Impact of Switching to Non-Menthol Cigarettes Among Smokers
Phase: NA
Conditions: Tobacco Use
Sponsor: Yale University

Page 1 of 16 
 
                    
                                    
HRP-503B – BIOMEDICAL RESEARCH PROTOCOL  
(2016-1) 
 
 
 
 
Protocol Title: Impact of Switching to Non-Menthol Cigarettes Among Smokers 
 
 
Principal Investigator: Krysten Bold, Ph.D. 
 
 
Version Date: 6/11/2018 
 
 
(If applicable) Clinicaltrials.gov Registration #: NCT03075839 
 
 
INSTRUCTIONS 
 
This template is intended to help investigators prepare a protocol that includes all of the necessary information 
needed by the IRB to determine whether a study meets approval criteria. Read the following instructions before 
proceeding: 
 
1. Use this protocol template for a PI initiated study that includes direct interactions with research 
subjects. Additional templates for other types of research protocols are available in the system Library. 
 
2. If a section or question does not apply to your research study, type “Not Applicable” underneath. 
 
3. Once completed, upload your protocol in the “Basic Information” screen in IRES IRB system.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Page 2 of 16 
 
SECTION I: RESEARCH PLAN 
 
1. Statement of Purpose: State the scientific aim(s) of the study, or the hypotheses to be tested.  
 
In this pilot study of 30 non-treatment-seeking adult smokers, we will investigate within-person 
changes in smoking behavior when current menthol smokers are systematically switched to using 
non-menthol cigarettes. We will recruit adult daily smokers who currently use menthol cigarettes, 
observe their smoking behavior with their usual brand of menthol cigarettes in vivo for two weeks, 
and then switch them to a matched-brand non-menthol cigarette for two weeks. We will assess the 
impact of switching on cigarette satisfaction (e.g., craving, liking, taste, willingness to continue use, 
intentions to quit) and smoking behavior, including compensatory use of other tobacco products or 
menthol products (e.g., gum, mints) to estimate the impact of eliminating characterizing menthol 
flavor in cigarettes on current menthol smokers. The results will provide novel information on how 
characterizing menthol flavor additives influence smoking satisfaction and behavior. The FDA could 
use these results to inform product standards and to predict the effects of restricting characterizing 
menthol flavor in cigarettes among current menthol smokers. Additionally, the results will inform 
future study designs by evaluating the feasibility of a cigarette switching paradigm and testing 
innovative methods to objectively monitor smoking behavior and menthol exposure. 
 
Aim 1: Investigate whether switching to non-menthol cigarettes changes cigarette satisfaction and 
smoking behavior  
 
Hypotheses: We expect that switching to a non-menthol cigarette will be less reinforcing and result 
in fewer cigarettes smoked per day, lower nicotine dependence, and greater quitting 
motivation/interest. Pilot data will be used to estimate effect sizes for these outcomes to inform the 
development of larger follow-up studies. 
 
Aim 2: Evaluate the utility of objective smoking measures to assess behavior and adherence to the 
switching paradigm 
 
Hypotheses: We expect that we will be able to quantify and verify self-reported smoking behavior 
with several objective measures of smoking behavior: collecting spent cigarette filters to measure 
number of cigarettes and quantify smoking intensity with filter weight and length, quantifying urine 
menthol glucuronide as a marker of menthol exposure. 
 
2. Background: Describe the background information that led to the plan for this project. Provide references to 
support the expectation of obtaining useful scientific data. 
 
Investigating menthol tobacco product use is critical for informing regulatory efforts. Although the 
Tobacco Control Act banned the sale of tobacco cigarettes with flavor additives, menthol flavor is 
currently exempt from this ban. While the overall rate of cigarette smoking has declined in recent 
years, the proportion of smokers using mentholated cigarettes has increased 1. Specifically, data 
from the National Survey on Drug Use and Health indicate the rate of past month menthol cigarette 
use increased from 7.7% in 2004 to 8.2% in 2010, while the rate of non-menthol cigarette use 
decreased from 17.1% to 14.6% during that time 1. Menthol additives are found in several nicotine 
containing products, including cigars, cigarillos, and e-cigarettes, although conventional cigarettes 
are still the most frequently used product by adult smokers 2. Menthol additives in tobacco pose a 
serious public health problem given evidence that smokers who use menthol cigarettes have 
greater risk of smoking-related morbidities 3, and worse cessation outcomes 4,5. Additionally, use of 
menthol cigarettes is associated with higher rates of smoking and dependence 6,7. Research is 

Page 3 of 16 
 
needed to better understand how menthol additives influence smoking behavior and enhance the 
addictive potential of tobacco products.  
 
3. Research Plan: Summarize the study design and research procedures using non-technical language that can 
be readily understood by someone outside the discipline. Be sure to distinguish between standard of care vs. 
research procedures when applicable, and include any flowcharts of visits specifying their individual times and 
lengths. Describe the setting in which the research will take place. 
 
