Effectiveness of a Smoking Cessation Algorithm Integrated Into HIV Primary Care
Phase: PHASE4
Conditions: HIV, AIDS, Smoking Cessation
Sponsor: University of Alabama at Birmingham

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Effectiveness of a Smoking Cessation Algorithm Integrated into HIV 
Primary Care 
Study Protocol 
NCT Number: NCT03670316 
Date: September 10, 2025 
Purpose and Background 
Aim 1: Compare the efficacy of Algorithm Treatment (AT) to Enhanced Treatment as Usual (eTAU) control group for 
smoking cessation among PLWH smokers engaged in HIV clinical care. We hypothesize that the AT group will have a 
significantly higher proportion of abstinence (biochemically confirmed primary outcome), 24-hour quit attempts, and greater reduction 
in mean number of cigarettes smoked per day at 6-months post randomization compared to those in the eTAU group. 
Aim 2: Characterize provider-, staff-, patient-, and clinic-level facilitators and barriers to integration of AT treatment and 
examine intervention cost effectiveness in care. We hypothesize that, compared to the eTAU, written pharmacological prescriptions 
for smoking cessation and provider knowledge and confidence to treat nicotine dependence will be significantly greater in the AT 
group. We will also describe clinic characteristics such as size, staffing patterns (e.g., number and type of staff, providers, etc.), 
average number of annual visits by patients, amount of Ryan White funding, and average appointment time to help inform a future 
wide-scale implementation project across all CNICS sites. 
Aim 3: Estimate the cost effectiveness of the intervention relative to the primary smoking outcomes. This will be done by 
examining the incremental cost per quit of AT vs. eTAU at 3- and 6-months post intervention. 
Site and Staff
The University of Alabama at Birmingham (UAB) 
Karen Cropsey, Psy.D., Principal Investigator 
Ellen Eaton, Co-Investigator 

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Bernadette Johnson, Program Director 
Mariel Parman, Study Coordinator 
The University of Washington (UW) 
Heidi Crane, MD Co-Investigator 
John Nguyen, Study Coordinator 
 
The Fenway Institute 
Conall O’Cleirigh, PhD, Co-Investigator 
Samantha McKetchnie, Project Manager 
Will Bauer, Study Coordinator 
 
Eligibility Criteria & Approach 
Eligibility:  
CNICS PRO platform will indicate if the patient is eligible or not for the Algorithm study based on smoking scores.  
Inclusion criteria:  
1. Age 18 or older 
2. Receiving HIV care at UAB, UW or Fenway 
3. Smoking 5 or more cigarettes per day for the past month. Black and Milds and other cigars don’t count.  
Exclusion criteria:  
1. Cognitive impairment such that unable to provide informed consent.  
2. Non-English speaking 
3. Acutely suicidal or intoxicated, manic, or otherwise not stable enough to provide informed consent.  
4. Currently receiving smoking cessation treatment 
 

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Recruitment Screening and Selection 
Participants in the clinic will be identified as eligible through the CNICS PROs (Patient Report Outcomes).  Patients enrolled in 
CNICS complete the PROs at clinic visits roughly 4-6 months apart (90 day minimum).  Patients use touch-screen PCs with an easy to 
navigate interface connected to a network.  The following is assessed: 
1.  Smoking: 
a. The Smoking questions are asked at each visit in which a patient completes the PRO. 
Pre Screening 
 
UAB 
Research staff will utilize a biweekly data query to identify patients who have previously completed a PRO and qualify based on their 
smoking score. RA/SC will also review the clinic provider schedule every morning to identify any new patients who haven’t 
completed a PRO.  
 
Screening 
Patients taking the PRO on the day of the Primary Care Provider (PCP) visit will be screened for the Algorithm study on the CNICS 
PRO platform based on the inclusion criteria mentioned above. The CNICS PRO will indicate if the patient is eligible/ineligible for 
the study. 
To check for eligibility: The patient must smoke 5 or more cigarettes daily to be eligible for the study and the suicide risk or IPV page 
was not initiated. 
Pages 
The Smoking section will trigger two pages/emails to study staff (page initiated through the University of Washington data system).   
1.  Page and Email- Sent at the completion of the Smoking section.  Includes:  patient’s ticket number (ticket generated 
through CNICS, valid only 48 hours), and day/time.   
 
