A Text Messaging Intervention for Smoking Cessation Among Community Health Center Patients
Phase: PHASE4
Conditions: Smoking Cessation
Sponsor: Massachusetts General Hospital

DETAILED PROTOCOL 
TITLE: A Text Messaging Intervention for Smoking Cessation Among Community Health Center 
Patients 
PRINCIPAL INVESTIGATOR: Gina Rae Kruse, MD 
GRANT NUMBER: 1K23DA03717-01A1 (NIH – National Institute on Drug Abuse), ECOR 
Claflin Distinguished Scholars Award  
VERSION DATE: June 4, 2018 
I. BACKGROUND SIGNIFICANCE  
a. Historical Background  
Smoking is the leading preventable cause of death in the US, responsible for over 
480,000 deaths per year.1,2 Among US smokers, 52% try to quit each year3 but less than one-
third use medication or counseling in their quit attempt.4 Text messaging shows promise as a 
way to assist smokers to quit. Over 90% of Americans own mobile phones5 and 72% of adult 
cell phone owners text.6 Text message interventions for smokers have increased tobacco 
abstinence rates by 36 to 70% compared to non-health related text messages and/or self-help 
materials.7-17 However, most prior studies of text messaging recruited smokers from the 
community who were planning to quit in the next month. There is little prior work evaluating text 
messaging for smokers in healthcare systems. Of the three prior text messaging studies that 
recruited smokers from healthcare settings, all targeted particularly motivated smokers including 
those already enrolled in a tobacco treatment program18, pregnant smokers,19 and patients with 
coronary disease.20 The effectiveness of delivering tobacco cessation assistance by text 
message for the broader population of smokers in primary care, including both those who are 
“ready to quit” now and those “not ready to quit”, is unknown.  
Healthcare systems are well-positioned to promote smoking cessation because 70% of 
smokers visit a physician each year21 and, although physicians often recommend quitting during 
these visits, competing priorities and time constraints prevent them from offering further 
assistance such as referral to counseling or medication.22 To address this treatment gap, new 
chronic disease management models of care delivery are being developed for tobacco users. 
These models supplement clinicians’ efforts during office visits by offering assistance including 
counseling, medication support and care coordination between visits. In these programs, 
smokers in a healthcare system are identified using the electronic health record (EHR).23 The 
program then reaches out to smokers independent of office visits to offer them help to quit. Prior 
studies of chronic disease management models for tobacco have used mailings and telephone 
calls between visits to engage smokers in tobacco cessation treatment. These studies reported 
an increase in use of treatment and tobacco abstinence.24-30 However, at a health system level, 
repeated mailings or phone calls are costly. Text messaging may be a less costly way to reach 
out to help smokers. Outreach by text message may also overcome barriers27,31 faced by low 
socioeconomic status (SES) smokers who have well-documented disparities in receipt of 
treatment.4,32,33  
Text messaging has been used in healthcare systems to promote medication adherence in 
other conditions including HIV, cardiac disease, mental illness, and for family planning.34-37 
Adherence to smoking cessation medications is at least modestly associated with cessation38-41 
and measures of adherence to smoking cessation medications suggest overall low adherence, 
both in terms of medication execution (total dose of medication) and persistence (duration of 
use) of medication use outside of clinical trials.42-47 Offering nicotine replacement therapy along 
with the medication adherence advice in the text messaging intervention will allow us to 

evaluate of the effect of adherence messages on medication use. Little work has been done to 
explore whether text messaging can effectively promote smoking cessation medication 
adherence in primary care.  
Chronic disease models also allow health systems to reach out to all smokers, not just those 
who are seeking treatment and ready to quit. In the US, 80% of smokers are “not ready to quit” 
in the next 30 days.48 From a public health standpoint, an effective intervention for this group 
may have an even greater impact than programs targeting the minority of smokers who are 
ready to quit.49 Furthermore, few evidence-based treatments are available to help “not ready to 
quit” smokers.21,50,51 
b. Preliminary work supporting the proposed study 
In prior work, I developed a text message program called the getReady2Quit program (R2Q) 
and pilot-tested its feasibility among CHC patients. We recruited smokers at MGH Revere and 
Charlestown using a proactive recruitment process which consisted of sending a letter from the 
subject’s PCP notifying them of the study, followed by a single text message invitation to opt-in 
to R2Q. Among 1,603 smokers, 1,279 (80%) had a mobile number in the EHR and 949 were 
approved by their PCP for the study. 9% (88 of 949) of smokers opted in to R2Q following the 
letter and single recruitment text and this included both ready to quit (68%) and not ready to quit 
smokers (32%). The R2Q pilot model had two components. Part 1 targeted smokers who were 
ready to quit in the next 30 days by proactively recruiting them to a text message program with 
content to support them through a quit attempt. Part 2 targeted smokers who were not ready to 
quit. They were sent novel motivational messages and advice to try a ‘Practice Quit Attempt’. 
This work demonstrated the feasibility of delivering a text messaging program to primary care 
patients. Subjects in the feasibility study are being recruited to participate in qualitative 
interviews to further improve the program design and content prior to the current trial. 
c. Study rationale 
The data summarized above demonstrate several issues that motivate the current study: 
1) despite the availability of effective treatments, primary are patients who smoke rarely use 
assistance when they try to quit, 2) text messaging interventions have been effective in helping 
smokers to quit in the community or school-based settings but have not been well studied in 
clinical populations, 3) text messaging has been used to promote medication adherence in other 
conditions and medication adherence is sub-optimal among smokers and 3) few treatments are 
available for smokers who are not ready to quit and mobile health interventions may be a way to 
nudge these smokers to act.  These observations suggest a need for new interventions that 
reach primary care smokers outside of the busy office visit using a convenient low-cost 
communication modality. 
I propose to conduct a 4-arm randomized controlled trial testing the effect of a text messaging 
intervention and mailed nicotine medication, alone and in combination to a control condition 
consisting of brief advice and usual care.  These intervention modalities have shown promise in 
non-clinical populations of smokers and there are several advantages of using text messaging 
interventions in healthcare systems: 
1) Text messaging programs originating from the physicians’ office may leverage the influence 
physicians have on smokers’ motivation to quit. Simple advice to quit smoking from a physician 
is a predictor of cessation and smokers’ cite advice from a doctor as an important motivation to 

quit.21 Individuals most often look to their own healthcare systems for health information 52 and 
this trust in their healthcare providers may make health promoting advice more potent if it is 
coming from local healthcare providers 
2) Integrating text messaging within healthcare systems also offers the opportunity to feedback 
patient information to PCPs to keep them informed of changes in patients’ smoking. Integrating 
text messaging within the healthcare system provides opportunities to coordinate with 
pharmacotherapy. Effective evidence-based treatment combines behavioral support and 
pharmacotherapy.21 
The PI for this study is on faculty in the MGH Division of General Internal Medicine and is a staff 
physician at MGH Revere.  The proposed trial will be funded by the PI’s Career Development 
(K23) Award from the National Institute on Drug Abuse at the National Institutes of Health, and 
by a grant to the PI from the MGH Executive Committee on Research Claflin Distinguished 
Scholars Award. 
 
