Protocol Submission

Protocol Submission.pdf

Experimental Study on the Public Display of Lists of Harmful and Potential Harmful Tobacco Constituents

Protocol Submission

OMB: 0910-0736

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Attachment 2

Form RIHSC-EXPD
APPLICATION FOR AN EXPEDITED RIHSC REVIEW OF RESEARCH
FDA Research Involving Human Subjects Committee
Sponsoring Office/Center: Center for Tobacco Products / Office of Science (Laura Shay, PhD, RN)
Principal Investigator: Jon Blitstein, PhD of contractor RTI (subcontracted to “Research Now”)
Protocol/Project Title: Experimental Study on the Presentation of Harmful and Potentially Harmful
Tobacco Constituents
INSTRUCTIONS: Please read Section 1, Applicability, below. If you feel your research could possibly be reviewed using
an expedited review procedure, then go on complete the checklist in Section 2 and sign page 2.

Section 1. Applicability
____________________________________________________________________________________
(A) Research activities that (1) present no more than minimal risk to human subjects, and (2) involve only
procedures listed in one or more of the categories in Section 2 below, may POSSIBLY be reviewed by the
RIHSC through the expedited review procedure. Any activity listed in Section 2 should not be deemed to be of
minimal risk simply because it is included on the list. Inclusion merely means that the activity is eligible for
review through the expedited review procedure when the specific circumstances of the proposed research
involve no more than minimal risk to human subjects.
(B) The categories in Section 2 apply regardless of the age of subjects, except as noted. Children are defined
in the HHS regulations as persons who have not attained the legal age for consent to treatments or procedures
involved in the research, under the applicable law of the jurisdiction in which the research will be conducted.''
45 CFR 46.402(a).
(C) The expedited review procedure may not be used where identification of the subjects and/or their
responses would reasonably place them at risk of criminal or civil liability or be damaging to the subjects'
financial standing, employability, insurability, reputation, or be stigmatizing, unless reasonable and appropriate
protections will be implemented so that risks related to invasion of privacy and breach of confidentiality are no
greater than minimal.
(D) The expedited review procedure may not be used for classified research involving human subjects.
(E) The standard requirements for informed consent (or its waiver, alteration, or exception) apply regardless of
the type of review expedited or convened utilized by the RIHSC.
Section 2. CHECK LIST FOR RESEARCH ACTIVITIES WHICH MAY BE REVIEWED THROUGH
EXPEDITED REVIEW PROCEDURES

_____________________________________________________________________
Minimal risk = the risks of harm anticipated in the proposed research are not greater, considering probability
and magnitude, than those ordinarily encountered in daily life or during the performance of routine physical or
psychological examinations or tests.
Yes
X

No
Can this study be classified as minimal risk, based on the definition above?
If yes, continue to questions on page 2. If no, project/protocol will require full board review.

By signing below, I assure that the information is accurate:
SIGNATURE (Center/Office Liaison)______Susan Rudy, MSN, CRNP /s/______DATE
_____7/10/2012______

Indicate which of these categories apply to your study/project/protocol (more than one may apply)
Once you have completed the checklist on this page, please sign and submit this form with the materials indicated.
_____________________________________________________________________________________________________________
THE FOLLOWING 9 CATEGORIES PERTAIN TO BOTH
INITIAL AND CONTINUING IRB REVIEW
Yes No
X Research on drugs for which an investigational new drug
application (21 CFR Part 312) is not required. (Note: Research
on marketed drugs that significantly increases the risks or
decreases the acceptability of the risks associated with the use
of the product is not eligible for expedited review.)
Yes No
X Research on medical devices for which (I) an
investigational device exemption application (21 CFR Part 812)
is not required; or (ii) the medical device is cleared/approved for
marketing and the medical device is being used in accordance
with its cleared/approved labeling.

electroencephalography, thermography, detection of naturally
occurring radioactivity, electroretinography, ultrasound,
diagnostic infrared imaging, doppler blood flow, and
echocardiography; (e) moderate exercise, muscular strength
testing, body composition assessment, and flexibility testing
where appropriate given the age, weight, and health of the
individual.
Yes No
X Research involving materials (data, documents, records,
or specimens) that have been collected or will be collected
solely for non-research purposes (such as medical treatment or
diagnosis). (Note: Some research in this category may be
exempt from the HHS regulations for the protection of human
subjects. 45 CFR 46.101(b)(4). This listing refers only to
research that is not exempt.)

Yes No
X Collection of blood samples by finger stick, heel stick,
ear stick, or venipuncture as follows (Circle a or b, whichever
applies):
(a) From healthy, non-pregnant adults who weigh at least 110
pounds. For these subjects, the amounts drawn may not
exceed 550 ml in an 8 week period and collection may not
occur more frequently than 2 times per week; or
(b) from other adults and children, considering the age,
weight, and health of the subjects, the collection procedure, the
amount of blood to be collected, the frequency with which it will
be collected. For these subjects, the amount drawn may not
exceed the lesser of 50 ml or 3 ml per kg in an 8 week period
and collection may not occur more frequently than 2 times per
week.

Yes No
X Collection of data from voice, video, digital, or image
recordings made for research purposes.

Yes No
X Prospective collection of biological specimens for
research purposes by noninvasive means. Examples: (a) hair
and nail clippings in a nondisfiguring manner; (b) deciduous
teeth at time of exfoliation or if routine patient care indicates a
need for extraction; (c) permanent teeth if routine patient care
indicates a need for extraction; (d) excreta and external
secretions (including sweat); (e) uncannulated saliva collected
either in an unstimulated fashion or stimulated by chewing
gumbase or wax or by applying a dilute citric solution to the
tongue; (f) placenta removed at delivery; (g) amniotic fluid
obtained at the time of rupture of the membrane prior to or
during labor; (h) supra- and subgingival dental plaque and
calculus, provided the collection procedure is not more invasive
than routine prophylactic scaling of the teeth and the
process is accomplished in accordance with accepted
prophylactic techniques; (I) mucosal and skin cells collected by
buccal scraping or swab, skin swab, or mouth washings; (j)
sputum collected after saline mist nebulization.

Yes No
X Research on individual or group behavior or
characteristics of individuals, such as studies of perception,
cognition, game theory, or test development, where the
investigator does not manipulate subjects behavior and the
research will not involve stress to subjects.

Yes No
X Collection of data through noninvasive procedures (not
involving general anesthesia or sedation) routinely employed in
clinical practice, excluding procedures involving x-rays or
microwaves. Where medical devices are employed, they must
be cleared/approved for marketing. (Studies intended to
evaluate the safety and effectiveness of the medical device are
not generally eligible for expedited review, including studies of
cleared medical devices for new indications.) Examples: (a)
physical sensors that are applied either to the surface of the
body or at a distance and do not involve input of significant
amounts of energy into the subject or an invasion of the
subject's privacy; (b) weighing or testing sensory acuity; (c)
magnetic resonance imaging; (d) electrocardiography,

Yes No
X
Research on individual or group characteristics or
behavior (including, but not limited to, research on perception,
cognition, motivation, identity, language, communication,
cultural beliefs or practices, and social behavior) or research
employing survey, interview, oral history, focus group, program
evaluation, human factors evaluation, or quality assurance
methodologies. (Note: Some research in this category may be
exempt from the HHS regulations for the protection of human
subjects. 45 CFR 46.101(b)(2) and (b)(3). This listing refers only
to research that is not exempt.)

THE LAST 2 CATEGORIES PERTAIN TO CONTINUING
REVIEW ONLY
Yes No
Continuing review of research previously approved
by the convened IRB as follows (Circle a, b, or c, whichever
applies):
(a) Where (I) the research is permanently closed to the
enrollment of new subjects; (ii) all subjects have completed all
research-related interventions; and (iii) the research remains
active only for long-term follow-up of subjects; or
(b) Where no subjects have been enrolled and no additional
risks have been identified; or
(c) Where the remaining research activities are limited to data
analysis.
Yes No
Continuing review of research, not conducted under
an investigational new drug application or investigational device
exemption where categories two (2) through eight (8) do not
apply but the IRB has determined and documented at a
convened meeting that the research involves no greater than
minimal risk and no additional risks have been identified.

