will gather initial data on the effectiveness 
of participant safety procedures including ability to screen out participants who are inappropriate 
for remote delivery of treatment due to safety concerns (e.g., suicide risk, severity of psychiatric 
symptoms) and ability to provide access to local mental health care when needed.    
 
Therapeutic alliance will be assessed using the client rated Working Alliance Inventory 
(WAI-C), Short Form at V2, V4, V6, V8, and V10.  116  To maintain boundaries in the therapeutic 
relationship between therapists and the participants with whom they are working, therapists will 
not be able to access responses or scores on these instruments.  
 
Feasibility Measures: AIM 4:  We will utilize a participant contact tracking database to 
document number of participants contacted to discuss participation in the study, number 
eligible, and number who consent to participate.  
Rate of recruitment will be calculated as the percentage of eligible participants who are 
consented to participate.   
Retention will be calculated as the percentage of enrolled participants who complete the 
4 ½ month postpartum assessments.   
Completion of treatment visits will be documented using the participant tracking 
database. These data will be used to calculate the average number of treatment sessions that 
participants attend and percentage of participants who complete the prenatal and postnatal 
treatment protocols.   
Completion of study measures will be calculated as the percentage of scheduled 
assessments completed per visit and percentage of scheduled assessments completed per 
measure.   
Rate of receipt of other smoking cessation, psychopharmacological or psychotherapeutic 
treatment following enrollment will be recorded in the database.   

Protocol 2020-0972 
December 28, 2023Page 29 of 48 
 
The rate of technical difficulty with smartphone delivery of treatment and assessments 
will be calculated as the percentage of treatment and assessment sessions that are interrupted 
due to technical difficulties with the smart phone.   
Verification of pregnancy.  Participants will confirm positive pregnancy status through 
study provided pregnancy test or provide paperwork verifying pregnancy status if the pregnancy 
test is inconclusive. 
Biochemical verification of self-report abstinence will be calculated as the ratio of 
received urine test results (cotinine and/or anabasine) to number of participants who self-
reported abstinence at 4 ½ months postpartum 
  
Acceptability of treatment will be assessed in both participants and therapists (see table 
of assessments for AIM 4) for timepoints.  Participants and therapists will be asked to provide 
ratings of their satisfaction with the BA and HW interventions.  Areas that will be included in 
these ratings are number of treatment sessions, timing of treatment sessions, and quality of 
interaction with therapists and study staff (for participants’ ratings) and quality of interaction with 
participants (for therapists’ ratings).   
Therapeutic alliance will be assessed using the client and therapist-rated Working 
Alliance Inventory, Short Form atPN2, PN4, PN6, PN8, PN10, PP1 & PP3 visits.  116  To 
maintain boundaries in the therapeutic relationship between therapists and the participants with 
whom they are working, therapists will not be able to access responses or scores on these 
instruments.  In addition, responses on this instrument will be used in data analyses only. 
 
AIM 3 and AIM 4 Assessments:  
 
Baseline characteristics of psychiatric disorders/symptoms and nicotine dependence.   
The Mini International Neuropsychiatric Interview (MINI) 7.0.2. 117 The MINI screens for 
several DSM-5 Axis I diagnoses.  Current Major Depressive Disorder, Past or current Bipolar I 
or II or Otherwise Specified Bipolar and lifetime or current Psychotic disorder will be assessed 
using specified modules from version 7.0.2 of the MINI.    
The Patient Health Questionnaire - Mood Module (PHQ-9).  is a 9 item self-report 
measure used that was developed to assess the participant’s mood over the last two weeks and 
is used for inclusion and also part of the Safety Monitoring Plan 
The Columbia Suicide Severity Rating Scale (C-SSRS) is a measure used to identify 
and assess individuals at risk for suicide. Questions are phrased for use in an interview format 
but can be completed as a self-report measure if necessary.  This is part of the Safety 
Monitoring Plan.   
The General Anxiety Disorder Scale (GAD 7). The GAD-7 is a validated, seven-item 
scale developed to assess the presence and severity of generalized anxiety disorder symptoms 
over the last two weeks and is also part of the Safety Monitoring Plan.  Empirically-derived cut-
offs can be used to quantify severity of reported symptoms. 
The Fagerstrom Test for Nicotine Dependence (FTND)118 is a 6-item scale that will be 
used to asses nicotine dependence at baseline for Aims 3 and 4.   
Biochemical verification of self-reported abstinence   Starting after the first treatment 
session, all participants in AIM 3 will be sent a urine cotinine test at every visit if they self-report 
abstinence in the last 7 days. In AIM 4, all participants will be sent a urine test (cotinine or 
anabasine) at every visit is they self-report abstinence in the last 7 days.  Participants will be 
asked to send a picture of the urine test to the research staff via text message or email and/or 
return the test via mail in the box provided to them.  This process is used in several of our 

Protocol 2020-0972 
December 28, 2023Page 30 of 48 
 
smoking cessation studies and offers the patient a convenient way to provide remote 
biochemical verification of self-reported abstinence. We will use a urine cotinine test that 
measures nicotine at 100 ng/mL, with a negative result . 
 
 
 
Outcome 
Timeline Follow-back Interview (TFBI)111 Self-reports of smoking will be collected from 
participants in Aims 3 and 4 at baseline using the TFBI. Starting at study entry, self-reported 
smoking will be collected daily with the daily diary Ecological momentary assessments (EMA) 
through the Qualtrics platform.  In the event the participant does not complete the EMA daily 
diary, smoking data will be collected at counseling visits.   
Biochemical Abstinence Verification  All participants who self-report as being abstinent 
at each treatment visit will be sent a urine test (cotinine or anabasine)to biochemically verify 
abstinence. Participants will be asked to send a picture of the urine test to the research staff via 
text message or email and/or return the urine samples via mail in the labeled box provided to 
them. This process is used in several of our smoking cessation studies and offers the patient a 
convenient way to verify smoking and to also provide remote biochemical verification of self-
reported abstinence. We will use a urine cotinine test that measures nicotine at 100 ng/mL, with 
a negative result to verify abstinence. Abstinence Definitions Point-prevalence abstinence at the 
end of prenatal treatment and end of postpartum treatment and 4 ½ months postpartum follow-
ups will be defined as both a self-report of not smoking during the previous 7 days and a 
negative result.   Regarding the primary outcome of abstinence at 4.5 months postpartum, 
because the study will allow for a variable quit date through the postpartum period, we will 
consider quit attempts up to week 14 of the postpartum period, which will allow for the 
recommended 2-week grace period for prolonged abstinence prior to the postpartum end of 
treatment.  Thus, prolonged abstinence at 4.5months postpartum will be defined as a self-report 
of not smoking from Week 16 through the 4.5-months postpartum follow-up and a negative 
result .   
The PHQ-9119 will be used to assess depression outcomes.  The PHQ-9 has been found 
to reliably measure response to depression treatment, including responsiveness to criterion 
standards for full, partial and remission of DSM-IV symptoms of major depression.120   
 
The GAD-7 will be used to asses anxiety outcomes.  The GAD-7 is a validated, seven-
item scale developed to assess the presence and severity of generalized anxiety disorder 
symptoms over the last two weeks.  Empirically-derived cut-offs can be used to quantify severity 
of reported symptoms. 
 
 
Treatment Mechanisms 
The PANAS121, a widely-used 10 item self-report measure of the experience of positive 
and negative affect within the past week, will be used in Secondary Aim 1 exploratory analyses 
of hypothesized BA mediators (PA and NA).  It will be assessed at baseline and each 
counseling visit. 
The PROMIS Cognitive Function-Abilities (CF-A) Short-form122 is from the Patient 
Reported Outcomes Measurement Information System.  This 8-item scale assesses perceived 
cognitive deficits, including mental acuity, concentration, memory, and perceived changes in 
these cognitive functions and the extent to which cognitive impairments interfere with daily 

Protocol 2020-0972 
December 28, 2023Page 31 of 48 
 
functioning.  It will be assessed at baseline and each counseling visit.  It will be used in 
Secondary Aim 1 exploratory analyses of hypothesized BA mediators (cognitive function). 
 
 
Nicotine Withdrawal  
The Wisconsin Smoking Withdrawal Scale (WSWS)123 This 28 item scale will be used to 
assess nicotine withdrawal symptoms.  
Smoking cessation or depression treatment following enrollment   
At each study visit, participants will be asked whether they have started any counseling 
or medications for the treatment of smoking or depression.  These data will be used as 
covariates in analyses of outcome, as needed. 
 