Overview: The proposed project will compare within-person effects of switching from menthol 
cigarettes to non-menthol cigarettes in current adult menthol smokers (n=30). The primary outcome 
of interest will be smoking behavior measured via daily monitoring and self-report. Self-reported 
smoking behavior will be verified by objective biomarkers of nicotine and menthol exposure and by 
asking participants to return all spent cigarette filters. We expect switching to a non-menthol 
cigarette will reduce smoking satisfaction and smoking behavior (e.g., fewer cigarettes per day, 
longer time to first cigarette in the morning) compared to a baseline period of smoking menthol 
cigarettes.  
 
Settings: Participants will be recruited from the community. Research study visits will take place at 
our outpatient research offices (34 Park Street CMHC or 1 Long Wharf SATU, New Haven, CT) or a 
location that is convenient for participants, such as their home or public place 
 
Procedures:  
Interested study candidates will be screened by telephone. Those meeting initial eligibility criteria 
will attend an in-person screening appointment to learn more about the research study, provide 
written informed consent, and complete intake measures. Eligible participants will then begin a four 
week monitoring period. Participants will be provided with free menthol cigarettes of their own usual 
brand to smoke for one week (Phase I, days 0-7) and then will be switched to non-menthol 
cigarettes for two weeks (Phase II, days 7-21). Participants will be provided with all cigarettes in 
both Phase I and II to control for the possibility of increased consumption due to free cigarettes (as 
seen in other studies, 8) and to encourage adherence to smoking the specified cigarette. To 
enhance the naturalistic nature of the study, research staff will provide subjects with their usual 
brand of menthol cigarettes (Phase I), and then will switch them to a matched-brand non-menthol 
cigarette (Phase II). At the end of the study, we will provide information on tobacco treatment 
programs to all participants. 
 
Screening Assessments: To screen for eligibility, participants will complete several assessments: 1) 
Cigarette preference questions assess current use of menthol cigarettes (i.e., “what brand of 
cigarettes do you prefer?” “what brand of cigarettes do you normally smoke?”). 2) Smoking history 
to assess smoking quantity and frequency such as number of cigarettes per day and number of 
years smoked. 3) Expired breath carbon monoxide (CO) measured in parts per million to confirm 
smoking status. 4) Drug use: to confirm participants are not currently using other substances (other 
than caffeine or nicotine) assessments will include i) a time-line follow-back interview to assess self-
reported drug use quantity and frequency, ii) urine drug toxicology screens, and iii) current blood 
alcohol level measured with a breathalyzer.  
 
Visit Assessments: Eligible individuals will complete self-report assessments at baseline and 
research visits: 1) Nicotine dependence, measured by 1) Time to first cigarette in the morning as an 
index of smoking reinforcement 9,10, 2) Fagerstrom Test for Nicotine Dependence 9 and Wisconsin 
Inventory of Smoking Dependence Motives 11,12 to assess multiple dimensions of tobacco 
dependence such as automaticity, loss of control, and affective enhancement. Additional 

Page 4 of 16 
 
assessments include: 3) Questionnaire on Smoking Urges-brief 13 to measure cigarette craving, 4) 
Wisconsin Smoking Withdrawal Scale 14, to assess 7 constructs of nicotine withdrawal: anger, 
anxiety, concentration, craving, hunger, sadness, and sleep and 5) Confidence and interest in 
quitting smoking, rated from 1 (not at all) to 10 (extremely) and 6) measures of smoking behavior 
and cigarette reinforcement and satisfaction.  
 
Biological Measures: Biomarkers of cigarette and menthol exposure will be collected at baseline 
and weekly research visits (day 7, 14, 21) to examine changes from baseline and to corroborate 
self-reported tobacco product use and menthol exposure during the trial. 1) Expired breath carbon 
monoxide (CO) measured in parts per million, 2) Urine cotinine to quantify nicotine exposure, 3) 
Menthol glucuronide measured in the same urine sample as a marker of menthol exposure. 
 
Adherence: Adherence to use of the specified cigarettes in Phase I and II will be closely monitored 
via subjective and objective measures. Participants will report the total number of cigarettes 
consumed each day and will be instructed how to save and return spent cigarette filters so the 
count can be verified by research staff, a procedure that has been utilized previously to verify 
adherence 15. Biological measures will monitor menthol exposure and can be compared between 
Phase I and Phase II to quantify reductions in menthol exposure. We aim to restrict access to 
menthol cigarettes during Phase II by recruiting only smokers who do not currently live with menthol 
smokers, collecting any remaining mentholated cigarettes from participants before switching to non-
menthol cigarettes, and providing free cigarettes to discourage substitution. Additionally, we will 
assess participants’ use of other mentholated products (e.g., mint toothpaste or gum) or other 
extraneous tobacco products that are not a part of the study (e.g., e-cigarettes, other tobacco 
products) each week during the trial. This will allow us to estimate any compensatory menthol or 
tobacco product use during the switching phase of the study. Lastly, we will incentivize participant 
reporting by providing compensation for returning spent cigarette filters. 
 
4. Subject Population: Provide a detailed description of the types of human subjects who will be recruited into this 
study. 
 
We will recruit current adult (at least 18 years old) daily smokers who report smoking at least 5 
cigarettes per day for at least the past 6 months. See detailed inclusion and exclusion criteria below. 
 
