Implementing Tobacco Use Treatment in HIV Clinics in Vietnam
Phase: NA
Conditions: Tobacco Use
Sponsor: New York University

 
 
 
STUDY PROTOCOL AND STATISTICAL ANALYSIS PLAN 
 
 
 
 
Implementing Tobacco Use Treatment in HIV Clinics in Vietnam: A 3 
arm Pragmatic Randomized Controlled Trial 
 
 
 
 
CLINICALTRIALS.GOV NUMBER: NCT05162911 
 
DATE: AUGUST 16, 2023 
 
 
 

Study # s19-01783 
 
 
 
 
 
 
 
 
 
 
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IMPLEMENTING TOBACCO USE TREATMENT IN HIV CLINICS IN VIETNAM: A 3 
ARM PRAGMATIC RANDOMIZED CONTROLLED TRIAL 
 
Principal Investigator: 
 
Donna Shelley MD MPH 
Population Health 
180 Madison Ave 
Email: donna.shelley@nyulangone.org 
Tel: 9174944210 
Additional Investigators: 
 
Nam Nguyen, MD DrPH 
Institute of Social and Medical Studies 
810 CT1A ĐN1, Ham Nghi Street, My Dinh 2 Ward, South Tu 
Liem District, Ha Noi, Viet Nam   
Email:  ntnam@isms.org.vn 
Tel: +84-4-35558288 
NYULMC Study Number: 
Study Number s19-01783  
Funding Sponsor: 
National Cancer Institute 
Phone: 240-276-6919 
IND/IDE Number: 
NA 
Regulatory Sponsor: 
NA 
Study Product: 
Implementing Tobacco Use Treatment in HIV Clinics in Vietnam 
Study Product Provider:  
NA 
ClinicalTrials.gov Number   NCT05162911 
Version number 
Version Date 
Summary of revisions made 
1.0 
11 FEB 2020 
Original 
2.0 
2 MAR 2020 
• We have revised the protocol as per the comments 
• Added funding source 
• Added NRT information sheet in protocol section 
• Revised medical clearance form in protocol section 
• Added fidelity checklist in protocol section 
• Revised written consent forms 
• Revised patient waiver of consent for the focus 
groups. 
• Added DSMB charter 
• Added IRB memo from IRB in Vietnam 
 
3.0 
30 MAR 2020 
• We have edited the protocol to note that materials that 
are not ready to be provided will be used only after 
NYULH and the local site IRB approval are obtained for 
these documents. 
• We have created and added the key information sheet  
• Focus group consent- We have added the risk which 
is breach of confidentiality 
4.0 
15 Sept 2020 
• We have edited the protocol to add individual patient 
interviews to aim 1 
• Waiver of written consent for interviews was added to 
the focus group waiver form 
5.0 
16 Dec 2021 
• We have edited the patient interview guide and 
consent 
• We added the provider interview guide and consent 
We edited the NRT type from patch to gum (Gum will be 
used instead of a patch because gum is 

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commercially available to patients post intervention 
while the patch is not.) 
• We edited the NRT information sheet to reflect change 
from patch to gum 
• We have edited the number of provider interviews 
from 8 to 12. 
6.0 
25 Feb 2021 
• Removed details related to focus groups proposed 
under aim 1. It was decided that individual interviews 
were more appropriate to obtain the necessary data.  
Focus groups were therefore removed from the 
protocol.  
• Removing focus groups required increasing individual 
interviews with patients in order to reach saturation. The 
number of individual interviews were estimated to be 15-
20; these have been increased to 24. Participant totals 
changed to reflect this change.  
• Data collection was modified to reflect that the AIM 2 
patient baseline survey will be administered either in 
person or by telephone; and the patient eligibility 
screener may be collected on paper or REDCap. We 
are remaining flexible to accommodate different 
characteristics of the study sites and staffing.  
• We changed the location of the study to Hanoi only.  
This change is due to COVID restrictions which limit 
travel within the country and reduction in budget.  
• The definition of standard care for the intervention was 
changed from 3As (Ask, Advise, Assist)+ referral to 2As 
(Ask, Advise) + referral. The text and figures were 
edited to reflect this change. This change was made in 
response to results of the formative data that 
demonstrated that physicians did not have time to 
provide more intensive assistance (the 3rd A) 
• Recruitment and enrollment information was edited to 
account for changes based on the formative research 
findings.   
• The Quitline referral process was changed in order to 
increase the likelihood that patients will receive 
counseling.  Patients will now be called by the Quitline 
rather than having to initiate the call.   
• Data protection around Quitline referral process was 
added. 
• The medical clearance form that listed the conditions 
that require precautions when prescribing   NRT was 
removed; questions were  moved to the screening for 
eligibility form, which is completed  by a nurse at each 
clinic. We have deleted uncontrolled hypertension and 
unstable angina based the current recommendations on 
risks of NRT. 
• The number of weeks that NRT will be provided was 
changed from 4 to 6 weeks. This was because the cost 
of gum is less than the patch which allows us to now 
provide the NRT for the recommended minimum 
number of weeks of treatment. 
• We are adding a pilot study in Aim 1 

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• We are adding a text message protocol to enhance 
the counseling intervention. Patients randomized to arm 
2 and 3 of the RCT will receive 2 messages per day for 
8 weeks and then one per day until end of treatment 
which is 12 months. 
 
7.0 
October 19 
• A set of cost questions was added to the patients 
baseline survey 
• Added a fourth aim that will study the relationship 
between food insecurity and tobacco use among people 
living with HIV/AIDS in Vietnam. This aim was added as 
part of a supplement that the team received.  
• Increased the sample size by 75 from 672 to 747 to 
include 75 non-smokers as part of Aim 4.  
• Added details about Aim 4 to the recruitment, 
enrollment, consent, and statistical considerations 
sections. 
• Revised OPC eligibility: patient minimum per site was 
changed from 250 to 240. A minimum number of 
providers per site was added, 4 providers per site to 
ensure that we had enough sites to enroll.  
• CO measure was changed from >8ppm to >10ppm 
which is consistent with the literature 
• Revised the protocol for the three arms to go back to 
the original 3As (Ask, Advise, Assist) vs 2As. This was 
based on findings from the formative assessment. 
Revised the workflow to reflect the RA obtains consent  
from the patient rather than the clinic nurse and that the 
RAs will be onsite to complete all consent and baseline 
survey forms. 
8.0 
December 29 
2022 
• Added bullet point added to patient eligibility inclusion 
criteria to address any potential double enrollment from 
any patient who participated in the intervention during 
wave 1 so they are not enrolled during wave 2. 
• Removed 12-month patient follow up survey, the 6-
month patient follow up survey provides sufficient 
information on intervention completion. 
  
9.0 
August 16 2023 
• Updated all mentions of conducting sustainability 
assessment at 12 months to conducting it at 18 months 
because we needed additional time after study 
completion to adequately assess sustainability. 

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Table of Contents 
Statement of Compliance ............................................................................................................... 6 
List of Abbreviations........................................................................................................................ 6 
Protocol Summary .......................................................................................................................... 7 
Schematic of Study Design............................................................................................................. 8 
1.   Key Roles .................................................................................................................................. 9 
2.  Background and Scientific Rationale......................................................................................... 9 
2.1 
BACKGROUND................................................................................................................................. 9 
2.2 
DESCRIPTION OF MEDICATION ......................................................................................................... 9 
2.2.1 
Dose and Rationale .................................................................................................................. 9 
2.3 
RATIONALE ................................................................................................................................... 10 
2.4 
POTENTIAL RISKS AND ENDPOINTS ................................................................................................ 10 
2.4.1 
Potential Risks ....................................................................................................................... 10 
2.4.2 
Potential Benefits ................................................................................................................... 10 
3.  Objectives  ............................................................................................................................... 10 
4.  Study Design and Endpoints ................................................................................................... 10 
4.1 
DESCRIPTION OF STUDY DESIGN ................................................................................................... 10 
4.2 
STUDY ENDPOINTS ....................................................................................................................... 11 
4.2.1 
Primary Study Endpoints........................................................................................................ 11 
4.2.2 
Secondary Study Endpoints ................................................................................................... 11 
5.  Study Enrollment and Withdrawal ........................................................................................... 11 
5.1 
INCLUSION CRITERIA ..................................................................................................................... 11 
      5.1.1      STUDY SITE ELIGIBILITY ……………………………………………………………………………...11 
      5.1.2       PATIENT INCLUSION CRITERIA ……………………………………………………………………….11 
      5.1.3       HEALTH CARE PROVERS AND STAFF INCLUSION CRITERIA ………………………………………..11 
5.2 
EXCLUSION CRITERIA …………………………………………………………………………………...11 
      5.2.1       PATIENT EXCLUSION CRITERIA ……………………………………………………………………..11 
          5.2.2.    Employee Exclusion Criteria………………………………………………………………………11 
5.3 
VULNERABLE SUBJECTS ................................................................................................................ 12 
5.4 
STRATEGIES FOR RECRUITMENT ……………………………………………………………………….12 
       5.4.1       AIM 1 AND 3 ………………………………………………………………………………………….12 
       5.4.2 AIM 2 AND 4 …………………………………………………………...............................................12 
     5.5 
DURATION OF STUDY PARTICIPATION ............................................................................................. 12 
5.6 
TOTAL NUMBER OF PARTICIPANTS AND SITES ................................................................................ 12 
5.7 
PARTICIPANT WITHDRAWAL OR TERMINATION ................................................................................ 12 
5.7.1 
Reasons for Withdrawal  ........................................................................................................ 12 
5.7.2 
Handling of Withdrawal .......................................................................................................... 13 
5.8 
PREMATURE TERMINATION OR SUSPENSION OF STUDY .................................................................. 13 
6.   Study Drug  .............................................................................................................................. 13 
6.1 
STUDY DRUG DESCRIPTION .......................................................................................................... 13 
6.1.1 
Acquisition .............................................................................................................................. 13 
6.1.2 
Packaging, and Labeling ........................................................................................................ 13 
6.1.3 
Storage  .................................................................................................................................. 13 
6.1.4 
Dosing, Route of Administration, and Duration of Therapy  .................................................. 13 
6.1.5 
Dose Adjustments  ................................................................................................................. 13 
6.1.6 
Tracking Dose ........................................................................................................................ 13 
6.2 
STUDY AGENT ACCOUNTABILITY PROCEDURES .............................................................................. 13 
6.3 
STUDY INTERVENTION ................................................................................................................... 14 
6.3.1 
Randomization ....................................................................................................................... 14 
6.3.2.   Administration of Intervention ................................................................................................. 14 
6.3.3 
Procedures for Training Interventionalists and Monitoring Intervention Fidelity .................... 15 
6.3.4 
Assessment of Subject Compliance with Study Intervention…………………………………..16 
7.  Study Procedures and Schedule ............................................................................................. 16 
7.1 
STUDY SCHEDULE ........................................................................................................................ 16 