II. 
Specific Aim 
Research Aim 1: To test, in a 4 arm pilot randomized controlled trial (N=50/group), the effect of 
delivering behavioral smoking cessation content by text message and mailed nicotine 
replacement therapy on self-reported quit attempts (intentional non-smoking for ≥24 hours), 
pharmacotherapy adherence, and smoking abstinence at the end of treatment.  
Hypothesis 1: A 12 week text messaging intervention (up to 30 days pre-quit through 8 
weeks post-quit) providing behavioral support will increase the proportion of smokers 
making a quit attempt compared to smokers receiving no text messaging.  
Hypothesis 2: A 12 week text messaging intervention will increase adherence to NRT 
compared to subjects receiving only 2 weeks of NRT as measured by: (a) duration of NRT 
use in days and (b) total mg of NRT used. 
Hypothesis 3: A 12 week text messaging intervention will increase the rate of biochemically 
confirmed past 7-day point prevalent tobacco abstinence at end of treatment compared to 
subjects receiving no text messaging intervention.  
Hypothesis 4: A 12 week text messaging intervention will increase the number of days not 
smoking compared to subjects receiving no text messaging intervention. 
Hypothesis 5: A 12 week text messaging intervention will decrease the number of cigarettes 
smoked compared to subjects receiving no text messaging intervention 
Study Design 

Stratified 
randomization
Week 12 
End of Rx 
assess
Figure. Pilot randomized controlled trial schema
Week 
1&2
NRT+TM
Text messages+ 
Mailed NRT
Potentially eligible 
smokers
Not reached
Not eligible
   PCP not approved
   Not a daily smoker
   NRT contraindication
   Declines to participate
TM
Text 
messages
Allocation
Follow-up
Assess readiness 
to quit
Week 6
NRT
Mailed NRT
BA
Brief advice
NRT adherence, quit attempt, 7-day PPA, days not smoked
Quit attempt,
7-day PPA, days not smoked
Quit attempt, CO, 
7-day PPA, days not smoked, treatment use
 
 
III. 
SUBJECT SELECTION 
Study staff will identify subjects through three methods: patients in the MGH Primary Care 
Practice Based research network listed as smokers in the electronic health record, patients 
responding to an advertisement on the Partners clinical trials website, patients seen by the 
MGH inpatient Tobacco Treatment Service. The Massachusetts General Primary Care Practice 
Based Research Network’s (MGPC-PBRN) linkage cohort.  An existing smoking algorithm will 
be applied to this cohort, which will identify smokers seen at MGH Primary Care practices 
during the past two years, identified as a current smoker (as reported within the calendar year 
based upon structured field in the EHR), and who have a listed telephone number.  These 
patients will be eligible for recruitment by PCP approval or documented Research Opportunities 
Direct to You (RODY) consent. For PCP approval, PCPs at participating practices will receive 
an email from study staff describing the study and asking permission to contact their patients 
who are smokers (see PCP Permission Email).  A list of potentially eligible smokers will be 
included in the email and the PCP will be asked to check-off any patient they do not want study 
staff members to contact.  All approved patients will receive a letter (see Opt Out Letter) signed 
by the PCP and PI explaining the study and offering a way to opt out of proactive outreach by 
telephone and email.  RODY consent patients will receive a letter from the PI only. Patients who 
do not opt out will receive a proactive call from the study research coordinator to recruit them for 
the study. Patients responding to an advertisement on the Partners Clinical Trials website will 
be contacted by phone and/or email. These subjects will have the same eligibility criteria except 
that MGH PCP will not be required, patients with a Partners PCP and an MGH medical record 
number are eligible. The MGH inpatient Tobacco Treatment Service counselors qualify as 

specialty providers who can give approval for their patients to be contacted for research 
purposes, introduce the study to the patient, and verbally obtain the patient's permission to be 
contacted by study staff. Patients referred by the TTS counselors will be sent letters from the 
study team and contacted proactively by telephone. 
 
To be eligible to participate, individuals must meet all of the following criteria: 
• 
Adults (≥18 years) 
Rationale: We wish to focus only on adult smokers since adolescent smokers present unique 
issues that merit separate consideration. 
• 
Smoking status of current smoker in structured field of EHR 
Rationale: Using the EHR to identify and reach out to smokers leverages smoking status 
documentation promoted by federal Meaningful Use standards and makes the intervention 
potentially scalable to any healthcare system with smoking status documented in their EHR. 
• 
Language listed as English in EHR 
Rationale: We do not have the resources to develop intervention materials in languages other 
than English at this time. 
• 
PCP within Partners Healthcare system and MGH medical record number 
Rationale: This intervention is designed to target patients engaged in primary care. Patients 
undergo chart review by PI as part of eligibility screening for possible contraindications to NRT 
and this is possible only with Partners primary care patients. Subjects require an MGH MRN 
because some patients will be randomized to NRT prescribed through MGH Epic and sent 
through the MGH pharmacy. Subjects who report cessation will also be asked to come to MGH 
for an exhaled carbon monoxide assessment to confirm tobacco abstinence at the end of the 12 
week study. 
• 
PCP visit in the past 2 years  
Rationale: We want to include patients who are actively engaged in primary care. 
• 
Mobile telephone number listed in EHR 
Rationale: We need an active mobile number for the patient to receive text messages. 
• 
Potential TSS referred subjects who have been recently hospitalized for a heart attack or chest 
pain may participate in the study with approval from their primary care physician.  
Rationale: Smokers who have been hospitalized for a recent heart attack or chest pain may 
likely use nicotine replacement therapy during their admittance. If there are no contradictions 
with other medications and their primary care physician approves of nicotine replacement 
therapy usage then it will be safe to enroll them. 
 
Individuals meeting any of the following criteria will be excluded from the study: 
• 
Not a current daily smoker defined as not having smoked ≥100 cigarettes in lifetime or not 
having smoked in the last 30 days 

