An Integrated Brief Alcohol and PTSD Intervention for Veterans in Primary Care
Phase: NA
Conditions: Stress Disorders, Post-Traumatic, Alcohol-Related Disorders
Sponsor: Syracuse VA Medical Center

An Integrated Brief Alcohol and PTSD Intervention for Veterans in Primary Care  
NCT03812146 
Document Date: May 6, 2021 (date of last IRB review of the protocol) 
 

Randomized Controlled Trial of PC-TIME 
 
Specific Aim 2 is to conduct a 2-arm pilot RCT of our adapted PC-TIME compared to a PC treatment as 
usual (PC-TAU) (n=60). All interventions will be completed in person. All participants will complete 
assessments at baseline, post-treatment, 14-week follow-up and 20-week follow-up. We will test our primary 
hypothesis that heavy drinking veteran PC patients receiving PC-TIME will reduce their percentage of heavy 
drinking days and PTSD severity compared to those receiving PC-TAU. 
 
C4.1. Description of the Sample. Veterans enrolled in PC within VA facilities in Syracuse and 
Binghamton, NY will be screened for eligibility. The open trial will not include Buffalo participants due to 
budgetary limitations, (i.e., unable to staff Buffalo in year 1 to recruit, assess and treat patients). Inclusion 
criteria: Patients who score a) 8-19 for men, 6-19 for women on the AUDIT and have past month drinking (i.e., 
have not quit drinking over the last month); and b) score ≥33 on the PTSD Checklist-5 (PCL-5) and report a 
traumatic event on the Criterion A screener. Exclusion criteria: Patients will be excluded if they 1) score a 20 or 
higher on the AUDIT as previous research has demonstrated the BMIs are less effective with very severe 
drinkers (see C2.2.a) and/or 2) demonstrate symptoms that would not allow them to actively engage in the 
intervention such as gross cognitive impairment and/or current symptoms of mania or psychosis. Patients will 
also be excluded if they have more pressing concerns that need to be addressed first: 3) in need of detox 
services, or 4) suicide attempt in the last two months or current intent to commit suicide. Patients with recent 
suicide attempts or intent may be enrolled following receipt of suicide prevention services. We will also exclude 
patients that 5) are already receiving psychotherapy for heavy drinking or PTSD outside of PC, 6) started or 
changed the dose of a psychotropic medication for heavy drinking or PTSD in the last two months that was 
prescribed outside of VA PC, and 7) voice a preference to be directly referred to VA specialty care for heavy 
drinking or PTSD. These final 3 exclusions are to allow the study to isolate the effects of the intervention and to 
ensure that patient preference for services is honored. In RCTs for Veterans with PTSD 63, 64, the effect of a 
psychotropic medication is typically considered to be stable after 2 months; therefore it should not confound 
the effect of the intervention.  
 
C4.2. Sample Size. We will recruit a total of 60 patients to retain a minimum sample size of 51 (85% 
retention) at 20-week follow-up. This retention rate was observed in our previous work (See A2.1, B1).  
 
C4.3. VA facilities. The Buffalo and Syracuse VA Medical Centers are located in urban areas and serve 
catchment areas that include many suburban and rural communities. Both medical centers have three PC 
clinics, with one in each facility dedicated to female veterans. The Binghamton VA Community Based 
Outpatient Clinic in located in a small city and provides PC and outpatient mental health services. According to 
the VA electronic medical record, over an 11-month period in 2016-2017, 782, 461, and 157 PC veterans 
screened positive on the AUDIT-C or PC-PTSD in Buffalo, Syracuse, and Binghamton, respectively. These 
three VA sites were chosen due to the affiliation of our study team to these locations and our previous success 
achieving strong recruitment and retention at these facilities. Recruitment at both Syracuse and Buffalo will be 
necessary to meet study enrollment goals and inclusion of the Binghamton clinic will allow us to investigate 
feasibility in a small clinic (common within the VA system). Also, running the study across three sites will 
provide feasibility data for the future full-scale multi-site RCT. As all three clinics are within the same VA 
network (VISN 2) and utilize the same model of PCMHI, we do not anticipate significant site differences.   
 