 
5. Subject classification: Check off all classifications of subjects that will be specifically recruited for enrollment in 
the research project. Will subjects who may require additional safeguards or other considerations be enrolled 
in the study? If so, identify the population of subjects requiring special safeguards and provide a justification 
for their involvement. 
 
☐Children 
 
 
☐ Healthy  
 
 
☐Fetal material, placenta, or dead fetus 
☐Non-English Speaking  
☐ Prisoners 
 
 
☐Economically disadvantaged persons 
☐Decisionally Impaired  
☐ Employees 
 
 
☐Pregnant women and/or fetuses 
☐Yale Students  
 
☒ Females of childbearing potential 
 
NOTE: Is this research proposal designed to enroll children who are wards of the state as potential subjects? 
Yes ☐  No ☒  
 
6. Inclusion/Exclusion Criteria: What are the criteria used to determine subject inclusion or exclusion? 
Inclusion Criteria:  

Page 5 of 16 
 
(1) 18 or older 
(2) English literate 
(3) Smoke at least 5 cigarettes per day for the past 6 months 
(4) Expired breath carbon monoxide level ≥ 6ppm at baseline or detected urine cotinine level with 
NicAlert test strip  
(5) Report currently smoking menthol cigarettes 
 
 
Exclusion Criteria:  
(1) Seeking smoking cessation 
(2) Currently using any stop smoking treatments 
(3) History of serious psychiatric condition (i.e., bipolar disorder, schizophrenia) 
(4) Current uncontrolled medical condition 
(5) Current use of other substances (excluding nicotine and caffeine) or a positive urine toxicology 
screen 
(6) Living with a menthol smoker (to limit access to menthol cigarettes during the non-menthol 
phase of the trial) 
(7) Female participants will be excluded if they are currently pregnant or breastfeeding or report an 
unwillingness to use effective birth control for the duration of the study 
 
7. How will eligibility be determined, and by whom? Write here 
 
Interested participants will call our office and will be provided with verbal information about the 
project. Interested participants will be initially screened by telephone and will provide their name 
and contact information and provide answers to short screening questions to assess age, smoking 
status, menthol preference, and to ensure they are not currently seeking smoking cessation 
treatment. Participants who meet initial eligibility screening will be invited to complete an intake 
session. At the intake session, participants will complete an informed consent form. Following this, 
a research assistant will obtain medical and substance use histories, urine drug and pregnancy 
tests, and breath CO levels. If study criteria are met, the participant will be scheduled for the 
subsequent sessions. 
 
8. Minimizing Risks: Describe the manner in which the above-mentioned risks will be minimized. 
 
Although we have assessed the proposed study as one of minimal risk, the potential exists 
for anticipated and/or unanticipated adverse events, serious or otherwise, to occur since it 
is not possible to predict with certainty the absolute risk in any given individual or in 
advance of first-hand experience with the proposed study methods. Therefore, we provide 
a plan for monitoring the data and safety of the proposed study as follows: 
Adverse events will be monitored for each subject participating in the study and attributed 
to the study procedures / design by Dr. Bold according to the following categories: 
a.) 
Definite: Adverse event is clearly related to investigational agent/participation. 
b.) 
Probable: Adverse event is likely related to investigational agent/participation. 
c.) 
Possible: Adverse event may be related to investigational agent/participation. 
d.) 
Unlikely: Adverse event is likely not to be related to the investigational 
agent/participation. 
e.) 
Unrelated: Adverse event is clearly not related to investigational 
agent/participation. 
 
The following scale will be used in grading the severity of adverse events noted during the 
study: 

Page 6 of 16 
 
1 Mild adverse event 
2 Moderate adverse event 
3 Severe unanticipated adverse event resulting in inpatient hospitalization or prolongation 
of existing hospitalization, a persistent or significant disability/incapacity, or a congenital 
anomaly/birth defect;  
4 Life threatening event or  
5 Fatal adverse event. 
 
In addition to grading the adverse event, Dr. Bold and the study team will determine 
whether the adverse event meets the criteria for a Serious Adverse Event (SAE).  An 
adverse event is considered serious if it: 
1. is life-threatening 
2. results in in-patient hospitalization or prolongation of existing hospitalization  
3. results in persistent or significant disability or incapacity  
4. results in a congenital anomaly or birth defect OR 
5. results in death 
6. based upon appropriate medical judgment, may jeopardize the subject’s health and may 
require medical or surgical intervention to prevent one of the other outcomes listed in this 
definition, or 
7. adversely affects the risk/benefit ratio of the study. 
 
The study team, in consultation with the Yale TCORS Independent Data Safety Monitoring 
Board (DSMB), will evaluate the adverse event and determine whether the adverse event affects the 
Risk/Benefit ratio of the study and whether modifications to the protocol or consent form are needed. 
The DSMB includes experts in the field of tobacco use behaviors. The DSMB will review the study 
information and the plans for review prior to the initiation of the studies.  They will provide an ongoing 
review every six months or more often if requested by the Board. The summary of the DSMB meeting 
will be submitted to the Yale HIC and to NIDA following each meeting.   
 