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7.1.1 
Screening ............................................................................................................................... 16 
7.1.2 
Enrollment/Baseline ............................................................................................................... 17 
7.1.3 
Study Visits............................................................................................................................. 17 
7.1.4 
Methods and Procedures ....................................................................................................... 17 
7.1.5 
Withdrawal/Early Termination Visit ........................................................................................ 17 
7.1.6 
Unscheduled Visit .................................................................................................................. 18 
     7.1.7     PARTICIPANT ACCESS TO STUDY AGENT AT STUDY CLOSURE ..................................................... 18 
     7.1.8     PROHIBITED MEDICATION  .......................................................................................................... 18 
7.1.9 
Final Study Visit ..................................................................................................................... 18 
8.  Assessment of Safety .............................................................................................................. 18 
8.1 
SPECIFICATION OF SAFETY PARAMETERS ...................................................................................... 18 
8.1.1 
Definition of Adverse Events (AE).......................................................................................... 18 
8.1.2 
Definition of Serious Adverse Events (SAE) .......................................................................... 18 
8.1.3 
Definition of Unanticipated Problems (UP) ............................................................................ 19 
8.2 
CLASSIFICATION OF AN ADVERSE EVENT........................................................................................ 19 
8.2.1 
Severity of Event .................................................................................................................... 19 
8.2.2 
Relationship to Study Agent ................................................................................................... 19 
8.2.3 
Expectedness ......................................................................................................................... 19 
8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT .............................................................. 19 
8.4 
REPORTING PROCEDURES – NOTIFYING THE IRB AND SPONSOR .................................................... 20 
8.4.1 
Adverse Event Reporting ....................................................................................................... 20 
8.4.2 
Serious Adverse Event Reporting .......................................................................................... 20 
8.4.3 
Unanticipated Problem Reporting .......................................................................................... 20 
8.4.4 
Reporting of Pregnancy ......................................................................................................... 21 
8.5 
REPORTING PROCEDURES – NOTIFYING THE STUDY SPONSOR ....................................................... 21 
8.6 
REPORTING PROCEDURES – NOTIFYING THE FDA.......................................................................... 21 
8.7 
HALTING RULES ............................................................................................................................ 21 
8.8 
SAFETY OVERSIGHT ...................................................................................................................... 21 
9.  Statistical Considerations ......................................................................................................... 21 
9.1 
STATISTICAL AND ANALYTICAL PLANS AND METHODS (SAP) ........................................................... 21 
9.2 
STATISTICAL HYPOTHESES ............................................................................................................ 23 
9.3 
PLANNED INTERIM ANALYSIS  ........................................................................................................ 23 
10.  Source Documents and Access to Source Data/Documents ............................................... 23 
11.  Quality Assurance and Quality Control ................................................................................. 23 
12.  Ethics/Protection of Human Subjects .................................................................................... 24 
12.1 
INFORMED CONSENT PROCESS ..................................................................................................... 24 
12.2 
PARTICIPANT AND DATA CONFIDENTIALITY ..................................................................................... 25 
13. Data Handling and Record Keeping ....................................................................................... 25 
13.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES .............................................................. 25 
13.2 
STUDY RECORDS RETENTION........................................................................................................ 25 
13.3 
PROTOCOL DEVIATIONS ................................................................................................................ 25 
13.4 
PUBLICATION AND DATA SHARING POLICY ..................................................................................... 26 
14. Study Finances ....................................................................................................................... 26 
14.1 
FUNDING SOURCE ........................................................................................................................ 26 
14.2 
COSTS TO THE PARTICIPANT ......................................................................................................... 26 
14.3 
PARTICIPANT REIMBURSEMENTS OR PAYMENTS ............................................................................. 26 
15. Study Administration ............................................................................................................... 26 
15.1 
STUDY LEADERSHIP ...................................................................................................................... 26 
16. Conflict of Interest Policy ........................................................................................................ 26 
17. References .............................................................................................................................. 27 
  
 
 

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STATEMENT OF COMPLIANCE. This study will be conducted in accordance with the Code of Federal 
Regulations on the Protection of Human Subjects (45 CFR Part 46), 21 CFR Parts 50, 56, 312, and 812 
as applicable, any other applicable US government research regulations, and institutional research 
policies and procedures. The International Conference on Harmonization (“ICH”) Guideline for Good 
Clinical Practice (“GCP”) (sometimes referred to as “ICH-GCP” or “E6”) will be applied only to the 
extent that it is compatible with FDA and DHHS regulations. The Principal Investigator will assure that 
no deviation from, or changes to the protocol will take place without prior agreement from the sponsor 
and documented approval from the Institutional Review Board (IRB), except where necessary to 
eliminate an immediate hazard(s) to the trial participants. All personnel involved in the conduct of this 
study have completed Human Subjects Protection Training. 
ABBREVIATIONS 
AE 
Adverse events 
AIDS 
Acquired Immunodeficiency syndrome  
ART 
Antiretroviral therapy 
 
CACE Complier Average Casual Effect 
CIOMS Council for International Organizations of Medical Science 
CO 
Carbon monoxide 
CRF    Case report form 
FDA 
Food and Drug Administration 
DSMB Data safety monitoring board 
GCP 
Guideline for Good Clinical Practice 
HIPAA Health Insurance Portability and Accountability Act of 1996 
HIV 
Human Immunodeficiency Virus 
ISMS 
Institute of Social and Medical Studies 
KI  
Key informant interviews 
MI 
Myocardial infarction 
NIDA 
National Institute on Drug Abuse 
NIH 
National Institutes of Health 
NRT 
Nicotine replacement therapy 
NYU 
New York University 
OPC  
Outpatient clinic 
OTC 
Over the counter 
PHI 
Protected health information 
PI 
Principal investigator 
PLWH People living with HIV 
QC 
Quality control 
RA 
Research assistant 
RCT 
Randomized controlled trial 
SAC 
Scientific Advisory Committee 
SAE 
Serious adverse event 
SAP 
Statistical and analytic plans 
SC 
Standard care 
SoM 
School of Medicine 
TUT 
Tobacco use Treatment 
UP 
Unreported problem 
VHW 
Village health worker 
WHO 
World Health Organization 
 
 
 
 
 
 
 

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PROTOCOL SUMMARY  
Title 
Implementation of tobacco use treatment in HIV clinics in Vietnam 
Brief Summary 
The primary objective of this study is to conduct a 3-arm randomized controlled trial 
(RCT) that compares the effectiveness of three multi-component interventions that are 
embedded in HIV outpatient clinics (OPCs): 1)3As+Referral (Standard Care (SC)): Ask 
about tobacco use, Advise to quit, Assist with brief counseling and Refer to Viet Nam’s 
national Quitline; 2) AAA+ +Counsel (Counsel=6-session cessation counseling 
intervention adapted for patients living with HIV/AIDS (PLWH) and delivered by a 
trained, onsite nurse; and 3) AAA+Counsel+N (N=nicotine replacement therapy (NRT)). 
The main outcome is biochemically validated 6-months smoking abstinence. We will 
recruit and randomize 672 patients across 13 outpatient clinics (OPCs) (48 per site, 16 
per arm). We will also recruit 75-nonsmokers to participate in a single survey to assess 
food safety. Therefore, the total sample = 747 patients.  
Phase 
Phase 3 
Objectives 
The primary objective of this study is to conduct a 3-arm RCT that compares the 
effectiveness of three multi-component interventions to increase smoking abstinence 
among PLWH. 
 
The secondary objective is to assess factors (health care setting, provider, and patient 
level factors) that may influence tobacco cessation, and sustainability of the 
interventions tested.  
The primary objective of the supplement is to examine the difference in household food 
insecurity among people living with HIV and the relationship between food insecurity 
and tobacco use in Vietnam.  
Methodology 
The is a 3-arm unblinded RCT 
Endpoint 
The primary endpoint is carbon monoxide confirmed smoking abstinence at 6 months. 
Study Duration 
Five years 
Participant Duration 
Patients and providers will be enrolled for 2 years 
Duration of IP 
administration 
Nicotine gum (for those randomized to Arm 3 in the RCT) will be given for 6 weeks. 
Population 
We are recruiting tobacco users who are patients at one of the 13 participating OPCs. 
All patients are Vietnamese. We will recruit women and men. For the research 
supplement (AIM 4) we will recruit non-smokers from the 13 OPCs.  
Study Sites 
13 HIV outpatient clinics in Hanoi 
Number of 
participants 
941 (includes providers and patient participants) 
Description of Study 
Agent/Procedure 
The intervention being tested in the RCT is behavioral only in ARM 1 and 2 and in ARM 
3 patients will also receive  nicotine gum for daily use for 6 weeks. 
Reference Therapy 
NA. There is no placebo. This is an effectiveness study using an over the counter drug. 
Key Procedures 
NA 

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Statistical Analysis 
The primary analytic approach used to compare study arms is conditional logistic 
regression. This fixed effects approach was chosen as primary because of the modest 
number of sites and the fact that they are not very heterogeneous.  Because some 
methodologists have advocated mixed effects models even when the number of sites is 
small, we will use a multilevel logistic regression model as an alternative, sensitivity 
analysis approach. In an intent-to-treat analysis of all study entrants, conditional logistic 
regression analysis will compare study arms on the primary outcome, 7-day point 
prevalence CO confirmed (<10 ppm) tobacco abstinence captured at 6-month follow up. 
The outcome will be regressed on indicator variables for study arm and OPC site will be 
the stratification variable. Pairwise comparisons of arms will be undertaken to determine 
which arms are significantly different. Pairwise comparisons will be adjusted for multiple 
comparisons using the Tukey method. Effect magnitudes will be based on odds ratios 
for the pairwise comparisons, which will be calculated by exponentiating the coefficients 
for pairwise contrasts. Secondary cessation outcomes, HIV-related outcomes, 
hypothesized mediators (e.g., risk perceptions, self-efficacy), and the food insecurity 
outcomes  also will be analyzed with conditional logistic regression, or a different fixed 
effects regression appropriate to the type of outcome variable. 
 