C4.4. Participant Recruitment. Recruitment will use a method already shown to be effective (see B1). 
Patients screening positive on the PC-PTSD screen and/or AUDIT-C, which are delivered as part of standard 
practice nationally in VA, will be referred by their PC or PCMHI providers. Research staff will facilitate the 
referral process by using electronic medical record data to create monthly lists of patients screening positive 
and then asking their providers to refer these patients to the study. Research staff will send a letter to all 
referred veterans introducing the study. Study staff will then contact referred patients by phone to assess their 
interest in participation. Interested patients will be scheduled for a baseline research appointment within their 
PC clinic where study eligibility will be determined, including administering the AUDIT and PCL-5. Women will 
be over-sampled by devoting study resources to recruit from the Women’s PC Clinics. To illustrate this 
recruitment method, in the Web CBT study (see B1) over a 27-month period 2,057 veterans screened positive 
on the AUDIT-C and/ or PC-PTSD within their PC clinic. Study staff was able to contact 973 of these veterans 
by phone and 217 were scheduled for a baseline interview. Of the 217, 162 were determined eligible to be 
randomized. These numbers equate to recruiting 5 eligible participants per month. Based on the success of 
prior studies and our anticipated recruitment pool at Buffalo, Syracuse and Binghamton, we expect to be able 
to enroll 3.5 eligible participants per month. This will allow us to recruit 60 participants over 17 months. 
 
C4.5. Assessment and Randomization. Baseline assessments will be conducted in person. Trained, VA-
based research staff will obtain informed consent and HIPAA authorization. An interactive program (Qualtrex) 
on a laptop computer will administer the questionnaires. We have used computerized assessment in several 
previous studies to facilitate data collection and entry and to provide the input for the computer-generated 
feedback sheet used within the BMI. Following completion of the computerized self-report measures, 
participants will be randomly assigned to treatment condition. Urn randomization will be used to ensure a 
balanced distribution of key patient factors across treatment groups 72. Included in the urn randomization: 1) 

AUDIT score > 15, 2) PCL-5 ≥ 50, 3) gender. Demographic and severity cut-points are informed by 
distributional data from previous study databases. We have used these variables in previous studies with 
success at obtaining similar groups in each treatment condition at baseline.  
 
Following randomization participants will complete the Clinical Administered PTSD Scale (CAPS-5). While 
a CAPS-5 is not needed to determine study inclusion, it will serve as the primary PTSD outcome measure 
because it is a more sensitive measure of PTSD severity than the PCL-5 self-report. We carefully considered 
whether PTSD diagnosis with the CAPS-5 should be required for study inclusion and decided that using the 
established cut-point on the PCL-5 provided a more ecologically valid measure for a PC-based study.  A 1-
hour clinical interview such as the CAPS-5 could not feasibly be used in typical PCMHI practice.  
 
A post-treatment assessment (8 weeks) and two follow-up assessments (14 weeks; 20 weeks) will be 
conducted following baseline (Table 5). For a brief treatment like PC-TIME, we expect the largest treatment 
effects (for both alcohol use and PTSD) to be at post-treatment. The purpose of follow-ups are to examine if 
change is maintained and to assess engagement in additional treatment. Our four assessment points will allow 
for a more precise trajectory of change overtime. We chose 20 weeks for our final follow-up because this is the 
longest interval that our study timeline would allow. Follow-ups will be in person or by phone (based on 
participant preference) by study staff and were designed to reduce participant burden and minimize drop-out. 
   C4.6. Participant Payment. Participants will be paid for time spent completing assessments at a rate of 
approximately $20/ hour (baseline session- $40, post-treatment (week 8)- $40, 14-week follow-up- $20, 20-
week follow-up- $20, $20 bonus for completing all study procedures) and can earn up to $160. Reimbursement 
will be by check mailed to the veteran’s home. Participants will not be reimbursed for intervention sessions.  
C5. Measures 
C5.1. Screening Measures 
Alcohol Use Disorders Identification Test (AUDIT) 73. This 10-item questionnaire, developed by the 
WHO, identifies patients whose alcohol consumption has become harmful. Questions are scored from 0-4 with 
a cumulative score range of 0-40. A score of 8 or higher reflects heavy use, 74 but more recent research has 
identified an alternative cut point of 6 or higher for females 75. The AUDIT is used to establish eligibility. 
PTSD Checklist-5 (PCL-5). This 20-item self-report measure asks respondents to rate how much they 
have been bothered by DSM-5 PTSD symptoms in the past month on a 0 - 4 Likert-type scale 76. The PCL-5 
will be administered with the extended criterion A (traumatic event) assessment. A cut point of 33 along with 
meeting criterion A will be required for study inclusion 77. The total score will be used to indicate PTSD severity 
at post-treatment and follow-up. 
 