Approach: 
Before entering the exam room listen at the door to be sure that the physician is not present and be mindful not to interrupt clinic staff 
who may be seeing the patient.    Once you have confirmed the patient is alone, greet the patient and approach about the study: 

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If participant responds ‘No’,   notify main study coordinator and note one of the refusal or postponement reasons below.  If a 
postponement, mark the patient’s next PRO date in the tracking log to reapproach then. 
Patients who refuse to participate will be informed that this is not a requirement for their care and that their relationship with the clinic 
will not be affected in any way. If the patient gives a postponement reason, ask the patient “may we contact you again?”.  If you 
receive a definite “NO”, communicate this to the main study coordinator so study staff will not approach this patient in the future and 
track the refusal in CNICS. They will note this for entry at the end of the day in the tracking database.   
Enrollment 
Target Enrollment:  
UAB: 250 
UW: 200 
Fenway: 150 
Total: 600  
Informed Consent: 
For eligible patients, informed consent will be obtained prior to participation in any study-related procedures. Only trained study 
personnel with appropriate Human Subjects training will detail the requirements of the consent form and study participation with 
potential enrollees. Study staff will ensure that the participant understands that their consent is voluntary to avoid coercion. Patients 
will be approached in private rooms or designated study space for informed consent procedures by trained study staff.  
When the research coordinator/study staff approaches the patient, they will let him/her know that it is important to understand the 
information on the consent. After going through the consent, they will allow time to read the consent form and answer any questions 
patient may have. The research coordinator/study staff will provide a copy of informed consent to the patient. Once patient signs the 
consent, the research coordinator/study staff will set him/her up for the carbon monoxide test. 
Study staff will approach the patient at a future visit if within the 6-month eligibility timeframe and they have not completed another 
PRO. Once they complete another PRO, eligibility will be based on their next (most recent) PRO. If the patient returns to clinic within 
6 months of the last PRO taken or before taking a new PRO, s/he remains eligible and can consent and complete other enrollment 
activities. If patient comes back after 6 months then s/he will remain eligible based on their next PRO. 

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In the CNICS PROs, update the drop down menu item for that participant to note they have “Consented” to the study. If time allows, 
collect patient’s phone number in order to contact them for follow-up visits and enrolling them in the texting portion of the study on 
Qualtrics.  
Assign the participant a study ID. UW starts at 100; UAB 500; Fenway 1,000. 
Carbon Monoxide Test 
RA conducts test with participant immediately following consent. If the provider is waiting to see the participant, the CO test can be 
done after the visit. RA will instruct participant on how to use CO monitor and will step outside of the room while the participant 
blows into the monitor.  Document the results in the tracking log. 
Randomization 
Randomization will be programmed into the CNICS PRO platform and will occur after the patient consents to the study. The 
randomization scheme is a 50/50 ratio between the intervention and control arms. Intervention vs. control status will be tracked in the 
PRO platform. 
Intervention Arm: 
Provider Confirmation 
1. If the  patient is in the intervention arm then: 
 
a. The patient’s provider will be sent a note in the EMR or give a hard copy note describing which medication the 
algorithm recommends he/she prescribe the patient.  
b. RC will send the physician the pharmacotherapy medication sheet (see Appendix) in the EMR for him/her to review the 
medication option derived from the algorithm, give him/her a hard copy of the pharmacotherapy medication sheet. 
Both Arms: 
Questionnaire Completion 
Give patient additional questionnaires to complete on tablet in separate research room either before or after the visit with provider, 
depending on the clinic flow that day. If the participant can’t stay to complete the additional questionnaires, you can schedule a time 
for him to return to complete them, so long as he picks up his prescription at the pharmacy if the provider decides to prescribe him 
medication. This must be done on the same day as the baseline visit. 
Questionnaires:  

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1. Demographics 
2. Smoking Behavior/History 
3. Hughes/Hatsukami Withdrawal Scale (HHWS) 
4. Fagerstrom Test for Nicotine Addiction (FTND) 
5. Questionnaire of Smoking Urges (QSU) 
6. Thoughts about Abstinence (TAA) 
Texting 
 
Participants will be sent a text-message based survey each week (11 total) between the Initial Visit and the End of Treatment Visit (12 
weeks post-Initial Visit). Response options will be listed after every question and participants will respond to the question with the 
letter or number included in parentheses. The questions below will be administered every week unless otherwise specified. 
The Qualtrics platform will be used to send the texts to the participant’s cell phone. If the participant doesn’t respond one week, call 
the participant to see if they will complete it over the phone. Otherwise, it will be marked as missing data. 
If the participant doesn’t have a cell phone that can receive texts, the research coordinator will call the participant weekly to 
administer the questionnaire over the phone. RAs will call twice over the course of the week (if the participant doesn’t answer the first 
time). After 2 calls, the data will be classified as missing. 
 