Subjects will be closely monitored for safety throughout the research trial. Although in our 
experience this is a very rare event, subjects who show significant deterioration (e.g., increased 
substance use or psychiatric symptoms, including significant suicidal or homicidal ideation), will be 
withdrawn from the study and referred for appropriate treatment.  
 
At any point if the investigator feels that subjects’ health or well-being may be threatened by 
continuation in the study, subjects will be withdrawn from the study. If participants have a medical 
emergency, they will be instructed to call 911. Subjects who experience a significant psychiatric or 
medical problem that requires overnight hospitalization at an acute care facility will be considered to 
have experienced an SAE.  
 
The Principal Investigator, Dr. Bold, will report the following types of adverse events to the Yale 
University Human Investigation Committee (HIC):  
a) serious AND unanticipated AND possibly, probably or definitely related events;  
b) anticipated adverse events occurring with a greater frequency than expected; and  
c) other unanticipated problems involving risks to subjects or others. 
 
These adverse events or unanticipated problems involving risks to subjects or others will be 
reported to the Yale HIC within 5 days of it becoming known to Dr. Bold. The procedures for SAE 
reporting include written documentation using the clinical notes related to the adverse event and 
specific forms detailing the event with a sign-off by all appropriate supervisory personnel. 

Page 7 of 16 
 
Communication of recommendations and decisions from all parties (Yale Human Investigation 
Committee) will be made back to Dr. Bold in a timely manner. 
 
i. What provisions are in place for management of interim results?  
The principal investigator is responsible for monitoring the data, assuring protocol 
compliance, and conducting the safety reviews at the specified frequency monthly.  
During the review process the principal investigator will evaluate whether the study 
should continue unchanged, require modification/amendment, or close to enrollment. 
The principal investigator and the Institutional Review Board (IRB) have the authority to 
stop or suspend the study or require modifications. 
ii. What will the multi-site process be for protocol modifications? N/A this is a single-site study 
 
9. Statistical Considerations: Describe the statistical analyses that support the study design.  
 
Data analyses will be conducted with SPSS software. Effect size estimates with 95% confidence 
intervals will be constructed for each aim to inform future studies. The primary statistical analyses 
will use within-person repeated measures to test for differences in smoking behavior (e.g., number 
of cigarettes per day, nicotine dependence) in menthol versus non-menthol phases. 
 
Justification for sample size: Estimation of sample size (n=30) is based on achieving a clinically 
meaningful precision in effect size estimates for the primary outcome of interest. A power analysis 
based on α=.05 and β=.80 suggests a sample size of 30 subjects is sufficiently powered to detect 
medium or large effects (d>.50) within-person. Although we will be unable to detect smaller effects, 
this sample size is reasonable for a pilot study, and data will be used to test the feasibility of the 
paradigm and adherence monitoring methodology and to estimate effect sizes to inform the optimal 
sample size for a larger follow-up study.  
 
Data Monitoring: Procedures for data collection, data management, monitoring of data quality and 
data analysis have been developed and refined in our previous tobacco studies. An experienced 
data analyst and the PI will supervise these procedures which include use of a computerized 
database to monitor research activities, screening and enrollment, compliance with protocol, 
completion of scheduled assessments, and data retrieval. Data quality will be ensured by: 1) 
extensive training/supervision of research staff in data collection; 2) preliminary review of all 
assessment instruments prior to data entry and checks for completeness and coding errors; 3) 
double data entry of written assessment instruments; 4) error-checking statistical programs. 

Page 8 of 16 
 
SECTION II: RESEARCH INVOLVING DRUGS, BIOLOGICS, RADIOTRACERS, PLACEBOS AND DEVICES 
 
 
If this section (or one of its parts, A or B) is not applicable, check off N/A and delete the rest of the section. 
 
A.  RADIOTRACERS 
☒N/A 
 
1. Name of the radiotracer: Write here 
 
2. Is the radiotracer FDA approved?    ☐YES  
☐NO 
 
If NO, an FDA issued IND is required for the investigational use unless RDRC assumes oversight.  
 
3. 
Check one:   ☐IND#  Write here or  ☐RDRC oversight (RDRC approval will be required prior to use) 
 
B.  DRUGS/BIOLOGICS    ☒N/A 
 
 
 
 
 B.  DEVICES 
 ☒N/A 
 
a)  
SECTION III: RECRUITMENT/CONSENT AND ASSENT PROCEDURES  
1. Targeted Enrollment: Give the number of subjects:  
a. Targeted for enrollment at Yale for this protocol: 30 
b. If this is a multi-site study, give the total number of subjects targeted across all sites: N/A 
 
2. Indicate recruitment methods below.  Attach copies of any recruitment materials that will be used. 
☒ Flyers 
☒ Internet/web postings 
☐ Radio 
☒ Posters 
☐ Mass email solicitation 
☐ Telephone 
☐ Letter 
☐ Departmental/Center website 
☐ Television 
☐ Medical record review*  
☐ Departmental/Center research boards 
☐ Newspaper 
☐ Departmental/Center newsletters 
☐ Web-based clinical trial registries 
☒ Clinicaltrials.gov  
☐ YCCI Recruitment database 
☒ Social Media (Twitter/Facebook):  
 
☐ Other:  
 
 
 