Rationale: EHR smoking status of current smoking will be verified by self-report using the CDC’s 
definition of current smoking. We exclude non-daily smokers because our primary outcome of 
self-reported quit attempts has not been well-studied among non-daily smokers. 
• 
Unwilling or unable to receive and participate with a text message program for up to 12 weeks. 
Rationale: We will not require that users have unlimited text messaging in their telephone plan, 
rather we will provide payment at baseline that should offset any costs incurred by sending or 
receiving text messages for the intervention. 
• 
Pregnant, planning to become pregnant in the next 3 months, or breastfeeding. 
Rationale: The use of nicotine replacement therapy in pregnant smokers requires close 
monitoring, and the treatment of pregnant smokers more generally presents unique challenges 
that go beyond the scope of the present study.  
Past 30 day use of nicotine replacement therapy, bupropion, or varenicline. For TTS referred  
patients: Use of nicotine replacement therapy in the 30 days prior to hospital admission 
Rationale: In order to better isolate treatment effects for the proposed interventions, we wish to 
focus on individuals who are not currently using medications to try to quit smoking. 
• 
Past 30-day use of Massachusetts state quitline, QuitWorks or SmokefreeTXT programs. For 
TTS referred patients: Use of Massachusetts state quitline, QuitWorks or SmokefreeTXT 
programs in the 30 days prior to hospital admission. 
Rationale: In order to better isolate treatment effects for the proposed interventions, we wish to 
focus on individuals who are not currently receiving behavioral interventions for smoking 
cessation. 
• 
Prior serious adverse reaction to the nicotine patch or lozenge defined as any reaction that was 
life-threatening, required hospitalization, or other clinical evaluation 
Rationale: Nicotine replacement therapy is a component of both arms of the study. 
• 
Weight < 100 pounds 
Rationale: Nicotine replacement therapy is a component of both arms of the study and requires 
clinical consultation for individuals under 100 pounds. 
• 
New or increasing chest pain or heart attack in the past 30 days.  
Rationale: Although likely safer than smoking cigarettes, use of nicotine replacement therapy 
might pose a risk to individuals with unstable cardiac conditions.  
• 
Ever been told by a doctor that patient has an irregularly fast, abnormal heartbeat 
Rationale: Although likely safer than smoking cigarettes, use of nicotine replacement therapy 
might pose a risk to individuals with unstable cardiac conditions. 
• 
Ever been told by a doctor that patient has dementia, psychosis or schizoaffective disorder. 
Rationale: This intervention is primarily conducted by telephone and we do not believe it is 
appropriate for patients with these conditions which may affect cognition and thought processes. 
For patients who are eligible by these criteria will be invited to participate in the study 
and complete verbal informed consent. Following verbal informed consent, the PI will review 
their medical chart for contraindications to nicotine replacement therapy and diagnoses of 
dementia, psychosis, schizophrenia, Alzheimer’s disease, delirium, or schizoaffective disorders. 
Any subjects with contraindications to NRT or these diagnoses will be notified that, following 

review of their medical record they are not eligible and they will be provided with information 
about the MGH tobacco cessation counseling services, the state quitline, and National Cancer 
Institute’s smokefreeTXT. Subjects without contraindications will be randomized. 
 
a. Source of subjects and recruitment methods 
Smokers will be recruited through four methods. The primary method is through 
proactive outreach to individuals who receive primary care at MGH and are identified in the 
health record as smokers. We will first ask PCPs to review their patients meeting inclusion 
criteria per electronic health records and designate any patients who they do not want us to 
contact for the study. We will then send letters, signed by the study PI and signed with 
secretarial notation by the PCP, to patients meeting the inclusion criteria to introduce the study. 
The letter will notify patients that they will be receiving a call about the study at their home or 
mobile telephone number as listed in their clinic registration. Patients will be provided with a 
number which they can call if they do not want to receive the telephone call or if they want to 
update their mobile telephone number. The letter will also include a study fact sheet. One week 
after the letter, participants who do not opt-out will then be contacted by telephone by a study 
RC to enroll and consent the patient to participate in the randomized trial. The RC will attempt to 
contact the patient up to 5 times (either 3 times leaving messages or 5 times if unable to leave 
messages) at the home or mobile phone number listed in their Epic registration data. At the 
recruitment phone call, the RC will assess patients for exclusion criteria. 
In addition to the primary recruitment method described above, we will recruit subjects 
through three other methods. 1)Potentially eligible MGH patients who have agreed to be 
contacted for research studies under the hospital’s [Partners/ MGH] Research Options Direct to 
You (RODY) program. We will draw a list of names based on the same eligibility criteria that has 
been initially used throughout the recruitment process. Once potential subjects have been 
identified, we will send them an Opt Out letter describing the study and explaining how they can 
either obtain more information or how they can be removed from our list within 1 week of letter 
receipt.  After 1 week, we will call these patients for prescreening to assess eligibility and 
interest. 
 
 2) We will advertise the study by posting an online advertisement on the Partners 
Clinical Trials website (https://clinicaltrials.partners.org/). Subjects who respond by email or 
telephone to this advertisement will be contacted by telephone or email by the clinical research 
coordinator. Interested subjects will be sent an informational letter and the study fact sheet. 
 
3) The MGH Inpatient Tobacco Treatment Service counselors can serve as specialty 
healthcare providers who can give approval for patients to be contacted for research purposes, 
briefly introduce the study to patients who smoke and verbally obtain the patients permission to 
be contacted by study staff. They will provide study pamphlets with the same information as is 
included in the online advertisement to interested patients. TTS counselor referred patients will 
be sent an informational letter and study fact sheet and called by telephone by the study RC. 
At time of the recruitment call, the RC will review the potential cost of the text messaging 
program which we expect to be up to 60 messages or a maximum cost of $15 per month. The 
RC will explain that we will pay research subjects $0.25 per message sent or received by the 
program up to 50$ or 200 messages. This is based on the amount of text messages sent 
between the most engaged participants and the program in our pilot study. In addition, 

payments will be offered for each telephone assessment including $20 for completion of 
baseline assessment, $10 at weeks 1, 2 and 6 for telephone assessment, $40 for completion of 
the 12 week end of treatment assessment, $20 fo CO measurement for those reporting 
abstinence, and $10 for those selected for an exit survey. Subjects randomized to the NRT or 
TM+NRT arms will be offered 2 weeks of nicotine patch and/or lozenge if they are daily smokers 
who are planning to quit in the next 30 days or one box of nicotine lozenges to use in a practice 
quit attempt for those not planning to quit in the next 30 days. Subjects who have ever had an 
allergy to adhesive tape, such as bandaids, or medical tape or who have not tolerated nicotine 
patches in the past will be offered lozenges only if randomized to the NRT or TM+NRT arms. 
Participants who decline to enroll will be given advice to quit and encouraged to talk to their 
doctor, call the MGH tobacco cessation counseling office, enroll in National Cancer Institute’s 
smokefreeTXT or call the state quitline. 
 
IV. 
SUBJECT ENROLLMENT 
 
a. Methods of enrollment, including procedures for patient registration and/or randomization  
 
This will be a 4 arm randomized controlled trial among 206 smokers who are patients at 
Massachusetts General Hospital and who receive primary care from a Partners primary care 
provider. Patients will be proactively recruited from MGH primary care practices. Patients will 
also be recruited from online advertisements on the Partners Clinical Trials website, from 
among MGH primary care patients who consent to participate in Research Offers Direct to You, 
and by referral from the MGH inpatient Tobacco Treatment Service counselors. We will recruit 
both smokers who are ready to quit smoking in the next 30 days and those who are not planning 
to quit in the next 30 days. The text message program is tailored to readiness to quit. For those 
ready to quit in the next 30 days, they will be sent messages based on the SmokeFreeTXT 
content. For those not ready to quit, we have developed content including motivational advice 
and tips to try a practice quit attempt for a few hours or days.53 The text message program will 
also include medication adherence support text messages based on the Information-Motivation-
Behavioral Skills model of adherence.54 Combination NRT is first-line therapy which is more 
effective than nicotine patch alone and will be offered to daily smokers, dosed per package 
instructions.21 Smokers who are not ready to quit and who are randomized to one of the two 
nicotine medication arms will be offered one box of lozenges to try in a practice quit attempt.53 
 