SIGNATURE (Center/Office Liaison)________Susan Rudy, MSN, CRNP /s/___________DATE ___7/10/2012________

Transmittal Memorandum
TO:

Chair, Research Involving Human Subjects Committee

From:

Susan Rudy, MSN, CRNP, CORLN
CTP Center/Office RIHSC Liaison

Date:

July 11, 2012

Protocol Title: Experimental Study on the Presentation of Harmful and Potentially Harmful
Tobacco Constituents
Principal Investigator: Contracted to “RTI” and Subcontracted to “Research Now”
FDA Sponsor (if PI is not from FDA): Laura E. Shay, PhD, RN
New Submission [ X ] Resubmission [ ] Amendment [ ] Continuing Review [ ]
RIHSC Protocol #_____________________(to be filled in by RIHSC Office if new submission)
By signing below, I assure that:
A. For protocols applying for RIHSC review:
1. The protocol/concept, as submitted, has undergone scientific review for technical
merit and programmatic relevance by my Center/Office and has been approved by the
Center Director/Office Director or designee.
2. The principal investigators are qualified to do the research.
3. The FDA sponsor has completed the required training in human subjects protection
and understands his/her obligations under the regulations and is qualified to provide
adequate oversight of this protocol.
4. The potential risks to the subjects are appropriate for the potential benefits.
5. The informed consent document conveys the risks and benefits in a clear,
scientifically accurate and balanced manner.
6. The completed submission form (Form RIHSC-PROT) or continuing review form
(Form RIHSC-CR) and, if appropriate, the request for expedited review form (Form
RIHSC-EXPD) and supporting information are accurate and have been attached.
7. An IDE/IND ____is___X____is not required.
B. For protocols requesting exemption from RIHSC review:
1. The protocol has undergone scientific review for technical merit and programmatic
relevance by my Center/Office and has been approved by the Center Director/Office
Director or designee
2. The completed exemption form (Form RIHSC-EXT) and supporting information are
accurate, and have been attached.
_Susan Rudy, MSN, CRNP /s/
Signature of Center /Office Liaison

7/11/2012
Date

See Addendum Attached

ADDENDUM to Transmittal Memo: Shay HPHC Experimental Study
Protocol Title: Experimental Study on the Presentation of Harmful and Potentially Harmful
Tobacco Constituents
FDA Sponsor: Laura E. Shay, PhD, RN
Request: Expedited Review (Minimal Risk study)
Reason for Addendum

The CTP RIHSC Liaison review of this protocol was limited to human subjects protections
issues and identified the need for clarifications. Because the submitted protocol is concurrently
under review with OMB under the Paperwork Reduction Act and because CTP is mandated to do
this study by section 904(d)(1) of the Food Drug and Cosmetics Act as amended by the Tobacco
Control Act (Public Law 111-31) with an imminent statutory deadline, we provide the Sponsor’s
responses to the identified issues in this cover memo addendum, rather than in a revised or
amended protocol.
Executive Summary
This protocol is for an experimental study designed to inform CTP’s decisions about how to
implement section 904(d)(1) of the Family Smoking Prevention and Tobacco Control Acto and
to provide information about how consumers understand information about harmful and
potentially harmful constituents in tobacco products. The Sponsor proposes an on-line 30-minute
survey of 3,150 participants aged 13 and over. Subjects are current tobacco users and minors
who are at risk for becoming tobacco users. Subjects are recruited from a pre-existing panel of
members of an online marketing research company, “Research Now,” who have supplied
identified demographics, interests and activities data upon joining the pre-existing registry.
Recruitment is accomplished by sending a general email to potentially eligible members, which
identifies the topic of the survey, but not the reason the recipient has been selected for invitation.
Minors are recruited only through their parents who are also members of the registry and are
enrolled only after parental consent, then minor assent. Survey data specific to this study is
collected after electronic informed consent, followed by screening questions to confirm
eligibility. Collected survey data is irreversibly unlinked from the respondent at the time of
collection. Subjects are rewarded in “e-Rewards” points “currency,” equivalent to $7.50.
There is an executed contract in place with Research Triangle Institute (“RTI”), Jon Blitstein,
Ph.D., PI, for conduct of the study, and RTI has subcontracted with “Research Now.” The RTI
IRB is also reviewing and overseeing the study.
This research is not exempt because it involves vulnerable subjects (minors). After considerable
interaction between the CTP_RIHSC and the Sponsor, we recommend this research for
expedited review and believe that it involves no greater than minimal risk under 45 CFR 46.404.
Informed consent complies with 45 CFR 46.117(c) and 45 CFR 46.408.

Review Interaction Summary Log
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Protocol submitted to CTP_RIHSC on 5/4/2012 (This was our first CTP_RIHSC
submission).
Review assigned to S. Rudy, CTP RIHSC Liaison alternate, by I. Chen, Clinical Team
Leader on 5/30/2012 (in RIHSC Liaison, Dr. Lacorte’s absence).
CTP RIHSC Liaison alternate, Susan Rudy, CRNP, met with the Sponsor, Laura Shay, on
5/31/2012 for clarifications.
S. Rudy sent a formal e-mail request to Sponsor for additional information and
clarifications on 6/1/2012
Sponsor submitted responses by email to S. Rudy on 6/5/2012
S. Rudy sent additional follow-up queries to Greta Tessman, MA, covering for Sponsor
on vacation, on 6/8/2012
I. Chen, Clinical Team Leader, informed Sponsor and Social Sciences team of new CTP
form documenting team / office / center sign-off for scientific and technical merit.
There was a meeting of the social sciences team (Choiniere, Tessman, & Johnson) with
the CTP_RIHSC team (Chen & Rudy) on 6/11 for clarifications (see separate minutes).
S. Rudy met with G. Tessman (covering for Sponsor) briefly, at her request, on 6/19/2012
to discuss data storage (contractors will erase data after passing to next entity) and the
issue of personally identifiable information (PII) (none is collected in the Agency survey
or received by CTP, documents are being rectified and clarified on this point)
The Sponsor submitted responses to our 6/8 AI request on 6/29/2012
S. Rudy met with the Sponsor on 7/2/2012 for additional clarifications
There was additional email discussion between S. Rudy and the Sponsor 7/3-7/9 to
clarify how data is collected such that PII is never linked initially and is never able to be
linked intentionally or unintentionally.
S. Rudy sent second request to Sponsor 7/10/2012 requesting signed memo of CTP
Center sign-off for scientific & technical merit.
Complete package submitted to FDA RIHSC by S. Rudy on 7/12/2012 (OMB / PRA
approval still pending).

Sponsor Qualifications
The Sponsor is a full-time FDA / CTP / OS employee, qualified by formal academic training
(PhD in Nursing), experience within CTP, and completion of specific training in Human Subject
Research Protections on 5/3/2011, expiration 4/20/2014, as offered by the CITI Social and
Behavioral Science Course.

Equitable selection of subjects
This study includes minors aged 13 and older as well as adults, with no upper age limit. We have
knowledge from clinical practice and published sources that children younger than age 13
participate in both experimentation with tobacco and regular tobacco use. The Sponsor explained
that the reason for not sampling children younger than age 13, is that they would not likely be
able to independently and reliably complete an online survey of this nature without parental
supervision and assistance. It is not feasible within the mandated timeline and budget to sample
younger children outside of this online survey contract mechanism.
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As an online survey, only people with access to the internet will be sampled and those without
access are excluded. With computers being present in schools, workplaces, and public arenas
such as libraries, and internet cafés, the majority of the U.S. population has access, whether or
not they are skilled or inclined to use computers. Smartphones have additionally increased
access. A recent study of 1620 people from low-income adult Supplemental Nutrition
Assistance Program Education participants in the Midwest found that approximately 50% had a
working computer in their home (Neuenschwander, Abbott, & Mobley, 2012). While the
proposed sampling schema may somewhat limit access to lower socioeconomic and elderly
participants, it stands a reasonable chance to obtain a representative sample and it is not feasible
within the mandated timeline and budget to sample additional strata of the population outside of
this online survey contract mechanism.
The study bears no upper age limit for participation and as written makes no requirement for
assuring that any elderly subjects will participate. The sampling schema is consistent with the
CTP mission, which is weighted toward prevention of smoking initiation and promotion of early
cessation. Elderly persons do own and use computers and are members of e-Rewards, available
for sampling, and thus the sampling schema bears a reasonable chance to obtain a representative
sample, including the elderly. It is not feasible within the mandated timeline and budget to
sample additional strata of the population outside of this online survey contract mechanism. In
addition, there is an adequate body of published work on issues of particular concern for product
labeling in the elderly, such as font size and style, contrast, and layout, as summarized by Rudy
(2008).
The age range of the e-Reward panel is 13-85 and above. The percentages of age ranges are
listed in the table below. Note that the HPHC information will eventually be publically available
on the FDA website. The likelihood that elders without computer access will seek out this
information is low. The on-line design of this study helps provide ecological validity of the user
population.
Age Range

Percent

13 - 14

0.12%

15 - 17

0.67%

18 - 24

9.53%

25 - 34

23.12%

35 - 44

20.78%

45 - 54

20.38%

55 - 64

17.11%

65 - 74

6.94%

75 - 84

1.15%

85 and above

0.11%

Not Provided

0.11%

References:
 Neuenschwander, L. M., Abbott, A., & Mobley, A. R., (2012). Assessment of lowincome adults’ access to technology; Implications for nutrition education. J Nutr Educ
Behav, 44(1), 60-65. DOI: 10.1016/jneb.2011.01.004
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Rudy, S. F. (2008). Editorial: Aging Eyes. ORL-Head and Neck Nursing, 26(1), 5-7.