SCHEMATIC OF DESIGN. This research has three phases. For Aim 1 we will conduct a formative 
assessment to inform further modifications to the intervention components. Participants in Aim 1 will be 
patients of the outpatient clinics (OPC) or health care providers who work there. Patients who use tobacco 
will be asked to participate in individual interviews (n=24 ). We will conduct key informant interviews with 
health care providers from 3 OPCs  (n=28) to adapt the intervention to the OPC clinical context. We will then 
conduct a pilot test of ARM 1 and 3 in one OPC with 16 patients. The recruitment and enrollment process 
will be the same as described for Aim 2.  For Aim 2 we will conduct a three-arm randomized controlled trial 
(RCT) to compare the effectiveness of three interventions aimed at increasing tobacco cessation rates 
among people living with HIV/AIDS (PLWH). Patients (n=672) will be recruited and enrolled from the 13 
OPCs.  All enrolled patients will complete a baseline survey in person. This survey will be administered once 
eligibility is established and consent is obtained. The consent and survey will last 30 minutes. Follow up 
surveys will occur at 3- and 6-months after enrollment. Follow up surveys will be conducted by telephone. At 
6-months follow up, patients who report smoking abstinence will be asked to come in person to the OPC 
and will complete a carbon monoxide test to validate self-report. We will conduct baseline and 12-month 
surveys with all health care providers in the study sites in person (n=98). For Aim 3 we will conduct 12-
month post intervention interviews and an 18-month survey to assess factors associated with 
implementation effectiveness and potential for sustainability. For Aim 4 we will enroll 75 more patients who 
are non-smokers for a total of (n=747) patients and assess the relationship between food insecurity and 
tobacco use among PLWH (75 smokers and 75 non-smokers), which includes administering the Household 
Food Insecurity Access Scale (HFIAS) survey to patients at baseline and 6-months. 
AIM 2 RCT:  
Patient surveys at baseline, 3, and 6 months 
Provider surveys baseline and 12 months, Provider KIs Baseline and 12 months, 
Provider sustainability survey at 18 months 
AIM 1: Enroll 
OPCs, KIs and 
surveys 
AIM 3: 
Provider  KIs 
and surveys 
3As+R 
3As+Counseling 
(C) 
Randomize 
patients 
3As+C+NRT 
Cessation
6mo 
CO 
confirmed 

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1. KEY ROLES 
Principal Investigator 
Donna Shelley, MD MPH 
Professor, Public Health Policy and Management 
NYU School of Global Public Health 
Professor, Population Health 
Department of Population Health 
NYU School of Medicine 
715 Broadway 
NY, NY 10012 
Donna.shelley@nyu.edu 
 
Principal Investigators 
Nam Nguyen, MD, DrPH 
Director-Institute of Social and Medical Studies 
19, Alley 6, Dong Bat Street, My Dinh 2 Ward, South Tu Liem District,  
Ha Noi, Viet Nam Phone/fax: 84-4-35558288 
ntnam@isms.or.vn 
www.isms.org.vn 
 
Co-Investigator 
Charles Cleland, PhD 
Division of Biostatistics 
Department of Population Health 
NYU School of Medicine 
180 Madison Ave 
NY, NY 10016 
Charles.cleland@nyulangone.org 
 
2. BACKGROUND AND SCIENTIFIC RATIONALE.  
2.1 BACKGROUND. Despite the existence of effective tobacco dependence treatments, cigarette 
smoking remains the leading cause of preventable morbidity and mortality in Viet Nam.1 Viet Nam 
also has one of the highest HIV burdens in the Asia and Pacific region. Over 300,000 adults aged 
15-49 are HIV infected, with 10,195 new HIV infections and 6,130 new cases of AIDS in 2015. In 
response to the epidemic, Viet Nam has rapidly expanded treatment services through a robust 
network of outpatient clinics (OPCs) for People Living with HIV/AIDS (PLWH) that provide free 
access to antiretroviral therapy (ART), testing and counseling. However, there are no tobacco 
cessation programs in OPCs. 
2.2 DESCRIPTION OF MEDICATION 
2.2.1 Dose and rationale. We will be using nicotine gum which is an FDA approved medication for 
smoking cessation. This medication is over the counter and therefore poses minimal risk. We will 
be providing gum of 2 mg for 6 weeks which is consistent with trials of efficacy.2,3 Despite the 
burden of disease related to tobacco use, there is a lack of evidence for the long-term 
effectiveness of tobacco cessation interventions for PLWH. Inadequate implementation of 
evidence-based tobacco use treatment interventions in HIV treatment settings exacerbates the 
health and economic burden caused by the high prevalence of smoking in Viet Nam. Developing 
and implementing effective tobacco cessation interventions is critical for optimizing treatment 
outcomes and survival for PLWH who use tobacco. 
 
 

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2.3 POTENTIAL RISKS AND BENEFITS 
2.3.1 Potential risks. This study poses minimal risk to both patients and employees enrolled in the 
study. Loss of confidentiality is the greatest potential risk to study subjects. All participants will 
receive an identification number that will be used for all forms, transcripts, surveys and intervention 
materials. For patients, we are using two behavioral interventions and nicotine gum. The nurse 
conducting enrollment will assess risk factors related to the use of nicotine replacement therapy 
(NRT) that would exclude patients from enrolling. Patients with a recent history of myocardial 
infarction (MI) (two weeks), serious underlying arrhythmias, and patients who are pregnant or 
nursing will not be offered NRT. It is important to note that the nicotine gum is an over-the-counter 
medication, with proven safety, and with minimal potential side effects. In addition, there are no 
significant interactions between NRT and HIV treatments (http://www.hivdruginteractions. 
org/PrintableCharts.aspx). Recent changes in FDA labeling also confirm that it is safe for tobacco 
users to use NRT while continuing to smoke. The FDA label for over the counter (OTC) NRT now 
says that: “concomitant use of OTC NRT products with cigarettes or with other nicotine-containing 
products does not raise significant safety concerns”. Employees in the participating health clinics 
will be asked to sign consent which will explain the voluntary nature of their participation and that 
they can withdraw their participation at any time without consequences in terms of risk to 
employment. Employee data will be treated as described above to ensure that their responses to 
survey questions and interviews remains confidential and cannot be linked to any employment 
records. The enrollment and consent procedures to ensure that there is no coercion are described 
below in section 12.1. 
2.3.2 Potential benefits. Patients who receive the counseling and/or nicotine gum may quit using 
tobacco. 
3. OBJECTIVES. The objectives of the main study are 1) to conduct a formative assessment to guide 
adaptations of the current intervention components to optimize implementation of tobacco dependence 
treatment, 2) to conduct a 3-arm randomized controlled trial (RCT) that compares the effectiveness of 
three multi-component interventions that are embedded in HIV OPCs, and 3) to assess barriers and 
facilitators to implementation and potential for sustaining gains. (See schematic above). The objectives 
of the supplement are 1) to estimate the difference in household food insecurity among PLWH who 
smoke compared with PLWH who are non-smokers at baseline. 2) to examine mechanisms linking 
smoking and household food insecurity among PLWH at baseline and 6-months follow-up, and 3) to 
assess the impact of a reduction in tobacco use and tobacco cessation on measures of food Insecurity 
at 6-month follow-up. 
4. STUDY DESIGN and ENDPOINTS 
4.1 DESCRIPTION OF STUDY DESIGN. This is a phase 3 pragmatic comparative effectiveness study. 
AIM 1: We will collect pretrial data using individual interviews with tobacco users to inform further 
tailoring of the intervention for HIV+ smokers and individual interviews (n=28) with health care providers 
in three OPCs. We will then conduct a pilot test of ARM 1 and 3 in one OPC with 16 patients. AIM 2: 
We will then conduct a 3-arm RCT to compare the effectiveness of three multi component interventions: 
1) Ask, Advise, Assist (AAA) + Refer to the national smokers’ Quitline ); 2) AAA+Counseling (Counsel) 
which adds referral to an onsite health worker for 6-sessions of cessation counseling tailored to PLWH; 
and 3) Addition of 6-weeks of nicotine gum (AAA+Counsel+N). Only ARM 3 participants will receive 
NRT. ARM 2 and 3 will receive two text messages daily for 8 weeks and then 1 per day for 4 weeks to 
reinforce the counseling protocol. A total of 747 participants will be recruited in 13 outpatient HIV clinics 
(OPCs) in Hanoi and randomized into one of the three arms (48 smokers per site, 16 per arm; about 5 
non-smokers per site). The primary outcome for smokers is 6-months biochemically validated smoking 
abstinence. We will conduct baseline in person surveys with all providers (n=98).  

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AIM 3: We will conduct 12-month post intervention interviews and 18-month surveys with healthcare 
providers and other key informants to assess factors associated with implementation effectiveness 
and potential for sustainability.  
AIM 4: We will collect data on food insecurity form 75 non-smokers and 672 smokers at baseline and 
6-months. 
4.2 STUDY ENDPOINTS4.2.1 Primary. The primary endpoint is carbon monoxide confirmed 
smoking abstinence at 6  
months. 
4.2.2 Secondary. The secondary patient outcomes are self reported smoking cessation  and  
reduction in number of cigarettes per day, and hypothesized mediators of the main outcome (risk  
perception, attitudes, norms and self-efficacy) at 3 and 6 months.  
 
5. STUDY ENROLLMENT AND WITHDRAWAL. 
5.1 INCLUSION CRITERIA.  
5.1.2. Study site eligiblity. We will recruit 13 OPCs from one city, Hanoi. The sites are very 
homogeneous in terms of staffing and infrastructure. Therefore, site eligibility will be based solely 
on the number of active patients to ensure adequate recruitment (>240 patients) and at least 4 
providers per site. The CDC of Hanoi will assist with site recruitment. 
5.1.3. Patient inclusion crieria. For Aim 1-3 men and women who are >18 , patients in the HIV 
OPCs, current tobacco users, live in Hanoi and reachable by phone are eligible. All patients of the 
OPCs are HIV+. We expect fewer women to be enrolled in all phases of this research because 
about 10-20% of patients in the OPCs are female, and their smoking prevalence is low (<2%). 
There are no enrollment restrictions based upon race and ethnicity. For the supplement we will 
enroll men and women who are >18 and patients in the HIV OPCs who are not current tobacco 
users. 
5.1.4. Health care providers and staff inclusion criteria. All providers and staff currently working 
at the OPC will be eligible. 
 
