CONFER OMB Approval Request Memorandum

FDA DOCUMENTATION FOR THE GENERIC CLEARANCE,
“TESTING COMMUNICATIONS ON DRUGS PRODUCTS”
OMB Control No. 0910-0695
PROJECT CONFER: Comprehension of Over-the-Counter Naloxone for Emergency Response
(#16081)

TITLE OF INFORMATION COLLECTION: Naloxone Cognitive Interviews to Optimize
the Drug Facts Label (Task 1)
DESCRIPTION OF THIS SPECIFIC COLLECTION
1.Statement of need:
Prevention and treatment of opioid overdose is an urgent public health priority. One way that
FDA is addressing this public health problem is by facilitating the development of
nonprescription (OTC) naloxone, which is currently only available by prescription. FDA is
implementing this through development of a model Drug Facts label (DFL) for an OTC
naloxone. This DFL is to include all the information (other than information highly specific to a
particular product) that a consumer would need to know to purchase naloxone appropriately, and
to use naloxone in an emergency opioid overdose situation. This model DFL will then undergo
label comprehension testing by an outside research organization. A pretested DFL with an
acceptable level of consumer comprehension would then be available, and commercial sponsors
could add their product-specific information to the DFL and conduct final consumer behavior
testing. RTI International and Concentrics Research (referred to hereafter as the RTI-Concentrics
team) will be partnering on this research study, each bringing to the project their unique expertise
in working with vulnerable populations (RTI) and label testing (Concentrics).We will conduct
this study in accordance with practices outlined in the FDA Guidance for Industry on Label
Comprehension Studies for Nonprescription Drug Products (FDA, August, 2010)
This application details procedures and materials for Task 1 only; we will update the
application for Tasks 2 and 3 with amendments as the procedures and materials for
subsequent Tasks are available and are informed by study results in Task 1.
The cognitive interviewing process to assess concepts and perceptions about the draft DFL (Task
1) comprises the first of three stages of a comprehensive label comprehension testing program:
Task 1: Cognitive Interviews to Optimize the Drug Facts Label (N=36). The purpose
of Task 1 is to obtain rapid feedback about the model DFL from potential end users of
OTC Naloxone through administration of unstructured cognitive interviews with user
segments defined by FDA (see section 3). We will conduct Task 1 activities through
partnerships with SouthLight Healthcare in Raleigh, North Carolina and through Shugoll
Research in the metro-DC area. Because the purpose of Task 1 is to obtain feedback on
the DFL for future testing, the sample for Task 1 is not intended to be nationally
representative.

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Task 2: Pilot Label Comprehension Study (N=36). The purpose of Task 2 is to design
and implement structured interviews to assess comprehension of pilot survey questions
and to inform sample sizing for the Task 3 Pivotal Study. Task 2 will involve the same
user groups as the previous Task (see section 3), but different participants. We propose to
conduct Task 2 activities through partnerships with community-based organizations in
Chicago, Illinois and through Shugoll Research in the metro-DC area. Because the
purpose of Task 2 is to test and refine survey items in preparation for the quantitative
survey (Task 3), the sample is not intended to be nationally representative.
Task 3: Quantitative Pivotal Comprehension Study (N=710). The purpose of Task 3
is to determine if a significant proportion of participants comprehend the key
communication objectives and meet the established thresholds for success. Task 3 will
involve the same user groups as the previous Tasks (see section 3), but different
participants. We will recruit participants from a larger and more geographically diverse
set of community-based organizations for Task 3 (up to 7 locations across the U.S.),
including the Concentrics Research testing facility in Indianapolis, Indiana for the “all
comers” group.
2.Intended use of information:
The study objective for Task 1 is to obtain feedback about the model DFL from potential end
users of OTC Naloxone through the administration of unstructured cognitive interviews with
defined user segments. The information collected in Task 1 will be used to inform the subsequent
study stages (Tasks 2 and 3).