The RC will not be blinded to treatment assignment because he/she will register subjects 
randomized to the text messaging arms in the text messaging program during the enrollment 
telephone call to verify receipt of an enrollment confirmation text message (“Hi [First name] 
Welcome to getReady2Quit (R2Q). Your messages and ratings will start soon. Reply STOP to 
quit, HELP for info. Msg&DataRatesMayApply”). Randomization will be done by a computer 
generated random sequence.  
 
b. Procedures for obtaining informed consent (including timing of consent process) 
 
Permission from primary care providers (PCP) or MGH inpatient Tobacco Treatment Service 
counselors will be obtained before making any patient contact unless the patient participates in 
‘Research Oppertunities Direct to You’ or proactively contacts the study in response to online 
advertisements. For PCP approval, providers will be given a list of smokers identified for the 
study and asked to identify any individuals who should not be (see “PCP Permission Email”) 
contacted.  Patients whose PCP’s consider them to be inappropriate or ineligible for the study 
will be excluded from participation regardless of RODY status or self-selection. MGH inpatient 

Tobacco Treatment Service counselors will introduce the study to interested patients they deem 
appropriate during a counseling visit. Patients who are considered eligible will be sent a letter 
from their PCP and a letter from the study PI if PCP approved, from the PI only if RODY 
consented, or the PI only if TTS counselor referred. The letter notifies patients that they will be 
receiving a telephone call inviting them to participate at the mobile telephone number listed in 
their clinic registration. The letters will include a copy of a study information fact sheet with 
informed consent content.  
 
Patients sent study introduction letters will be provided with a number which they can 
call in the letter if they do not want to receive the telephone call or if they want to update their 
mobile telephone number. Approximately one week after the letter, smokers who do not opt out 
will be contacted by telephone by a study RC who will screen for eligibility.  
 
Patients who proactively contact the study will be sent more information on the study via  
mail and email. Patients with MGH MRNs and a Partners PCP will be considered eligible to 
proceed.  
 
Eligible subjects who are interested in enrolling will be offered a call back the next day to 
allow 24 hours to consider enrollment. For those that decline this additional time or at the time of 
the call the next day, the study RC will complete verbal informed consent (see “Consenting call 
script”). For those subjects who complete verbal informed consent but report they no longer 
have a copy of the study information fact sheet that was mailed with the Opt Out Letter, a new 
copy of the study information fact sheet will be mailed. Following verbal informed consent, the 
PI will screen the medical chart of consented subjects for NRT contraindications or diagnoses in 
the exclusion criteria (dementia, psychoses, and schizoaffective disorder). Subjects without 
contraindications will undergo baseline survey and then be randomized.  
 
Rationale: There is a precedent for mailing nicotine replacement therapy to smokers after 
telephone screening for contraindications to the medication. The precedent is based on the 
methods used by the Massachusetts State quitline, we include screening questions used by the 
quitline in our eligibility screener. Our approach to screening for medical contraindications is 
more robust than that used by the quitline in that the PI-Dr. Kruse-will also conduct a chart 
review for medical contraindications or psychiatric diagnoses that may make a remotely 
conducted study inappropriate. Finally, Partners has approved at least two other randomized 
controlled trials that mailed nicotine replacement therapy following verbal consent and 
telephone screening (protocol 2009-P-001137/3 and 2011-P-000644/1).  
 
c. Treatment assignment, and randomization  
Those who consent and enroll will be randomly assigned to one of 4 groups: 
1. Brief advice (BA):  Brief advice to quit smoking 
Rationale: All subjects will receive brief advice from a trained RC. All primary care subjects also 
have access to guideline-concordant tobacco treatment 21 through their primary care provider 
(PCP). Their PCP can refer them to in-person or telephone counseling and can prescribe 
medications. This constitutes a scientifically and ethically appropriate standard against which to 
measure the experimental interventions. 
 
2. Nicotine replacement therapy (NRT):  Brief advice + 2 weeks of nicotine patches and/or 
lozenges mailed to subject 

Rationale: In order to test the effect of text messaging on medication adherence, we need to 
have treatment groups receiving medication and medication plus text messaging. To deliver 
medication, mailed NRT, like text messaging, reaches patients outside of the busy office visit. 
Mailed NRT alone has also been shown to increase cessation 55 and may itself be an effective 
intervention compared to standard care. 
 
3. Text messaging (TM):  Brief advice + 12 week personalized, tailored text messaging program. 
Rationale: Text messaging shows promise as an intervention to help smokers to quit.8,56 
However, it has not been well tested among primary care patients. Text messaging may 
connect those primary care smokers who do not access currently available treatment services 
like telephone counseling or prescribed medication with assistance outside of the clinic office.  
 
4. Text messaging and nicotine replacement therapy (TM+NRT):  Brief advice + 12 week 
personalized, tailored text messaging program + 2 weeks of nicotine patches and/or lozenges 
mailed to subject. 
Rationale: As above, in order to test the effect of text messaging on medication adherence, we 
need to have treatment groups receiving medication and medication plus text messaging. Text 
messaging has been shown to increase medication adherence in other conditions 34-37 and 
medication adherence is suboptimal among users of smoking cessation medications. 38,39,41 
Integrating text messaging within healthcare systems offers opportunities to coordinate with 
pharmacotherapy and this 4 group design allows us to test the effect of text messaging alone on 
smoking outcomes and the effect of text messaging on NRT use. 
We will use stratified block randomization. We will stratify by practice and readiness to 
quit in the next 30 days. We will use variable block sizes. Subjects will be randomized 
1:1:1:1. 
After verbal consent and chart review by the PCP. Randomized enrollees will be asked 
to complete a baseline telephone survey. After completion of the baseline survey, 
participants will be mailed a $20 gift card. 
Following the telephone survey, smokers randomized to the text messaging arms (TM 
and TM+NRT) will have their mobile numbers, and first names entered into the 
MobileCommons web-based platform. The program will be tailored to readiness to quit 
and user-entered quit date and personalized with individual’s first name. 
Participants randomized to NRT or TM + NRT arms will be offered nicotine patches 
and/or nicotine lozenges in a two-week allotment.  Daily smokers with a quit date will be 
offered patch and lozenge. Smokers not ready to quit will be encouraged to use 
lozenges when not smoking during practice quit attempts53. Patches will be dosed 
according to reported cigarette consumption per day and lozenges will be dosed 
according to time to first cigarette as per package instructions. Smokers with a previous 
allergy to skin adhesives with an unknown tolerance of or known intolerance to nicotine 
patches will only be offered lozenges if randomized to the NRT or TM+NRT arms. The 
prescriptions will be sent to the MGH outpatient pharmacy by printing and faxing the 
prescription with a cover sheet which lists the study fund to bill  or by e-prescription with 
the study information and study fund to bill in the comments to pharmacy section. The 
MGH pharmacy will then mail the 2 week supply of medication directly to the study 
subject.If the pharmacy discovers any issues with mailing they will notify us and we will 
attempt to notify IRB within 1 working day. For any issues with subjects not receiving 

medications that are discovered at the week 1 and 2 telephone surveys, we will notify 
IRB within 5 working days. 
 