Additional Measures 
 
Childhood Trauma questionnaire (CTQ).  This is a standardized 28-item self-report 
inventory that measures the severity of five different types of childhood trauma.  Approximately 
5 minutes is required to complete the questionnaire.  A 5-point likert scale is used for the 
responses from Never true to Very often true.   
Medical History.  This questionnaire assesses the participants current relevant medical 
history at the time of the baseline visit.      
The Baseline Demographic and Smoking History Form. These questions expand on 
the data obtained during the pre-screening, providing more detailed information on 
demographics, information on smoking history (e.g., years smoked, current smoking rate, other 
nicotine/tobacco use) is also obtained. These questions have been used in our previous and 
current cessation studies to provide descriptive data for the study population. 
Ecological Momentary Assessments (EMA)/Daily Diary. Our EMA methodology is 
modeled after several of our previous studies in which we enrolled very diverse smoking 
populations69,70. In this study, EMA assessments will be implemented through a Qualtrics link 
sent to the smartphone provided to the participant. A daily diary assessment will occur only 
once per day, every day throughout the treatment phase of the study. The participant will be 
prompted by text message to complete the daily diary EMA assessment and will assess events 
from the previous day such as cigarettes and other tobacco use.  At participant request, EMA 
links can be sent to the participant’s personal phone via SMS message or email address.  
EMA trainings will be provided to participants as needed. Total time devoted to EMA is fairly 
reasonable (approximately 5 minutes/day on average), Missed EMA assessments will not be 
logged as protocol deviations because they are expected in smoking cessation trials. 
 
Measures of Treatment Fidelity   
We have included the following recommended procedures124 for the ongoing 
assessment of treatment fidelity. To monitor and improve therapist training and delivery of 
treatment during the Stage IA pilot study, all BA and HW sessions will be videotaped.  Two 
treatment sessions (session 1 and one session randomly selected from sessions 2-5) in both 
conditions will be rated by Drs. Blalock (PI),  Hubley, or a PI designee shortly following the 
sessions, using BA, HW and smoking cessation rating forms (see Aim 2 Research Design).  
During the Stage IB trial, all BA and HW sessions will be videotaped, and 20% of randomly 
chosen sessions will be rated by Dr. Blalock,  Hubley, or a PI designee  Dr. Blalock  or a PI 
designee will provide regular supervision throughout the Stage IB trial, with guidance from Dr. 
Hubley.  Fifteen percent of the BA and HW sessions that are rated will be rated by a second 
rater with expertise in the BA or HW smoking cessation interventions.  All videotaped sessions 
will be destroyed within 5 years of completion of treatment fidelity assessment of Aim 4 
sessions. 

Protocol 2020-0972 
December 28, 2023Page 32 of 48 
 
Benchmarks for Establishing Feasibility and Acceptability  
A priori benchmarks for feasibility and acceptability will focus on retention at the 4.5-
month postpartum assessment and completion of treatment visits. The study will be considered 
feasible if both the rate of retention at the 4.5-month postpartum assessment and average 
percentage of completed treatment sessions across subjects are 70% or above unless, in the 
case either rate is lower than 70%, we have convincing arguments that they can be improved 
sufficiently by modifying recruitment or intervention strategies.  We will calculate statistics to 
estimate these feasibility parameters and calculate their 90% confidence intervals (CI), based 
on our sample size.   
 
Adverse Event Monitoring & Concomitant Medication.  
Adverse events and concomitant medications will be assessed throughout the study.  Our 
procedures for assessing adverse events follow standard FDA and clinical practice guidelines 
and are well established in our research programs.  Adverse event (AE) terminology and grades 
will be determined using the Common Terminology Criteria for Adverse Events (CTCAE), 
version 5.0, published by the U.S. Department of Health and Human Services.  Only psychiatric 
adverse events, whether or not related to the treatment, will be reported.  The counseling 
component will be overseen by PI Dr. Blalock.   
 
Adverse events will be reviewed by the PI and further reviewed by the medical team when 
appropriate. Adverse event monitoring will stop at the final treatment visit, or earlier if the ppt 
withdraws or becomes lost to follow up.  Those AEs that are probably, possibly or definitely 
related to the treatment will be followed until resolution or end of study, whichever comes first. In 
the case of reports of suicidal ideation, depression or anxiety which we believe may be related 
to treatment, if possible, we will engage in our normal psychological assessments. This may not 
always be possible if reported by phone. In any case, procedures for Good Clinical Practice will 
be followed with respect to medical management of the symptoms. A specific plan for 
monitoring increased depression, anxiety, and suicidality is presented (Appendix. C-SSRS). The 
clinical assessment tools we use are the PHQ 9, GAD 7, and C-SSRS.  The procedures are 
outlined (Appendix. Safety Monitoring Plan) apply to both symptoms of anxiety, depression, and 
suicidality. Treatment- emergent psychosis is extremely rare in smoking cessation trials. If it 
does occur, it will be captured by our assessment of adverse events. These cases will be 
referred for further evaluation by a Ph.D. Clinical Psychologist. The PI is responsible for 
determining the attribution of adverse events to the treatment.  
 
Serious Adverse Event Reporting (SAE) Reporting  
An adverse event or suspected adverse reaction is considered “serious” if, in the view of either 
the investigator or the sponsor, it results in any of the following outcomes:  
• Death  
• A life-threatening adverse drug experience – any adverse experience that places the patient, 
in the view of the initial reporter, at immediate risk of death from the adverse experience as it 
occurred. It does not include an adverse experience that, had it occurred in a more severe form, 
might have caused death.  
• Inpatient hospitalization or prolongation of existing hospitalization  
• A persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions.  
• A congenital anomaly/birth defect.  
 

Protocol 2020-0972 
December 28, 2023Page 33 of 48 
 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition. 
Examples of such medical events include allergic bronchospasm requiring intensive treatment in 
an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse (21 CFR 312.32).  
• Important medical events as defined above may also be considered serious adverse events. 
Any important medical event can and should be reported as an SAE if deemed appropriate by 
the Principal Investigator.  
• All events occurring during the conduct of a protocol and meeting the definition of a SAE must 
be reported to the IRB in accordance with the timeframes and procedures outlined in “The 
University of Texas M. D. Anderson Cancer Center Institutional Review Board Policy for 
Investigators on Reporting Serious Unanticipated Adverse Events for Drugs and Devices”.  
• Serious adverse events will be captured from the time of the first protocol-specific intervention, 
until the last treatment visit, unless the participant withdraws consent. Serious adverse events 
must be followed until clinical recovery is complete and laboratory tests have returned to 
baseline, progression of the event has stabilized, or there has been acceptable resolution of the 
event.  
 
It is the responsibility of the PI and the research team to ensure that serious adverse events are 
reported according to the Code of Federal Regulations, Good Clinical Practices, the protocol 
guidelines, the sponsor’s guidelines, and Institutional Review Board policy. 
 
 
STATISTICAL DESIGN AND POWER 
We will employ a randomized, controlled between groups design in which 60 depressed 
pregnant smokers will be randomly assigned, using a form of adaptive randomization called 
minimization, to either Behavioral Activation (BA) or Health and Wellness (HW).  We will stratify 
treatment assignment by baseline depression, smoking rate, and gestational age. 
 
Data analyses will be conducted by our University of Texas Health Science Center 
collaborator Charles Green, Ph.D.  Dr. Green will be provided deidentified data from which to 
conduct the analyses and thus will not have access to participants’ protected health information 
(PHI). 
General Data Analytic Strategy:  Bayesian Statistical Methods  
Developing effective behavioral interventions requires incremental improvement of 
theoretically sound treatments based on systematically accruing data.  Often this incremental 
development is hampered by statistical tools not appropriate to the task.  Classical, Frequentist 
statistics have advanced the science of behavioral interventions substantially but are less 
informative for the initial test of a new treatment.  The reliance of the Frequentist framework on 
dichotomous, null hypothesis-testing provides some control of the error rate in the context of 
multiple repeated trials; however, this is not what early-phase treatment testing requires.  
Developing nascent treatments requires investigators to bet on an alternative hypothesis. 
Investigators evaluating a theoretically sound intervention want to know the probability that the 
approach confers some level of benefit given the observed data: that is, they want to know the 
probability that the alternative hypothesis is true.  While Frequentist inference does not directly 
address this issue, Bayesian statistical inference provides a principled approach to answer this 
question.  Indeed, addressing the so-called “Pipeline Problem” in developing clinical 
applications, the FDA has indicated that Bayesian statistics offers one avenue for improved 