5.2 EXCLUSION CRITERIA  
5.2.1. Patient Exclusion Criteria The few individuals for whom there is a need for precaution in 
using NRT  will be excluded 
• 
recent myocardial infarction (2 weeks) 
• 
serious underlying arrhythmias 
• 
patients who are pregnant or nursing 
• 
any patient who participated in the study during wave 1 at OPC site 1-5 and then 
transferred to OPC site 6-13 during wave 2  
We will also exclude those who are unable to demonstrate capacity for consent and patients 
already enrolled in a tobacco use treatment program.  
 
Our pilot data indicate that about half of tobacco users in these sites are dual users (cigarettes and 
waterpipe); only about 12% use waterpipe alone. VQUIT found that dual users who received VHW 
counseling had 6-month CO confirmed quit rates that were comparable to patients who used 
cigarettes only. Therefore, we will not exclude dual users. We will exclude waterpipe only users 
because the intervention is based on effectiveness data for dual and cigarette users and there is a 
lack of evidence for efficacy or effectiveness of NRT use in this population. 
5.2.2. Employee exclusion criteria. Employees who are unwilling to sign consent will be excluded. 
 

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5.3 VULNERABLE SUBJECTS.  Employees are considered a vulnerable population. Research staff 
who work for the research institute (ISMS) will be responsible for consenting employees. Research 
staff are trained to emphasize that participation is voluntary and employees’ decision will not affect 
their job evaluation, promotions and work-related assignments.  
 
5.4 STRATEGIES FOR RECRUITMENT.  
5.4.1. AIM 1. We will work with the Hanoi CDC who will contact OPCs to inform potential study sites 
for about the study aims and obtain permission to have ISMS research staff contact them to provide 
additional information and assess eligibility. We will then reach out to set up a meeting with the 
medical directors to describe the study. If they are interested in participating the site will be enrolled. 
For individual interviews, patients will be screened at one of the three OPCs that agree to 
participate in the Aim 1 data collection. They will be screened for current tobacco use in the waiting 
room, asked to participate if they meet eligibility criteria, and given a date and time for the 
interviews. Verbal consent will be obtained prior to completing the screening questionnaire. Health 
care providers who work in the participating OPCs will be asked to attend a brief meeting in that 
site. Providers will be told about the project, including the data collection. They will be asked if they 
are willing to participate in the KIs at baseline (AIM 1). Those who agree will be contacted by a 
Research Assistants (RA) to set up a time for KI and obtain verbal consent. The pilot study will use 
the Aim 2 RCT recruitment approach. (see below)  
5.4.2. AIM 2. 13 OPCs will be enrolled in the study as per the protocol described above. We 
propose to enroll 672 patients (48 per site). Patients arriving for previously scheduled clinic visits 
will be asked about their tobacco use by a trained nurse who is responsible for checking patients in 
at the time of their visits. The nurse will describe the study and screen for eligibility. Eligible patients 
will be introduced to the RA who will be onsite. The RA will read the consent and if the patient is 
willing to participate and signs the consent form the RA will enroll them, complete the baseline 
survey and randomize to one of the three study arms. Health care providers will again be asked to 
participate in a brief meeting to discuss the details of the RCT. We will then use the same 
recruitment process as in AIM 1. However, at this time we will be obtaining written consent to 
complete baseline and 12-month surveys and a post intervention KI at 12 months.  
5.4.3.  AIM 3. At the time of enrollment in AIM 2, providers will also be asked to participate in the 
KIs 12 months after the intervention period. Consent will be obtained at the time they enroll in AIM 
2. For the 18-month sustainability survey, written consent will be obtained at the time they are 
approached to participate in the survey.  
5.4.4. Aim 4. We will enroll 75 patients who are non-smokers using the same strategy as AIM 2.  
5.5 DURATION OF STUDY PARTICIPATION. Patient individual interview participants will be asked to 
participate for the single session. Providers and patients who participate in the RCT will be enrolled for 
2 years. Patients who are non-smokers (n=75) participating in the diversity supplement study will be 
enrolled for six months.   
 
5.6 TOTAL NUMBER OF PARTICIPANTS AND SITES. For Aim 1, we will conduct 24 patient 
interviews and 28 provider interviews across 3 OPCs. We will recruit 16 patients in the one OPC that 
will serve as the pilot study site. For Aim 2 we include 672 patients (48 patients per site, 16 per arm). 
Surveys will be conducted, at baseline, with all health care providers in the 13 sites in person (n=98). 
For Aim 3, we will repeat surveys and KIs among the 48 providers with 2 health care providers per site, 
13 sites, (n=28) at 12-months post intervention, and will separately conduct a sustainability survey at 
18-months with the same providers. For Aim 4, we will include 75 patients (at least 5 patients per site). 
5.7 PARTICIPANT WITHDRAWALS OR TERMINATION.  
5.7.1. Reason for withdrawal. This is a minimal risk study so we do not expect participants to 
withdraw for a safety-related issue. However, participants (providers and patients) are free to 

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withdraw from participation in the study at any time upon request without any impact on their ability to 
continue to receive care or to be employed.  
5.7.2. Handling of withdrawal. We will track all withdrawals and reasons for withdrawals. Participation 
is voluntary and all study participants may withdraw from the study at any time without penalization. 
However, patient participants in the Aim 2 RCT will be encouraged to continue to participate in the 
primary outcome assessment of smoking cessation (i.e., follow up telephone surveys and if reported 
quitting, return for subsequent carbon monoxide assessment), unless a participant withdraws 
consent. Patients and providers enrolled in the longitudinal monitoring of cessation (patient surveys) 
and provider-level constructs (provider surveys and KIs) are considered lost to follow up after 4 
attempts to contact them by phone. No replacement of participants who withdraw or discontinue early 
will occur. Date and reason for withdrawal will be recorded.  
5.8 PREMATURE TERMINATION OR SUSPENSION OF STUDY. This study may be temporarily 
suspended or prematurely terminated if the Ministry of Health retract their current strong support for this 
project. Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to the study principal investigators (PI) 
(Nguyen/Shelley). If the study is prematurely terminated or suspended, the PIs will promptly inform the 
IRB and will provide the reason(s) for the termination or suspension. Circumstances that may warrant 
termination or suspension include, but are not limited to: a) Insufficient compliance to protocol 
requirements, b) Loss of institutional political support, c) Determination that the study procedures are 
too invasive. The study may resume once concerns about safety, protocol compliance, data quality are 
addressed and satisfy the sponsor and/or IRB. 
 
6. STUDY DRUG 
6.1 STUDY DRUG DESCRIPTION. Nicotine gum has been FDA approved for over 20 years. They 
are available as over the counter medications. Nicotine gum is a form of nicotine replacement 
therapy that delivers a specific dose of nicotine to people who use tobacco in order to reduce 
withdrawal symptoms when they are trying to quit. Gum is placed in the mouth and chewed multiple 
times per day. 
6.1.1. Acquisition: Nicotine gum will be purchased in Vietnam.  
6.1.2. Packaging and labelling. The gum comes in boxes of 12 tablets, each tablet contains  2 
mg of nicotine. One box can be used for 1 to 1.5 days. 
6.1.3 Storage. NRT is stored in locked cabinets at ISMS and at the pharmacy of each OPC. The 
medication does not require any special temperature or storage conditions. 
6.1.4 Dosing, route of administration and duration of therapy. All patients will receive 6 weeks 
of 2 mg nicotine gum.  
6.1.5 Dose adjustments. All patients will be given a one-page information sheet that explains 
potential side effects and includes the site study PI contact information. If a patient who is 
experiencing side effects associated with a need to reduce the dose (i.e., palpitations, nausea, 
light headedness) we will change the number of pieces of gum used per day. This is extremely 
rare and usually due to the fact that the patient is continuing to smoke while using the gum. 
Patients will be advised, again, to not smoke while using NRT. 
6.1.6. Tracking dose. The counselors have a tracking form to assess use of NRT. This form is 
completed at each counseling session and includes three questions that ask if the patient used 
the NRT provided, if the patient used the gum since the last session as directed, how many 
pieces of nicotine gum they used since their last session and how many boxes were used. 
6.2 STUDY AGENT ACCOUNTABILITY PROCEDURES. ISMS research staff will be responsible for 
dispensing the NRT to OPC pharmacies. Subjects will receive 6 weeks of gum starting at the first 
week of counseling and dispensed at each follow up session up to 6 weeks,   We will order enough 
for the number of subjects we plan to enroll in ARM 3 which includes NRT. RAs will sign out the 
number of boxes they are taking to the field during the enrollment period and give NRT to the 

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pharmacist. When providing the gum to patients, the pharmacists will input patient name, date, time, 
the patient’s ID, # boxes provided, the lot number for each box and expiration date on the NRT 
tracking form. The patient will sign that form to indicate that they have received the medication to the 
patient. All NRT not dispensed (because of fewer enrollees on a particular day) will be returned to 
the ISMS office and locked in a storage cabinet. Regular study drug reconciliation will be performed 
to document drug assigned, drug consumed, and drug remaining. See Section 6.3.6 for how 
counselors will track patient NRT use. . Reconciliation will be logged on the drug reconciliation form, 
and signed and dated by the study team. At the end of the study period we will destroy all unused 
medication as per safety instructions for discarding NRT gum.  
6.3. STUDY INTERVENTION ARMS 
6.3.1.  Randomization 
Once RAs enroll a patient in the study and the baseline survey is completed (i.e., signed consent), 
they will use a preprogrammed system in REDCap to randomize patients to one of the three study 
arms. Our biostatistician will create the REDCap database that will prompt randomization to the 
appropriate condition.  
6.3.2. Administration of Intervention. Below we describe the protocol for the RCT intervention 
components. The materials related to the intervention described below (i.e., brochures, counseling 
manual and counseling session tracking booklet) will only be used after NYULH and local site IRB 
approval are obtained for these documents. 
ARM 1. Ask, Advise, Assist (AAA) and Refer. The research team will send patient contact 
information to the Quitline which will proactively call the patient. We will train providers and 
develop a tool kit that will include information for providers and patients.   
 