3.Description of respondents:
The study population for Task 1 will consist of four user groups defined by FDA:
1. Group 1 (n=9): Prescription opioid users, including those in drug treatment programs,
as well as family/friends of users who are not users themselves (i.e. associates).
2. Group 2 (n=9): Heroin users, including those in drug treatment programs, as well as
their associates.
3. Group 3 (n=9): Adolescents (ages 15-17) who are prescription opioid users and/or
heroin users, including those in drug treatment programs and/or their adolescent
associates.
4. Group 4 (n=9): All comers, primarily consisting of low literacy general consumers and
including some pregnant women.
We have developed separate screener questionnaires for Groups 1 – 3 (Attachment A) Group 4
(Attachment B) to assess for potential eligibility.

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Eligibility Criteria
Individuals will be included in the study if the following criteria are met. Collection of
information on drug use is for screening purposes only and will be assessed by self-report; no
medical records or samples will be used in this study.

Group 1 – Prescription Opioid Users & Associates (n=9)
1.
2.
3.
4.

Male or female, of any race
18 years of age or older
Self-reported use of prescription opioids in the past 30 days (if user)
Self-reported associate of prescription opioid user (if associate)

Group 2 – Heroin Users & Associates (n=9)
1. Male or female, of any race
2. 18 years of age or older
3. Self-reported use of heroin in the past 30 days (if user)
4. Self-reported associate of heroin user (if associate)
Group 3 – Adolescent Prescription Opioid Users & Adolescent Associates (n=9)
1. Male or female, of any race
2. 15 to 17 years of age
3. Self-reported use of prescription opioids in the past 30 days (if users)
4. Self-reported use of heroin in the past 30 days (if user)
5. Self-reported associate of 15-17 year old prescription opioid user or heroin user (if
associate)
Group 4 – All comers (n=9)
1. Male or female, of any race
2. 18 years of age or older
3. Score 60 or below on REALM
4. Some participants must be pregnant
In addition to this screening information, we will collect ancillary data on use during the past 90
days and frequency of prescription opioid and/or heroin during the past 30 days to distinguish
heavy from recreational users. These data will be used for analyses purposes only.

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Participants will be excluded from the study if any of the following criteria are met.
1. The participant or anyone in their household is currently employed by any of the
following:
 A marketing or marketing research company
 An advertising agency or public relations firm
 A pharmacy or pharmaceutical company
 A manufacturer of medicines
 A managed care or health insurance company
 A healthcare practice
2. The participant has ever been trained or employed as a healthcare professional.
3. The participant normally wears corrective lenses, contacts or glasses to read and does not
have them with him/her at the time of the interview.
4. The participant is appears to be significantly impaired (e.g. under the influence of drugs
or alcohol) at the time of the interview as observed by the study staff and incapable of
providing proper consent or interpretation of verbal or written instructions or materials.
All study staff will be trained by qualified researchers on how to identify significant
impairment.
5. The participant has participated in any clinical trial, product label study or marketing
research study involving a healthcare product or topic in the previous twelve (12) months.
6. The participant cannot read, speak and/or understand English.
FDA has requested that at least 30% of the participants in Groups 1-3 be of lower literacy and
that all or nearly all Group 4 participants have low literacy. We will use a validated, one-item
question to assess for potential low-literacy at the initial screening for adults (Wallace et al.,
2006). We will not use this screening item with adolescents, as it has not been validated for this
population. The Rapid Estimate of Adult Literacy in Medicine (REALM) and Rapid Estimate of
Adolescent Literacy in Medicine (REALM-Teen), also validated literacy screening tools, will be
used to assess literacy on-site after consent but prior to conducting the study interview (Davis et
al.,1993; Davis et al., 2006). Individuals who are screened for eligibility with the REALM but
are ultimately excluded due to their scores will still receive the study incentive.
Recruitment Partners (Task 1)
To recruit participants for Tasks 1 we will work with SouthLight Healthcare
(http://www.southlight.org/), a community-based organization located in Raleigh, North Carolina
(Groups 1-3) and Shugoll Research, a recruiting firm located in the metro-DC area (Group 4).

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Recruitment partners and materials for Tasks 2 and 3 are in development; details will be
provided as future amendments to this application.
a. SouthLight Healthcare
SouthLight Healthcare has provided comprehensive substance abuse programs for adolescents,
adults, and families in the Raleigh area for over 45 years. SouthLight is an ideal partner for
recruitment of user groups 1-3 due to their client volume and the breadth of services they
provide.
Participants will be recruited from multiple programs within SouthLight:


The adult outpatient clinic that provides daily medication-assisted therapy for the
management of opioid dependence.