V. 
STUDY PROCEDURES 
 
The following interventions and procedures will be applied to 6 pre-test subjects (3 in each 
treatment arm) and then we will aim for 200 subjects in the randomized trial. 
 
a. Text messaging intervention 
Patients randomized to the text messaging program are offered a 12-week text 
messaging program (up to 4 weeks pre-quit, and 8 weeks post-quit attempt). The text 
messaging intervention will use content from the National Cancer Institute’s SmokeFreeTXT 
library57, content for smokers not ready to quit from SmokeFreeTXT and our pilot feasibility 
study, and new messages supporting nicotine replacement medication adherence. 
SmokeFreeTXT content is tailored to smokers with a quit date in the next 30 days. It includes 
messages with tips for behavioral tips for cessation, motivational and encouraging messages, 
and fact-based messages about smoking including health risks (see attached Text Message 
Campaign). Smokers are also periodically asked how they are feeling. Their response to this 
message triggers a tailored motivational message in response. Messages will refer patients to 
the local tobacco counseling service. Smokers can also request specific advice to deal with 
cravings, mood symptoms, or slips by texting keywords “CRAVE”, “MOOD”, or “SLIP”. 
Participants will have access to a study telephone line for the duration of the intervention.  
The content for smokers who do not have a quit date in the next 30 days will include 
advice to try making a practice quit attempt and motivational messages. This idea of practicing 
quitting is based on the idea of quit induction. Pre-quit activities that increase self-efficacy and 
motivation and move a smoker towards action and a serious quit attempt. 53 We developed 
some content promoting practice quit attempts and motivational advice and pilot tested it (see 
“Preliminary work supporting the proposed study” above). The National Cancer Institute has 
also developed content for smokers not ready to quit which includes advice to try a practice quit 
attempt. This content was shared with the PI and was released February 2016 as part of 
SmokeFreeTXT (see attached Text Message Campaign).  
The novel content encouraging NRT use and promoting adherence will include advice 
for proper use of NRT, education about medication safety 58,59, reminders to use the patch every 
day, reminders to use lozenges at the first sign of craving, and motivational messages about the 
effectiveness of these medications. These messages are based on the Information-Motivation-
Behavioral Skills theoretical model of medication adherence (Fisher 2006).  
Finally, the text messaging program will be tailored to the individual and MGH.  Text 
messages will include the telephone number for the MGH tobacco cessation counseling 
services LivingTobacco-Free which accept self-referrals as well as the number for the 
Massachusetts state quitline. 
Smokers receiving the intervention will be sent from 0 and 5 text messages per day. This 
is the message volume used by most smoking cessation text messaging programs.60 Smokers 
are asked to enter a quit date in the first 30 days after enrollment. Those without a quit date will 
be sent the practice quit attempt messages. At the end of the practice quit attempt messages 
subjects will be asked again if they have a quit date in the next 30 days. For those who are 
ready to quit at time of enrollment, or those who become ready to quit after the practice attempt, 
up to 5 messages per day are delivered in the 2 weeks leading up to the self-designated quit 

date and the 2 weeks after the quit date when they are at greatest risk for relapse.61 Messages 
then decrease to 3 messages per week for 8 weeks after the attempt.  
b. Drugs used 
Subjects randomized to the NRT or TM + NRT arms will be offered nicotine replacement 
therapy dependent on their smoking patterns and readiness to quit. 
Daily smokers planning to quit in the next 30 days will be offered combination nicotine 
replacement therapy including nicotine patches and nicotine lozenges. Daily smokers will be 
offered nicotine patches (14 or 21 mg patches) and lozenges (2 or 4 mg lozenges). Smokers 
who smoke ≥10 cigarettes per day will be offered 21 mg patches, those who smoke <10 
cigarettes per day will be offered 14 mg patches. Daily smokers who smoke within 30 minutes of 
awakening will be also offered the 4 mg lozenges. Daily smokers who smoke >30 minutes of 
awakening will be offered 2 mg lozenges. Daily smokers with a prior reaction to adhesives from 
bandaids or the nicotine patch will be offered lozenges only. 
Smokers not planning to quit will be offered one box of lozenges (72 count box of 4 mg 
or 2 mg lozenges based on time to first cigarette as above per package instructions) to use 
when they are not smoking during their practice quit attempt 53. 
The efficacy and safety of mailing nicotine replacement therapy to general population 
has recently been demonstrated 55.  
NRT prescriptions will be entered into the EHR and signed by the study PI (Gina Kruse), 
printed and faxed to the MGH Outpatient pharmacy. The MGH Outpatient pharmacy will send 
the NRT by mail to the subject.  
NRT will be distributed in a two-week allotment. The RC will screen participants for any 
self-reported contraindications to NRT use or other exclusion criteria before enrollment. High-
risk comorbidities (e.g. cardiovascular disease, uncontrolled hypertension) will also be assessed 
but will not be grounds for withholding NRT since the risks of continued smoking outweigh the 
potential risks of using NRT in these conditions. After verbal consent, the PI will screen medical 
records of subjects randomized to NRT for contraindications or exclusion criteria prior to 
randomization. Participants will be instructed not to use the patch or lozenges while smoking, 
but rather to commence use when/if they make a quit attempt or practice quit attempt (lozenges 
only). The most common side effect of transdermal NRT is skin irritation. Other possible but rare 
side effects of all forms of NRT include cardiovascular (chest pain, hypertension, tachycardia, 
palpitations), metabolic (hot flashes, sweats), gastrointestinal (diarrhea, dyspepsia, 
nausea/vomiting, flatulence/gas, hiccups), musculoskeletal (arthralgia, myalgia), neurologic 
(headaches, dizziness), ophthalmic (lacrimation, nystagmus), respiratory (coughing), 
oropharyngeal (dry mouth, alteration of taste) and psychiatric (sleep disturbance, vivid dreams) 
manifestations.62 The most common side effects of nicotine lozenges include mouth irritation or 
ulcers, nausea, vomiting, hiccups, abdominal pain, diarrhea, headaches and palpitations. 
Randomized trials of combination nicotine replacement therapy have shown increased report of 
adverse events but not more serious adverse events or study withdrawal among subjects 
receiving combination therapy compared with subjects receiving NRT monotherapy. The risk of 
nicotine toxicity is rare in clinical trials. Among trial subjects who achieve higher cotinine levels 
with nicotine therapy than with smoking alone, the most common symptoms reported were 
nausea, vomiting, palpitations, dizziness, and headaches and all occurred in 0.5% or fewer trial 
subjects.63 
All study subjects will be asked about adverse reactions to the nicotine patch or lozenge 
at weeks 1, 2 and 6. 