ARM 2: AAA plus referral to onsite counselor (Counsel). Multisession counseling: We will 
provide a packet for each patient 
randomized to ARM 2 or 3 to the 
designated nursing staff that has been 
trained to provide the counseling 
intervention that includes all intervention 
handouts. The nurse counselor will 
receive a manual, session tracking 
booklet and fidelity checklist. Nurse 
manuals will include additional 
information about NRT to be reviewed 
with patients in ARM 3 and a document 
to use to track the use of the nicotine 
gum during each session. Our decision to train nurses is consistent with the staffing infrastructure, 
recommendations from the OPC directors and Provincial health directors and Dr. Nguyen’s 
experience working in these sites. Participants will receive six sessions of in person and 
telephone counseling depending on their preferences (Table 2). There is evidence that a greater 
number of sessions may be associated with higher smoking abstinence rates among PLWH, but 
these outcomes are short-term (3 month), with a loss of effect by 6 months. Therefore, there is no 
definitive research on the optimal number of sessions that will lead to long-term outcomes in 
PLWH. Rather, the literature suggests that it is not only the number of contacts but also the timing 
(i.e., need for contact over a longer period of time to maintain abstinence).4-8Therefore, the 
number of sessions and timing is based on an extensive review timing (i.e., need for contact over 
a longer period of time to maintain abstinence).4-8Therefore, the number of sessions and timing is 
based on an extensive review of the literature, including relevant research conducted by Dr. Go 
(consultant) among PLWH in Viet Nam98 and our pilot research that explored feasibility based on 
patient and counselor time demands. 
Table 2. Counseling protocol 
Sess. 
Wk Content 
1 
1 
Build motivation, significance of quitting for HIV+ 
smokers, elicit triggers, quit plan  
2 
2 
Dealing with withdrawal, managing stress, refusal skills 
3 
3 
Managing high risk situations (e.g., other substances), 
coping with thoughts and feelings 
4 
4 
Review problem solving, stress management and 
building social support  
5 
8 
Maintaining commitment and motivation, anticipating 
and preventing slips 
6 
12 
Successes and challenges, long term relapse prevention  

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Patients will receive 4 sessions in the first 4 weeks and sessions at 8 and 12 weeks that 
focus on maintaining long-term abstinence (Table 2). The first session will last 45 minutes and the 
following sessions about 30 minutes each. The first session will be scheduled within one week, 
with sessions 2 through 4 scheduled weekly and the two additional sessions scheduled for weeks 
8 and 12. The counseling manual, tailored to PLWH in Viet Nam, will integrate motivational 
interviewing techniques with a social cognitive skills building approach, both of which have been 
found effective in increasing long-term abstinence in general populations of smokers and short-
term abstinence in PLWH and in smokers enrolled in the VQUIT counselingintervention.4-15 
ARM 3: AAA+Counsel+N (Nicotine gum). At the end of the first session patients will be taken to 
the pharmacists who will give participants the first week  supply of nicotine gum and a one-page 
instruction sheet on use, potential side effects and who to call if they have concerns. ARM 2 and 3 
will receive two text messages daily for 8 weeks and then 1 per day for 4 weeks to reinforce the 
counseling protocol.  
6.3.3. Procedures for Training Interventionalists and Monitoring Intervention Fidelity. 
6.3.4. Clinician Training: All clinical and support staff will attend a 2-day training that includes 
building skills to screen all patients for tobacco use, offer brief cessation advice and refer patients 
to the Quitline. We will conduct a one-day booster training after 3 months to reinforce treatment 
protocols and concepts. In VQUIT, we achieved 98% attendance for the 3-day training. The 
curriculum for this proposed study is being adapted from the VQUIT training which was informed 
by the US Guideline: Treating Tobacco Use and Dependence,10 additional literature on effective 
interventions for TUT8-10 and the World Health Organization’s (WHO) guideline: “Strengthening 
Health Systems for Treating Tobacco Use”.16  Based on findings from AIM 1, we will further adapt 
the training to address HIV-specific consequences of tobacco use and barriers to quitting. The 
training will be conducted by Drs. Shelley and Nguyen. We will evaluate the adequacy of training 
with pre-and post-surveys at the initial and booster trainings. ISMS staff and Dr. Nguyen will make 
the training available online to address potential staff turnover (which is rare in these sites) and to 
increase potential for dissemination in HIV OPCs. 
6.3.5. Counselor Training. Two nurses from each site will participate in a 4-day training with the 
that will include an interactive approach using videotaped examples of counseling techniques and 
role-playing to ensure proficiency in motivational and skill building techniques. The counselor 
training is based on the curricula that was adapted for VQUIT and will be further tailored for this 
study (AIM 1). Counselors will receive monthly supervision by trained ISMS staff and attend a 
booster training one month after the initial training. Standardized training, supervision and the 
inclusion of a booster session will help ensure intervention fidelity.  
6.3.6. Fidelity. We will assess fidelity in several ways. Patient baseline and 3- and 6-months 
surveys will assess receipt of standard care (i.e., brief provider advise if they spoke with the 
Quitline). We will assess NRT use at each  counseling session up to week 6 ). Counselors will ask 
patients:  How many boxes of NRT did you use since the last session, if the patient used the gum 
since the last session as directed, and how many pieces of NRT are you chewing each day?  
Fidelity to counseling manual: After each contact, counselors will also complete a fidelity checklist 
which is used as our primary measure. ISMS staff will review observations and checklists in 
supervision meetings. Additionally counseling sessions will be assessed by asking the counselors 
to record a random sample of sessions. A trained RA will listen to tapes and use a checklist to 
assess adherence to the manual.  
Fidelity to treatment condition assignment: To reduce potential for contamination our REDCap 
database will prompt randomization to the appropriate condition and pharmacists will provide the 
NRT to participants to ensure only those in ARM 3 receive the medication. Given the additional 
training and time required to deliver counseling, we do not expect that participants assigned to 
ARM 1 will receive the intensive counseling we are testing in ARM 2 and 3. This was confirmed in 

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the pilot study. However, 3- and 6-months follow-up patient surveys will assess any use of NRT 
and other cessation services across all study arms. 
6.3.7 Assessment of Subject Compliance with Study Intervention. As noted above, 
counselors will track completion of all sessions and we will track use of NRT will be tracked by 
both the counselors.  
7. STUDY PROCEDURES AND SCHEDULE 
7.1 STUDY SCHEDULE 
7.1.1. Screening 
AIM 1: Individual interviews with patients: A nurse will assess eligibility among patients that they 
are checking in for regularly scheduled appointment and explain that we are conducting a study 
and describe the purpose of the study. Patients will then be asked if they are willing to complete 
screening questions to assess eligibility. If eligible, the subject will be asked to choose from 
several dates to participate in an interview. No screening data will be kept for the purpose of the 
study unless subjects consent to participation. All study related activities and study data collection 
will occur only AFTER verbal consent is obtained. We are requiring that the interviews are 
audiotaped and therefore will let potential participants know that at the time they are screened to 
offer them an opportunity to decline at that time. However, we will again explain that the interview 
will be audio taped prior to beginning the interview during the verbal consent process at which 
time they will have another chance to opt out.  
Key informant interviews with providers will be conducted in aim 1 to inform the design of the 
intervention. Health care workers will be told about the study at a group meeting. It will be made 
clear to them that participation is voluntarily, and they don’t have to participate. A research 
coordinator will follow up with a phone call to schedule interviews. We will obtain verbal consent. 
Once the intervention components are finalized, we will conduct a pilot study in one OPC with 16 
patients randomized to ARM 1 and 3 of the proposed RCT. Screening and recruitment will follow 
the approach described in Aim 2 below. 
AIM 2: Patient recruitment: Nurses will assess smoking status at the time patients register for 
their visit. If patients are current smokers, nurses will briefly describe the RCT study and explain 
that those patients who are interested in participating will be screened for eligibility. Patients who 
refuse to be screened or who do not meet eligibility criteria will be provided a cessation brochure. 
Those patients who meet eligibility criteria will be introduced to the onsite RA. The RA will read 
the consent and the patient will sign a paper version in the clinic. Once they consent, the RA will 
conduct the baseline survey and randomize patients before their provider visit. The consent 
process and survey will take about 30-40 minutes. 
Healthcare provider recruitment: Health care workers will be told about the study at a group 
meeting. It will be made clear to them that participation is voluntarily and they don’t have to 
participate. This will be repeated at the time of the consent process. All health workers are 
eligible. Research staff will follow-up to contact providers and staff to make appointments for to 
administer the baseline and follow up surveys. Written consent will be obtained at the time of the 
baseline survey. Health care providers who participate in surveys will be asked to complete the 
survey again at 12 months post intervention. We are requiring that the interviews are audiotaped, 
as described above. We will let potential participants know about the audio taping at the time we 
describe the study to offer them and opportunity to decline at that time if that is a reason they do 
not want to participate. However, we will again explain that the interviews will be audio taped prior 
to beginning at which time they will have another chance to opt out.   
AIM 3: Provider interviews. Health care workers who were enrolled in AIM 2 will have been 
consented to also participate in interviews and surveys post intervention to assess the 
implementation process. 
AIM 4: Patient recruitment: non-smokers will be recruited using the methods described for 
recruiting smokers as detailed in AIM 2 patient recruitment above.  