Recruitment and rewards for vulnerable subjects
1. Justification for research on vulnerable subjects: This study includes a cohort of minors
aged 13 to 17 and asks sensitive questions about illegal and parentally disallowed
behavior of smoking cigarettes. The use of cigarettes below age 18 is illegal in some
states and the sale of cigarettes to minors is illegal in all states. The protocol adequately
justifies soliciting sensitive information from minors. Because the public display of the
harmful and potentially harmful constituent (HPHC) information will not be limited to
adults, it is important that CTP study youth’s reactions to this information.
2. The submitted protocol is unclear on how subjects are recruited and what the incentive
reward is.
All subjects are recruited via a subcontractor, Research Now, an online marketing
research company that manages an internet consumer panel called, “e-Rewards.” The
company independently recruits panels of potential respondents for many types of
marketing research based on internet responses to a broad range of questions on
demographics, interests and activities. A subpanel of potentially interested and applicable
respondents is then invited to participate in specific marketing research (such as the CTP
proposed study) as needs arise per contractual arrangements. Respondents who
participate in panels and subpanels are rewarded using a points system, so that no reward
is linked to participation in a particular study, except by a number of points rewarded for
completion of the study. Points earned for completing a study or for a cumulative number
of completed studies can then be traded by the participant for a variety of rewards, which
include clothing and accessories, food and dining, gifts, magazines, and travel and
lodging. The array of potential rewards does not include money. Completion of the ~30minute electronic survey, nets an e-Rewards “currency” of $7.50 which is nominal and
incidental.
Risks and Benefits
Privacy and confidentiality issues for respondents
The primary risk for subjects and the investigators / sponsor in this online questionnaire
study is the potential for inadvertent breach of privacy and confidentiality of the data.
The protocol includes physical data security, good information management practices and
computer processes for data security (e.g., password protections, access granted only per
need to know, encryption of transferred data) following DHHS and FDA regulations and
policies as well the Council of American Survey Research Organizations® Code of
Standards and Ethics for Survey Research. The protocol (p. 6) states that “data coming
directly from the survey engine are stored in a proprietary database. While this data is not
encrypted, once inside the firewall, they are stored in a relational database protected by
several layers of intrusion detection and access control.” We understand that stored data
should be encrypted and requested the Sponsor to provide additional information about
data security for this study.
The protocol states (p. 5) that personal information will not be shared with third parties
without the respondent’s permission “…unless it is required by law to protect their rights
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or to comply with judicial proceedings, court order, or other legal process.” However,
informed consent documents (Appendix A, p.1) state only that “no one will be able to
link your responses to your identity” and do not discuss any mechanism or situation
whereby personal information may be shared with a third party.
The privacy promise information that potential respondents see before agreeing to
participate and complete the survey is said in the protocol to be available from a
particular website link. However, on reviewer testing, the link was “broken” displaying a
message that the site is no longer functioning. We asked the Sponsor to provide the
functioning web link and / or the content of the privacy information the participants will
see.
In several rounds of follow-up communication and clarification the following acceptable
clarifications are submitted. Note that the Sponsor had follow-up communications with the
contractor, but the CTP_RIHSC reviewer had communications only from the Sponsor:
1. The functioning link to privacy information for participants is now
http://www.e-rewards.com/privacypolicy.do
See the privacy statement also as Attachment 1 to this memo and the member agreement
as Attachment 2 to this memo. The site does not seek to collect individually identifiable
information about children under 18 years of age.
2. E-Rewards participates in the TRUSTe Privacy Seal Program
http://www.truste.org/consumers/watchdog_complaint.php.
E-Rewards provides their physical address as well as electronic contact information to
participants.
3. The PII that is collected (i.e., name, address, internet protocol address, cookies and
advanced cookies) is never linked to the responses to this FDA / CTP survey by any
involved entity at any point in time, even briefly. The following protections are in place
to assure privacy and confidentiality:
a. The email invitation for survey participation issued to a subset of adult e-Rewards
members does identify that the survey pertains to tobacco products but does not
identify the recipient as a smoker and even if it did, this would not be sensitive
information for adult legal smokers.
b. The email invitation for survey participation issued to a subset of adult parents of
minors who are members of e-Rewards and are tobacco users or are at risk to become
tobacco users, identifies that the survey pertains to tobacco products, but states the
reason for the invitation to be only that a teenager is thought to reside in the
household. It does not state or insinuate that the teens are smokers.
c. E-mail invitations to participate in the survey are not issued directly to minors; they
are issued only to adult parents of minors, requiring parental consent before the child
can access the survey via their e-Rewards account.
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d. Survey computer coding never links the survey responses to the PII during the
informed consent process, survey response process or rewards process, and thus it is
impossible for e-Rewards technical computer staff, RTI staff, or FDA / CTP Sponsor
or OIM staff to connect survey responses to individuals, and likewise hackers would
be unable to connect survey responses to respondents.
e. The language aimed at participants in the e-Rewards privacy statement is clear that
PII is shared only in anonymous singular summary and aggregate form (both terms
are defined and explained) with site Sponsors, reward partners, panel partners,
marketing partners, clients (FDA / CTP is a client), and third parties for purposes of
marketing and research, with some exceptions. The detailed circumstances under
which PII may be shared comply with federal guidelines and standards (e.g., audits,
legal queries, etc.) and apply only to the ability to release that a person is a member of
e-Rewards. By their computer coding, it is impossible for any involved party to
identify what individuals were invited to participate in this FDA / CTP survey, as
well as which individuals accepted the invitation, or what specific responses they
gave. The demographic information received by RTI and FDA / CTP only includes
general, categorical measures of race/ethnicity, sex, education, income, occupation,
and city/state (optional). As defined by NIST 800-122 (2010) and OMB (March 22,
2010), this demographic information does not contain PII
(https://irb.llnl.gov/pdfs/SOP_14.pdf), http://csrc.nist.gov/publications/nistpubs/800122/sp800-122.pdf . The data received in FDA / CTP from e-Rewards is not able to
be linked back to the e-Rewards participant database.
4. Research Now (a.k.a. “e-Rewards”) encrypts the stored data. After sending the data to
RTI, they will delete it completely from storage. After data cleaning and analysis, RTI
will pass the raw data to FDA / CTP for storage and will destroy data files after
successful transmission. FDA / CTP will store data on its secure servers for at least 3
years. All involved parties comply with the standards and guidelines around data and
information systems and security outlined in NIST Special Publication 800-53. Per this
publication. “Special Publications (SPs) are developed and issued by NIST as
recommendations and guidance documents. For other than national security programs
and systems, federal agencies must follow those NIST Special Publications mandated in a
Federal Information Processing Standard. FIPS 200 [FIPS Publication 200, 2006]
mandates the use of Special Publication 800-53, as amended.”
The last edition of NIST Special Publication 800-53 was published in 2009 (Revision 3)
(http://csrc.nist.gov/publications/nistpubs/800-53-Rev3/sp800-53-rev3-final.pdf). The
data is categorized as “low” impact level.
RTI security professionals are experienced with all security documentation and processes
necessary to obtain an Authority to Operate, and with all applicable Department of Health
and Human Services (HHS), Federal Information Security Management Act, Health
Insurance Portability and Accountability Act, NIST, and other federal policies and
regulations that may apply. RTI project team members and security professionals will
ensure that all HHS-related technical and security standards, processes, and procedures
are followed.

5. The duration for retention of records by FDA / CTP will initially be 3 years beyond
completion of the study, pending further guidance from the CTP Office of Policy.

Informed consent
The submitted (5/4/2012) protocol contains no informed consent language aimed at parents of
participating minors, which does not comply with 45 CFR 46.408. The protocol states (p. 7) “ eRewards’ invitation to youth does encourage parents to know about and approve of youth
involvement in the panel and surveys. However, no active parental consent is required or
requested.” The Sponsor clarified verbally on 5/31/2012 that this content pertains to the broad
recruitment of youth for any and all studies offered through e-Rewards. We asked the Sponsor to
provide the consent language and process for the parents of minor participants in this specific
study.
The submitted protocol (5/4/2012) does not detail the informed consent process for any
participants and contains language (p. 6) that is unclear as to the timing of informed consent in
relationship to participant screening for the study. We asked the Sponsor for full details on
informed consent.
The FDA sponsor clarifies that the contractor “e-Rewards” collects a full set of demographic
information, along with a profile of interests and activities, as part of enrolling its huge database
of members along with a membership agreement. This process is pre-existing and completely
outside of the submitted study procedures. A small subset of the total “e-Rewards” membership
are invited to participate in the submitted study survey based on their demographics and
interests, known to e-Rewards but not to the contractor RTI or to the Sponsor, FDA / CTP.
Informed Consent Process
Eligible adults and parents of minors are sent a recruitment email if they have age and smoking
status eligibility per the pre-existing e-Rewards database. Minors are not recruited unless their
parents are also members of e-Rewards. The specific recruitment messages sent to adults and to
parents of minors is submitted 7/2/2012 in Attachments A & B, and includes the reason for the
message.
The informed consent process for minors:
Parents who agree that their child may wish to participate in the survey after reading the
recruitment e-mail, proceed by clicking on a hyperlink embedded in the recruitment email. This
hyperlink takes them to screens containing the informed consent language. They give parental
consent by clicking in the box next to “Yes, I agree to let my child participate in this study” at
the bottom of the informed consent screen. When parents thus give consent, this allows the
minor to access the survey when next signing on to their e-Rewards account (i.e., no recruitment
e-mail is ever sent to the minor). When the minor signs onto the survey, the first screen presented
is the “Youth Assent Form for Youth Recruited via Parent and Youth Panels.” The minor must
select “Yes, I agree to participate in this study” at the bottom of the page before they can access
the verification screening questions (e.g., age and smoking status). The verification question
responses must confirm their eligibility for taking the survey, and then they are granted access to
the survey questions.
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The informed consent process for adults:
Adults who wish to participate in the survey after reading the recruitment e-mail, proceed by
clicking on a hyperlink embedded in the recruitment email. This hyperlink takes them to screens
containing the informed consent language. When they consent by clicking a box indicating
consent, they are taken to screens containing two eligibility verification screening questions. If
their answers to these two screening questions verify their eligibility, they are next taken to the
survey content screens.