* Requests for medical records should be made through JDAT as described at 
http://medicine.yale.edu/ycci/oncore/availableservices/datarequests/datarequests.aspx 
 
3.  Recruitment Procedures:  
a. Describe how potential subjects will be identified. Potential subjects will be recruited through 
methods previously used by our team and found to be effective in recruiting smokers. 
Recruitment methods include flyers, online advertisements (e.g., Facebook, Cragislist), on 
public boards in New Haven, and by word of mouth. We will provide a $25 referral bonus to 
any current or previous participants if they refer someone who is eligible for the study. We 

Page 9 of 16 
 
will tell subjects only that someone they referred is eligible. We will not release individual 
names.  
 
b. Describe how potential subjects are contacted. Potential participants can contact the study to 
determine eligibility through phone call, text message, or a website that will direct them to a 
Yale Qualitrics website where interested participants can complete a brief screening 
questionnaire.  
c. Who is recruiting potential subjects? The PI and research staff will recruit potential subjects. 
 
 
4. Assessment of Current Health Provider Relationship for HIPAA Consideration: 
Does the Investigator or any member of the research team have a direct existing clinical relationship with any 
potential subject?  
☐Yes, all subjects 
☐Yes, some of the subjects 
☒No 
 
If yes, describe the nature of this relationship. Write here 
5. Request for waiver of HIPAA authorization: (When requesting a waiver of HIPAA Authorization for either the 
entire study, or for recruitment purposes only.  Note: if you are collecting PHI as part of a phone or email 
screen, you must request a HIPAA waiver for recruitment purposes.) 
Choose one:  
☐ For entire study  
☒ For recruitment/screening purposes only  
☐ For inclusion of non-English speaking subject if short form is being used and there is no translated HIPAA 
research authorization form available on the University’s HIPAA website at hipaa.yale.edu. 
 
i. Describe why it would be impracticable to obtain the subject’s authorization for use/disclosure of this 
data:  
ii. If requesting a waiver of signed authorization, describe why it would be impracticable to obtain the 
subject’s signed authorization for use/disclosure of this data: We request a waiver of signed 
authorization only for initial participant recruitment/screening purposes to obtain interested 
participants’ phone numbers and/or email for voice and text communication to make initial 
contact with the research team. At the first phone contact with the research team, 
participants will provide verbal consent for the screening process. If participants prefer to 
complete the online screener through the Yale Qualtrics system, participants will provide 
signed consent in the online screening survey. Participants will be asked to provide brief 
demographic information and smoking status information to determine initial eligibility prior 
to setting up an in-person intake appointment where formal written informed consent will be 
obtained.  
 
The investigator assures that the protected health information for which a Waiver of Authorization has been 
requested will not be reused or disclosed to any person or entity other than those listed in this application, except 
as required by law, for authorized oversight of this research study, or as specifically approved for use in another 
study by an IRB. 
 

Page 10 of 16 
 
Researchers are reminded that unauthorized disclosures of PHI to individuals outside of the Yale HIPAA-Covered 
entity must be accounted for in the “accounting for disclosures log”, by subject name, purpose, date, recipients, 
and a description of information provided.  Logs are to be forwarded to the Deputy HIPAA Privacy Officer. 
 
6. Process of Consent/Assent: Describe the setting and conditions under which consent/assent will be obtained, 
including parental permission or surrogate permission and the steps taken to ensure subjects’ independent 
decision-making.  
 
After the screening process is complete and the participant is found to be eligible, the RA/PI will 
schedule them for an in person intake.  At this intake, all eligible participants will be asked for 
written consent using the Yale HIC approved combined consent/HIPAA form. The entire consent 
form will be reviewed in detail with the participant in a private, one-on-one setting at the first intake 
appointment. All risks and potential benefits will be described. Any questions the participant may 
have will be addressed. If the participant wishes, they may take the consent form home and 
consider it further before signing. They may also request to speak to anyone on the research team 
about questions they have or to consult others, including their physician and family members. Once 
the participant has signed the consent, they may withdraw consent at any time. Informed consent 
must be obtained prior to performance of any protocol specific procedures. All participants will 
receive a signed copy of the consent form to retain for their records. All eligible participants will also 
be asked to provide contact information in the following manner.  In addition to providing their own 
personal contact information, participants will be asked to give the names of two friends or relatives 
whom we can contact to obtain this information. We will contact these individuals only if we are 
unable to contact the participant directly and then only for the purpose of obtaining a forwarding 
address and phone number. Participants will be made aware of this information and potential 
reason for contacting the listed friends/relatives. We will inform the person that the participant has 
authorized us to contact them and they will be asked if they are willing to give out this information. If 
they decline, they will not be contacted again. 
 
7. Evaluation of Subject(s) Capacity to Provide Informed Consent/Assent: Indicate how the personnel obtaining 
consent will assess the potential subject’s ability and capacity to consent to the research being proposed.  
 
We will not be enrolling participants with limited decision-making capacity. We plan to exclude 
individuals with current serious psychiatric or medical illnesses. During the consenting process, the 
research assistant will read and review the consent form with the prospective participant. The 
research assistant will then ask the potential participant various questions about the consent form 
and study protocol to ensure the prospective participant sufficiently understands the study and the 
nature of their consent to participate.  
 