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7.1.2 Enrollment/Baseline.  
AIM 1: Patient Interviews: We will confirm eligibility and then ask participants to choose an 
interview date. Participants will be offered an explanation of the purpose of the study, given a one-
page description with a number to call if they have additional questions. We will obtain verbal 
consent at the time of the or interview immediately before it begins.  
AIM 1 and 3: Provider surveys and KIs: We will confirm eligibility which only includes that the 
provider is currently working at the OPC. Providers will be asked to provide verbal consent for 
preintervention interviews and written consent to enroll in the longitudinal assessment (surveys 
and KIs). The initial survey and KI will occur at baseline and then they both will be repeated at 12 
months. A separate survey to assess sustainability will be conducted at 18 months, for which 
written consent will be obtained before administering the survey. 
AIM 2 RCT and AIM 4: Nurses will assess smoking status at the time patients register for their 
visit. Nurses will describe the study and explain that those patients who are interested in 
participating will be screened for eligibility. Patients who refuse to be screened or who do not 
meet eligibility criteria will be provided a cessation brochure. Those patients who meet eligibility 
criteria will be introduced to the study RA. The RA will obtain written consent. Once they consent, 
the RA will conduct the baseline survey and randomize patients.  The consent process and survey 
will take about 30-45 minutes. 
7.1.3 Study visits 
AIM 1 Patients: The first and final visit for patients in AIM 1 is the interview. Patients enrolled in 
the AIM 1 pilot study will complete the same study visits as described below in Aim 2. 
AIM 1-3 Providers: Provider visits include in person KIs for Aim 1 (n=28). For Aim 2 providers will 
be asked to complete a baseline survey (n=98) and KIs (n=28) across the 13 study OPCs. For 
AIM 3 we will repeat the survey and KIs at 12 months, and separately conduct a sustainability 
survey at 18 months.  
AIM 2 RCT and AIM 4: Patients will be asked to complete a baseline, 3-, and 6-month survey. 
The baseline survey will take place in person. All other surveys will be conducted by telephone, 3 
and 6-months. At 6-months follow up patients who report smoking abstinence will be asked to 
come in person to the OPC and will complete a carbon monoxide test at the OPC to validate self-
report. 
7.1.4.  Methods and Procedures. 
AIM 1: Patient Interviews. Experienced interviewers from our partnering institution in Vietnam 
(i.e., Institute for Social and Medical Studies, ISMS) will conduct these interviews (n=24). The 
number of interviews will depend on reaching saturation.  
AIM 1-3: Health care provider surveys and interviews. All interviews and surveys will be 
administered by experienced ISMS staff. The interviews will be digitally recorded, transcribed and 
translated and stored as described above. We will not conduct the interviews if participants refuse 
to have the interview recorded. Surveys are administered using REDCap on iPads at baseline 
and 12 months and 18 months post intervention.  
AIM 2 RCT and AIM 4: All patient surveys are administered using REDCap. The baseline patient 
survey is conducted in person at the time of enrollment. All other surveys will be conducted by 
telephone, 3- and 6- months. At 6-months follow up patients who report smoking abstinence will 
be asked to come in person to the OPC and will complete a carbon monoxide test at the OPC to 
validate self-report. The CO test involves the patient blowing through a small cardboard tube into 
a small handheld monitor which measures the amount of CO expired. A positive test (i.e., still 
smoking) will be defined as >10ppm. The CO test visit will take about 20 minutes and the findings 
will be recorded in REDCap.  
7.1.5. Withdrawal/Early termination visit. The clinical site, patients and providers may  withdraw 
from the study at any time. 

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7.1.6. Unscheduled Visit. For the AIM 2 RCT, unscheduled visits to the nurse counselor will be 
discouraged. All provider surveys and key informant interviews will be scheduled. 
7.1.7. Participant access to study agent at study closure. We will not be providing NRT after 
the study closes.  
7.1.8. Prohibited medications. There are no prohibited medications. Patients will be able to 
continue with all of their current medications.  
7.1.9. Final Study Visit.  
Patients: the visit at 6 months post enrollment is a telephone survey followed by in-person CO 
confirmation test if the patient reports that they have stopped smoking. We will remind patients 
about the Quitline service that they can access for additional support and give them the number to 
call.  
Providers: the visit at 18 months post enrollment is an in-person survey to assess sustainability.  
8. ASSESSMENT OF SAFETY 
8.1 SPECIFICATION OF SAFETY PARAMETERS. This is a minimal risk study. Patients enrolled in 
the RCT will receive a standard care behavioral intervention from their health care providers (brief 
counseling plus Quitline counseling) vs provider brief counseling plus the addition of 6 sessions of 
nurse delivered counseling vs brief physician counseling + multisession nurse delivered counseling 
+NRT. Eligibility for NRT will be assessed at the time study eligibility is assessed and prior to 
enrollment. It is important to note that the nicotine gum is an over-the-counter medication, proven 
safe, with minimal potential side effects. In addition, there are no significant interactions between 
NRT and HIV treatments (http://www.hivdruginteractions. Patients with a recent history of MI (four 
weeks), uncontrolled hypertension, arrhythmia, or worsening angina pectoris will not be eligible to 
enroll. Potential side effects related to NRT will be assessed by the nurse counselor at each 
counseling visit and reported in the tracking form that counselors use to document visits. The length 
of treatment with NRT (6 weeks) will generally coincide with those visits. At the time of enrollment 
participants in the nicotine gum arm will be told of the common side effects (e.g., Rash, mouth, 
tooth, or jaw problems, palpitations) they may experience and asked to report any problems to the 
nurse and/or doctor in the clinic or to call the contact number on the consent form. They will also be 
told how to reduce the likelihood of common side effects, including not smoking while using the 
gum. Counselor training will include information about potential sides effects and to explore 
potential reasons for side effects and suggest ways to reduce side effects. The PIs will be contacted 
within 24 hours if the physician or counselor believes there is an AE or SAE, otherwise, forms will 
also be reviewed by the ISMS and NYU PIs weekly to assess the need to reduce the dose or 
discontinue the medication.  
8.1.1. Definition of Adverse Events 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in 
severity during the course of the study.  Intercurrent illnesses or injuries should be regarded as 
adverse events.  Abnormal results of diagnostic procedures are considered to be adverse events if 
the abnormality: 
• 
results in study withdrawal 
• 
is associated with a serious adverse event 
• 
is associated with clinical signs or symptoms 
• 
leads to additional treatment or to further diagnostic tests 
• 
is considered by the investigator to be of clinical significance 
8.1.2 Definition of Serious Adverse Event 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that 
is:  
• fatal 
• life-threatening 

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• requires or prolongs hospital stay 
• results in persistent or significant disability or incapacity 
• a congenital anomaly or birth defect 
• an important medical event 
Important medical events are those that may not be immediately life threatening, but are clearly of 
major clinical significance. They may jeopardize the subject, and may require intervention to 
prevent one of the other serious outcomes noted above. For example, drug overdose or abuse, a 
seizure that did not result in in-patient hospitalization, or intensive treatment of bronchospasm in 
an emergency department would typically be considered serious. All adverse events that do not 
meet any of the criteria for serious are regarded as non-serious adverse events.  
8.1.3. Definition of Unanticipated Problems  
Any incident, experience, or outcome that meets all of the following criteria:  
• Unexpected in nature, severity, or frequency  (i.e. not described in study-related documents 
such as the IRB-approved protocol or consent form, the investigators brochure, etc) 
• Related or possibly related to participation in the research (i.e. possibly related means there is a 
reasonable possibility that the incident experience, or outcome may have been caused by the 
procedures involved in the research) 
• Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
8.2. CLASSIFICATION OF AN ADVERSE EVENT 
8.2.1.  Severity of Event 
For AEs not included in the protocol defined grading system, the following guidelines will be used 
to describe severity. 
• Mild – Events require minimal or no treatment and do not interfere with the participant’s 
daily activities. 
• Moderate – Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with functioning. 
• Severe – Events interrupt a participant’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating. 
8.2.2. Relationship to the study agent. The PIs will assess if the AE is related or not related to 
the NRT. 
• Related – The AE is known to occur with the study agent, there is a reasonable 
possibility that the study agent caused the AE, or there is a temporal relationship 
between the study agent and event. Reasonable possibility means that there is 
evidence to suggest a causal relationship between the study agent and the AE. 
• Not Related – There is not a reasonable possibility that the administration of the study 
agent caused the event, there is no temporal relationship between the study agent and 
event onset, or an alternate etiology has been established. 
8.2.3. Expectedness. Dr. Shelley and Nguyen will be responsible for determining whether an AE  
is expected or unexpected. An AE will be considered unexpected if the nature, severity, or 
frequency of the event is not consistent with the risk information previously described for the 
study agent. 
 
8.3 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT 
The occurrence of an AE or SAE may come to the attention of study personnel during a clinic visit 
with the provider or the nurse counselor during the intervention period or telephone surveys at 3 
months). All AEs, including local and systemic reactions not meeting the criteria for SAEs, will be 
captured on the appropriate reporting form. Information to be collected includes event description, 
time of onset, participants’ self-assessment of severity, relationship to study product, and time of 

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resolution/stabilization of the event. All AEs occurring while in the study will be documented 
appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered 
as baseline and not reported as an AE. However, if the study participant’s condition deteriorates at 
any time during the study, it will be recorded as an AE. UPs will be recorded in the data collection 
system throughout the study. 
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the 
event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
 
The PI will record all reportable events with start dates occurring any time after informed consent is 
obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation. 
At each study visit, the investigator will inquire about the occurrence of AE/SAEs since the last visit. 
Events will be followed for outcome information until resolution or stabilization. All unresolved 
adverse events will be followed by the investigator until the events are resolved, the subject is lost 
to follow-up, or the adverse event is otherwise explained.  At the last scheduled visit, the 
investigator will instruct each subject to report any subsequent event(s) that the subject, or the 
subject’s personal physician, believes might reasonably be related to participation in this study.  
The investigator will notify the study sponsor of any death or adverse event occurring at any time 
after a subject has discontinued or terminated study participation that may reasonably be related to 
this study.   
 
8.4 REPORTING PROCEDURES-NOTIFYING THE IRB AND SPONSOR 
8.4.1 Adverse Event Reporting Adverse events will be communicated to the School of Medicine 
(SoM) and ISMS IRB at the time of continuing review in summary or aggregate form, to the DSMB 
in aggregate form at each scheduled meeting, and to the Program Officer at NIH in 
aggregate/summary form in the annual Progress Report. Non-harmful/Expectable events are not 
recorded or reported to the IRB. 
8.4.2 Serious Adverse Event Reporting (1) Report event to IRB within 24 hours using the SoM 
Report form, (2) Report event to NIH Program Officer and DSMB within 24 hours, (3) Report 
additional details of event and actions taken to IRB, DSMB, and NIDA Program officer within 72 
hours, (4) Communicate DSMB findings to IRB and NIH, (5) Respond to requests for additional 
information by and/or recommendations from the IRB, DSMB and NIDA. 
8.4.3. Unanticipated Problem (UP) Reporting Incidents or events that meet the OHRP criteria 
for UPs require the creation and completion of an UP-report form. It is the site investigator’s 
responsibility to report UPs to their IRB and to the study sponsor. The UP report will include the 
following information: 
• Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number; 
• A detailed description of the event, incident, experience, or outcome; 
• An explanation of the basis for determining that the event, incident, experience, or 
outcome represents an UP; 
• A description of any changes to the protocol or other corrective actions that have been 
taken or are proposed in response to the UP. 
To satisfy the requirement for prompt reporting, UPs will be reported using the following 
timeline: 
• UPs that are SAEs will be reported to the IRB and to DSMB and study sponsor within 24 
hours of the investigator becoming aware of the event. 