The informed consent language provided for adult participants (Attachment A, 7/2/2012 –
Replaces Appendix A in the 5/4/2012 protocol), Parents of minors (Attachment B submitted
7/2/2012) and minor assent language (Attachment B submitted 7/2/2012) roughly complies with
45 CFR 46.116 General requirements for informed consent. The minor exception is that there is
no study contact person named if the subject feels they are somehow harmed or injured by the
study (45 CFR 46(a) (7)), which is acceptable, since injury is not anticipated in this study and is
extremely unlikely to occur in an electronic survey. In addition, adults are not told how many
participants are in the study, which is optional under 45 CFR 46.116 (b) (6).
The permission of just one parent is acceptable for this research because it is minimal risk
research under 45 CFR 46.404.
There is no hard copy of such an online consent to be signed, witnessed and filed as required by
45 CFR 46.117. By reading the consent and clicking “accept,” then completing the survey
questions, the subject is consenting. This mechanism is standard in the industry of online
minimal risk surveys and has been used by CTP and previously approved by the FDA RIHSC
(e.g., RIHSC Protocol# 10-111TP). The lack of a written / signed informed consent document is
acceptable for this research under 45 CFR 46.117(c) because such a written informed consent
document would breach subject confidentiality and this is a minimal risk study.
The informed consents contain no exculpatory language.

DEPARTMENT OF HEALTH AND HUMAN SERVICES
_________________________________________________________________________________________________________
Food and Drug Administration
Center for Tobacco Products
9200 Corporate Boulevard
Rockville MD 20850-3229

Experimental Study on the Presentation of
Harmful and Potentially Harmful Tobacco Constituents
Laura E. Shay
Center for Tobacco Products
May 4, 2012
Introduction
The Tobacco Control Act (Public Law 111-31) amends the FD&C Act to grant FDA
authority to regulate the manufacture, marketing, and distribution of tobacco products to protect the
public health and to reduce tobacco use by minors. Section 904(d)(1) of the FD&C Act states, “Not
later than 3 years after the date of enactment of the Family Smoking Prevention and Tobacco
Control Act, and annually thereafter, the Secretary shall publish in a format that is understandable
and not misleading to a lay person, and place on public display (in a manner determined by the
Secretary) the list [of harmful or potentially harmful constituents] established under [section
904(e)]” of the Act. Section 904(e) of the FD&C Act directs FDA to establish “a list of harmful and
potentially harmful constituents, including smoke constituents, to health in each tobacco product by
brand, and by quantity in each brand and subbrand.” On January 31, 2011, FDA announced the
availability of a final guidance representing the Agency's current thinking on the meaning of the
term "harmful and potentially harmful constituent" (see 76 FR 5387). On April 3, 2012, FDA
published a notice in the Federal Register establishing a list of the harmful and potentially harmful
constituents (HPHCs) in tobacco products and tobacco smoke (see 77 FR 20034).
FDA’s Center for Tobacco Products requires data on how consumers may respond to
information about HPHCs in order to determine the appropriate format of the HPHC list provided to
the public.
Purpose and Use of the Information Collection
FDA’s Center for Tobacco Products will conduct an experimental study to help inform
decisions about how to implement section 904(d)(1) of the Act and to provide information about
how consumers understand information about HPHCs. The established list of HPHCs (see 77 FR
20034) contains complex scientific information that may be difficult for consumers to understand,
therefore making the information potentially misleading. Section 904(d)(1) requires a version of this
list be made available to the public. The Act states that this list must be “understood and not
misleading to a lay person.” The research goals are to evaluate the impact of different list formats
on the public’s ability to understand HPHC information, and to assess the potential impact on
consumer behavior from exposure to the list.
The impact of different list formats on comprehension will be evaluated by measuring
respondents’ understanding of the following concepts: (1) the chemicals come from the tobacco leaf
itself and from different parts of a tobacco product such as the tobacco smoke, glues, inks, paper,
and additives; (2) for smokeless products, many of the chemicals come from the tobacco leaf itself;
for smoked products, many of the chemicals come from burning the tobacco leaf; (3) tobacco

companies are required to test their tobacco products and smoke for the chemicals on the list and
report the amounts to the FDA; (4) science has linked the chemicals on these lists to health
problems or potential health problems; (5) these lists do not necessarily identify all of the health
problems that may be caused by the tobacco product; (6) these lists do not necessarily include all of
the chemicals in the tobacco product that may be harmful; (7) the amount of a chemical listed for a
specific tobacco product does not necessarily indicate the likelihood of experiencing a health
problem; (8) the number of chemicals listed for a specific tobacco product does not necessarily
indicate the likelihood of experiencing a health problem; (9) when a chemical is listed without a
quantity it may mean: the chemical was not detected or the information is not currently available.
The potential impact of different list formats on consumer behavior will be evaluated by
measuring the exposure to a list on susceptibility to initiation of tobacco use, motivation and
confidence to quit using tobacco, and risk perceptions about tobacco use.
Methods and Study Population
The respondent universe for the experimental study is (1) current adult smokers aged 25
years old and older, (2) young adult smokers aged 18 to 24 years old, (3) youth smokers aged 13 to
17 years old, (4) adult smokeless tobacco users aged 18 and older, and (5) youth age 13 to 17 years
old who may be susceptible to initiation of smoking. The five separate quota samples will be
selected from the e-Rewards online member panel, a national opt-in email list sample. Sampled
panel members will receive an email inviting them to participate in the study. Panel members who
choose to participate will complete the questionnaire (see Appendix A). Completed surveys will be
monitored to ensure samples are diverse in terms of age, gender, education, and ethnicity/race. We
estimate 3,150 respondents will complete a survey.
For the information collection, e-Rewards will send email invitations to the target audiences
using their market research panel. Each invitation will contain the survey title, the length of the
survey, incentive amount provided for successful completion of the survey, and instructions for
accessing the secure website for the survey. Once a panel member enters the secure web site, a brief
introduction will be presented informing the panel member of the confidential and voluntary nature
of the survey (see attached). Individuals who consent to participate in the survey will be able to
access the survey by clicking on the link to the survey URL. Respondents who access the
questionnaire will be randomly assigned to an experimental condition.
This experimental study will be conducted using an Internet panel and a questionnaire
designed to measure responses to the HPHC list formats and collect demographic and smoking
status information from the participant. Participants will be randomly assigned to an exposure or
control condition. Participants in the exposure condition will view one of 6 HPHC list formats (see
Appendix B) for a hypothetical brand of cigarettes, smokeless tobacco product, or roll-your-own
tobacco product. RTI will analyze information collected from the study, the results of which will
inform FDA’s implementation of a publicly displayed list of HPHCs by brand and subbrand as
required by the Tobacco Control Act.
The proposed design implements the experimental study with each of five target groups: (1)
current adult smokers aged 25 years old and older, (2) young adult smokers aged 18 to 24 years old,
(3) youth smokers aged 13 to 17 years old, (4) adult smokeless tobacco users aged 18 and older, and
(5) youth age 13 to 17 years old who may be susceptible to initiation of smoking. In the
2

experiment, we are testing 6 HPHC list formats and 1 control condition (no HPHC list seen) for
either a hypothetical cigarette, smokeless tobacco product, and roll-you own tobacco product for a
total of 63 cells. Half of the formats will contain additional written information and half will not
(see Appendix B), Each cell will contain 50 respondents for a total sample size of 3,150 (See Table
1).
Table 1
Product

Cigarettes

Population

Adult smoker (n=350)
Young adult smoker
(n=350)
Youth smoker (n=350)

Smokeless

RYO

Youth at risk for
initiation (n=350)
Adult smokeless
(n=350)
Youth smoker
(n=300)
Adult smoker (n=350)
Young adult smoker
(n=350)
Youth smoker (n=350)

N=3,150

Information

Present
Not present
Present
Not present
Present
Not present
Present
Not present
Present
Not present
Present
Not present
Present
Not present
Present
Not present
Present
Not present

Format 1
(Full List)
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
900

Format 2
(Tested/
not tested)
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
900

Format 3
(Tested only)

No List
(control)

50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
900

50
50
50
50
50
50
50
50
50
450

Summary of Protocol
Survey:


Survey screener – confirm eligibility.



Random assignment to treatment or control.



Treatment groups are exposed to one of 6 HPHC list formats for either a cigarette,
smokeless tobacco, or roll-your-own tobacco product; Control groups are not
exposed to a list.



Respondents answer questions while being exposed to a HPHC list. The questions
assess general comprehension about HPHCs in tobacco products. Additional
questions assess susceptibility to initiation of tobacco use (youth high risk nonsmokers), motivation and confidence to quit tobacco use, and risk perceptions about
tobacco use.