Protocol 2020-0972 
December 28, 2023Page 34 of 48 
 
methodological efficiency.125–130  Decision-making based on an initial trial of a treatment is 
assisted by estimates of the probability of an effect of some specified magnitude.  These 
statements, not part of the conventional, Frequentist statistical lexicon, are accessible via 
Bayesian approaches, particularly with small sample sizes.131, 132   
   Detailed descriptions of Bayesian statistical reasoning exist elsewhere.133–135 Succinctly, 
Frequentist models estimate the probability of observing the data (or data more extreme) given 
that the null hypothesis is true; Bayesian analyses estimate the probability of the alternative 
hypothesis given the observed data.135  Bayesian probability estimates incorporate prior 
information about plausible parameter values (i.e., the prior distribution) and the observed data 
(i.e., the likelihood).  Combining these two distributions forms the posterior distribution which 
permits evaluation of the probability that the true value of the parameter falls in some range. 
Simulated Example: As an example of applying a Bayesian analysis, the Figure below 
depicts the prior and posterior distributions for the probability, and the posterior distribution of 
the relative risk of smoking abstinence as a function of intervention based on simulated data.  
Panel A shows the prior and posterior distributions of the absolute probability of treatment 
initiation as a function of the intervention.  The prior distributions (dashed lines) assume that for 
both intervention conditions all probabilities of smoking abstinence are equally likely (i.e., 
~Beta[a=1, b=1]).  The posterior distributions (solid lines) reflect anticipated intervention effects:  
1) N= 60 participants randomized in a 
1:1 ratio, 2) 7.6% and 25% rates of 
abstinence at six months post-partum 
in the control and intervention 
conditions, respectively (i.e., 
~Beta[a=3.28, b=28.72] and 
~Beta[a=8.5, b=23.5] for control and 
intervention conditions, respectively). 
Panel B reflects the posterior 
distribution of the relative risk 
(calculated directly from the 
distributions in Panel A (i.e. 
p(Abstinence in 
Intervention)/p(Abstinence in Control)) 
for smoking abstinence.  From a 
Frequentist perspective, this would 
yield a Fisher Exact p < 0.18 and 
relative risk of 2.67 (95% CI 0.78-9.09). 
(Note: For the Frequentist calculations, 
to address the non-integer nature of 
the estimated frequencies, coupled with the low numbers in the control condition we chose to 
round any fraction for abstinence upward.  This had the effect of producing a slightly higher 
effect in the control condition (n = 3 versus n  = 2 abstinent) therefore rendering the simulated 
effect size more conservative).  A fundamental difficulty is that the Frequentist approach cannot 
provide any indication regarding the relative probability of different values within the 95% 
Confidence Interval being the true parameter.  The Bayesian estimate of the relative risk is 
slightly different (rounding was necessary in estimating the Frequentist but not the Bayesian 
solution), RR = 2.73, (95% CI: 0.90-11.44), however since these estimates are based on a 
posterior distribution it is possible to discuss the probability that an effect of a given magnitude 
is the governing parameter.  Defining benefit as any RR > 1, the simulated posterior distribution 
shows that there is a 96% chance that the intervention confers this benefit and a more stringent 
definition (Relative Risk > 1.50) is associated with an 85% probability that intervention confers 
Panel A 
Panel B 

Protocol 2020-0972 
December 28, 2023Page 35 of 48 
 
benefit.  We stipulate that an intervention effect that has at least a 75% probability of increasing 
the relative risk of abstinence by >1.25 will warrant further investigation in a larger trial.   While 
the above simulation provides a straight-forward example of how Bayesian modeling works, it is 
often necessary to use more sophisticated Bayesian approaches (e.g., logistic regression with 
Monte Carlo Markov Chain estimation methods).  As such, final analyses will utilize Bayesian 
generalized linear modeling with multilevel-modeling for repeated measures data. 
Bayesian Modeling Strategy Initial analyses examining group differences for baseline 
variables will use cross-tabulation, ANOVA’s, and examination of correlations between baseline 
variables and specified outcomes.  For the purposes of evaluating the comparability of groups, a 
posterior probability of > 95% will constitute evidence for statistically reliable differences.  
Baseline or demographic variables on which group differences are detected, and which are 
correlated with outcomes, meet the definition of confounders136, 137 and will result in two sets of 
analyses: one in which the relevant variable is included as a covariate and one in which it is not.  
This will permit determination of the degree to which any group differences might confound 
conclusions regarding treatment. 
    
Broadly, the data analytic strategy will use generalized linear and multilevel models 
(SAS 9.4, R v. 3.5, and Stan 2.17) for both discrete (e.g. smoking abstinence) and continuous 
(e.g. depression) outcomes.138–140  Cross-sectional continuous (depression), dichotomous 
(smoking abstinence) and time-to-event (retention) data will be evaluated using generalized 
linear modeling or proportional hazards regression.  All analyses will apply intention-to-treat 
principles with missing imputed as non-abstinent for smoking outcomes. For outcomes other 
than smoking, Bayesian approaches will implement joint modeling of observed outcomes and 
the missing data which is robust to ignorable missingness (i.e., MCAR and MAR).141  Sensitivity 
analyses will evaluate robustness of analytic conclusions to missing data. Non-ignorable 
missing data patterns will be addressed through pattern-mixture modeling methods.142  
Convergence of Bayesian analyses on the posterior distributions via Monte-Carlo Markov chain 
(MCMC) will be assessed via graphical (Trace Plot, Autocorrelation Plot) and quantitative 
(Gelman-Rubin Diagnostics and Effective Sample Size) evidence.  Evaluation of posterior 
distributions will permit statements regarding the probability that effects of varying magnitudes 
exist, given the data.  Specification of diffuse, neutral priors will reflect the initial uncertainty 
regarding effect sizes.  For all generalized linear models, priors for regression coefficients will 
be specified as ~Normal (µ=0, σ2=1 x 104), level one error variances will be specified as ~Half-
Normal (µ=0, σ2=1 x 104).  Choice of prior distribution for level two variances will follow 
Gelman’s recommendations.143  Bayesian Structural Equation Modeling (BSEM) prior 
specification will adapt recommendations from Muthén and Asparouhov.144  Priors for the 
comparison of proportions will be specified as ~Beta (α=1.0, β=1.0).  
    
Mediational modeling will examine the degree to which putative mechanisms of 
behavioral change transmit the effects of the intervention on the specified outcomes.  BSEM will 
investigate mediation of treatment effects by hypothesized mechanisms (positive and negative 
affect and cognitive deficits) utilizing MPlus v. 8.0.144–146  Measurement of positive and negative 
affect will use the PANAS.  Measurement of cognitive deficits will use the CF-A. Models will 
evaluate whether change over time (captured using growth factors) in positive affect, negative 
affect and cognitive deficits, measured with the PANAS and CF-A, mediates the effect of 
treatment at six months post-partum. Examination of the posterior distribution of the indirect 
effects will evaluate the probability that mediational effects exist. For model simplicity it may be 
necessary to break these analyses into two distinct mediation models.  However MCMC 
estimation has demonstrated superior small sample performance relative to maximum 
likelihood-based approaches in continuous, normally distributed data.147, 148  As discussed in the 
Specific Data Analytic section, minimal variability in growth factors representing change over 

Protocol 2020-0972 
December 28, 2023Page 36 of 48 
 
time, which may be partially a function of small sample size will result in use of an alternative 
approach.    
 
Specific Data Analyses: Aim 4 
The specific quantitative, analytic plan will focus on Primary Aim 4 and Secondary Aim 1.  
Primary Aims 
Aim 4 (Stage IB) 
Conduct a preliminary randomized trial with depressed pregnant smokers comparing the 
BA to HW to evaluate the following: 1) The effect of BA on abstinence at 4 ½ months 
postpartum, which is a primary outcome. Logistic modeling will evaluate smoking 
abstinence, measured by biochemically verified TLFB, at 4 ½ months postpartum as a function 
of treatment group. 2) The effect of BA on depression at 4 ½ months postpartum, which is 
a primary outcome. Generalized linear modeling will evaluate depression, measured by the 
PHQ-9, at 4 ½ months postpartum as a function of treatment group. 3) Feasibility of 
depressed pregnant smokers’ acceptance of the smartphone delivery of BA and HW, and 
assessment components indicated by a) retention, which is a primary outcome, b) 
completion of prenatal and postpartum sessions, which is a primary outcome c) 
completion of study assessments, which is a secondary outcome d) strength of 
therapeutic alliance from both the participant and therapist perspective, which is a 
secondary outcome and e) participant and therapist ratings on satisfaction 
questionnaire, which is a secondary outcome.  Survival analysis will evaluate retention by 
modeling time to drop-out as a function of treatment condition.  Binomial logistic modeling will 
evaluate the proportion of completed sessions as a function of treatment condition across the 
entire study as well as in the pre-natal and post-partum periods separately. Generalized linear 
models will evaluate participant and clinician measures of therapeutic alliance, measured by the 
WAI, as a function of treatment group.  Similarly, generalized linear modeling will evaluate 
satisfaction as a function of treatment group. 4) Feasibility of study procedures as indicated 
by a) percentage of sessions interrupted by technical difficulties, which is a secondary 
outcome, and b) percentage of urine tests (cotinine and/or anabasine) received for 
biochemical verification of self-reported abstinence at 4 ½ months postpartum follow-up, 
which is a secondary outcome.  Binomial logistic models will evaluate the proportion of 
sessions interrupted for technical difficulties and the proportion of biochemically verified 
abstinence measures as a function of treatment.  These analyses will provide estimates with 
95% credible intervals for each of these proportions in each group that will permit assessment of 
feasibility.  
 