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• Any other UP will be reported to the IRB and to DSMB and sponsor within one week of 
the investigator becoming aware of the problem. 
• All UPs will be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures), the supporting agency head (or designee), and OHRP 
within 72 hours of the IR’s receipt of the report of the problem from the investigator. 
8.4.4. Reporting Pregnancy. Pregnant women are excluded from the study because of 
questions about the safety of NRT during pregnancy.  
8.5  REPORTING PROCEDURES NOTIFYING THE STUDY SPONSOR (see section 8.4).  
8.6. REPORTING PROCEDURES – NOTIFYING THE FDA (NA) 
8.7. HALTING RULES. (NA) This is a minimal risk study. Only those participants randomized to 
receive the over the counter drug, nicotine gum, will be receiving medication. If patients who are 
receiving NRT experience side effects these will be addressed as described above. If they must 
discontinue the nicotine gum they can still choose to continue to participate in the counseling 
component of the intervention. 
8.8. SAFETY OVERSIGHT. It will be the responsibility of the PIs to oversee the safety of the study.  
This safety monitoring will include careful assessment and appropriate reporting of AEs and SAEs 
as noted above, as well as the construction and implementation of a site data and safety-monitoring 
plan. Safety oversight will be under the direction of a DSMB composed of individuals with the 
appropriate expertise, including a tobacco use treatment expert, an HIV expert and a biostatistician. 
The DSMB will meet at least semiannually to assess safety and efficacy data on each arm of the 
study. The DSMB will operate under the rules of an approved charter that will be written and 
reviewed at the organizational meeting of the DSMB. Each data element that the DSMB needs to 
assess will be clearly defined. The DSMB will provide its input to Drs. Shelley and Nguyen. The 
primary responsibilities of the DSMB are to 1) periodically review and evaluate the accumulated 
study data for participant safety, study conduct and progress, and, when appropriate, efficacy, and 
2) make recommendations concerning the continuation, modification, or termination of the trial. The 
DSMB will consider study-specific data as well as relevant background knowledge about the 
intervention, or patient population under study.  
 
9.0  STATISTICAL CONSIDERATIONS 
9.1 STATISTICAL AND ANALYTIC PLANS AND METHODS (SAP) 
AIM 1: To explore barriers to tobacco cessation among HIV+ smokers.  
Survey data will be summarized using descriptive statistics. Qualitative data from the audio 
recordings of the KIs will be transcribed verbatim in Vietnamese by ISMS, translated into English 
and back translated. Two trained NYU and ISMS coders will analyze the interview data using a 
priori concepts that emerge from the quantitative data and both an inductive and deductive 
approach (open coding and coding of theoretical constructs). We will use Atlas ti. to facilitate our 
multi-step iterative coding and analyses. Data coding will begin with independent reading of the 
transcripts to identify preliminary themes and relevant patterns, followed by focused coding to 
identify clustered concepts and to organize ideas, and finally identification of major themes. 
Throughout, coders will meet to review their coding, conduct team debriefing meetings, and reach 
consensus on code names and meanings. Once all transcripts have been collaboratively coded, 
analytic domains will be identified and major and minor thematic areas described. 
AIM 2: (Primary effectiveness endpoint analysis) To compare the effectiveness of three 
interventions to increase tobacco cessation among PLHW who smoke. The primary analytic 
approach used to compare study arms is conditional logistic regression.17,18 This fixed effects 
approach was chosen as primary because of the modest number of sites and the fact that they are 
not very heterogeneous. Because some methodologists have advocated mixed effects models 
even when the number of sites is small,19,20 we will use a multilevel logistic regression model as an 
alternative, sensitivity analysis approach. In an intent-to-treat analysis of all study entrants, 

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conditional logistic regression analysis will compare study arms on the primary outcome, 7-day 
point prevalence CO confirmed (<10 ppm) tobacco abstinence captured at 6-months follow up. 
The outcome will be regressed on indicator variables for study arm and OPC site will be the 
stratification variable. Pairwise comparisons of arms will be undertaken to determine which arms 
are significantly different. Pairwise comparisons will be adjusted for multiple comparisons using the 
Tukey method.21 Effect magnitudes will be based on odds ratios for the pairwise comparisons, 
which will be calculated by exponentiating the coefficients for pairwise contrasts. Secondary 
cessation outcomes,  HIV-related outcomes, and hypothesized mediators (e.g., risk perceptions, 
self-efficacy) also will be analyzed with conditional logistic regression, or a different fixed effects 
regression appropriate to the type of outcome variable. Multilevel regression will be used as 
sensitivity analysis. To calculate indirect effects of study arm on abstinence via potential mediators, 
the Mplus statistical modeling software will be used with bootstrapping of products of direct 
effects.22,23 Patient characteristics (e.g., sex, substance use, health) will be included as covariates 
in all analysis and explored as potential effect modifiers. To examine effects of fidelity or “dose” of 
intervention, we will estimate effects of receiving the full dose of each intervention component, or 
not, using complier average causal effect estimation.24,25 Using patient characteristics associated 
with receiving a full dose among those offered each component, the Complier Average Casual 
Effect (CACE) approach finds similar patients not offered the component but likely to receive a full 
dose if they had been offered. This permits patients who receive the full dose of specific 
components to be compared with similar patients not offered the component, in order to estimate 
intervention effects for “compliers” only. Identifying the intervention’s impact on compliers deepens 
our understanding of to whom the results apply, and to whom they do not, thereby suggesting 
possible adaptations of components with less than perfect fidelity or uptake. CACE is a type of per 
protocol analysis, with similarities to other approaches for estimating causal effects with 
noncompliance or partial dose, which constitutes a shift from estimating effects of treatment 
offered to treatment received. 
AIM 3: Given the small sample size of provider surveys, we will use descriptive statistics to 
summarize the quantitative data and assess changes pre and post-trial in provider and clinic-level 
factors. We will use bivariate analysis to explore differences by study site and to assess 
relationships between provider and perceived intervention characteristics (Table 3) and adherence 
(fidelity) to standard care (i.e., Ask, Advise, Assist, Refer) based on their self-report (survey 
Appendix). Qualitative data from providers and program directors will be transcribed, translated, 
and back translated. Dr. Nguyen’s fluency in English and Vietnamese will ensure “conceptual 
equivalence.” Two trained NYU and ISMS coders will analyze the interview data using a priori 
concepts that emerge from the quantitative data and both an inductive and deductive approach 
(open coding and coding of theoretical constructs).26,27 We will use Atlas ti. to facilitate our multi-
step iterative coding and analyses. Data coding will begin with independent reading of the 
transcripts to identify preliminary themes and relevant patterns, followed by focused coding to 
identify clustered concepts and to organize ideas, and finally identification of major themes. 
Throughout, coders will meet to review their coding, conduct team debriefing meetings, and reach 
consensus on code names and meanings. Once all transcripts have been collaboratively coded, 
analytic domains will be identified and major and minor thematic areas described. 
Our analysis will also integrate the data to examine how qualitative themes converge with or 
expand on quantitative findings. This will include creating a table that examines key constructs 
from our frameworks with responses from all sources of data. We will then triangulate findings from 
pre and post assessments by developing a thematic matrix that includes system, clinic and 
provider-level characteristics, and compare side by side, those factors that were identified as 
faciliating or hindering the implementation process. Findings will be used to create a heuristic 
model to inform further optimization of the implementation process, and sustainability, if found 

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effective. Data will be shared with the SAC during meetings to inform discussions about strategies 
for faciliating sustainablity and dissemination.  
AIM 4: When comparing smokers and non-smokers at baseline on the HFIAS, power is 80% to 
detect a standardized mean difference of d=0.46 (about half a standard deviation, a difference of 3 
HFIAS points assuming a standard deviation of 6) given the proposed sample size of n= 150 (75 
smokers and 75 non-smokers). When estimating the relation between income and HFIAS, power is 
80% to detect a squared multiple correlation of R2=.05 given the proposed sample size of n=150. 
When estimating the impact of smoking cessation on HFIAS at the 6-month follow-up, power is 
80% to detect a standardized mean difference of d=0.89 (about nine tenths of a standard 
deviation, a difference of 6 HFIAS points) given the proposed sample size of n=75 smokers at 
baseline and assuming at least 16% of smokers (n=12) achieve cessation.   
9.2 STATISTICAL HYPOTHESIS. The primary hypothesis is that more intensive counseling 
delivered by a trained nurse (ARM 2) will be more effective than provider brief counseling plus 
Quitline counseling  (ARM 1) in increasing smoking abstinence. We further hypothesize that adding 
nicotine replacement therapy to the more intensive counseling will increase cessation rates more 
than the intensive counseling alone (ARM 3).  
9.3 PLANNED INTERIM ANALYSIS 
We will conduct descriptive statistics to be presented to the DSMB at the biannual meetings. This 
will include analysis of recruitment progress to address any barriers and to review the safety data.  
 
10. SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS. The study case report 
form (CRF) is the primary data collection instrument for the study.  All data requested on the CRF 
must be recorded.  All missing data must be explained.  If a space on the CRF is left blank because 
the procedure was not done or the question was not asked, write “N/D”.  If the item is not applicable 
to the individual case, write “N/A”.  All entries should be printed legibly in black ink. If any entry error 
has been made, to correct such an error, draw a single straight line through the incorrect entry and 
enter the correct data above it.  All such changes must be initialed and dated.  For clarification of 
illegible or uncertain entries, print the clarification above the item, then initial and date it. Access to 
study records will be limited to IRB-approved members of the study team. The investigator will 
permit study-related monitoring, audits, and inspections by the IRB, the sponsor, government 
regulatory bodies, and University compliance and quality assurance groups of all study related 
documents (e.g. source documents, regulatory documents, data collection instruments, study data 
etc.).  The investigator will ensure the capability for inspections of applicable study-related facilities. 
Participation as an investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and applicable University compliance and quality assurance 
offices. 
 