Measures
Key Outcomes


Comprehension - total correct responses to questions assessing the communication
objectives



Risk Perception
o Perceptions of harmfulness of the stimulus product (i.e. brand X cigarette)
o Perceptions of harmfulness of tobacco use



Unintended consequences
o Quit intentions
o Openness to smoking (youth)

Covariates:
Age, gender, race, SES (income and education), health literacy
Analysis plan
Primary analyses
1. Tests of treatment effects on comprehension:
Hypotheses 1: Exposure to the list of HPHCs will improve comprehension of
communication objectives, and thus treatment groups will have higher comprehension
scores relative to control groups.
Hypothesis 2: The presentation of supplemental information will improve
comprehension and thus treatment groups presented with information will have higher
comprehension scores relative to groups not presented with information.
2. Contrasts between treatment groups: comparison of list formats to ascertain relative
effectiveness.


For comprehension of communication objectives, contrasts will be made between
treatment groups (adjusted for multiple comparisons) to assess group differences in
understanding based on list format.

Secondary Analyses
3. Tests for group differences in risk perceptions, quit intentions and susceptibility to
initiation, based on list exposure and list format.
4. Test for moderating effects of product type and population: Tests for interaction effects
will be used to determine if the impact of list format on key outcomes differs by (a)
product type and (b) age group.
4

The sample design is adequately powered to test the primary research hypotheses:


Exposure to a list of HPHCs, with supplemental information, will result in better
comprehension of the communication objectives.

The experimental design includes three list format conditions (with and without additional
information) and a control group, with a total of 3,150 participants. Each list format condition (with
and without additional information) includes 900 participants, for a total of 2700 exposure
participants, and the control group includes 450 participants. Our primary test compares exposure
participants to control participants.
For the purpose of sample size calculations, the proportion of participants who comprehend
communication objectives will serve as the outcome. Our calculations assume comprehension is
assessed as a binary outcome. Data will be analyzed using a logistic regression model with no
covariates. Based on these assumptions, the test statistic will have 80% statistical power to observe
a difference of 8.2 percentage points or larger if the comprehension rate among the control group is
low (e.g., 50%). If the comprehension rate among the control group is higher (e.g., 75%), the test
statistic will have 80% statistical power to observe a difference of 6.7 percentage points or larger.
This power analysis also applies to examples of measures that employ Likert scale ratings, as these
measures will be dichotomized prior to analysis, e.g., assigning high ratings a value of 1 and low
ratings a value of 0. For outcomes based on a continuous measure, the sample design is powered to
detect statistically significant differences of 0.17 standard deviation units or greater. For a scale
with a range of 0 – 100, a mean value of 50, and a standard deviation of 15, the test will have 80%
statistical power can detect a significant difference between the exposure and control conditions of
2.55 points or greater.
Confidentiality
Assurance of Privacy Provided to Respondents
All data will be collected with an assurance that the respondents' answers will remain
confidential. The study instrument will contain a statement that responses will be kept Private.
Private information is protected from disclosure under the Freedom of Information Act (FOIA)
under sections 552(a) and (b) (5 U.S.C. 552(a) and (b)), and by part 20 of the agency’s regulations
(21 CFR part 20). Identifying information will not be included in the data files delivered by
contractors to the agency.
Privacy will be assured by using independent contractors, RTI and e-Rewards, to collect the
information, by enacting procedures to prevent unauthorized access to respondent data, and by
preventing the public disclosure of the responses of individual participants. The contractors will
only share data and/or information with FDA in an aggregated form or format, which does not
permit FDA to identify individual respondents.
Neither e-Rewards nor RTI will share personal information regarding panel members with
any third party without the participant’s permission unless it is required by law to protect their
rights or to comply with judicial proceedings, court order, or other legal process. Identifying
information will not be included in the data files delivered to the agency. FDA and RTI will receive
5

data for analysis in aggregate form. Although e-Rewards retains contact information on participants
for honoraria purposes, individually identifiable information is not shared with anyone, including
FDA and RTI; it is stored separately from the survey data file and is not linked in any way to
participant responses.
RTI maintains restricted access to all data preparation areas (i.e., receipt and coding). All
data files on multi-user systems will be under the control of a database manager, with access limited
to project staff on a “need-to-know” basis only. E-Rewards takes the following security measures
to ensure separation between respondents’ identity and their survey data. First, the survey
instrument has no personally identifying information (PII) on it. No respondent name, address,
email address, phone number or any other kind of PII appears on the survey. The only way a survey
is identified is with a digital identification number. Second, while the invitation method, whether
email, mail or direct mail will inherently have PII information included, this will not be combined
with survey responses, so the responses from the survey are not linked to the PII. Third, screener
data shall be considered part of the survey data. E-Rewards will provide the results of the screener
questions for all panelists, regardless of whether they qualify for the study. However, e-Rewards
will not retain responses to screening questions for those who are deemed ineligible for any other
purpose outside the scope of this project. Fourth, e-Rewards will retain study records for the
duration of the study. Upon final delivery of data files to RTI and completion of the project, eRewards will destroy all study records including data files upon request. E-Rewards will not be
able to supply or access this information for any reason, even at the request of RTI, once destroyed.
Finally, data coming directly from the survey engine are stored in a proprietary database. While this
data is not encrypted, once inside the firewall, they are stored in a relational database protected by
several layers of intrusion detection and access control. Data files delivered to RTI by e-Rewards
will be sent via encrypted files.
All electronic data will be maintained in a manner that is consistent with the Department of
Health and Human Services ADP Systems Security Policy as described in DHHS ADP Systems
Manual, Part 6, chapters 6-30 and 6-35. All data will also be maintained in consistency with the
FDA Privacy Act System of Records #09-10-0009 (Special Studies and Surveys on FDA Regulated
Products).
Justification for Sensitive Questions
The public display of the list of HPHC required under section 904(d)(1) is not restricted to
adults thus, it is important to understand youth responses to the HPHC information. In order to
identify those youth at risk of smoking or already smoking we need to ask the youth potentially
sensitive questions about tobacco use. These questions are potentially sensitive because tobacco use
among youth under 18 years of age is illegal in a few states and sales to youth under 18 years of age
is illegal in all states.
To alleviate any potential concern for the youth, we will take all necessary measures to
ensure privacy. Also, no personal identifying information will be attached to the data used for
analysis – e-Rewards keeps personal identifying information to invite youth to participate in surveys
but this information will not be shared with RTI (this restriction is stated in the sub-contract
between RTI and e-Rewards).

E-Rewards has a standing panel of youth ages 13-17 form which our sample will be
recruited. The u.talk.back® panel was created specifically to reach children aged 13-17 years old
directly, without parental involvement. The Federal law protecting children, Children's Online
Privacy Protection Act (COPPA), does not restrict this type of activity for children aged 13 years
old and older. No personally identifying information will be released, per the u.talk.back® member
and privacy agreements (http://www.utalkback.com/privacypolicy.do). In summary, e-Rewards’
activities for this study will be fully compliant not only with the Federal Law, but with the Council
of American Survey Research Organizations® (CASRO) Code of Standards and Ethics for Survey
Research, a tough, internationally-cited set of standards, which has long been the benchmark for the
industry.
E-Rewards’ invitation to youth does encourage parents to know about and approve of youth
involvement in the panel and surveys. However, no active parental consent is required or requested.
For this study, when the youth are invited to join our specific survey, both parental consent and
youth assent will be requested and required. In the invitation for our specific study it will be
emphasized that youth responses are strictly confidential and that youth will be instructed to NOT
take the survey under their parents’ supervision nor to share their answers or opinions with their
parents. We will emphasize to the youth and parents that will want to encourage honest responses to
the questions so that we can measure a valid youth response to the HPHC list formats.
Questionnaire
See Appendix A
Test Stimuli
See Appendix B

Appendix A
Questionnaire
Intro1
[DISPLAY FOR ADULTS]
This study is funded by the U.S. Food and Drug Administration’s (FDA’s) Center for Tobacco
Products (CTP) and conducted by RTI International. This survey asks you about your smoking
habits and your opinions about tobacco products. Your participation in this research study is
completely voluntary, and you may skip any questions you do not want to answer. No one will
be able to link your responses to your identity. This survey will take about 20 minutes to
complete.
If you have any questions about this study, you may call Katherine Kosa of RTI at
1-800-334-8571, extension 23901. If you have any questions about your rights as a study
participant, you may call RTI’s Office of Research Protection at 1-866-214-2043
Intro2
[DISPLAY FOR YOUTH]
This study is funded by the U.S. Food and Drug Administration’s (FDA’s) Center for Tobacco
Products (CTP) and conducted by RTI International. This survey asks teenagers what they think
about cigarette smoking and other tobacco products. About 1,700 teenagers will complete this
survey. This survey will take about 20 minutes to complete.
Your participation in this research study is completely up to you. As part of the survey, you will
view some information related to cigarette smoking and other tobacco products. You’ve probably
read similar information online or in health class. The survey asks questions about your
experiences and thoughts regarding cigarette smoking. You may skip any questions you do not
want to answer. During the survey, we do not ask for your name; therefore, your name will not
be connected to your answers. Additionally, we will not share any information you provide in the
survey with anyone outside the research team, including your parents.
To ensure your answers are kept private, please complete the survey in a place where no one can
look over your shoulder and view your answers. Also, please complete the survey in one sitting
and close the screen when you are done taking the survey.
If you have any questions about the study, you may call Katherine Kosa of RTI at
1-800-334-8571, extension 23901. If you have any questions about your rights as a study
participant, you may call RTI’s Office of Research Protection at 1-866-214-2043.
S. Screening Questions
S1. What is your age? _______years old
[IF S1 < 13, NOT ELIGIBLE.]
S2. Have you ever smoked a cigarette, even one or two puffs? (Select one.)
1) Yes
2) No
1