 
c. Devices 
We will attempt to obtain exhaled carbon monoxide samples from study participants who self-
report 7 day point prevalent abstinence at end of treatment using the coVita | Bedfont Micro+ 
Smokerlyzer carbon monoxide monitor.  The device will be used, maintained, and calibrated in 
accordance with the manufacturer’s instructions. 
Subjects randomized to the TM and TM + NRT arms will have their mobile telephone number, 
first name and PCP’s name entered into the MobileCommons web-based text messaging 
platform. Their name will be used to personalize text messages. 
 
d. Study visits and parameters to be measured 
This study will be primarily conducted by telephone contact, email if the participant 
chooses, and mailings with a single in-person contact for subjects reporting abstinence from 
smoking at the end of treatment to collect an exhaled carbon monoxide sample to confirm 
abstinence. Subjects will be contacted by telephone and data collected by self-report at time of 
enrollment (baseline assessment interview), and by telephone or email for 1, 2, and 6 weeks 
after enrollment (follow-up outcome assessments), and end of treatment (primary outcome). 
We will also offer a qualitative exit interview to be completed by phone for 10 participants 
per intervention arm (TM, TM+NRT, and NRT). 
Baseline assessment:  
Variables obtained from the EHR: 
• 
Demographic factors: age, sex, health insurance (commercial, Medicare, Medicaid, no 
insurance or other), name, and address 
• 
Medical history: coronary heart disease, COPD, diabetes, hypertension, cancer 
• 
Practice characteristics: PCP, practice, number of visits to practice in past year 
Variables obtained from baseline telephone interview:  
• 
Smoking patterns: daily or non-daily, years smoked, Fagerstrom test for nicotine dependence 
(includes time to first cigarette after waking and cigarettes smoked per day)64, number of 
previous quit attempts defined as any serious quit attempt lasting ≥24 hours 65 ever and in the 
last 12 months, during the past 30 days, on how many days did you have at least one cigarette, 
and do you ever use menthol cigarettes.  
• 
Demographic factors: ethnicity, race (white, black, Native American, Asian, Native Hawaiian or 
other Pacific Islander, other, unknown), and education 
• 
Any prior use of smoking cessation medication (nicotine patch, lozenge, gum, inhaler or nasal 
spray, varenicline, or buproprion) 
• 
Any prior use of behavioral treatment for smoking cessation (clinic or class, in-person 
counseling, telephone counseling, text messaging, alternative therapy, self help materials, or 
online communities and applications) 
• 
Past month use of other tobacco products-cigars, cigarillos, smokeless tobacco, hookah, or e-
cigarette 
Motivation to quit, confidence to quit, and perceived 2-week distress measured using single-item 
instruments with 11-item likert scale  

• 
Readiness to quit 66 
• 
Measures of psychosocial mechanisms targeted by the text messaging  
• 
PHQ-2 and GAD-2 screening for depression and anxiety 
• 
Single item alcohol67 and substance use disorder68 screening questions and past month illegal 
use of drugs69 
• 
On an average day, about how many text messages do you send and receive on your cell 
phone? 
• 
Cell phone carrier, type (smartphone) and plan details (pay per text or unlimited text 
messaging). 
• 
Email for subjects that want the follow up surveys emailed 
• 
Social security number for payment purposes 
 
Outcome assessments:  
Medication use outcomes will be assessed by telephone interview at week 1 and 2 by a second 
research coordinator blinded to treatment assignment: number of days patch was used in the 
last week and number of lozenges used each of the last two days. These will be used to 
calculate total duration of medication.70.  
1 &2 week telephone outcome assessments 
• 
Have you used nicotine patch in the past 7 days? 
o How many days in the past week did you use a nicotine patch? 
• 
Have you used nicotine lozenges in the past 7 days?  
o How many days in the past 7 days did you use a nicotine lozenge? 
o  On days when you use lozenge, how many do you use on average? 
• 
Since starting the study, have you stopped smoking cigarettes for 1 day or longer 
because you were trying to quit smoking? 
o If yes→On how many of the past 7 days did you have at least one cigarette? 
If 0→Have you smoked cigarettes, even a puff in the past 7 days? 
• 
Have you experienced any side effects in the last 7 days from quit smoking 
medications? 
• 
Receipt of text messages since last assessment. 
• 
Only Week 2→ Would you like more nicotine medication? A refill request would be sent 
to your PCP and it will be billed through your regular insurance. 
6  week telephone outcome assessments 
• 
Have you used nicotine patch in the past 7 days? 
o How many days in the past week did you use a nicotine patch? 
• 
Have you used nicotine lozenges in the past 7 days?  
o How many days in the past 7 days did you use nicotine lozenges?  
o On days when you use lozenge, how many do you use on average? 
• 
Since starting the study,have you stopped smoking cigarettes for 1 day or longer 
because you were trying to quit smoking? 
o If yes→In the past 30 days, how many days did you not smoke cigarettes? 
o If yes→On how many of the past 7 days did you have at least one cigarette? 
If 0→Have you smoked cigarettes, even a puff in the past 7 days? 
• 
Have you experienced any side effects in the past 30 days from quit smoking 
medications? 
• 
Receipt of text messages since last assessment 
 
12 week end-of-treatment telephone outcome assessment 

Quit attempt and smoking cessation outcomes will be assessed by telephone at 12 weeks (end 
of treatment) 
PRIMARY OUTCOME: Self-reported quit attempt in the last 12 weeks defined as intentional not 
smoking for 24 hours or more (“Since the start of the study, have you quit smoking intentionally 
for 1 day or longer” in addition to past follow up reports of quit attempts). We recognize that 
tobacco abstinence for more than one day is the desired outcome but feel this intermediate 
outcome is appropriate in the context of a pilot study with limited resources.  
SECONDARY OUTCOMES: 
How many times did you try to quit during the study? 
Have you smoked, even a puff, in the past 7 days? (7 day PPA) 
In the past 30 days, how many days did you not have a cigarette? 
How many cigarettes do you now smoke per day? 
Motivation to quit, confidence to quit, and perceived 2-week distress measured using single-item 
instruments with 11-item likert scale  
Use of evidence based treatment and behaviorial treatment in the past 12 weeks (NRT, 
varenicline, bupropion, clinic or class, in-person counseling, telephone counseling, text 
messaging, alternative therapy, self help materials, or online communities and applications) 
Past month use of other tobacco products including electronic cigarettes 
Side effects of quit smoking medications in the past 12 weeks 
Satisfaction with treatment 
Exhaled CO in ppm among subjects reporting 7 day PPA 
 
Up to 10 attempts will be made to reach study subjects for each outcome assessment (weeks 1, 
2, 6 and 12). 
 
Measures of intervention utilization:  
Intervention utilization will be obtained from MobileCommons software. 
 