8. Non-English Speaking Subjects: Explain provisions in place to ensure comprehension for research involving 
non-English speaking subjects. If enrollment of these subjects is anticipated, translated copies of all consent 
materials must be submitted for approval prior to use.  
 
N/A 
 
As a limited alternative to the above requirement, will you use the short form* for consenting process if you 
unexpectedly encounter a non-English speaking individual interested in study participation and the translation of 
the long form is not possible prior to intended enrollment?  YES ☐  NO ☒ 
 

Page 11 of 16 
 
Note* If more than 2 study participants are enrolled using a short form translated into the same language, then 
the full consent form should be translated into that language for use the next time a subject speaking that 
language is to be enrolled. 
 
Several translated short form templates are available on the HRPP website (yale.edu/hrpp) and translated HIPAA 
Research Authorization Forms are available on the HIPAA website (hipaa.yale.edu). If the translation of the short 
form is not available on our website, then the translated short form needs to be submitted to the IRB office for 
approval via modification prior to enrolling the subject.   Please review the guidance and presentation on use of the 
short form available on the HRPP website. 
 
If using a short form without a translated HIPAA Research Authorization Form, please request a HIPAA waiver in the 
section above.  
 
9. 
Consent Waiver: In certain circumstances, the HIC may grant a waiver of signed consent, or a full waiver of 
consent, depending on the study. If you will request either a waiver of consent, or a waiver of signed consent for 
this study, complete the appropriate section below.   
 
☐Not Requesting any consent waivers  
 
☒Requesting a waiver of signed consent: 
☒ Recruitment/Screening only (if for recruitment, the questions in the box below will apply to 
recruitment activities only) 
☐ Entire Study (Note that an information sheet may be required.) 
 
 
  
  ☒ Requesting a waiver of consent: 
☒ Recruitment/Screening only (if for recruitment, the questions in the box below will apply to 
recruitment activities only) 
☐ Entire Study   
 
 For a waiver of signed consent, address the following: 
• Would the signed consent form be the only record linking the subject and the research?  YES ☐  NO ☐  
• Does a breach of confidentiality constitute the principal risk to subjects? YES ☐  NO ☐ 
  
 OR 
• Does the research pose greater than minimal risk? YES ☐    NO☒  
• Does the research include any activities that would require signed consent in a non-research context? YES ☐   
NO ☒ 

Page 12 of 16 
 
 
 
 
 
 
 
 
 
 
SECTION IV: PROTECTION OF RESEARCH SUBJECTS 
 
    Confidentiality & Security of Data: 
1. What protected health information (medical information along with the HIPAA identifiers) about subjects will 
be collected and used for the research?   We will collect names and demographic information. Identifiable 
information will be collected and used to enroll and contact participants. It will only be used for this 
purpose. This information will be stored in locked cabinet apart from the research records. 
 
2. How will the research data be collected, recorded and stored? Research data will be collected using in-
person interviews, survey assessments, objective measures of smoking behavior, and self-reports. 
All identifiable information (names and demographic information) will be stored in a locked file cabinet. 
All participants will be assigned a study participant ID made up of numbers and letters. Subsequently, 
participants will be identified in the Case Report Forms (CRFs) only by that number (e.g., CM24). A 
list of IDs and the corresponding names will be maintained by the Principal Investigator and stored in 
a locked research cabinet. All other research data (interviews, survey assessments, objective 
measures of smoking behavior, and self-reports) will not contain identifiable information and will be 
labeled only with the subjects’ unique numerical indicator.  
 
3. How will the digital data be stored? ☐CD  ☐DVD  ☐Flash Drive  ☐Portable Hard  Drive   ☒Secured Server  
☐Laptop Computer  ☒Desktop Computer  ☐Other 
 
Digital data with PHI will be stored on a secured server. Digital data without PHI may be stored and 
analyzed on a laptop or desktop computer. 
 
4. What methods and procedures will be used to safeguard the confidentiality and security of the identifiable 
study data and the storage media indicated above during and after the subject’s participation in the study?  
 
Several steps will be taken to safeguard the confidentiality of subjects and their data. Right to privacy 
for participation in this research will be protected through coding of data and proper storage of 
For a full waiver of consent, please address all of the following: 
• 
Does the research pose greater than minimal risk to subjects?   
☐ Yes If you answered yes, stop. A waiver cannot be granted.   
☒ No 
• 
Will the waiver adversely affect subjects’ rights and welfare? YES ☐    NO☒ 
• 
Why would the research be impracticable to conduct without the waiver? We request a waiver of 
signed authorization only for initial participant recruitment/screening purposes to obtain 
interested participants’ phone numbers and/or email for voice and text communication to make 
initial contact with the research team.  
• 
Where appropriate, how will pertinent information be returned to, or shared with subjects at a later date? 
At the first phone contact with the research team, participants will provide verbal consent for the 
screening process. Participants who meet initial eligibility during the screening process will be 
invited for an in-person meeting to learn more about the study, ask any questions, and provide 
written informed consent before beginning research activities. 