S3. Do you use smokeless tobacco products, such as snuff, dip, or Snus…? (Select one.)
1) Every day
2) Some days
3) Rarely
4) Not at all
[IF 13 ≤ S1 < 18 AND S2 =2 AND S3=4, GO TO S5.]
[IF S2 =2 AND S3≠4 (SMOKELESS ONLY = YES), GO TO SECTION A.]
[IF S1 ≥ 18 AND S2 = 2 AND S3=4 NOT ELIGIBLE.]
S4. During the past 30 days, how many days did you smoke a cigarette? (Select one.)
1) 0 days
2) 1 or 2 days
3) 3 to 5 days
4) 6 to 9 days
5) 10 to 19 days
6) 20 to 29 days
7) All 30 days
[If S1 ≥ 18 AND S4 = 1 AND S3=4 NOT ELIGIBLE.]
[If S1 ≥ 18 AND S4 = 1 AND S3≠4 (SMOKELESS ONLY = YES), GO TO SECTION A.]
[If S1 ≥ 18 AND S4 ≠ 1 GO TO S8.]
[IF 13 ≤ S1 < 18 AND S4 ≠ 1 (CURRENT YOUTH SMOKER=YES) GO TO Section B.]
[IF 13 ≤ S1 < 18 AND S4 = 1 AND S3≠4 (SMOKELESS ONLY =YES) GO TO Section B.]
S5. Do you think you will smoke a cigarette at any time in the next year? (Select one.)
5) Definitely Not
6) Probably Not
7) Probably Yes
8) Definitely Yes
S6. Do you think in the future you might try a cigarette? (Select one.)
1) Definitely Not
2) Probably Not
3) Probably Yes
4) Definitely Yes
S7. If one of your best friends offered you a cigarette, would you smoke it? (Select one.)
1) Definitely Not
2) Probably Not
3) Probably Yes
4) Definitely Yes
[IF S5 = S6 = S7 = 2, 3, 4 (YOUTH SUSCEPTIBLE TO SMOKING = YES). IF S5 = S6 =
S7 = 1 NOT ELIGIBLE.]
2

S8. Have you smoked at least 100 cigarettes in your entire life?
1) Yes
2) No
[IF S1 ≥ 25 AND S8 = 1 (CURRENT ADULT SMOKER=YES). IF 18 ≤ S1 ≤ 24 AND S8 = 1
= 2 (YOUNG ADULT SMOKER=YES). IF S1 ≥ 25 AND S8 = 2 NOT ELIGIBLE.]
SECTION B: TOBACCO USE BEHAVIOR
[FOR B1-B3, EXCLUDE YOUTH SUSCEPTIBLE TO SMOKING AND SMOKELESS
ONLY.]
The next set of questions asks about your use and beliefs about tobacco.
B1. On average, in the past 30 days, about how many cigarettes did you smoke a day? (Select
one.)
1) Fewer than 5 cigarettes
2) 5-9 cigarettes
3) 10 cigarettes (1/2 a pack)
4) 11-19 cigarettes (more than 1/2 pack but less than 1 pack)
5) 20 cigarettes (1 pack) or more
B2. When you smoke, how often do you use hand-rolled or “roll-your-own” cigarettes? (Select
one.)
1) Never
2) Rarely when I smoke
3) Sometimes when I smoke
4) Often when I smoke
5) Always when I smoke
B3. On the days that you smoke, how soon after you wake up do you have your first cigarette?
(Select one.)
1) Within 5 minutes
2) 6-30 minutes
3) 31-60 minutes
4) After 60 minutes
[IF S3 ≠ 4, THEN B4-B6; OTHERWISE SKIP.]
The next set of questions asks about your use of smokeless tobacco.
B4. During the past 30 days, how many days did you use a smokeless tobacco product, such as
snuff, dip, or Snus…? (Select one.)? (Select one.)
1. 0 days
2. 1 or 2 days
3. 3 to 5 days
4. 6 to 9 days
5. 10 to 19 days
6. 20 to 29 days
7. All 30 days
3

B5. On average, in the past 30 days, about how many times did you use smokeless tobacco a
day? (Select one.)
1. Once a day
2. 2 to 3 times a day
3. 4 to 5 times a day
4. More than 5 times a day
B6. On the days that you use smokeless tobacco, how soon after you wake up do you place your
first dip? (Select one.)
1. Within 5 minutes
2. 6-30 minutes
3. 31-60 minutes
4. After 60 minutes
SECTION A: COMMUNICATION OBJECTIVE QUESTIONS
[RANDOMLY ASSIGN R TO TREATMENT AND STIMULI or CONTROL.]
[IF TREATMENT GROUP, DISPLAY TEXT AND RANDOMLY SELECT AND DISPLAY
STIMULI IN POP-UP WINDOW. KEEP STIMULI VISIBLE THROUGHT SECTION A.]
Please click on the icon here to display a list of chemicals that are in [smokeless tobacco
products such as snuff, dip, or Snus / cigarettes / roll-your-own cigarettes]. Please take a
moment to look over this list. You can keep the list open while you complete the survey and can
click on the icon at any time to view the list.
Please use information provided on the list to answer the following questions.
A1. Do chemicals in cigarettes come from…? (Select one for each item.) [RANDOMIZE
LIST.]
Yes
1. The tobacco leaf
2. Tobacco smoke
3. The cigarette carton
4. Glues, inks, and paper
5. The filter
6. Additives

[CONTROL & TX=CIG & RYO.]
A2. How many of the chemicals in cigarettes come from the tobacco leaf and the smoke?
(Select one.)
1) None of the chemicals
2) A few of the chemicals
3) Many of the chemicals
4) All of the chemicals
[CONTROL & TX=SMK.]
A3. How many of the chemicals in smokeless tobacco products come from the tobacco leaf?
(Select one.)
1) None of the chemicals
2) A few of the chemicals
3) Many of the chemicals
4) All of the chemicals
A4. For each question, please answer YES or NO. (Select one for each question.)
[RANDOMIZE LIST.]
Yes
1. Imagine one tobacco product has a greater number of
chemicals than another tobacco product. Can you tell
which of these products is more likely to cause a tobaccorelated health problem?
2. Formaldehyde has been linked to cancer. Now imagine
one brand of tobacco product has more formaldehyde in it
than another brand. Can you tell which of these brands of
tobacco product is more likely to cause cancer?
A5. Who tests tobacco products for harmful chemicals? (Select one.)
1) Tobacco farmers
2) Federal government
3) State and local health departments
4) Tobacco companies
5) No one
6) None of the above

A6. For each of the following statements, please select True or False. (Select one for each
statement.) [RANDOMIZE LIST.]
True

False

1. Researchers have linked some of the chemicals from
tobacco products to health problems.
2. Researchers have discovered all of the health problems
that may be caused by harmful chemicals from tobacco
products.
3. Researchers have discovered all of the harmful chemicals
that come from using tobacco products.
4. All tobacco products contain chemicals that may cause
harm.
5. Research is ongoing to find out which chemicals cause
harm.
6. Nicotine causes cancer.
7. Nicotine is one reason why people have trouble quitting
tobacco products.
A7. For each question, please answer YES or NO. (Select one for each question.)
[RANDOMIZE LIST.]
Yes

1. Can you tell a tobacco user’s chance of developing a
tobacco-related health problem by counting the total
number of chemicals in his/her tobacco product?
2. Can you tell a tobacco user’s chance of developing a
health problem by looking at the amount of a harmful
chemical in his/her tobacco product?
[IF TX GROUP]
A8. For each of the following statements, please select True or False. (Select one for each
statement.) [RANDOMIZE LIST.]
True
1. When a chemical is listed without an amount it may mean
the chemical was not detected.
2. When a chemical is listed without an amount it may mean
the information is not currently available.

False

SECTION C: DESIRE TO QUIT / STAGE OF CHANGE
[FOR C1-C3, EXCLUDE YOUTH SUSCEPTIBLE TO SMOKING AND SMOKELESS
ONLY.]
C1. Are you seriously considering stopping smoking within the next 6 months? (Select one.)
1) Yes
2) No
C2. Are you planning to stop smoking within the next 30 days? (Select one.)
1) Yes
2) No
C3. On a scale from 1 to 5 with 1 being “not at all” and 5 being the “a lot,” how much do you
want to quit smoking? (Select one.)
1) Not at all
2) .
3) .
4) .
5) A lot
[IF S3 ≠ 4]
C4. Are you seriously considering stopping using smokeless tobacco products such as snuff, dip,
or Snus within the next 6 months? (Select one.)
1) Yes
2) No
[IF S3 ≠ 4]
C5. Are you planning to stop using smokeless tobacco products such as snuff, dip, or Snus within
the next 30 days? (Select one.)
1) Yes
2) No
[IF S3 ≠ 4]
C6. On a scale from 1 to 5 with 1 being “not at all” and 5 being the “a lot,” how much do you
want to stop using smokeless tobacco? (Select one.)
6) Not at all
7) .
8) .
9) .
10) A lot