1. How many cigarettes did you smoke yesterday? 
a. Participant responds with number of cigarettes smoked 
2. Are you taking any medications to help you quit smoking? 
a. (Y) Yes 
b. (N) No 
3. How good are you at taking your smoking medications as prescribed? 
a. (0) Poor 
b. (1) Fair 
c. (2) Good 
d. (3) Very Good 
4. How confident do you feel that you can quit smoking?  
a. (0) Not at all confident 
b. (1) A little confident 
c. (2) Both confident and not confident 

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d. (3) Somewhat confident 
e. (4) Very confident 
5. In the last month, how often have you felt nervous or stressed?  
a. (0) Never 
b. (1) Almost never  
c. (3) Sometimes  
d. (4) Fairly often  
e. (5) Very often 
End of Visit: 
 
1. Give participants $20 and confirm follow-up appointment time in 12 weeks.  
2. Confirm the best number to reach the patient at for the weekly text-it surveys. 
3. At the end of the visit, give the patient referral to quit line and a hand out containing smoking cessation tips. 
 
Tracking of Study Participants  
Study staff will use the CNICS database to capture baseline, 12 week-end of treatment, 1, 3 and 6 month post-treatment assessments, 
as well as viral loads, and carbon monoxide measurements.  Study staff will use excel logs to capture prescreening, enrollment, 
randomization, timeline/window of outcome assessments, status of assessments, reminder call status for assessments. All study staff 
will be trained in Human Subjects Protections, and this data will be handled in accordance with UAB, UW, and Fenway electronic 
storage and data transfer guidelines. 
 
MEDICATION INFORMATION 
 
If medication is prescribed, the pharmacy will provide a medication fact sheet for the participant and a brief demonstration on how to 
administer the medication.    
 
 
Medication List 
 
Name 
Method 
Dosage 
Side Effects 

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Nicotine Patch 
Patch 
7 mg/14 mg/21 mg 
Mild itching, redness, 
burning, and stinging at 
the application site may 
occur. Nausea, 
dizziness, flushing, 
heartburn, headache, 
trouble sleeping, 
dizziness, anxiety, 
depression. 
Nicotine Gum 
Gum 
2 mg/4mg 
Mouth/Jaw Pain 
Hiccups 
Heartburn 
Nausea 
Indigestion 
Lozenges 
Lozenge 
2 mg/4 mg 
Nausea 
Mouth/Jaw Pain 
Hiccups 
Sore Throat 
Heartburn 
Irregular/fast heartbeat 
Nicotrol Nasal Spray  
Spray 
2 mg/4 mg 
Nasal Irritation 
Watery Eyes 
Runny Eyes 
Coughing 
Sneezing 
Nicotrol Inhaler 
Inhaler 
2 mg/4 mg 
Coughing 
Headache 
Throat Irritation 
Nausea 
Jaw/Neck Pain 
Bupropion 
(Wellbutrin/Zyban) 
Tablet 
 150 mg 
Anxiety, dry mouth, 
hyperventilation, 

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irregular heartbeats, 
irritability, restlessness,  
shaking, trouble 
sleeping  
Varenicline (Chantix) 
Tablet 
.5 mg/1 mg 
 Nausea, sleep 
problems (trouble 
sleeping or vivid, 
unusual, or strange 
dreams), constipation, 
gas, vomiting 
 
 
Refills of Medication 
UAB: The same refill system used in the clinic will apply- the patient can come pick up their meds without calling or can call ahead of 
time to ensure the med is ready; this would be the pharmacy number and not the refill number.    
 
Billing for Medication for Study  
UAB: The 1917 Pharmacy will bill the study for any medications (copays or full drug cost) that are not covered by the intervention 
participant’s insurance.  
 
Stocking of Meds in 1917 Pharmacy 
UAB: The 1917 Pharmacy stocks nicotine patches, lozenges, bupropion and Varenicline. Nicotine gum, nasal spray and inhalers will 
be ordered as needed. 
 
Follow-up Visits 
12 week End of Treatment: 
1. If visit is in person, conduct CO test and document results in tracking log. 
2. Patient given QQs (FTND, QSU, HHWS, TAA) and QQ on smoking behavior/medication use after patient has seen providers. 
3. Give patient $40 and schedule next study visit.  
1 Month Post-Treatment Follow-up: 

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1. If visit is in person, conduct CO test and document results in tracking log. 
2. Patient given QQs (FTND, QSU, HHWS, TAA) and QQ on smoking behavior/medication use. -can be done via text/e-mail if 
unable to come to clinic. Done after patient has seen providers. 
3. Give patient $40 and schedule next study visit. 
3 Month Post-Treatment Follow-up: 
1. If visit is in person, conduct CO test and document results in tracking log. 
2. Patient given QQs (FTND, QSU, HHWS, TAA, Treatment Satisfaction Survey) and QQ on smoking behavior/medication use. 
-can be done via text/e-mail if unable to come to clinic. Done after patient has seen providers. 
3. Give patient $40 and schedule next study visit. 
6 Month Post-Treatment Follow-up: 
1. If visit is in person, conduct CO test and document results in tracking log. 
2. Patient given QQs (FTND, QSU, HHWS, TAA) and QQ on smoking behavior/medication use. -can be done via text/e-mail if 
unable to come to clinic. Done after patient has seen providers. 
3. Give patient $50. 
Retention Procedures 
Continue to attempt to reach the participant up to six months after the final follow-up visit. After the 6-month mark, the participant can 
be marked lost to follow-up. 
 