Specific Analyses: Secondary Aim 1 (Stage IB) 
Evaluate change in hypothesized treatment mechanisms including positive affect, 
negative affect and cognitive impairment in relation to treatment effects on smoking and 
depression.  It would be ideal to evaluate the change in positive affect, negative affect and 
cognitive impairment as mediators of treatment effects on 4 ½ month post-partum outcomes via 
structural equation modeling.  Specifically, we could model the change over time in each 
mediator and evaluate the degree to which each growth factor might transmit the effect of 
treatment.  However, it is possible that a sample size of N = 50 will not provide enough 
variability to estimate certain parameters implied by such a model (e.g. the slope of change in 
each of these mediators may have minimal variance and function poorly as a mediator).  If this 
latter scenario obtains, we will evaluate each component of a mediational analysis in separate 
analyses to evaluate the evidence for mediation of treatment effects by positive affect, negative 
affect and cognitive impairment.  Specifically we will: a) evaluate the change over time in each 
mediator as a function of treatment using multi-level modeling; b) Evaluate the effect of 

Protocol 2020-0972 
December 28, 2023Page 37 of 48 
 
treatment on the outcome (smoking cessation or depression); and c) evaluate the outcome 
(smoking cessation or depression) as a function of change in the mediator captured either 
through a difference score (six months – baseline) or residual change score (six months 
residualized on baseline.  While the former (SEM) approach would provide a more elegant test 
of the overall model of behavior change, the latter may be necessary based on the properties of 
the sample. 
 
  
 
 
 
 
PARTICIPANT SAFETY MONITORING PLAN 
Assessment of Worsening Depression, Anxiety and Suicide Risk  
 
As outlined in the Safety Monitoring Protocol and Procedures (see Appendix), we will 
evaluating and assessing the severity of depressive and anxiety symptoms, other psychiatric 
disorders as well as suicide risk, using information from the PHQ-9, C-SSRS, and MINI 
administered at screening (AIM 1), and the PHQ-9, C-SSRS, MINI and  and Generalized 
Anxiety Disorder – 7 (GAD-7), administered at screening (AIM 3 & Aim 4).  Additionally, we will 
be assessing for depressive and anxiety symptoms and suicide risk at the counseling sessions 
throughout treatment and have outlined procedures for monitoring changes of these symptoms 
and ideations (Appendix Safety Monitoring Plan).  The document also outlines procedures for 
addressing other mental health concerns, reporting of elder or child abuse and neglect, 
domestic/intimate partner violence and crises that occur during sessions.  
 
 
 
  Participants who are rated on the Columbia-Suicide Severity Rating Scale at screening 
as having active suicidal ideation with some intent to act and active suicidal ideation with 
specific plan and intent, who fall within the extremely severe range of depressive symptom 
severity, who endorse having severe vegetative symptoms, bipolar symptoms, psychotic 
symptoms, or who are experiencing symptoms associated with Axis I disorders that place them 
at risk of harm will be further evaluated by a designated Master’s or Ph.D. level Mental Health 
Professional (MHP) to make an appropriate treatment disposition. When needed, participants 
will be referred to collaborators at The University of Texas Health Science Center (UTH) to 
manage the action plan/treatment interventions as they deem appropriate or provided with 
outside referral(s). 
 
 
Vulnerable Subjects 
 
There is no additional risk to pregnant women and their fetuses posed by participation in 
the study.  The intervention seeks to reduce smoking and depression in women in both the 
prenatal and postpartum period.  Reduction in smoking and depression during these periods 
may benefit both the woman, the fetus and the neonate.  
 
Procedures to protect confidentiality include: 1) Study participation will be confidential 
and not included in participants’ medical records. 2) Confidentiality will be protected by 
identifying all subjects by ID numbers only with their names kept within a MD Anderson 
approved secure web-based applications and institutionally approved databases (see Data 
management, Quality, and Security section). 3) Participants will not be identified in any public 
reports or documents. Only the PI and data manager have access to the master file linking ID 
and other data to participant names. All information will be reported in aggregate form and 
individual participants will not be identified in any public reports or documents.  We expect these 
procedures to be highly effective for protecting participant confidentiality. 

Protocol 2020-0972 
December 28, 2023Page 38 of 48 
 
 
Information collected during participation in the study will be kept confidential.  In order 
to protect the participant’s information, we received a NIDA (National Institute on Drug Abuse) 
Certificate of Confidentiality.  We will treat all responses confidential to the extent possible.  We 
will follow the HIPAA rules as mandated by MD Anderson and NIDA. 
 
 
DATA MANAGEMENT, QUALITY & SECURITY  
 
As part of the ongoing monitoring of the project, study investigators and staff are responsible for 
ensuring that data quality assurance procedures are developed and maintained. Several 
procedures will be used to maintain the integrity of the data. 
 
REDCap  For AIM 1, process measures, participant contact and clinical progress notes 
will be collected and  managed using REDCap (Research Electronic Data Capture, 
www.project-redcap.org) electronic data capture tools hosted at MD Anderson. REDCap is a 
secure, web-based application with controlled access designed to support data capture for 
research studies, providing: 1) an intuitive interface for validated data entry; 2) audit trails for 
tracking data manipulation and export procedures; 3) automated export procedures for 
seamless downloads to common statistical packages; and 4) procedures for importing data from 
external sources. In the case of multi-center studies REDCap uses Data Access Groups (DAGs) 
to ensure that personnel at each institution are blinded to the data from other institutions. 
REDCap (https://redcap.mdanderson.org) is hosted on a secure server by MD Anderson 
Cancer Center's Department of Research Information Systems & Technology Services. 
REDCap has undergone a Governance Risk & Compliance Assessment (August 2016) by MD 
Anderson's Information Security Office and found to be compliant with HIPAA, Texas 
Administrative Codes 202-203, University of Texas Policy 165, federal regulations outlined in 
21CFR Part 11, and UTMDACC Institutional Policy #ADM0335. 
Trained data collectors will use the databases uploaded to or enter directly into the MD 
Anderson REDCap system. Automated prompts may facilitate some participant contact and 
treatment delivery activities. MD Anderson's Research Information Systems and Technology 
Services (RISTS) group provides deployment and integration support for research data 
management using the REDCap (Research Electronic Data Capture; www.project-redcap.org) 
application.149 REDCap (https://redcap.mdanderson.org) allows researchers and program 
directors at MD Anderson to create projects with data collection instruments and share those 
projects with colleagues. Researchers and program directors can capture and analyze data 
through a simple web-based interface. REDCap is a two-tier pHp-based web application that 
can be hosted on a variety of hardware and operation systems.  
 
For AIMs 3 & 4, all data will be stored in the institutionally approved Tobacco Research and 
Treatment Program (TRTP) database (APPID-264846) in a centralized location on institutional 
servers behind the firewall, which is backed up daily, with access limited to specific users at the 
discretion of the PI. The PI will assure that audits of selected subsets of data are performed and 
that appropriate safeguards of participant privacy are maintained. Privacy safeguards will 
include appropriate password protection and physical security for all computer systems.  
Additional quality assurance procedures include a data collection protocol documented 
in a procedure manual; and regular meetings between the study statistician, the PI, data 
managers, and other project staff to review problems and solutions, and discuss concerns. Data 
entry systems, whether via Qualtrics or hand entry with verification, specifically provide field 
checks, range checks for continuous variables and valid value checks for categorical variables; 
checks for legitimate dates and times and logical consistency. During data collection, we will 

Protocol 2020-0972 
December 28, 2023Page 39 of 48 
 
issue reports weekly, or even following any new data entry, depending on the needs of the 
project. Queries and reports will be provided to the PI. Preliminary review will be initiated shortly 
after data collection begins to allow monitoring of data quality. 
Videoconferencing Software We will work with MD Anderson Infosecurity to identify a 
HIPAA compliant videoconferencing software package through which to deliver the treatment 
sessions.   
Focus Group Protected Health Information  Data and identifiers from focus group 
audiotaped interviews will be stored behind the institutional firewall on encrypted servers with 
restricted access only to study team members and will not be reused or disclosed to any other 
person or entity (except where required by law), or for other research, without prior approval 
from the IRB.  Electronic data and identifiers will be retained indefinitely on MD Anderson 
servers behind the institutional firewall and will be archived per institutional standards.  
 