11. QUALITY ASSURANCE AND QUALITY CONTROL (QC).  
QC procedures will be implemented beginning with the data entry system and data QC checks that 
will be run on the database will be generated. Any missing data or data anomalies will be 
communicated to the site(s) for clarification/resolution. Following written Standar Operating 
Procedures, the monitors will verify that the clinical trial is conducted and data are generated, 
documented (recorded), and reported in compliance with the protocol, GCP, and the applicable 
regulatory requirements (e.g., Good Laboratory Practices (GLP), Good Manufacturing Practices 
(GMP)). The investigational site will provide direct access to all trial related sites, source 
data/documents, and reports for the purpose of monitoring and auditing by the sponsor, and 
inspection by local and regulatory authorities. 
 
 
 

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12. ETHICS/PROTECTION OF HUMAN SUBJECTS 
The investigator will ensure that this study is conducted incompliance with the Declaration of 
Helsinki, Council for International Organizations of Medical Science (CIOMS), International Ethical 
Guidelines for Biomedical Research Involving Human Subjects (2002), or another country’s ethical 
policy statement, whichever provides the most protection to human subjects. 
12.1 INFORMED CONSENT PROCESS AIM 1. Individual Interview with patients documentation of 
consent:  Patients will be screened by the nurse for eligibility as described above, asked to 
participate if they meet eligibility criteria, and given a date and time to speak to the RA. Verbal 
consent will be obtained prior to completing the screening questionnaire. All study related activities 
and study data collection will occur only AFTER a consent is obtained. We are requiring that 
interviews are audiotaped and therefore will let potential participants know that at the time they are 
screened to offer them an opportunity to decline at that time. We will again explain that interviews 
will be audio taped prior to beginning the interview at which time they will have another chance to 
opt out. We have requested a waiver of written consent and authorization. Participants will be given 
an information sheet that includes a number to call if they have additional questions. The interviews 
will take about 45-60 minutes.  We will make it clear to the subjects that participation in the 
interviews is separate from any ongoing care they may receive in at the clinic and that participation 
is voluntary.  We will emphasize that they are free to stop participation at any time and are free to 
refuse to answer specific questions in any assessment and can decline participation in any 
intervention activity.  
Key informant interview with provider verbal consent: For the preintervention provider KIs we will 
obtain verbal consent at the time of the interview. We are requiring that interviews are audiotaped 
and therefore will let potential participants know that the time they are screened to offer them an 
opportunity to decline at that time. We have requested a waiver of written consent and 
authorization. 
Pilot testing of RCT: The same process used for Aim 2 will be used to conduct screening and 
consenting of patients for the pilot test of ARM 1 and 3 in one OPC. 
AIM 2  and AIM 3. Provider survey and KIs documentation of consent: Health care workers will be 
told about the study at a group meeting. It will be made clear to them that participation is voluntarily 
and they don’t have to participate. This will be repeated at the time of the consent process. All 
health workers are eligible. Research staff will follow-up to contact providers and staff to make 
appointments for interviews and to administer the baseline and follow up surveys. Written consent 
will be obtained at the time of the baseline survey and interview prior to starting any data collection. 
Health care providers who participate in interviews and surveys will be asked to complete the 
survey and KIs again at 12 months post intervention. None of the research staff have any role in 
evaluating the employees or role in firing or hiring decisions. We will obtain written consent because 
of the longitudinal nature of the data collection (i.e., providers will be asked to participate in a survey 
at baseline and then at 12 months, in KIs at baseline and 12 months, and a sustainability survey at 
18 months). Health care workers have the right to refuse to participate without any compromise to 
their employment or status.  
AIM 2 RCT. Patient survey. A nurse who typically registers patients when they arrive at the OPC 
will screen all patients for tobacco use as part of that registration process. If they are a smoker the  
nurse will briefly describe the study and explain that those patients who are interested in 
participating will be screened for eligibility.  Those patients who meet eligibility criteria, based on 
this initial screening will be introduced to the RA to complete the consent and baseline assessment 
procedures before their provider visit.  
 
AIM 4. Patient survey for non-smokers. The consent process will follow the same steps as AIM 2 
RCT above. 
 

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For all participants, we will emphasize that they are free to stop participation at any time and are 
free to refuse to answer specific questions in any assessment and can decline participation in any 
intervention activity. Participants will be informed that their decision to participate or decline to enroll 
in the study or any aspect of the study will not affect any services they receive at the clinic or their 
employment. Patients who smoke and  decline to participate, will be offered the educational 
materials which include the Quitline number.  
12.2 PARTICIPANT AND DATA CONFIDENTIALITY 
Only the (1) Participant Log, (2) computerized tracking database, and (3) paper consent form will 
link the participant's name to his/her identification number. The Participant Log is password-
protected electronic file containing a list of identification numbers, the participant's name, 
intervention arm assignments (0, 1, 2), and date of screening for and enrollment into the study. A 
secure, online, password-protected database built on a REDCap platform and linked to a secure 
web-based platform will be used to manage recruitment, eligibility assessment, randomization to 
study conditions, and survey collection and tracking. If paper copies of the patient eligibility 
screener are collected, the nurse will keep these in a locked cabinet at each OPC. Paper copies of 
the screener and consent forms will be picked up weekly by the ISMS RA and transferred to a 
locked cabinet at ISMS office, where only the RA and PI in Vietnam will have access to the 
cabinets. Paper copies of the screener will be coded and entered into REDCap and destroyed once 
entered into the database. Information about study subjects will be kept confidential and managed 
according to the requirements of the Health Insurance Portability and Accountability Act of 1996 
(HIPAA).  Those regulations require a signed subject authorization informing the subject of the 
following:  
• 
What protected health information (PHI) will be collected from subjects in this study 
• 
Who will have access to that information and why 
• 
Who will use or disclose that information 
• 
The rights of a research subject to revoke their authorization for use of their PHI.  
In the event that a subject revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of subject 
authorization.  For subjects that have revoked authorization to collect or use PHI, attempts 
should be made to obtain permission to collect at least vital status (i.e. that the subject is 
alive) at the end of their scheduled study period. 
 
13. DATA HANDLING AND RECORD KEEPING 
13.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES. We will use REDCap to 
collect survey data for providers and staff.  Paper versions of the patient eligibility screener and  
signed consent forms will be stored in locked cabinets. Qualitative interviews will be digitally 
recorded. The RAs will download the recordings to a password protected computer on the same 
day the data is collected. The recordings will be transcribed by ISMS staff who did not attend the 
interviews within a week of recording and any identifiable information will be removed. The audio 
recordings will not have any identifiable information. Once transcribed, the taped session will be 
deleted by the RA. Data will be sent to the Quitline by ISMS via email using encrypted and 
password protected documents. Passwords to access the documents will be sent in a separate 
email. The Quitline will keep the data in a secure server at Bach Mai Hospital. The NYU project 
analyst will conduct all database development, data management and data quality assurance 
activities for the study under the supervision of the study biostatistician.  
13.2 STUDY RECORDS RETENTION Study documents will be retained for at least 5 years after 
final reporting/publication. No records will be destroyed without the written consent of the sponsor. 
13.3 PROTOCOL DEVIATIONS All deviations in protocol will be addressed in study source 
documents, reported to the NYULMC IRB. 
13.4 PUBLICATION AND DATA SHARING POLICY 

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This study will comply with the NIH Public Access Policy, which ensures that the public has access 
to the published results of NIH funded research. It requires scientists to submit final peer-reviewed 
journal manuscripts that arise from NIH funds to the digital archive PubMed Central upon 
acceptance for publication. 
 
14. STUDY FINANCES 
14.1 FUNDING SOURCE. This study is financed through a grant from the US National Cancer   
Institute.  
14.2 COSTS TO PARTICIPANTS. No costs will incur as a result of participating in the study. 
14.3 PARTICIPANT REIMBURSEMENTS OR PAYMENTS. The following is a list of the payments  
developed by our partners in Viet Nam: 1) Quantitative survey with smokers: $3/person/each time  
(4 surveys per subject, at baseline, 3 and 6 months), 2) Health care provider surveys:  
$5/person/each time (baseline survey and 12 months post intervention survey). 3) Interviews with  
smokers: $4/person. 4) Key informant interviews: $5 per person. 5) sustainability survey: $4.5 per 
person. Our team has extensive experience enrolling participants in research in Viet Nam and 
therefore we believe we have developed an incentive plan that is consistent with the norms in Viet 
Nam and will reduce the risk of coercion. 
 
15. STUDY ADMINISTRATION 
15.1 STUDY LEADERSHIP 
This protocol describes a multiple-PI collaborative project bringing together two well-established  
investigators with complementary skills and expertise, a shared commitment to the objectives of this  
study and a history of collaboration. A MPI plan will address the need for leadership with  
multidisciplinary expertise. The MPIs include Dr. Donna Shelley a Professor in the Dept of  
Population Health at the NYU School of Medicine and Professor of Public Health Policy and  
Management in the NYU School of Public Health. Dr. Nam Nguyen is Director of ISMS. The  
partnership between Drs. Shelley and Nguyen bridges expertise in epidemiology, policy evaluation,  
behavioral science, implementation science and health services research. Both investigators have  
established a track record for collaborative research, which provides evidence that they are  
capable of acting at an appropriate level of authority and responsibility to direct the project. 
We will also convene an external advisory committee to ensure that the research is aligned with key  
stakeholders’ goals for understanding the impact of the policy, and to provide a platform for  
disseminating findings and scale up of best practices more widely. Members will include leaders  
from the Ministry of Health, academic institutions, and HIV clinical leadership at the Provincial and  
District level. Members will meet twice a year with the study investigators. We will engage them to  
review assessment tools, provide national and local context. 
 
16. CONFLICT OF INTEREST POLICY. The independence of this study from any actual or perceived 
influence is critical. Therefore, any actual conflict of interest of persons who have a role in the 
design, conduct, analysis, publication, or any aspect of this study will be disclosed and managed. 
Furthermore, persons who have a perceived conflict of interest will be required to have such 
conflicts managed in a way that is appropriate to their participation in the study. The study 
leadership in conjunction with the NIH National Cancer Institute – Tobacco Control Research 
Branch has established policies and procedures for all study group members to disclose all conflicts 
of interest and will establish a mechanism for the management of all reported dualities of interest.  

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