 
 
 
 
 
Timepoint 
Compensation 
Baseline 
$20 
12 Week End of Treatment 
$40 
1 mo Post-Treatment 
$40 
3 mo Post-Treatment 
$40 
6 mo Post-Treatment 
$50 
Summary of Compensation 

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Data Collection and Management 
All study documentation will be kept in locked file cabinets in study personnel’s offices at UAB, UW, and Fenway. The CNICS database can only 
be accessed by CNICS personnel using UAB, UW, and Fenway computers of encrypted laptops.  
Data Analysis 
Using Pearson's chi-square test for 2 independent proportions, we will analyze the difference in the proportion of participants with 7-
day point-prevalence cessation at 6 months between the treatment arms. Participants for whom we do not have 6-month follow-up data 
will be assumed to be smoking. We do not anticipate any difference in baseline variables between arms, but if differences do exist, we 
will utilize a multivariate logistic regression model with cessation as the outcome, treatment group as the primary independent 
variable, and imbalanced variables which are known to be correlated with cessation as additional independent variables. The same 
approach will be taken for 24-hour quit attempt – dichotomized yes/no – at 6 months. For cigarette reduction, we will look at the 
change in number of cigarettes smoked per day at baseline and 6-month follow-up. Either a 2 independent sample t-test or the non-
parametric Wilcoxon Rank-sum test as appropriate will be used to test for a difference in the change in cigarettes per day between the 
2 groups. If necessary, an ordinary least squares regression model with change in cigarettes per day as the outcome adjusting for 
baseline 
In addition to these primary analyses, we will examine outcomes by sex and racial groups to determine moderator effects. For 
sensitivity analyses, we will exclude participants without 6-month follow-up data. We will also 1) consider count regressions models 
that can account for time from enrollment until 6 month visit (such as Poisson regression) if actual timing of planned 6-month follow-
up visits differs enough between participants; 2) repeat all analyses using end of treatment and 6-month follow-up outcomes; 3) 
consider employing models that treat site as a clustering variable (such as Cochran-Mantel-Haenzel [41] and Generalized Estimating 
Equation); and 4) fit longitudinal models with data from all timepoints. These longitudinal modals will examine the interaction 
between treatment group and time. Exploratory analyses will be conducted stratified by site, cigarettes per day at enrollment, and quit 
goal. 
Protection of Human Subjects 
Our team has devised a comprehensive plan for ensuring protection of human subjects throughout the course of the proposed study. 
We will utilize an English-language consent form with common phrasing that describes that no special privileges or considerations 
will be conferred because of study participation, and that access to medical care will not be affected by the potential participant’s 
decision to enroll in the study. The procedures listed in the following sections detail procedures that have been approved and utilized 
during recent years of clinical and behavioral trials at each site for collaborative research that utilizes sensitive information from 

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participants. Our team will make every effort to protect all participants’ confidential and private information in order to minimize 
possible study-associated risks.  
All findings related to this research will be available and provided to study participants in accordance with standard practices. Clinical 
and measurement data used for research studies will be released only in de-identified fashion. 
In addition, all study personnel are required to renew Human Subjects trainings annually, or in accordance with their site regulatory 
mandates.  
 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Algorithm 
ALL  
Do you want to 
quit smoking 
today? 
Yes 
No 
Are you willing to 
take a pill twice a 
day? 
Yes 
No 
 
21mg 
Patch 
 
14mg Patch 
 
>10 CPD 
<10 CPD 
>10 CPD 
<10 CPD 
Failed quit attempt 
using NRT? 
No 
Varenicline 
Cigarettes 
Per Day? 
Yes 
Cigarettes 
Per Day? 
How soon after you wake up do 
you have your 1st cigarette? 
Past failure QA using Varenicline 
Yes 
No 
How soon after you wake up do 
you have your 1st cigarette? 
Past failure QA using Bupropion 

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21mg Patch  
AND 
 4mg Lozenges 
 
21mg Patch  
AND 
2mg Lozenges 
<30 min 
>30 min 
Cigarettes 
Per Day? 
>10 CPD 
Bupropion 
AND 
21 mg Patch 
<10 CPD 
Bupropion 
AND 
14 mg Patch 
<30 min 
>30 min 
 
14mg Patch  
AND 
 2mg Lozenges 
 
14mg Patch  
AND 
4mg Lozenges 
Yes OR No