 
Data Storage Participants’ names and identifiers will be linked to the project 
identification number in databases—located on MD Anderson servers behind institutional 
firewalls—that will be password protected, with access restricted to the project staff, Principal 
Investigator and study collaborators.  Electronic data and identifiers will be retained indefinitely 
on MD Anderson servers behind the institutional firewall and will be archived per institutional 
standards.  Paper records will be kept in a locked file room. Names will not be identified in any 
reports resulting from the study, and no individual information will be released to anyone outside 
of the study.  Data will be secured in password-protected computer files and reported at the 
group level.  Data will not be destroyed and will be archived per institutional standards.  
 
 
 
 
 
 
 

Protocol 2020-0972 
December 28, 2023Page 40 of 48 
 
References 
1. 
Flick LH, Cook CA, Homan SM, McSweeney M, Campbell C, Parnell L. Persistent tobacco use during 
pregnancy and the likelihood of psychiatric disorders. Am J Public Health. 2006;96(10):1799–1807. 
2. 
Goodwin RD, Keyes K, Simuro N. Mental disorders and nicotine dependence among pregnant 
women in the United States. Obstetrics & Gynecology. 2007;109(4):875–883. 
doi:10.1097/01.AOG.0000255979.62280.e6. 
3. 
Smedberg J, Lupattelli A, Mårdby AC, Øverland S, Nordeng H. The relationship between maternal 
depression and smoking cessation during pregnancy—a cross-sectional study of pregnant women 
from 15 European countries. Archives of women's mental health. 2015;18(1):73–84. 
doi:10.1007/s00737-014-0470-3. 
4. 
Goodwin RD, Cheslack-Postava K, Nelson DB, et al. Serious Psychological Distress and Smoking 
During Pregnancy in the United States. 2008-2014. Nicotine Tob.Res. 2017;19(5):605–614. 
doi:10.1093/ntr/ntw323. 
5. 
Meghea CI, Rus IA, Rus D. Risk factors associated with nicotine dependence in a sample of 
Romanian pregnant smokers. Eur J Obstet Gynecol Reprod Biol. 2012;163(1):22–26. 
doi:10.1016/j.ejogrb.2012.03.033. 
6. 
Whitaker RC, Orzol SM, Kahn RS. The co-occurrence of smoking and a major depressive episode 
among mothers 15 months after delivery. Prev.Med. 2007;45(6):476–480. 
7. 
Lieberman E, Gremy I, Lang SM, Cohen AP. Low birth weight at term and the timing of fetal 
exposure to maternal smoking. JAMA. 1994;84(7):1127–1131. doi:10.2105/AJPH.84.7.1127. 
8. 
Vardavas CI, Chatzi L, Patelarou E, et al. Smoking and smoking cessation during early pregnancy and 
its effect on adverse pregnancy outcomes and fetal growth. European Journal of Pediatrics. 
2010;169(6):741–748. doi:10.1007/s00431-009-1107-9. 
9. 
Cnattingius S. The epidemiology of smoking during pregnancy: Smoking prevalence, maternal 
characteristics, and pregnancy outcomes. Nicotine Tob.Res. 2004;6(2 supp 2):125–140. 
doi:10.1080/14622200410001669187. 
10. Shah NR, Bracken MB. A systematic review and meta-analysis of prospective studies on the 
association between maternal cigarette smoking and preterm delivery. American Journal of 
Obstetrics & Gynecology. 2000;182(2):465–472. doi:10.1016/S0002-9378(00)70240-7. 
11. Blizzard L, Ponsonby AL, Dwyer T, Venn A, Cochrane JA. Parental smoking and infant respiratory 
infection: how important is not smoking in the same room with the baby? Am J Public Health. 
2003;93(3):482. 
12. Ladomenou F, Kafatos A, Galanakis E. Environmental tobacco smoke exposure as a risk factor for 
infections in infancy. Acta Paediatrica. 2009;98(7):1137–1141. 
13. Leung GM, Ho LM, Lam TH. Secondhand smoke exposure, smoking hygiene, and hospitalization in 
the first 18 months of life. Archives of Pediatrics and Adolescent Medicine. 2004;158(7):687. 
14. US Department of Health and Human Services. The Health Consequences of Involuntary Smoking: a 
report of the Surgeon General. Rockville, MD; 1986. 
15. Mannino DM, Moorman JE, Kingsley B, Rose D, Repace J. Health effects related to environmental 
tobacco smoke exposure in children in the United States: data from the Third National Health and 
Nutrition Examination Survey. Archives of Pediatrics and Adolescent Medicine. 2001;155(1):36. 
16. Anderson HR, Cook DG. Passive smoking and sudden infant death syndrome: review of the 
epidemiological evidence. Thorax. 1997;52(11):1003. 

Protocol 2020-0972 
December 28, 2023Page 41 of 48 
 
17. Grote NK, Bridge JA, Gavin AR, Melville JL, Iyengar S, Katon WJ. A meta-analysis of depression during 
pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch 
Gen Psychiatry. 2010;67(10):1012–1024. doi:10.1001/archgenpsychiatry.2010.111. 
18. Dieter JNI, Field T, Hernandez-Reif M, et al. Maternal depression and increased fetal activity. Journal 
of Obstetric, Gynecologic and Neonatal Nursing. 2001;21(5):468–473. 
19. Goedhart G, Snijders AC, Hesselink AE, van Poppel MN, Bonsel GJ, Vrijkotte TGM. Maternal 
depressive symptoms in relation to perinatal mortality and morbidity: Results from a large 
multiethnic cohort study. Psychosom Med. 2010;72(8):769–776. 
20. Gold KJ, Dalton VK, Schwenk TL, Hayward RA. What causes pregnancy loss? Preexisting mental 
illness as an independent risk factor. Gen.Hosp.Psychiatry. 2007;29(3):207–213. 
21. Marcus S, Lopez JF, McDonough S, et al. Depressive symptoms during pregnancy: Impact on 
neuroendocrine and neonatal outcomes. Infant Behavior and Development. 2011;34(1):26–34. 
doi:10.1016/j.infbeh.2010.07.002. 
22. McFarland J, Salisbury AL, Battle CL, Hawes K, Halloran K, Lester BM. Major depressive disorder 
during pregnancy and emotional attachment to the fetus. Archives of women's mental health. 
2011;14(5):425–434. doi:10.1007/s00737-011-0237-z. 
23. Schwebel DC, Brezausek CM. Chronic maternal depression and children's injury risk. J 
Pediatr.Psychol. 2008;33(10):1108–1116. doi:10.1093/jpepsy/jsn046. 
24. Dennis CL, McQueen K. The relationship between infant-feeding outcomes and postpartum 
depression: a qualitative systematic review. Pediatrics. 2009;123(4):e736-e751. 
25. Nishioka E, Haruna M, Ota E, et al. A prospective study of the relationship between breastfeeding 
and postpartum depressive symptoms appearing at 1-5 months after delivery. Journal of Affective 
Disorders. 2011;133(3):553–559. doi:10.1016/j.jad.2011.04.027. 
26. O'Brien LM, Heycock EG, Hanna M, Jones PW, Cox JL. Postnatal depression and faltering growth: a 
community study. Pediatrics. 2004;113(5):1242–1247. 
27. Wojcicki JM, Holbrook K, Lustig RH, et al. Chronic maternal depression is associated with reduced 
weight gain in latino infants from birth to 2 years of age. PloS one. 2011;6(2):e16737-e16737. 
28. Guttmann A, Dick P, To T. Infant hospitalization and maternal depression, poverty and single 
parenthood a population based study. Child: care, health and development. 2004;30(1):67–75. 
29. Mandl KD, Tronick EZ, Brennan TA, Alpert HR, Homer CJ. Infant health care use and maternal 
depression. Archives of Pediatrics and Adolescent Medicine. 1999;153(8):808. 
30. McLennan JD, Kotelchuck M. Parental prevention practices for young children in the context of 
maternal depression. Pediatrics. 2000;105(5):1090. 
31. Leiferman J. The effect of maternal depressive symptomatology on maternal behaviors associated 
with child health. Health Educ.Behav. 2002;29(5):596–607. 
32. Downey G, Coyne JC. Children of depressed parents: An integrative review. Psychol Bull. 
1990;108(1):50. 
33. Fiore MC, Jaen CR, Baker TB, et al. Treating Tobacco Use and Dependence: 2008 Update, Clinical 
Practice Guideline. PM:18807274. Updated March 04, 2015. 
34. Lumley J, Oliver S, Waters E. Interventions for promoting smoking cessation during pregnancy. 
Cochrane Database Syst.Rev. 2000;2:CD001055-CD001055. 
35. Jones M, Lewis S, Parrott S, Wormall S, Coleman T. Re-starting smoking in the postpartum period 
after receiving a smoking cessation intervention. A systematic review. Addiction. 2016;111(6):981–
990. doi:10.1111/add.13309. 