SECTION D: RISK PERCEPTION
D1. On a scale of 1 to 5 with 1 being not harmful at all and 5 being extremely harmful, how
harmful to someone’s health is…? (Select one for each statement.) [RANDOMIZE 1-3.]
not at all
harmful
1

extremely
harmful
5

1. Smoking cigarettes
2. Smoking roll-your-own tobacco
3. Using smokeless tobacco
4. [TX = CIG. SHOW STIMULI.] Smoking this
brand of cigarettes
5. [TX = RYO. SHOW STIMULI.] Smoking this
brand of roll-your-own tobacco
6. [TX = SMK. SHOW STIMULI.] Using this
brand of smokeless tobacco
D2. How strongly do you agree or disagree with the following statement? There is no safe
tobacco product. (Select one.)
1) Strongly agree
2) Somewhat agree
3) Somewhat disagree
4) Strongly disagree
[FOR D3-D7, EXCLUDE YOUTH SUSCEPTIBLE TO SMOKING AND SMOKELESS
ONLY.]
D3. How likely do you think you are to get a disease from smoking cigarettes? (Select one.)
1) Very unlikely
2) Somewhat unlikely
3) Somewhat likely
4) Very likely
D4. Do you think your smoking has affected your health? (Select one.)
1) Yes
2) No
D5. How concerned are you that your smoking could affect your health? (Select one.)
1) Not at all concerned
2) Only slightly concerned
3) Fairly concerned
4) Very concerned
8

D6. Do you think that your smoking has affected the health of someone else (e.g. spouse,
partner, child, grandchild)? (Select one.)
1) Yes
2) No
D7. How concerned are you that your smoking could affect the health of someone else? (Select
one.)
1) Not at all concerned
2) Only slightly concerned
3) Fairly concerned
4) Very concerned
[IF S3 ≠ 4]
D8. How likely do you think you are to get a disease from using smokeless tobacco? (Select
one.)
1) Very unlikely
2) Somewhat unlikely
3) Somewhat likely
4) Very like
[IF S3 ≠ 4]
D9. Do you think your use of smokeless tobacco has affected your health? (Select one.)
1) Yes
2) No
[IF S3 ≠ 4]
D10. How concerned are you that your use of smokeless tobacco could affect your health?
(Select one.)
1) Not at all concerned
2) Only slightly concerned
3) Fairly concerned
4) Very concerned

SECTION E: YOUTH BELIEFS/ATTITUDES ABOUT TOBACCO USE
[IF YOUTH SUSCEPTIBLE TO SMOKING]
E6. On a scale of 1 to 5 with 1 being strongly disagree and 5 being strongly agree, how much
do you agree or disagree that cigarette smoking is…? (Select one for each item.)
[RANDOMIZE LIST.]
strongly
strongly
disagree
agree
1
2 3 4
5
1. Glamorous
2. Rebellious
3. Cool
4. Disgusting
5. Foolish
SECTION E: HEALTH LITERACY
The remaining questions are not about tobacco. These questions are to help us get a better sense
of who you are and how you make decisions about your health. The information below is from
the back of a container of a pint of ice cream. Please use this information to answer the
following questions.

F1. If you eat the entire container, how many calories will you eat?
________________ Calories
[ENTER NUMBER]
F2. If you are allowed to eat 60 grams of carbohydrates as a snack, how many cups of ice cream
could you have?
________________ Cups
[ENTER NUMBER]
F3. Your doctor advises you to reduce the amount of saturated fat in your diet. You usually have
42 g of saturated fat each day, which includes one serving of ice cream. If you stop eating ice
cream, how many grams of saturated fat would you be consuming each day?
________________ Grams
[ENTER NUMBER]
F4. If you usually eat 2,500 calories in a day, what percentage of your daily value of calories will
you be eating if you eat one serving?
________________ %
[ENTER NUMBER]
For the next few questions, pretend that you are allergic to the following substances: penicillin,
peanuts, latex gloves, and bee stings.
F5. Is it safe for you to eat this ice cream?
1) Yes
2) No
[If F5 = 1 GO TO G1]
F6. Why isn’t it safe to eat this ice cream? (Select one)
1) It is high in calories
2) It contains peanut oil
3) It is high in fat
4) The ice cream container is coated with latex
5) People who are allergic to penicillin should not eat ice cream
CLOSING QUESTIONS
G1. What is your sex? (Select one.)
1) Male
2) Female
G2. Are you Hispanic or Latino? (Select one.)
1 Yes
2 No
99 I do not wish to answer
11

G3. What is your race? (Select all that apply.)
1 American Indian or Alaska Native
2 Asian
3 Black or African American
5 Native Hawaiian or Other Pacific Islander
6 White
99 I do not wish to answer
[ADULTS ONLY]
G4. What is the highest level of school you completed or the highest degree you
received? (Select one.)
1 Never attended school
2 Grades K through 8 (Elementary or grade school)
3 Grades 9 through 12 (Some high school)
4 Grade 12 (High school graduate) or GED
5 Some college
6 College graduate
7 Postgraduate/masters/doctorate/law/MD
99 I do not wish to answer
[YOUTH ONLY]
G5.What grade or year of school are you currently in? (Select one.)
1 4th grade
2 5th grade
3 6th grade
4 7th grade
5 8th grade
6 9th grade
7 10th grade
8 11th grade
9 12th grade or GED
10 Not currently in school
11 Graduated high school or GED
99 I do not wish to answer
[ADULTS ONLY]
G6. What was your annual household income from all sources in 2011? Was it…? (Select one.)
1 Less than $25,000
2 Between $25,000 and $49,999
3 Between $50,000 and $74,999
4 More than $75,000
99 I do not wish to answer

[ADULTS ONLY]
G7. Which statement best describes your current employment status? (Select one.)
1. Working full time as a paid employee
2. Working full time, self-employed
3. Not working, on temporary layoff from a job
4. Not working, looking for work
5. Not working, retired
6. Not working, disabled
7. Not working, other
G8. Please enter your 5-digit zip code –OR– your city and state.
5-digit zip code: ________________________
–OR–
City: ________________________
State (2 letter abbreviation): ________________________
99
I do not wish to answer
Thank you for completing today’s survey. You will be awarded XX for completing this survey.
If you would like to learn more about the dangers of smoking or to get information about quitting
smoking, please visit www.smokefree.gov.

Appendix B
Test Stimuli

Attached are the list formats for smokeless tobacco. The same formats will be
tested for cigarettes and roll‐your own tobacco.

U.S. Food and Drug Administration

Logo Sheet 1298.01

Tobacco Product: Brand X Smokeless Tobacco
KEY
Tobacco
Amount Per Gram

Chemicals have been linked to:
CHEMICAL

Acetaldehyde

0.1 – 3.5 µg

Arsenic

1.1 – 57.3 ng

Benzo[a]pyrene

0.1 – 3.1 µg

Cadmium

0.5 – 19.4 µg

Crotonaldehyde

0.2 -72.3 µg

Formaldehyde

0.1 – 1.6 µg

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

0.97 – 72.3 µg

11.3 – 26.7 mg
0.9 – 6.9 µg

AD
n

n
n

Nicotine
N-Nitrosonornicotine (NNN)

Cancer

Heart and Blood Vessel Problems

Reproductive Problems

Addiction

Not Detected

The information is not currently
available

There are many other chemicals that have been linked
to the health problems on this list. The information on
these chemicals is not currently available.

A machine is used to test for these chemicals. The amount of chemical that gets into the body may be
higher or lower depending on how a person uses the tobacco product. Companies may use different tests to
measure these chemicals. Results may vary.

mg= milligram
µg = microgram
ng = nanogram
pg= picogram

U.S. Food and Drug Administration

Logo Sheet 1298.01

Tobacco Product: Brand X Smokeless Tobacco
KEY
Tobacco
Amount Per Gram

Chemicals have been linked to:
CHEMICAL

Acetaldehyde

0.1 – 3.5 µg

Arsenic

1.1 – 57.3 ng

Benzo[a]pyrene

0.1 – 3.1 µg

Cadmium

0.5 – 19.4 µg

Crotonaldehyde

0.2 -72.3 µg

Formaldehyde

0.1 – 1.6 µg

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

0.97 – 72.3 µg

11.3 – 26.7 mg
0.9 – 6.9 µg

AD
n

n
n

Nicotine
N-Nitrosonornicotine (NNN)

Cancer

Heart and Blood Vessel Problems

Reproductive Problems

Addiction

Not Detected

The information is not currently available on the following chemicals.