Two residential facilities for adults, one of which treats pregnant and postpartum women
with substance use disorders and another that offers supervised independent living for
chronically addicted adults who have experienced homelessness or have co-occurring
mental health disorders.



The youth and family services program that provides prevention, education, and
treatment services to youth who have or are at risk for addiction.

To ensure we are able to achieve the desired sample in the time allotted, we are implementing a
multipronged recruitment strategy that assumes that the majority of interviews will be scheduled
prior to data collection:
1. We will provide SouthLight staff with a Provider Information Sheet about the study so
they are aware of the organization’s involvement and how they can be of assistance
(Attachment C). In addition, they can use the Provider Information Sheet to inform their
discussions with clients who may be eligible for the study.
2. We will post study flyers at each SouthLight location (Attachment D). The flyer
provides information about the study and contact information should they wish to be
screened for eligibility.
3. We will give SouthLight staff palm cards with details about the study to distribute to
clients who express interest in participating in addition to placing them in client waiting
areas (Attachment E).
The materials make it clear that we are interested in recruiting associates in addition to users.
They direct individuals to call the study’s toll-free number or contact us by email if they are
interested in learning more. A designated RTI staff member will field all phone calls and emails.
The RTI staff member will assess eligibility using the Group 1-3 screener (Attachment A).
Regarding associates, we anticipate that some will be exposed to flyers and palm cards placed
throughout the clinic as they may be clients themselves or when they transport clients to and

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from clinic appointments. Others may learn of the study through word of mouth. We expect that
most associated will be family members of the adolescent users.
If we are unable to fully recruit for the data collection prior to the interview dates, we will recruit
additional participants onsite. Research study staff will be onsite during peak flow hours to
recruit additional participants by handing out flyers and palm cards. We will also ask providers
onsite to assist in recruitment efforts by referring patients who have appointments to the research
study staff.
All study staff will participate in a cultural competence training to ensure implementation of best
practices that adhere to the highest ethical standards when working with drug-using populations
(National Commission for the Protection of Human Subjects of Biomedical Behavioral Research,
1978). Researchers with expertise in illicit opioid use and working with this population will
conduct the training.
SouthLight will receive a small honorarium ($30 per recruited participant) in appreciation of
their time.
Shugoll Research
We will partner with Shugoll Research in the metro-DC area to recruit the group 4 (all-comers
group). RTI has a longstanding relationship with Shugoll Research and they have experience
recruiting low literacy and hard-to-reach populations. Shugoll’s location on the DC metro stop is
accessible to diverse populations, and their facility provides a 1-way mirror for FDA
observation.
Recruiters from Shugoll Research will identify potential participants through their community
partners and will contact them by telephone to assess eligibility using the Group 4 screener
(Attachment B). Interviews will be conducted in-person at the Shugoll facility.
4.Date(s) to be Conducted:
Data collection for Task 1 will take place during a 4-6 week time frame after OMB and FDA
RIHSC approval is received.
5.How the Information is being collected:

Task 1 is comprised of one-time, unstructured cognitive interviews to evaluate and optimize the
draft DFL. These one-on-one interviews will be conducted in person with participants in each of
the four user groups. RTI and Concentrics Research will work in a 2-person team at each
location. RTI staff will coordinate data collection logistics and assess individuals for drug or
alcohol-related impairment prior to checking them in. Concentrics Research staff will administer
informed consent and the REALM test, conduct the interviews, and analyze and report on
findings. All interviewers are experienced and qualified in cognitive interviewing methods. This
is an interview study only; no drug will be administered or dispensed.
Once at the study location (a private office or conference room at SouthLight), the participant
will be provided with an Agreement to Participate (ATP) that outlines the purpose and voluntary
nature of the study (Attachment F). Both adult (age 18 and over) and adolescent (age 15-17)