Protocol 2020-0972 
December 28, 2023Page 42 of 48 
 
36. Albrecht SA, Caruthers D, Patrick T, et al. A randomized controlled trial of a smoking cessation 
intervention for pregnant adolescents. Nursing Research. 2006;55(6):402–410. 
37. Dornelas EA, Magnavita J, Beazoglou T, et al. Efficacy and cost-effectiveness of a clinic-based 
counseling intervention tested in an ethnically diverse sample of pregnant smokers. 
Patient.Educ.Couns. 2006;64(1-3):342–349. 
38. Bradizza CM, Stasiewicz PR, Zhuo Y, et al. Smoking Cessation for Pregnant Smokers. Development 
and Pilot Test of an Emotion Regulation Treatment Supplement to Standard Smoking Cessation for 
Negative Affect Smokers. Nicotine Tob.Res. 2017;19(5):578–584. doi:10.1093/ntr/ntw398. 
39. Melvin C, Gaffney C. Treating nicotine use and dependence of pregnant and parenting smokers: an 
update. Nicotine Tob.Res. 2004;6 Suppl 2:S107-S124. 
40. French GM, Groner JA, Wewers ME, Ahijevych K. Staying smoke free: An intervention to prevent 
postpartum relapse. Nicotine Tob.Res. 2007;9(6):663–670. 
41. Hannover W, Thyrian JR, Roske K, et al. Smoking cessation and relapse prevention for postpartum 
women: results from a randomized controlled trial at 6, 12, 18 and 24 months. Addict.Behav. 
2009;34(1):1–8. 
42. Johnson JL, Ratner PA, Bottorff JL, Hall W, Dahinten S. Preventing smoking relapse in postpartum 
women. Nursing Research. 2000;49(1):44. 
43. McBride CM, Curry SJ, Lando HA, Pirie PL, Grothaus LC, Nelson JC. Prevention of relapse in women 
who quit smoking during pregnancy. Am J Public Health. 1999;89:706–711. 
44. McBride CM, Baucom DH, Peterson BL, et al. Prenatal and postpartum smoking abstinence a 
partner-assisted approach. Am J Prev Med. 2004;27(3):232–238. 
45. Pbert L, Ockene JK, Zapka J, et al. A community health center smoking-cessation intervention for 
pregnant and postpartum women. Am J Prev Med. 2004;26(5):377–385. 
46. Secker-Walker RH, Solomon LJ, Flynn BS. Individualized smoking cessation counseling during 
prenatal and early postnatal care. American Journal of Obstetrics & Gynecology. 1994;171:1347–
1355. 
47. Van't Hof SM, Wall MA, Dowler DW, Stark MJ. Randomised controlled trial of a postpartum relapse 
prevention intervention. Tob Control. 2000;9(Suppl 3):III64-III66. 
48. Wall MA, Severson HH, Andrews JA. Pediatric office-based smoking intervention: impact on 
maternal smoking and relapse. Pediatrics. 1995;96(4):622–628. 
49. Agboola S, McNeill A, Coleman T, Leonardi BJ. A systematic review of the effectiveness of smoking 
relapse prevention interventions for abstinent smokers. Addiction. 2010;105(8):1362–1380. 
50. Levitt C, Shaw E, Wong S, Kaczorowski J. Systematic review of the literature on postpartum care: 
effectiveness of interventions for smoking relapse prevention, cessation, and reduction in 
postpartum women. Birth. 2007;34(4):341–347. 
51. Cinciripini PM, Blalock JA, Minnix JA, et al. Effects of an intensive depression-focused intervention 
for smoking cessation in pregnancy. J Consult.Clin.Psychol. 2010;78(1):44–54. 
doi:10.1037/a0018168. 
52. Meernik C, Goldstein AO. A critical review of smoking, cessation, relapse and emerging research in 
pregnancy and post-partum. British Medical Bulletin. 2015;114(1):135–146. 
doi:10.1093/bmb/ldv016. 
53. Coleman-Cowger VH. Smoking cessation intervention for pregnant women: a call for extension to 
the postpartum period. Matern.Child Health J. 2012;16(5):937–940. 

Protocol 2020-0972 
December 28, 2023Page 43 of 48 
 
54. Jacobson NS, Martell CR, Dimidjian S. Behavioral activation treatment for depression: Returning to 
contextual roots. Clinical Psychology: Science and Practice. 2001;8(3):255–270. 
55. Dimidjian S, Hollon SD, Dobson KS, et al. Randomized trial of behavioral activation, cognitive 
therapy, and antidepressant medication in the acute treatment of adults with major depression. J 
Consult.Clin.Psychol. 2006;74(4):658–670. doi:10.1037/0022-006X.74.4.658. 
56. Dimidjian S, Goodman SH, Sherwood NE, et al. A pragmatic randomized clinical trial of behavioral 
activation for depressed pregnant women. J Consult.Clin.Psychol. 2017;85(1):26–36. 
doi:10.1037/ccp0000151. 
57. MacPherson L, Tull MT, Matusiewicz AK, et al. Randomized controlled trial of behavioral activation 
smoking cessation treatment for smokers with elevated depressive symptoms. J 
Consult.Clin.Psychol. 2010;78(1):55–61. doi:10.1037/a0017939. 
58. Martínez-Vispo C, Rodríguez-Cano R, López-Durán A, Senra C, Fernández Del Río E, Becoña E. 
Cognitive-behavioral treatment with behavioral activation for smoking cessation. Randomized 
controlled trial. PloS one. 2019;14(4):e0214252. doi:10.1371/journal.pone.0214252. 
59. Mathew AR, Hogarth L, Leventhal AM, Cook JW, Hitsman B. Cigarette smoking and depression 
comorbidity. Systematic review and proposed theoretical model. Addiction. 2017;112(3):401–412. 
doi:10.1111/add.13604. 
60. Dimidjian S, Barrera MJ, Martell C, Munoz RF, Lewinsohn PM. The origins and current status of 
behavioral activation treatments for depression. Annu.Rev Clin Psychol. 2011;7:1–38. 
61. Dimaggio G, Shahar G. Behavioral activation as a common mechanism of change across different 
orientations and disorders. Psychotherapy (Chic). 2017;54(3):221–224. doi:10.1037/pst0000117. 
62. Egede LE, Acierno R, Knapp RG, et al. Psychotherapy for depression in older veterans via 
telemedicine. A randomised, open-label, non-inferiority trial. Lancet Psychiatry. 2015;2(8):693–701. 
doi:10.1016/S2215-0366(15)00122-4. 
63. Yuen EK, Herbert JD, Forman EM, et al. Acceptance based behavior therapy for social anxiety 
disorder through videoconferencing. J Anxiety Disord. 2013;27(4):389–397. 
doi:10.1016/j.janxdis.2013.03.002. 
64. Luxton DD, Pruitt LD, Wagner A, Smolenski DJ, Jenkins-Guarnieri MA, Gahm G. Home-based 
telebehavioral health for U.S. military personnel and veterans with depression. A randomized 
controlled trial. J Consult.Clin.Psychol. 2016;84(11):923–934. doi:10.1037/ccp0000135. 
65. Yuen EK, Gros DF, Price M, et al. Randomized Controlled Trial of Home-Based Telehealth Versus In-
Person Prolonged Exposure for Combat-Related PTSD in Veterans. Preliminary Results. J Clin 
Psychol. 2015;71(6):500–512. doi:10.1002/jclp.22168. 
66. Acierno R, Knapp R, Tuerk P, et al. A non-inferiority trial of Prolonged Exposure for posttraumatic 
stress disorder. In person versus home-based telehealth. Behav Res Ther. 2017;89:57–65. 
doi:10.1016/j.brat.2016.11.009. 
67. Arnow BA, Steidtmann D, Blasey C, et al. The relationship between the therapeutic alliance and 
treatment outcome in two distinct psychotherapies for chronic depression. J Consult.Clin.Psychol. 
2013;81(4):627–638. doi:10.1037/a0031530. 
68. Holtrop JS, Meghea C, Raffo JE, Biery L, Chartkoff SB, Roman LA. Smoking among pregnant women 
with Medicaid insurance: are mental health factors related? Matern.Child Health J. 2010;14(6):971–
977. 
69. Maxson PJ, Edwards SE, Ingram A, Miranda ML. Psychosocial differences between smokers and non-
smokers during pregnancy. Addict.Behav. 2012;37(2):153–159. 