Page 13 of 16 
 
research records. All research data that is collected will be assigned a study participant number and 
that number will be the only link between participant names/identifying information and the digital 
databases. The names of participants will not be associated with this data and assessments will be 
maintained according to participant study number. A master list connecting participant study numbers 
to participant names will be kept in a locked file cabinet where it can only be accessed by senior level 
project staff. Any information published as a result of the study will be in aggregate and such that it 
will not permit identification of any participant. 
 
We are not directly assessing incidents of child abuse or elderly abuse. However, if this information 
is disclosed by a participant or volunteer in the context of this research, a report will be made to the 
Department of Child and Families Services or other agency as required by law. Subjects will be 
informed of this limit to confidentiality as it is stated in the informed consent document. 
 
All investigators and key personnel have taken the required Yale University HIPAA training. Right to 
privacy for participation in this research will be protected through coding of data and proper storage 
of research records. A list of numbers and the corresponding names will be maintained by the 
Principal Investigator in a locked research cabinet.   
 
Individually identifiable health information will be protected in accordance with the Health Insurance 
Portability and Accountability Act of 1996 and by additional protections of substance abuse treatment 
records afforded under Code of Federal Regulations (CFR) Part 2, Subpart E. All research personnel 
will be trained on human subjects protection and HIPAA procedures. 
 
All portable devices must contain encryption software, per University Policy 5100.  If there is a technical reason a 
device cannot be encrypted please submit an exception request to the Information Security, Policy and Compliance 
Office by clicking on url http://its.yale.edu/egrc or email it.compliance@yale.edu 
 
5. What will be done with the data when the research is completed? Are there plans to destroy the identifiable 
data? If yes, describe how, by whom and when identifiers will be destroyed. If no, describe how the data and/or 
identifiers will be secured. The data will be stored in a locked room for 7 years after the final data is 
collected. After this point, the Data Manager and Principal Investigator will oversee the process in 
which data is destroyed or de-identified. 
 
6. If appropriate, has a Certificate of Confidentiality been obtained?  
 
A certificate will not be requested. 
 
SECTION V: POTENTIAL BENEFITS 
 
 
Potential Benefits: Identify any benefits that may be reasonably expected to result from the research, either to 
the subject(s) or to society at large. (Payment of subjects is not considered a benefit in this context of the risk 
benefit assessment.)  
 
There is a need to understand menthol cigarette use, given the high rates of use among cigarette 
smokers and negative impact on morbidity and mortality. The purpose of this study is to evaluate 
whether switching menthol smokers to non-menthol cigarettes reduces the subjective reward of 
smoking and reduces smoking behavior and nicotine dependence. This study may help to inform 
federal policy regulations by the FDA to restrict menthol additives in tobacco products and reduce the 
appeal and addictive potential of these products.  

Page 14 of 16 
 
 
         SECTION VI: RESEARCH ALTERNATIVES AND ECONOMIC CONSIDERATIONS 
 
1. Alternatives: What other alternatives are available to the study subjects outside of the research?  
 
This is not a treatment study. Anyone interested in quitting smoking will be provided with a 
treatment referral and will not be eligible to participate in this study. All participants will receive 
information about available smoking cessation services at the end of the study.  
 
2. Payments for Participation (Economic Considerations): Describe any payments that will be made to subjects, 
the amount and schedule of payments, and the conditions for receiving this compensation. 
 
Participants will be compensated $40 for the baseline intake appointment and will receive $25 for 
each subsequent study visit (days 0-21) reach a maximum of $140 for study visits. Participants will 
be incentivized to provide adherence measures and will earn additional weekly compensation (e.g., 
completing self-report assessments ($10/week), and returning spent cigarette filters ($10/week)). 
Total maximum compensation for completing study tasks including bonuses: $300.  
 
3. Costs for Participation (Economic Considerations): Clearly describe the subject’s costs associated with 
participation in the research, and the interventions or procedures of the study that will be provided at no cost 
to subjects.  
 
There are no costs for participation. 
4. In Case of Injury: This section is required for any research involving more than minimal risk, and for minimal 
risk research that presents the potential for physical harm (e.g., research involving blood draws). 
 
a. Will medical treatment be available if research-related injury occurs? Write here 
b. Where and from whom may treatment be obtained? Write here 
c. Are there any limits to the treatment being provided? Write here 
d. Who will pay for this treatment? Write here 
e. How will the medical treatment be accessed by subjects? Write here 
 
(a-e) If a participant is injured as a direct result of participation in this study, treatment will be provided. 
The participant and/or his or her insurance carrier will be expected to pay the costs of this treatment. 
No additional financial compensation for injury or lost wages is available.  Participants will not waive 
their legal rights by participating in this study. 
 
IMPORTANT REMINDERS 
 
Will this study have a billable service?  Yes ☐  
 No☒ 
 
A billable service is defined as any service rendered to a study subject that, if he/she was not on a study, would 
normally generate a bill from either Yale-New Haven Hospital or Yale Medical Group to the patient or the patient’s 
insurer. The service may or may not be performed by the research staff on your study, but may be provided by 
professionals within either Yale-New Haven Hospital or Yale Medical Group (examples include x-rays, MRIs, CT 
scans, specimens sent to central labs, or specimens sent to pathology). Notes: 1. There is no distinction made 
whether the service is paid for by the subject or their insurance (Standard of Care) or by the study’s funding 

Page 15 of 16 
 
mechanism (Research Sponsored). 2. This generally includes new services or orders placed in EPIC for research 
subjects.  
 