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participants will be required to provide written consent to be in the study. This study will not
require parental consent in addition to participant consent for the adolescent group (ages 15-17),
which is consistent with published guidelines for market research stipulating that parental
consent is required for participants under the age of 13 (MRA, 2007). Further, the study poses no
more than minimal risk to participants regardless of age; the purpose of the study is to provide
feedback on a DFL and assess comprehension of information. The study questionnaire will not
collect sensitive information. In addition, recruitment of adolescent populations could not be
practically carried out should parental consent also be required. Adolescents who are patients in
the treatment centers where data collection will occur might not be accompanied by a parent
(e.g., they may be dropped off for treatment appointments or accompanied by another relative,
sibling or friend). It should also be noted that adolescents who are in attendance for treatment
have consented to be there. Participants who sign the ATP will next undergo a literacy
assessment using the Rapid Estimate of Adult Literacy in Medicine (REALM) Test for
participants who are ages 18 and older or the Rapid Estimate of Adolescent Literacy in Medicine
(REALM-Teen) Test for participants who are ages 15-17. FDA has requested that
approximately 30% of group 1-3 participants be of lower literacy and that all or nearly all of
group 4 participants are of lower literacy defined as a REALM score of <60.
Following the literacy assessment, the participant will be given the naloxone DFL (Attachment
G). The moderator will leave the room to give the participant the opportunity to review the DFL
at his/her own pace. Once the participant indicates he/she is finished reading the labeling, the
moderator will return to the room and begin the cognitive label assessment interview.
Participants will be asked exploratory, open-ended questions to assess their understanding and
interpretation of the text and pictograms included on the DFL (see Moderator guide, Attachment
H). The DFL will be provided on paper similar in size and shape to the planned commercial
package. The DFL may be revised iteratively throughout the interviews, and additional concepts
to address points of confusion may be shown to participants as appropriate.
The interviews will be audio recorded. For group 4RTI staff will also take notes during the
interviews to record nonverbal cues and behaviors (e.g. apparent participant confusion or
difficulty in evaluating the labeling) to accompany the final audio-recording. RTI staff will take
notes outside of the interview room from behind a one-way mirror to avoid the possibility of
distracting the participant or making him/her uncomfortable. For groups 1-3, RTI staff will take
notes only if it is feasible to do without being in the same room as the participant (e.g., from
behind a partition). Total interview time will be 45 minutes, which includes time to administer
the REALM.
Once the interview is completed, RTI staff will provide the participant with a monetary
incentive. Participants in groups 1-3 and group 4 will receive the equivalent of $60 and $75,
respectively. Section 7 provides justification for the incentive amounts.
After the data collection is complete at all locations, the audio-recordings will be transcribed and
the moderator will create a summary report of the observations and insights from the interviews.
Upon completion of Task 1 activities, FDA and the RTI-Concentrics Research team will
determine whether a second round of testing on a revised DFL is needed. If additional testing
is deemed appropriate, we will recruit the same numbers (N=36), but different participants
from the same 4 user groups and locations and using the same study procedures.