Protocol 2020-0972 
December 28, 2023Page 44 of 48 
 
70. Mullen PD, Richardson MA, Quinn VP, Ershoff DH. Postpartum return to smoking: who is at risk and 
when. Am J Health Promot. 1997;11(5):323. 
71. Solomon LJ, Quinn VP. Spontaneous quitting: Self-initiated smoking cessation early in pregnancy. 
Nicotine Tob.Res. 2004;6(Suppl. 2):S203-S216. 
72. Rounsaville BJ, Carroll KM, Onken LS. A stage model of behavioral therapies research: Getting 
started and moving on from stage I. Clinical Psychology: Science and Practice. 2001;8(2):133–142. 
73. Arnow BA, Manber R, Blasey C, et al. Therapeutic reactance as a predictor of outcome in the 
treatment of chronic depression. J Consult.Clin.Psychol. 2003;71(6):1025–1035. 
74. Blalock JA, Fouladi R, Cinciripini PM, et al. Cognitive and behavioral mediators of combined 
pharmacotherapy and psychotherapy of chronic depression. Cognitive Therapy and Research. 
2008;32:197–211. 
75. Keller MB, McCullough JP, Klein DN, et al. A comparison of nefazodone, the cognitive behavioral-
analysis system of psychotherapy, and their combination for the treatment of chronic depression. 
N.Engl.J.Med. 2000;342(20):1462–1470. doi:10.1056/NEJM200005183422001. 
76. Klein DN, Castonguay LG, Arnow B, et al. Therapeutic alliance in depression treatment: Controlling 
for prior change and patient characteristics. J Consult.Clin.Psychol. 2003;17(6):997–1006. 
77. Klein DN, Santiago NJ, Vivian D, et al. Cognitive behavioral analysis system of psychotherapy as a 
maintenance treatment for chronic depression. J Consult.Clin.Psychol. 2004;72(4):681–688. 
78. Maddux RE, Riso LP, Klein DN, et al. Select comorbid personality disorders and the treatment of 
chronic depression with nefazodone, targeted psychotherapy, or their combination. J.Affect.Disord. 
2009;117(3):174–179. 
79. Manber R, Arnow B, Blasey C, et al. Patient's therapeutic skill acquisition and response to 
psychotherapy, alone or in combination with medication. Psychol Med. 2003;33:693–702. 
80. Schatzberg AF, Rush AJ, Arnow BA, et al. Chronic depression: medication (nefazodone) or 
psychotherapy (CBASP) is effective when the other is not. Arch Gen Psychiatry. 2005;62(5):513–520. 
81. Santiago NJ, Klein DN, Vivian D, et al. The therapeutic alliance and CBASP-specific skill acquisition in 
the treatment of chronic depression. Cognitive Therapy and Research. 2005;29(6):803–817. 
82. Vocisano C, Klein DN, Arnow B, et al. Therapist variables that predict symptom change in 
psychotherapy with chronically depressed outpatients. Psychotherapy: Theory, Research, Practice, 
Training. 2004;41(3):255–265. 
83. Blalock JA, Fouladi R, Wetter DW, Cinciripini PM. Depression in pregnant women seeking smoking 
cessation treatment. Addict.Behav. 2005;30(6):1195–1208. doi:10.1016/j.addbeh.2004.12.010. 
84. Blalock JA, Robinson JD, Wetter DW, Cinciripini PM. Relationship of DSM-IV-based depressive 
disorders to smoking cessation and smoking reduction in pregnant smokers. Am.J Addict. 
2006;15:268–277. 
85. Blalock JA, Nayak N, Wetter DW, et al. The relationship of childhood trauma to nicotine dependence 
in pregnant smokers. Psychol. Addict. Behav. 2011;25(4):652–663. doi:10.1037/a0025529. 
86. Blalock JA, Minnix JA, Mathew AR, Wetter DW, McCullough JP, Cinciripini PM. Relationship of 
childhood trauma to depression and smoking outcomes in pregnant smokers. J Consult.Clin.Psychol. 
2013;81(5):821–830. 
87. Cinciripini PM, McClure JB, Wetter DW, et al. An evaluation of videotaped vignettes for smoking 
cessation and relapse prevention during pregnancy: The Very Important Pregnant Smokers (VIPS) 
Program. Tob Control. 2000;9(Suppl. 3):61–63. 

Protocol 2020-0972 
December 28, 2023Page 45 of 48 
 
88. Parrott CE, Blalock JA, Vincent JP. An examination of the factor structure of the Wisconsin Inventory 
of Smoking Dependence Motives (WISDM-68) in a sample of pregnant smokers; 2012. 
89. Stotts AL, Northrup TF, Cinciripini PM, et al. Randomized, controlled pilot trial of bupropion for 
pregnant smokers: challenges and future directions. Am.J.Perinatol. 2015;32(4):351–356. 
90. Martell C.R., Dimidjian S., Herman-Dunn R. Behavioral activation for depression: A clinician's guide. 
New York: Guilford Press; 2010. 
91. Quinn G, Ellison BB, Meade C, et al. Adapting smoking relapse-prevention materials for pregnant 
and postpartum women: formative research. Matern.Child Health J. 2006;10(3):235–245. 
92. Ershoff DH, Solomon LJ, Dolan-Mullen P. Predictors of intentions to stop smoking early in prenatal 
care. Tob Control. 2000;9(Suppl. 3):41–45. 
93. Kahn RS, Certain L, Whitaker RC. A reexamination of smoking before, during, and after pregnancy. 
Am J Public Health. 2002;92(11):1801–1808. 
94. Tong VT, Jones JR, Dietz PM, Bombard JM. Trends in Smoking Before, During, and After Pregnancy: 
Pregnancy Risk Assessment Monitoring System (PRAMS), United States, 31 Sites, 2000-2005. 
MMWR Morb.Mortal.Wkly.Rep. 2009;68:1–29. 
95. Heppner WL, Ji L, Reitzel LR, et al. The role of prepartum motivation in the maintenance of 
postpartum smoking abstinence. Health. Psychol. 2011;30(6):736–745. 
96. Kendzor DE, Businelle MS, Costello TJ, et al. Early breastfeeding predicts continued smoking 
abstinence among women who quit smoking due to pregnancy. Baltimore, MD; February. 
97. Ma Y, Goins KV, Pbert L, Ockene JK. Predictors of smoking cessation in pregnancy and maintenance 
postpartum in low-income women. Matern.Child Health J. 2005;9(4):393–402. 
98. Polanska K, Hanke W, Sobala W. Smoking relapse one year after delivery among women who quit 
smoking during pregnancy. International Journal of Occupational Medicine and Environmental 
Health. 2005;18(2):159–165. 
99. Polanska K, Hanke W, Sobala W, Lowe JB, Jaakkola JJK. Predictors of smoking relapse after 
delivery:prospective study in Central Poland. Matern.Child Health J. 2011;15:1–8. 
100. Reitzel LR, Vidrine JI, Li Y, et al. The influence of subjective social status on vulnerability to 
postpartum smoking among young pregnant women. Am J Public Health. 2007;97:1476–1482. 
101. Solomon LJ, Higgins ST, Heil SH, Badger GJ, Thomas CS, Bernstein IM. Predictors of postpartum 
relapse to smoking. Drug Alcohol. Depend. 2007;90(2-3):224–227. 
102. Onwuegbuzie AJ, Leech NL. A call for qualitative power analyses. Quality & Quantity. 2007;41:105–
121. 
103. Cresswell JW. Qualitative inquiry and research design: Choosing among five appraoches. Thousan 
Oaks, CA: Sage; 2007. 
104. Ragin CC. The comparative method: Moving beyond qualitative and quantitative strategies: 
University of California Press; 2014. 
105. Glaser B, Strauss A. The discovery of grounded theory: Strategies for qualiative research. New 
Brunswick, London: Aldine Transaction; 1967. 
106. Glaser BG. The constant comparative method of quaitative analysis. Social Problems. 
1965;12(4):436–445. 
107. Kreuger RA. Focus groups: A practical guide for applied research. Oaklland, CA: SAGE Publications; 
2000. 
108. G GE. Criterion for assessing the trusthworthiness of naturalistic inquiries. Educational 
Communication and Technology. 1981;29:75–91. 