If answered, “yes”, this study will need to be set up in OnCore, Yale’s clinical research management system, for Epic 
to appropriately route research related charges. Please contact oncore.support@yale.edu 
 
Are there any procedures involved in this protocol that will be performed at YNHH or one of its affiliated entities?  
Yes ☐  No ☒  
 
If Yes, please answer questions a through c and note instructions below.   
a. Does your YNHH privilege delineation currently include the specific procedure that you will perform? Yes ☐  No 
☐ 
b. Will you be using any new equipment or equipment that you have not used in the past for this procedure? Yes 
☐  No ☐ 
c. Will a novel approach using existing equipment be applied? Yes ☐  No ☐ 
  
If you answered “no” to question 4a, or "yes" to question 4b or c, please contact the YNHH Department of 
Physician Services (688-2615) for prior approval before commencing with your research protocol. 
 
IMPORTANT REMINDER ABOUT RESEARCH AT YNHH  
Please note that if this protocol includes Yale-New Haven Hospital patients, including patients at the HRU, the 
Principal Investigator and any co-investigators who are physicians or mid-level practitioners (includes PAs, APRNs, 
psychologists and speech pathologists) who may have direct patient contact with patients on YNHH premises 
must have medical staff appointment and appropriate clinical privileges at YNHH. If you are uncertain whether 
the study personnel meet the criteria, please telephone the Physician Services Department at 203-688-2615. By 
submitting this protocol as a PI, you attest that you and any co-investigator who may have patient contact has a 
medical staff appointment and appropriate clinical privileges at YNHH. 
 
 
 
1. 
SAMHSA. The NSDUH Report: Recent Trends in Menthol Cigarette Use. Center for Behavioral 
Health Statistics and Quality2011. 
2. 
Agaku IT, King BA, Husten CG, et al. Tobacco product use among adults—United States, 2012–
2013. MMWR. Morbidity and mortality weekly report. 2014;63(25):542-547. 
3. 
Vozoris NT. Mentholated cigarettes and cardiovascular and pulmonary diseases: a population-
based study. Arch Intern Med. 2012;172(7):590-593. 
4. 
Smith SS, Fiore MC, Baker TB. Smoking cessation in smokers who smoke menthol and non‐
menthol cigarettes. Addiction. 2014;109(12):2107-2117. 
5. 
Delnevo CD, Gundersen DA, Hrywna M, Echeverria SE, Steinberg MB. Smoking-cessation 
prevalence among US smokers of menthol versus non-menthol cigarettes. Am J Prev Med. 
2011;41(4):357-365. 
6. 
Ahijevych K, Garrett BE. The role of menthol in cigarettes as a reinforcer of smoking behavior. 
Nic Tob Res. 2010;12:S110-S116. 
7. 
Azagba S, Minaker LM, Sharaf MF, Hammond D, Manske S. Smoking intensity and intent to 
continue smoking among menthol and non-menthol adolescent smokers in Canada. Cancer 
Causes & Control. 2014;25(9):1093-1099. 

Page 16 of 16 
 
8. 
Donny EC, Denlinger RL, Tidey JW, et al. Randomized trial of reduced-nicotine standards for 
cigarettes. N Engl J Med. 2015;373(14):1340-1349. 
9. 
Heatherton TF, Kozlowski LT, Frecker RC, FAGERSTROM KO. The Fagerström test for 
nicotine dependence: a revision of the Fagerstrom Tolerance Questionnaire. British journal of 
addiction. 1991;86(9):1119-1127. 
10. 
Baker TB, Piper ME, McCarthy DE, et al. Time to first cigarette in the morning as an index of 
ability to quit smoking: implications for nicotine dependence. Nic Tob Res. 2007;9(Suppl 
4):S555-S570. 
11. 
Piper ME, Piasecki TM, Federman EB, et al. A multiple motives approach to tobacco 
dependence: the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68). Journal of 
consulting and clinical psychology. 2004;72(2):139. 
12. 
Smith SS, Piper ME, Bolt DM, et al. Development of the brief Wisconsin inventory of smoking 
dependence motives. Nic Tob Res. 2010;12(5):489-499. 
13. 
Toll BA, Katulak NA, McKee SA. Investigating the factor structure of the Questionnaire on 
Smoking Urges-Brief (QSU-Brief). Addict Behav. 2006;31(7):1231-1239. 
14. 
Welsch SK, Smith SS, Wetter DW, Jorenby DE, Fiore MC, Baker TB. Development and 
validation of the Wisconsin Smoking Withdrawal Scale. Exp Clin Psychopharmacol. 
1999;7(4):354. 
15. 
Mercincavage M, Souprountchouk V, Tang KZ, et al. A randomized controlled trial of 
progressively reduced nicotine content cigarettes on smoking behaviors, biomarkers of exposure, 
and subjective ratings. Cancer Epidemiology Biomarkers & Prevention. 2016:cebp. 1088.2015.