Mini-Mental Status Exam (MSE). This interview determines if a patient has cognitive dysfunction and 
should therefore not be recruited. The MSE has sections on orientation (8 items), memory (2 items), and 
attention (2 items). Patients who score under 18 (highest score is 26) will not be enrolled. We have used this 
MSE in similar studies with good success 15, 66. 
C5.2 Outcome Measures 
Alcohol Use and Alcohol-Related Problems. Alcohol use and problems will be assessed using the 30-
day Timeline Follow Back Interview (TLFB) 78, 79 and the Short Inventory of Problems (SIP) 80. Indices from the 
TLFB include percentage of heavy drinking days (> 4/5 drinks in one day for women/men), percentage of 
drinking days, average number of drinks per drinking day, and a dichotomous variable indicating whether one’s 
past 30-day drinking pattern would be classified as excessive drinking by the CDC; (i.e., ≥ 8/15 drinks per 
week for women/men) 81, 82. The 15-item SIP yields a total score with high internal consistency (.98) and is a 
valid measure of adverse alcohol consequences. 
Clinician Administered PTSD Scale-5 (CAPS-5). This 30-item structured interview assesses DSM-5 
symptoms of PTSD 83. It includes assessment of traumatic events and symptom severity ratings are based on 
symptom frequency and intensity. CAPS-5 will be administered by study staff at baseline and post-treatment 
and will be the primary measure of change in PTSD symptom severity. A 10-point decrease is considered 
clinically significant as is associated with meaningful improvement in quality of life for veterans with PTSD 84.  
C5.4. Secondary Outcomes  
Post-intervention Treatment Engagement. With HIPAA authorization, information from participants’ VA 
administrative data will be extracted to assess if treatment condition relates to engagement in specialty mental 
health and substance use visits. Number of visits attended and prescriptions of psychiatric and substance use 
medications between enrollment and 20 week follow-up will be extracted for each participant. Drs. Possemato 
and King have expertise in this type of data extraction. In addition, participants will be asked about non-VA 
treatment at each assessment point using the Treatment Services Review 86.  
C6 Treatment Conditions 
 
C6.1. Experimental Condition: PC-TIME. Participants randomized to the PC-TIME condition will 
participate in the intervention developed in the earlier study phases (see C1.2). Sessions will be conducted in-
person and will be recorded for the purpose of monitoring protocol adherence. 
 
C6.2. Control Condition: PC-TAU. PC-TAU consists of mandatory annual screens for all patients with the 

AUDIT-C and PC-PTSD. Patients who score a 4 or higher on the AUDIT-C receive a Brief Advice intervention 
from their PC medical provider that is built into the electronic medical record as a mandatory response to a 
positive screen. In addition, patients who score positive on the AUDIT-C or PC-PTSD are offered a referral to 
the PCMHI provider within the PC clinic. PCMHI in VA consists of licensed, independent providers (typically 
psychologists or clinical social workers) providing brief assessment and interventions to veterans and 
consultation to other members of the PC team. Patients are often treated in PC for a few sessions then 
referred to specialty mental health and substance abuse care, if problems persist. On average, 4 PCMHI 
sessions are provided to PTSD patients typically focused on assessment, psycho-education, and supportive 
counseling 10. VA PC patients often decline referrals for alcohol use following the receipt of brief advice. There 
will be variability in the amount of provider contact PC-TAU participants receive, therefore we will closely 
measure the number and type of PC-TAU contacts and consider it as a covariate in our analyses.  
 
More structured interventions were considered as comparison conditions to provide tighter control over the 
interventions and maximize internal validity. However, we opted not to manualize or alter PC-TAU as this 
would result in comparing two experimental treatments and would not answer our primary research question: Is 
PC-TIME superior to existing PC-based treatment? The advantages of using the PC-TAU control are that it 1) 
provides an efficacy evaluation in a real-world practical setting, 2) optimizes the generalizability of findings to 
other VAs, as the PC-TAU services at our sites are representative of most VA PC settings, 3) controls for non-
specific factors such as interaction with the VA staff and receiving treatment that is problem-specific (e.g., Brief 
Advice for alcohol use), and 4) does not deprive veterans of receiving usual care services.   
 