Protocol 2020-0972 
December 28, 2023Page 46 of 48 
 
109. OTRC. Insight Platform: About INSIGHT. https://otrc.stephensoncancercenter.org/Mobile-Health-
Technology/Insight-Platform. Updated August 04, 2019. 
110. Jordan PW, Thomas B, Weerdmeesler, B. A., McClelland, A. L., eds. Usability Evaluation in Industry: 
SUS: a quick and dirty usability scale. London: Taylor and Francis; 1986. 
111. Brown RA, Burgess ES, Sales SD, Whiteley JA, Evans DM, Miller IW. Reliability and validity of a 
smoking timeline follow-back interview. Psychol. Addict. Behav. 1998;12(2):101–112. 
doi:10.1037/0893-164X.12.2.101. 
112. Pocock SJ. Clinical trials. New York: John Wiley & Sons; 1983. 
113. Posner K, Brown GK, Stanley B, et al. The Columbia-Suicide Severity Rating Scale: Initial validity and 
internal consistency findings from three multisite studies with adolescents and adults. Am J 
Psychiatry. 2011;168(12):1266–1277. 
114. Zimmerman M, Mattia JI. A self-report scale to help make psychiatric diagnoses. The Psychiatric 
Diagnostic Screening Questionnaire. Arch Gen Psychiatry. 2001;58(8):787–794. 
115. Pew Research. Mobile-technology and home broadband 2019. 
https://www.pewresearch.org/internet/2019/06/13/mobile-technology-and-home-broadband-
2019/. 
116. Busseri MA, Tyler JD. Interchangeability of the Working Alliance Inventory and Working Alliance 
Inventory, Short Form. Psychol Assess. 2003;15(2):193–197. 
117. Sheehan DV, Lecrubier Y, Sheehan KH, et al. The validity of the Mini International Neuropsychiatric 
Interview (MINI) according to the SCID-P and its reliability. Eur Psychiatry. 1997;12:232–241. 
118. Heatherton TF, Kozlowski LT, Frecker RC, Fagerström KO. The Fagerström Test for Nicotine 
Dependence: A revision of the Fagerström Tolerance Questionnaire. Br.J.Addiction. 
1991;86(9):1119–1127. doi:10.1111/j.1360-0443.1991.tb01879.x. 
119. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: Validity of a brief depression severity measure. 
J.Gen.Intern.Med. 2001;16(9):606–613. doi:10.1046/j.1525-1497.2001.016009606.x. 
120. Löwe B, Unützer J, Callahan CM, Perkins AJ, Kroenke K. Monitoring depression treatment outcomes 
with the Patient Health Questionnaire-9. Med.Care. 2004;42(12):1194–1201. 
121. Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and 
negative affect: The PANAS Scales. J Pers Soc Psychol. 1988;54:1063–1070. doi:10.1037/0022-
3514.54.6.1063. 
122. Lai J-S, Wagner LI, Jacobsen PB, Cella D. Self-reported Cognitive Concerns and Abilities: Two sides of 
one coin? Psycho-Oncology. 2014;23(10):1133–1141. 
123. Welsch SK, Smith SS, Wetter DW, Jorenby DE, Fiore MC, Baker TB. Development and validation of 
the Wisconsin Smoking Withdrawal Scale. Exp Clin Psychopharmacol. 1999;7(4):354–361. 
doi:10.1037/1064-1297.7.4.354. 
124. Bellg AJ, Borrelli B, Resnick B, et al. Enhancing treatment fidelity in health behavior change studies: 
Best practices and recommendations from the NIH Behavior Change Consortium. Health. Psychol. 
2004;23(5):443–451. 
125. FDA. Inovation/Stagnation: Challenge and Opportunity on the Critiical Path to New Medical 
Products.http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html; 2004. 
126. FDA. Innovation or Stagnation: Critical Path Opportunities List; 2006. 
127. O'Neill RT. FDA's Critical Path Initiative: A Perspective on Contributions of Biostatistics. Biom.J. 
2006;48(4):559–564. doi:10.1002/bimj.200510237. 

Protocol 2020-0972 
December 28, 2023Page 47 of 48 
 
128. Temple R. How FDA currently makes decisions on clinical studies. Clinical Trials. 2005;2(4):276–281. 
doi:10.1191/1740774505cn097oa. 
129. Woodcock J. FDA introductory comments. clinical studies design and evaluation issues. Clinical 
Trials. 2006:2: 273-275. 
130. Fitzmaurice GM, Laird NM. Generalized linear mixture models for handling nonignorable dropouts 
in longitudinal studies. Biostatistics. 2000;1(2):141–156. 
131. Lilford RJ, Thornton JG, Braunholtz D. Clinical trials and rare diseases: a way out of a conundrum. 
BMJ. 1995;311(7020):1621–1625. 
132. Spiegelhalter DJ, Myles JP, Jones DR, Abrams KR. An introduction to Bayesian methods in health 
technology assessment. BMJ. 1999;319(7208):508–512. 
133. Berry DA. Bayesian clinical trials. Nature Reviews Drug Discovery. 2006:5, 27-36. 
134. Goodman SN. Introduction to Bayesian methods I. measuring the strength of the evidence. Clinical 
Trials and Meta-Analysis. 2005;2:282–290. 
135. Wijeysundera DN, Austin PC, Hux JE, Beattie WS, Laupacis A. Bayesian statistical inference enhances 
the interpretation of contemporary randomized controlled trials. J Clin Epidemiol. 2009;62(1):13–
21. doi:10.1016/j.jclinepi.2008.07.006. 
136. Assmann SF, Pocock SJ, Enos LE, Kasten LE. Subgroup analysis and other (mis)uses of baseline data 
in clinical trials. Lancet. 2000;355(9209):1064–1069. 
137. Pocock SJ, Assmann SF, Enos LE, Kasten LE. Subgroup analysis, covariate adjustment and baseline 
comparisions in clinical trial reporting. Current practice and problems. Stat Med. 2002;21:2917–
2930. 
138. R Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria: R 
Foundation for Statistical Computing; 2017. 
139. SAS Institute I. SAS v. 9.4. Cary, NC USA: SAS Institute, Inc; 2002-2012. 
140. Carpenter B, Gelman A, Hoffman MD, et al. Stan. A probabilistic programming language. Journal of 
Statistical Software. 2017;76(1). doi:10.18637/jss.v076.i01. 
141. Best N, Thomas, A. (2000) . (Editors ). (pp. 387-402). Bayesian Graphical Models and Software for 
GLMs. In: D. Dey, S. K. Ghosh, Mallick BK, eds. Generalized Linear Models: A Bayesian Perspective. 
New York: Marcel Dekker, Inc.; 2000. 
142. Best N, Thomas A. Bayeisan Graphical Models and Software for GLMs. In: Dipak D, Sujit K, Ghosh PK, 
Bani K, Mallick, eds. In Generalized Linear Models: A Bayesian Perspective. New York: Marcel 
Dekker, Inc; 2000:387–402. 
143. Gelman A. Prior distributions for variance parameters in hierarchical models. Bayesian Analysis. 
2006;1(3):515–553. 
144. Muthen BO, Asparouhov T. Bayesian structural equation modeling: a more flexible representation 
of substantive theory. Psychol Methods. 2012;17(3):313–335. 
145. Arbuckle JL. Amos 6.0 User's Guide. Spring House, PA: Amos Development Corporation; 2005. 
146. Muthén LK, Muthén BO. Mplus user's guide. Los Angeles: Muthen & Muthen; 2012. 
147. Dunson DB, Palomo J, Bollen K. Bayesian Structural Equation Modeling; 01.01.2005. 
148. Lee S-Y, Song X-Y. Evaluation of the Bayesian and Maximum Likelihood Approaches in Analyzing 
Structural Equation Models with Small Sample Sizes. Multivariate Behav Res. 2004;39(4):653–686. 
doi:10.1207/s15327906mbr3904_4. 

Protocol 2020-0972 
December 28, 2023Page 48 of 48 
 
149. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture 
(REDCap)--a metadata-driven methodology and workflow process for providing translational 
research informatics support. J Biomed Inform. 2009;42(2):377–381. doi:10.1016/j.jbi.2008.08.010.