ADHERENCE: length of active time in the text messaging program. At least twice per week a 
text message will be followed by another text message asking respondents if they found the 
message useful. Active time will be defined as number of days from enrollment to last reply to 
these usefulness messages.  
ENGAGEMENT: number of messages sent from participant to the server. Messages from the 
participant could be in response to the periodic questions about how they are feeling or to 
request specific help with cravings, mood symptoms, or slips. We will exclude responses to the 
receipt confirmation messages from this total.  
COMPLAINTS: due to technical issues or programmatic issues received by the technical 
helpline.  
 
e. Remuneration 
We will pay subjects $0.25 per text message sent or received from the program server up to 
$50 or 200 text messages. Participants will be issued $20 for completion of the baseline survey 
and $10 for follow-up surveys at 1, 2 and 6 weeks after enrollment. Participants will be issued 
another $40 after completion of the outcome telephone interview. Participants will be issued $20 
if they complete a CO measurement. A small subset of participants will be issued a $10 gift card 
for a qualitative exit interview. All payments for surveys and for the CO measurement will be 
issued by a gift card. Text message reimbursement will be issued by check every 4 weeks. 
 
VI. 
BIOSTATISTICAL ANALYSIS 
 

At the start of the project, MGH Primary Care Practice Based Research Network staff will 
identify the target population of documented smokers in MGH primary care practices and create 
a database that includes baseline variables from the EHR. We will use REDCap to collect 
baseline self-reported data and outcomes. At the end of the study we will merge the EHR data 
from the Primary Care Practice Based Research Network, REDCap, and MobileCommons for 
analysis (see Data Collection sheets). 
 
Data analysis 
The sample of smokers enrolled in the study will be characterized on baseline measures from 
the EHR and compared to the population of smokers whom we attempted to contact in order to 
determine the sample’s representativeness to the target population. Variables include 
demographics, medical history, and practice characteristics. We will also compare baseline 
characteristics collected from the EHR and from baseline interviews between the 4 randomized 
groups to determine the success of randomization. The primary outcome analysis will be 
conducted as intention-to-treat, comparing the primary outcome using chi-square analysis or 
multiple logistic regression analysis if any baseline factor is significantly imbalanced by group 
(p<0.05) as independent variables. The 4 arm design allows for analysis as a factorial design. 
We will first test for interaction between the NRT and TM interventions and if no interaction is 
detected we will test the effect of text messaging using both TM and TM+NRT arms compared 
to BA and NRT arms. If interaction is present, we will compare the TM arm to BA for our primary 
analysis. We will secondarily compare the groups in terms of self reported 7 day PPA, 
biochemically confirmed abstinence, number of days not smoked, use of ≥1 evidence based 
treatments, and cigarettes per day using chi-square or t-tests or logistic or linear regression if 
groups are imbalanced. We will also compare the TM+NRT group with the NRT group in terms 
of total days of medication used and total mg of medication used over 2 weeks using linear 
regression. We will conduct stratified analyses of the primary outcome, 7 day PPA, treatment 
use and days not smoked by readiness to quit in the next 30 days. 
 
 
Sample size 
Hypothesis 1: A 12 week text messaging intervention (up to 30 days pre-quit through 8 weeks 
post-quit) providing behavioral support will increase the proportion of smokers making a quit 
attempt compared to a control group receiving brief advice.  
The sample size for this pilot study is selected to adequately estimate recruitment rates, 
retention, and to get a preliminary estimate of prevalence of clinical outcomes. We anticipate we 
can recruit 200 patients by proactive outreach over 12 months. With 50 patients per group and 
25% loss to follow-up we will have 81% power to detect a relative risk of self-reported ≥24 hour 
quit attempts of 1.8 for text messaging versus brief advice groups. We base this estimate on 
meta-analyses of smoking cessation text messaging trials, mostly from community settings or 
school-based settings, report a relative risk of 1.4 for 7-day point prevalence abstinence and 1.6 
for prolonged abstinence measured at six-months.8,71   
Hypothesis 2: A 12 week text messaging intervention providing personalized, tailored behavioral 
support and advice about using nicotine replacement therapy (NRT) plus 2 weeks of NRT 
mailed to the participant will increase adherence to NRT compared to subjects receiving only 2 
weeks of NRT as measured by duration of NRT use in days. 
For our secondary outcome of medication adherence, we estimate patients randomized to the 
NRT will use a mean 9 days of medication based on the offer to mail them 2 weeks of 
medication for free.72 With this sample size, we also have 80% power to detect an increase in 
days of NRT use from 9 to 12 days in NRT vs. NRT+TM. 

Hypothesis 3: A 12 week text messaging intervention will increase the rate of biochemically 
confirmed past 7-day point prevalent tobacco abstinence at end of treatment compared to 
subjects receiving no text messaging intervention.  
We do not expect to have power to detect cessation in this pilot study. With 100 subjects and 
25% loss to follow-up we will have 80% power to detect an increase from 6% among the BA & 
NRT groups to 22% in TM & TM + NRT groups. 
Regardless, this pilot study aims to generate an estimate of effect size on cessation at 12 weeks 
for further studies. 
Hypothesis 4: A 12 week text messaging intervention will increase the number of days not 
smoking compared to subjects receiving no text messaging intervention. 
Assuming α=0.05 and 25% loss to follow-up, leaving 75 patients, we have 68% power to detect 
an increase in days not smoked from 0.2 in groups receiving no text messaging (BA & NRT) to 
1 in groups receiving text messaging (TM & TM + NRT) assuming a standard deviation of 2. 
Hypothesis 5: A 12 week text messaging intervention will decrease number of cigarettes 
smoking compared to subjects receiving no text messaging intervention. 
Assuming α=0.05 and 25% loss to follow-up, leaving 75 patients, we have 75% power to detect 
a decrease in cigarettes smoked per day from 15 among those receiving no text messaging (BA 
& NRT) to 12 in groups receiving text messaging (TM & TM + NRT) assuming a standard 
deviation of 7. 
 
 
VII. 
RISKS AND DISCOMFORTS  
 
a. Complications of surgical and non-surgical procedures 
Not applicable  
 
b. Drug side effects and toxicities  
Side effects of the nicotine patch may include itching, burning or tingling when the patch is 
applied.  This usually goes away within an hour, and is a result of nicotine coming in contact 
with the skin; redness or swelling at the patch site for up to 24 hours; dizziness; headache; 
upset stomach; vomiting; diarrhea; and palpitations.   
 