The information is not currently
available

Tobacco
Amount Per Gram

CHEMICAL

Aflatoxin B1

Ammonia

Anabasine

Benz[a]anthracene

Benzo[b]fluoranthene

Benzo[k]fluoranthene

Beryllium

Chromium

Chrysene

Coumarin (banned in food)

Dibenz[a,h]anthracene

Ethyl carbamate (urethane)

Indeno[1,2,3-cd]pyrene

Lead

Mercury

Naphthalene

Nickel

N-Nitrosodiethanolamine (NDELA)

N-Nitrosodimethylamine (NDMA)

N-Nitrosomorpholine (NMOR)

N-Nitrosopiperidine (NPIP)

N-Nitrosopyrrolidine (NPYR)

N-Nitrososarcosine (NSAR)

Nornicotine

Polonium-210

Selenium

Uranium-235

Uranium-238

n
n

mg= milligram
µg = microgram
ng = nanogram
pg= picogram

U.S. Food and Drug Administration

Logo Sheet 1298.01

Tobacco Product: Brand X Smokeless Tobacco
KEY
Tobacco
Amount Per Gram

Chemicals have been linked to:
CHEMICAL

Acetaldehyde

Aflatoxin B1

Ammonia

Anabasine

0.97 – 72.3 µg

n
n

Benz[a]anthracene

Benzo[b]fluoranthene

Benzo[k]fluoranthene

Benzo[a]pyrene

1.1 – 57.3 ng

Beryllium

0.1 – 3.1 µg

Cadmium

Chromium

Chrysene

Coumarin (banned in food)
Crotonaldehyde

Dibenz[a,h]anthracene

Ethyl carbamate (urethane)

Formaldehyde

Indeno[1,2,3-cd]pyrene

Lead

Mercury

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

Naphthalene

Nickel

0.5 – 19.4 µg

0.2 -72.3 µg

0.1 – 1.6 µg

11.3 – 26.7 mg

AD
n

Arsenic

0.1 – 3.5 µg

N-Nitrosodiethanolamine (NDELA)

N-Nitrosodimethylamine (NDMA)

N-Nitrosomorpholine (NMOR)

0.9 – 6.9 µg

N-Nitrosonornicotine (NNN)

N-Nitrosopiperidine (NPIP)

N-Nitrosopyrrolidine (NPYR)

N-Nitrososarcosine (NSAR)

Nornicotine

Polonium-210

Selenium

Uranium-235

Uranium-238

Cancer

Heart and Blood Vessel Problems

Reproductive Problems

Addiction

Not Detected

The information is not currently
available

mg= milligram
µg = microgram
ng = nanogram
pg= picogram

n
n

Nicotine

n
n

U.S. Food and Drug Administration

Logo Sheet 1298.01

Tobacco Product: Brand X Smokeless Tobacco
All tobacco products contain chemicals.

KEY

The purpose of this list is to provide information about the chemicals in this tobacco product

Chemicals have been linked to:

that researchers have linked to health problems. Research is on going to find out which chemicals
in tobacco and tobacco smoke cause harm.

Cancer
Heart and Blood Vessel Problems

There may be other health problems and chemicals that have not been discovered yet.
Tobacco companies test their tobacco for these chemicals and report the amounts to the FDA.

Reproductive Problems

Please note: There is no safe tobacco product. Based on what we currently know, you can not

Addiction

tell your chance of developing a health problem by the number of chemicals or the amount of a
chemical in a tobacco product.

ND
F

TOBACCO

Not Detected
The information is not currently
available

Amount
Per Gram
per gram

CHEMICAL

0.97 – 72.3 µg

Acetaldehyde

0.1 – 3.5 µg
SMOKE
1.1 – 57.3 ng

Arsenic

Benzo[a]pyrene

0.1 – 3.1 µg

Cadmium

0.5 – 19.4 µg

Crotonaldehyde

0.2 -72.3 µg

Formaldehyde

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

per
cigarette

0.1 – 1.6 µg
P Lmg
ANT
11.3 – 26.7
FOUND IN

0.9 – 6.9 µg

amount per
gram of
tobacco

Nicotine

N-Nitrosonornicotine (NNN)
amount per
cigarette

TOBACCO

n
n

Where do these chemicals
come from?
per gram

SMOKE

FOUND IN

SMOKE

Many of these chemicals come from
the tobacco leaf. The rest come
from additives and the pouch if one is
present.
per
cigarette

FOUND IN

PLANT

amount per
gram of
tobacco

There are many other chemicals that have been linked
to the health problems on this list. The information on
these chemicals is not currently available.

mg= milligram
µg = microgram
ng = nanogram
pg= picogram

FOUND IN

SMOKE

amount per
cigarette

U.S. Food and Drug Administration

Logo Sheet 1298.01

Tobacco Product: Brand X Smokeless Tobacco
All tobacco products contain chemicals.

KEY

The purpose of this list is to provide information about the chemicals in this tobacco product

Chemicals have been linked to:

that researchers have linked to health problems. Research is on going to find out which chemicals
in tobacco and tobacco smoke cause harm.

Cancer
Heart and Blood Vessel Problems

There may be other health problems and chemicals that have not been discovered yet.
Tobacco companies test their tobacco for these chemicals and report the amounts to the FDA.

Reproductive Problems

Please note: There is no safe tobacco product. Based on what we currently know, you can not

Addiction

tell your chance of developing a health problem by the number of chemicals or the amount of a
chemical in a tobacco product.

ND
F

TOBACCO

Not Detected
The information is not currently
available

Amount
Per Gram
per gram

CHEMICAL

0.97 – 72.3 µg

Acetaldehyde

0.1 – 3.5 µg
SMOKE
1.1 – 57.3 ng

Arsenic

Benzo[a]pyrene

0.1 – 3.1 µg

Cadmium

0.5 – 19.4 µg

Crotonaldehyde

0.2 -72.3 µg

Formaldehyde

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

per
cigarette

0.1 – 1.6 µg
P Lmg
ANT
11.3 – 26.7
FOUND IN

0.9 – 6.9 µg

amount per
gram of
tobacco

Nicotine

n
n

N-Nitrosonornicotine (NNN)
amount per
cigarette

Where do these chemicals
come from?
per gram

SMOKE

FOUND IN

SMOKE

TOBACCO

Many of these chemicals come from
the tobacco leaf. The rest come
from additives and the pouch if one is
present.
per
cigarette

The information is not currently available on the following chemicals.

FOUND IN

PLANT

amount per
gram of
tobacco

Amount Per Gram

CHEMICAL

Aflatoxin B1

Ammonia

Anabasine

Benz[a]anthracene

Benzo[b]fluoranthene

Benzo[k]fluoranthene

Beryllium

Chromium

Chrysene

Coumarin (banned in food)

Dibenz[a,h]anthracene

Ethyl carbamate (urethane)

Indeno[1,2,3-cd]pyrene

Lead

Mercury

Naphthalene

Nickel

N-Nitrosodiethanolamine (NDELA)

N-Nitrosodimethylamine (NDMA)

N-Nitrosomorpholine (NMOR)

N-Nitrosopiperidine (NPIP)

N-Nitrosopyrrolidine (NPYR)

N-Nitrososarcosine (NSAR)

Nornicotine

Polonium-210

Selenium

Uranium-235

Uranium-238

n
n

mg= milligram
µg = microgram
ng = nanogram
pg= picogram

FOUND IN

SMOKE

amount per
cigarette

U.S. Food and Drug Administration

Logo Sheet 1298.01

Tobacco Product: Brand X Smokeless Tobacco
All tobacco products contain chemicals.

KEY

The purpose of this list is to provide information about the chemicals in this tobacco product

Chemicals have been linked to:

that researchers have linked to health problems. Research is on going to find out which chemicals
in tobacco and tobacco smoke cause harm.

Cancer
Heart and Blood Vessel Problems

There may be other health problems and chemicals that have not been discovered yet.
Tobacco companies test their tobacco for these chemicals and report the amounts to the FDA.

Reproductive Problems

Please note: There is no safe tobacco product. Based on what we currently know, you can not

Addiction

tell your chance of developing a health problem by the number of chemicals or the amount of a
chemical in a tobacco product.

ND
F

TOBACCO

Not Detected
The information is not currently
available

Amount
Per Gram
per gram

CHEMICAL

0.97 – 72.3 µg

Acetaldehyde

F
SMOKE
F

Aflatoxin B1

Anabasine

Ammonia
n

Arsenic

Benz[a]anthracene

Benzo[b]fluoranthene

Benzo[k]fluoranthene
SMOKE
per
Benzo[a]pyrene amount
cigarette

Beryllium

0.1 – 3.1 µg

Cadmium

Chromium

Chrysene

Coumarin (banned in food)

0.1 – 3.5 µg
F

per
cigarette

F
FP L A N T
FOUND IN

1.1 – 57.3 ng

amount per
gram of
tobacco

FOUND IN

Dibenz[a,h]anthracene

Ethyl carbamate (urethane)

Formaldehyde

Indeno[1,2,3-cd]pyrene

Lead

Mercury

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

Naphthalene

Nickel

0.2 -72.3 µg

0.1 – 1.6 µg

11.3 – 26.7 mg

N-Nitrosodiethanolamine (NDELA)

N-Nitrosodimethylamine (NDMA)

N-Nitrosomorpholine (NMOR)

0.9 – 6.9 µg

N-Nitrosonornicotine (NNN)

N-Nitrosopiperidine (NPIP)

N-Nitrosopyrrolidine (NPYR)

N-Nitrososarcosine (NSAR)

Nornicotine

Polonium-210

Selenium

Uranium-235

Uranium-238

per gram

SMOKE

per
cigarette

FOUND IN

PLANT

amount per
gram of
tobacco

mg= milligram
µg = microgram
ng = nanogram
pg= picogram

n
n

Nicotine

Where do these chemicals
come from?
Many of these chemicals come from
the tobacco leaf. The rest come
from additives and the pouch if one is
present.

Crotonaldehyde

0.5 – 19.4 µg

TOBACCO

n
n

FOUND IN

SMOKE

amount per
cigarette

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File Title	Microsoft Word - 2_CTP Shay HPHC RIHSC-EXPD.doc
Author	SHAYL
File Modified	2012-09-13
File Created	2012-09-13