Statistical Analysis Plan 
For this treatment development grant application, assessment of feasibility and acceptability of the 
intervention and research procedures is the primary goal. As this trial will provide us with feasibility information 
for a larger trial, we will describe the number of participants screened and enrolled per month, proportion of 
screened participants who are eligible to enroll, completion rates of follow-up assessments, retention rates in 
study conditions, and the rate and timing of patient drop-out. Graphs will be utilized to display rates of 
intervention and assessment retention at each measurement time. Confidence intervals (95%) will be 
calculated and used in design considerations of a larger trial. Participant retention rates in both study 
interventions will be described with mean, standard deviations and confidence intervals. PC-TIME therapist 
fidelity with be described quantitatively with the mean number of items endorsed on fidelity checklists. Items 
with lower fidelity will be described to inform future PC-TIME training curriculums. For client satisfaction total 
CSQ scores and scores on individual CSQ items will be described with means, standard deviations and 
confidence intervals to understand the satisfaction and acceptability in each condition.  
For other outcomes, we are well aware that effect size estimates with small samples have large standard 
errors and therefore wide confidence intervals 92 and believe that the most important factor in determining 
sample size for a Stage II clinical trial is have adequate power to detect a clinically relevant difference between 
conditions if one truly exists. Nonetheless, pilot data can be used to demonstrate whether the effects of 
treatment looks promising across a set of outcome variables, to begin to examine distribution of outcome 
variables to inform future analytic strategies, and to suggest, in concert with results from larger scale clinical 
trials in related fields, the range of effect sizes that would be reasonable to expect in a future trial. As a result, 
we will obtain the between treatment condition effect size estimates (with 95% confidence intervals) at each 
assessment (e.g., Cohen’s d or h) as well as the correlation between the same dependent variable at adjacent 
assessments. These parameters will provide one source of information that will be used to help determine 
necessary sample size for a future clinical trial. We will have complete data on approximately 51 participants 
(the minimum expected after participant loss due to attrition), within the recommended sample size for 
treatment development of 15 to 30 participants per cell 93. Primary analyses will be intent-to-treat (using data 
from all treatment enrollees). Secondary completer analyses (including only subjects who attend at least 4 of 
the 5 scheduled sessions) will also be conducted. In examining our draft treatment manual, we determined that 
at least 4 sessions are necessary to receive an adequate does of the essential elements of treatment. We will 
also report attendance and treatment satisfaction to assess intervention feasibility and acceptability. 
D1. RCT Primary Analyses: Alcohol Use, PTSD, and Negative Consequences (Aim 2) 
Preliminary analyses will examine distributional properties of variables and correlations among DVs. For 
highly collinear DVs, we will consider data reduction methods such as principal components analyses to create 
composite scores (this reduces the total number of tests conducted). Because we use in-person (or phone) 
assessments, missing data for specific questions and measures are expected to be minimal (see D3 for 
missing data). We will conduct multilevel growth curve modeling permitting us to estimate the between- and 
within-person change trajectories over time (Time: baseline, week 8 [post-tx], week 14 [F/U 1], week 20 [F/U 
2]) and intervention impact (Group: PC-TIME, PC-TAU) on a given outcome variable. Time will serve as the 
Level 1 predictor and treatment condition on Level 2 to yield the following fixed effect equation: DV (percent of 
heavy drinking days or PTSD severity) = β00 + β10Timeti + β01Treatmenti + β11Timeti * Treatmenti + eti. Raw data 
will be plotted and model fit indices will be used to determine whether change is optimally modeled linearly or 

curvilinearly. Growth modeling is a powerful and flexible method well-suited for handling longitudinal data 
particularly in cases with there is missing data, nonlinear trajectories, and time-varying covariates.   
We do expect to observe a linear or curvilinear decrease in heavy drinking and PTSD severity with a 
significant treatment effect such that the aggregate trajectory for the PC-TIME condition will demonstrate the 
greatest reduction (steepest slope) of drinking behaviors and PTSD severity. We also anticipate observing a 
significant interaction effect where we expect no differences in the mean intercept between the groups at 
baseline but group differences in the mean slope or trajectory of change over time. In preliminary analyses, we 
will examine the equivalence of the random assignment of groups with regards to key baseline characteristics. 
This will involve comparison of treatment groups on sociodemographic characteristics and alcohol-related 
variables. In the unlikely event that groups differ significantly on any characteristics we will run analyses with 
indicated covariates to control for baseline differences on outcomes. Attrition effects will be evaluated by 
testing whether systematic differences exist between participants who complete the research and those who 
drop out to determine the nature of the potential bias introduced by attrition. Based on prior trials, we anticipate 
the level of attrition will be low (<15%) and equal across groups (see D3 for missing data). Data analysis will 
follow a sequence designed to answer the primary outcome question: “Does PC-TIME reduce heavy drinking 
and PTSD severity relative to PC-TAU?” All analyses assume two-tailed alpha = .05.  
We will test the effects of PC-TIME, compared to PC-TAU, on primary variables (percentage of heavy 
drinking days, average number of drinks per drinking day, a dichotomous variable indicating whether one’s 
past 30-day drinking pattern would be classified as excessive (see C5.2), PTSD severity, and drinking-related 
problems at post-treatment. Depending on the nature of the variable, the analyses will use either a normal 
distribution (e.g., for the SIP and PCL-5) or a Poisson or negative binomial model for count data (e.g., number 
of drinks). The intervention condition will be dummy-coded using PC-TAU as the reference group and will be 
included as a time-invariant covariate on Level 2 of the multilevel growth model 94. If any covariates are 
identified as necessary during preliminary analyses, these will also be included in the model.  
D3. Missing Data  
Missing data can complicate interpretation of clinical trial outcomes. Although our follow-up rates in similar 
clinical trials are high (87 to 93%), some data will inevitably be missing. We will explore patterns of missing 
data to determine possible mechanisms of missingness (e.g., if missingness is associated with baseline 
measures). If data are determined to be missing at random, missing data will be modeled using Full 
Information Maximum Likelihood (FIML) methods which produces unbiased estimates by using a likelihood 
function based on existing data to estimate missing values 96.