Side effects of the nicotine lozenge include mouth irritation or ulcers, in addition to nicotine-
related side effects of dizziness; headache; upset stomach; vomiting; diarrhea, and palpitations. 
 
c. Device complications/malfunctions 
Errors in the text messaging platform include skipped text messages or failure to respond to a 
user-initiated text message. While this may affect the fidelity and clarity of the text messaging 
intervention we do not think this poses a risk to subject health or well-being. 
 
d. Psychosocial (non-medical) risks 
i). Psychological discomfort: Quitting smoking can be psychologically stressful and, at times, 
physically uncomfortable because of cravings and nicotine withdrawal symptoms.  
 
ii). Risks to privacy: Text messages are not a secure messaging platform. Any person using the 
subject’s designated phone can see the messages which may include information about quitting 

smoking. It may be psychologically stressful for subjects if other persons see text messages 
disclosing their smoking status. We will also collect and record identifying information (e.g. 
name, date of birth and social security number) and ask about potentially sensitive topics 
(smoking history, depression screening questions, anxiety screening questions, alcohol and 
substance use disorder screening questions). Name, telephone number, and smoking status will 
be shared with the text messaging vendor. The vendor underwent risk assessment  by 
Research Information Security to evaluate their data security practices. 
 
e. Radiation risks  
Not Applicable 
 
VIII. 
POTENTIAL BENEFITS 
 
a. Potential benefits to participating individuals  
Smoking is the leading preventable cause of death in the U.S. and most individuals make 
several quit attempts before successfully quitting. A benefit to participating in the trial will be the 
opportunity to receive tobacco cessation interventions at no financial cost to the participant. This 
includes brief advice from study staff trained in tobacco cessation treatment. Subjects may 
receive up to 2 weeks of nicotine patches, nicotine lozenges or combination nicotine 
replacement therapy for daily smokers. Combination therapy is associated with higher rates of 
tobacco cessation in comparison to patches alone or unassisted quitting. Participants may also 
receive behavioral support by text message and medication adherence support to help them 
navigate their planned quit attempt.  
 
b. Potential benefits to society (e.g., increased understanding of disease process, etc.) 
We anticipate that our proposed research program will result in important knowledge 
contributions. The knowledge gained in mobile interventions will represent an important 
contribution to the evidence base for addressing tobacco use among primary care patients who 
suffer from high rates of tobacco dependence and tobacco related illness. 
 
IX. 
MONITORING AND QUALITY  
 
a. Independent monitoring of source data 
 
All EHR and survey data will be collected using password-protected laptop or desktop 
computers with full disk encryption.  We will use the Partners-hosted Research Electronic Data 
Capture (REDCap) application for data collection and management.  REDCap is a secure, 
HIPAA compliant web-based application hosted by Partners HealthCare Research Computing, 
Enterprise Research Infrastructure & Services (ERIS).  Because a Partners username is 
required for logging in to REDCap, all activity on study documents is electronically logged and 
therefore traceable.  REDCap has built-in functions providing real-time data entry validation to 
help ensure accuracy and completeness.  Data will be collected according to a standardized 
protocol that will detail which data elements should be collected during each study interaction 
and the methods for doing so.  We will operationalize this protocol by using the calendar 
function in REDCap to specify which data collection forms to administer on which dates for each 
participant.  Each data collection form will have instructions or prompts for collecting the 
required data elements, and the response fields for each item will have appropriate ranges and 
formats to ensure that the data is entered in a valid way.  
 
The PI will review all study data once per week to monitor its integrity.  Additionally, the PI, 
biostatistician, and/or data analyst will download the study data on a weekly basis from the 

Partners REDCap server and back it up to the PI’s SFA on the Partners network, which is 
protected by the Partners IS firewall, backed up nightly, and accessible only to authorized study 
staff.  Only the minimum necessary number of study staff will have access to this data.  Data 
analyses will be conducted by authorized study staff on the downloaded data files residing on 
the PI’s Partners SFA.  The data will not be transferred to investigators outside the Partners 
system. 
 
Data will also be collected in the text messaging web-based platform in a database that includes 
identifiers of first name, telephone number and smoking status. This data will consist of all 
messages sent to participant from the server and all messages sent by the participant to the 
server. Once per week the PI will review all messages sent from participants to the server for 
possible disclosure of urgent or emergent medical information to the server.  
 
 
b. Safety monitoring (e.g., Data Safety Monitoring Board, etc.) 
 
The PI and her designated research coordinator, working in concert with the Partners IRB, will 
be responsible for the monitoring of adverse events in study participants.  
 
Adverse reactions to nicotine medication: The research coordinator will ask all participants 
about adverse events at telephone contacts scheduled at week 1, week 2, and week 6 follow up 
and subjects will also be given a phone number to report any such events between study visits. 
The PI will review the safety and progress of the trial, including adverse event assessments, 
biweekly. Mild reactions will be reviewed by the PI and may prompt a dose reduction or 
cessation of patch or lozenge use. Severe reactions will be referred to emergency medical 
services. Subjects will be advised not to report events by text message. As above, the PI will 
also review text messages sent by subjects to the server biweekly in case subjects report 
adverse events or other health issues by text message. Adverse events will be documented, 
reviewed by the PI and reported to the IRB at the annual review or sooner based on the severity 
and nature of the event.  All serious adverse events (i.e. hospitalization, death) will be reported 
within 5 days to the IRB, following institutional guidelines, and carefully reviewed by the PI to 
assess the likelihood that the event was related to the nicotine patch, lozenges, or text 
messages.  A full written report using the PHRC Adverse Event From will be submitted to IRB 
within 10 working days/14 calendar days. 
 
Risk to privacy: We will adhere to data management procedures described above to help 
ensure the safety and integrity of data collected about study participants. All identifying 
information will be saved securely within the REDCap database and not recorded on paper 
forms.  Only the minimum necessary number of study staff will have access to this data.  At the 
conclusion of the study, personal identifiers will be removed from the dataset and all analyses 
will occur in a de-identified fashion.  To mitigate privacy risks associated with mobile phone use, 
participants will be instructed to safeguard their phone when not in use and to not leave it laying 
out in plain view if they do not wish others to see the content of any text messages sent to their 
phone.  Partners Research Information Security reviewed the data security practices of the text 
messaging vendor. Information shared with the vendor includes name, telephone number and 
smoking status as well as any data entered by the patient as part of the text messaging 
program. 
 
c. Outcomes monitoring 

Because of the short duration and pilot nature of the proposed study, we will not conduct a 
formal interim analysis of the data or define rules for early stopping of the trial. 
d. Adverse event reporting guidelines 
 
Serious adverse events, defined as adverse events which are life threatening, require 
hospitalization, cause persistent or significant disability or incapacity, or events otherwise 
judged to represent significant hazards, which are reported by participants or the clinical staff 
caring for them will be documented in a serious adverse event report and submitted to the 
Partners IRB and institutional safety officer within 10 days of notification of the event. The report 
will include a description of the event, when and how it was reported, and any official chart 
records or study documents to corroborate the event. Participants will be referred for immediate 
medical evaluation of any serious adverse events. A summary safety report detailing all adverse 
events and their handling will be included in annual study progress reports to the Partners IRB 
and the NIH funding agency. Adverse event reports and annual safety summaries will be 
documented by study ID number; personal identifiers will not be included in these reports. 
 
e. Protocol adherence 
The study coordinators will be trained on the data collection protocols described above.  Their 
understanding of these protocols will be assessed by asking them to demonstrate competency 
in using the REDCap data collection forms.  Additionally, the research coordinator(s) 
responsible for providing brief advice to study participants will be trained in advance on the 
protocol to ensure consistency in advice across participants. 
 
During the trial, adherence to the study procedures will be monitored by assessing whether the 
appropriate data collection modules were administered on the appropriate dates for each 
participant.  Remediation and/or refresher training will be provided to study staff as needed to 
address any concerns.  Additionally, the PI will meet with all study staff once weekly to review 
the day-to-day workings of the trial and to identify any problems related to the study protocol. 
 
 
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