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6.Confidentiality of Participants:
All study participants will be informed both as part of the written consent and again during the
interviews that no reports or other information will identify participants by name, that all
information will be anonymized and reported in aggregate, and that their information will be
kept private to the extent possible given the study methods. For all interviews, all notes taken
will be kept in a locked file cabinet or on a password-protected computer. Any forms related to
the project that have names or other information that could identify individual respondents will
be kept separate from the interview data provided to FDA. The information will be kept in a
secured fashion that will permit access only by authorized project staff. All personally
identifiable information will be removed from transcripts, audio files, reports, and all other
materials before RTI-Concentrics provides them to FDA. All files will be stored on passwordprotected computers at RTI, Concentrics and FDA. These confidentiality methods will be
approved by Concentrics’ Institutional Review Board and FDA’s Research Involving Human
Subjects Committee, (RIHSC) prior to collecting any information.
7. Amount and justification for any proposed incentive
Monetary incentives are intended to recognize the time burden placed on participants, encourage
their cooperation, and convey appreciation for their contributions to the research. Incentives help
ensure that sufficient numbers of participants can be recruited to participate in the data
collection. Research has shown that monetary incentives improve response rates (Ryu et al.,
2006; Singer et al., 1999), thus it is likely that without the incentive as an inducement, more
people would need to be screened to achieve the desired cooperation rate, thus increasing the
burden hours and overall time needed to complete data collection activities.
Participants in Groups 1–3 will receive the equivalent of $60 for participating in Task 1
interviews; this amount is somewhat lower relative to other FDA studies, but it is an amount that
has been used successfully for other RTI-lead interviews of a similar length with drug users. Our
goal was to select an amount that would be attractive to participants, but was not so large as to
appear coercive, which is a consideration when conducting research with vulnerable populations
(Festinger et al., 2005). Participants in Group 4 will receive $75. The amount for this group is
higher because the appearance of coercion is not as sensitive of an issue when conducting
general population studies. Further, participants in Group 4 will be required to travel to the
Shugoll location in the metro-DC area and thus participants may incur more time in commuting
and some travel costs. The $75 amount is the minimum of what Shugoll Research suggests to be
able to successfully recruit participants for this study.
8. Questions of a Sensitive Nature
None of the interview questions for Task 1 are of a sensitive nature. We will ask potentially
sensitive questions about opioid use only during the screening process when assessing study
eligibility (see screening materials, Attachments A and B). As previously described, the focus of
these interviews is to discuss comprehension of key messages in the naloxone DFL (e.g., call 911
immediately). As part of the informed consent procedures, interviewers will explain to
participants that they do not need to answer any questions that make them feel uncomfortable
and can stop participation at any time. To ensure cultural competence, all interviewers will

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participate in a cultural sensitivity training led by an expert in the area of illicit opioid use and
working with this vulnerable population.
9. Description of Statistical Methods
We will use transcribed audio files, interview notes and participant screener data and
demographics when summarizing findings for this study. The screener data and demographics
will be summarized in aggregate format with no personally identifiable information in table and
text format to describe study participants. Data collected through the interviews will all be
qualitative data, thus we will conduct a thematic analysis of all data.
Analyses will be organized around the major topics included in the interview guides. Project
team members trained in qualitative analysis methods will work together to prepare an analysis
plan and review the data. All analyses will be data-driven. The analysis team will meet
periodically to discuss findings and overall themes, as well as recommendations for the
quantitative work. These will be summarized into a final report with quotations from the
interviews provided as examples for the key themes.

BURDEN HOUR COMPUTATION (Number of responses (X) estimated response or
participation time in minutes (/60) = annual burden hours):

Task 1
Task 1:
Optional 2nd
round of data
collection
Task 2
Task 3

Type/Category
of Participant

No. of Participants

350
36
350

Participation
Time
(minutes)
5
45
5

Burden
(hours)
29.2
27
29.2

Screener
Interview
Screener

Interview
Total (Task 1)
Screener
Interview
Screener
Interview
Total
(Tasks 1-3)

36
772
350
36
910
710
2778

45
5-45 minutes
5
45
5
30
5-45 minutes

27
112.4
29.2
27
75.8
355
599.4

Note: We are estimating 350 participants screened to obtain 36 completed interviews for Task 1.
This estimates includes all user groups 1-4. We anticipate needing to screen the largest number
of participants (300) to obtain 9 completed interviews for the group 4“all-comers” due to the
requirement of including all or nearly all low-literacy participants and some pregnant women.
We anticipate screening a smaller number of participants (50) to complete 27 interviews for user
groups 1-3 given the targeted recruitment approach and relaxed criteria for low literacy. The
burden hour computations also account for the possibility of a second round of testing for Task 1
activities, per FDA’s recommendation. Based on results for Task 1, we may adjust these
calculations for future tasks (Task 2 and 3) in our study amendments.

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REQUESTED APPROVAL DATE: August/September 2016
NAME OF PRA ANALYST & PROGRAM CONTACT: Domini Bean;
[email protected]; 301-796-5733.
FDA CENTER: CDER
References
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Crouch, M. A. (1993). Rapid estimate of adult literacy in medicine: a shortened screening
instrument. Family medicine, 25(6), 391-395.
Davis, T. C., Wolf, M. S., Arnold, C. L., Byrd, R. S., Long, S. W., Springer, T., ... & Bocchini, J.
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