[Federal Register Volume 85, Number 19 (Wednesday, January 29, 2020)]
[Notices]
[Pages 5213-5217]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-01555]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2019-N-2313]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Study of Oncology 
Indications in Direct-to-Consumer Television Advertising

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that a 
proposed collection of information has been submitted to the Office of 
Management and Budget (OMB) for review and clearance under the 
Paperwork Reduction Act of 1995.

DATES: Fax written comments on the collection of information by 
February 28, 2020.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
Fax: 202-395-7285, or emailed to oira_submission@omb.eop.gov. All 
comments should be identified with the OMB control number 0910-NEW and 
title ``Study of Oncology Indications in Direct-to-Consumer Television 
Advertising. '' Also include the FDA docket number found in brackets in 
the heading of this document.

FOR FURTHER INFORMATION CONTACT: Ila S. Mizrachi, Office of Operations, 
Food and Drug Administration, Three White Flint North, 10A-12M, 11601 
Landsdown St., North Bethesda, MD 20852, 301-796-7726, 
PRAStaff@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. Background

    In compliance with 44 U.S.C. 3507, FDA has submitted the following 
proposed collection of information to OMB for review and clearance.

Study of Oncology Indications in Direct-to-Consumer Television 
Advertising

(OMB Control Number 0910-NEW)

    Section 1701(a)(4) of the Public Health Service Act (42 U.S.C. 
300u(a)(4)) authorizes FDA to conduct research relating to health 
information. Section 1003(d)(2)(C) of the Federal Food, Drug, and 
Cosmetic Act (FD&C Act) (21 U.S.C. 393(d)(2)(C)) authorizes

[[Page 5214]]

FDA to conduct research relating to drugs and other FDA regulated 
products in carrying out the provisions of the FD&C Act.
    The Office of Prescription Drug Promotion's (OPDP) mission is to 
protect the public health by helping to ensure that prescription drug 
promotional material is truthful, balanced, and accurately 
communicated, so that patients and healthcare providers can make 
informed decisions about treatment options. OPDP's research program 
provides scientific evidence to help ensure that our policies related 
to prescription drug promotion will have the greatest benefit to public 
health. Toward that end, we have consistently conducted research to 
evaluate the aspects of prescription drug promotion that we believe are 
most central to our mission, focusing in particular on three main topic 
areas: Advertising features, including content and format; target 
populations; and research quality. Through the evaluation of 
advertising features we assess how elements such as graphics, format, 
and disease and product characteristics impact the communication and 
understanding of prescription drug risks and benefits; focusing on 
target populations allows us to evaluate how understanding of 
prescription drug risks and benefits may vary as a function of 
audience; and our focus on research quality aims at maximizing the 
quality of research data through analytical methodology development and 
investigation of sampling and response issues. This study falls under 
the topic of advertising features (content and format).
    Oncology products are increasingly being promoted to consumers via 
direct-to-consumer (DTC) television advertising. Oncology indications 
are often complicated and supported by different clinical endpoints 
such as overall survival, overall response rate, and progression-free 
survival (Ref. 1) that are referenced in the DTC TV ads. The first 
objective of this project is to determine whether disclosing 
information about the nature of the endpoints that support the 
indications for oncology products helps consumers understand the drug's 
efficacy. This objective complements OPDP's research examining 
disclosing information about FDA's accelerated approval pathway to 
consumers (May 8, 2019, 84 FR 20148) and OPDP's research on disclosing 
oncology information to healthcare professionals (OMB control number 
0910-0864--Disclosures of Descriptive Presentations in Professional 
Oncology Prescription Drug Promotion). Although these studies all 
contribute to our knowledge of the communication of cancer treatment 
information, the current study specifically examines particular 
endpoints that are well-known to the professional oncology community 
and are now used in DTC advertising.
    Because of the length of some indications, sponsors sometimes 
convey some of the indication in superimposed text rather than in the 
audio in the TV ads. The second objective is to test whether consumers 
adequately comprehend indication statements when portions of the 
indication are presented only in the superimposed text of television 
ads while other information is conveyed in the audio. This objective 
extends OPDP's previous research on the use of dual-modality risk 
presentations (presenting the information in two modes at the same 
time; OMB control numbers 0910-0634--Experimental Evaluation of the 
Impact of Distraction, 0910-0652--Experimental Study: Toll-Free Number 
for Consumer Reporting of Drug Product Side Effects in Direct-to-
Consumer Television Advertisements for Prescription Drugs, and 0910-
0772--Eye Tracking Study of Direct-to-Consumer Prescription Drug 
Advertisement Viewing) to the context of indication statements. This 
previous research supports the use of dual modality to increase 
consumers' understanding of risk information (January 27, 2012, 77 FR 
4273) (Refs. 2 and 3).
    We plan to conduct two rounds (one for each objective) of nine 1-
hour in-person cognitive interviews of adults 18 years of age or older 
to refine the questionnaires and stimuli (18 participants total). We 
plan to conduct two pretests (one for each objective) not longer than 
20 minutes, administered via internet panel, to test the experimental 
manipulations and pilot the main study procedures.
    We plan to conduct two main studies (one for each objective) not 
longer than 20 minutes, administered via internet panel. For Study 1, 
we will create two television ads for fictitious oncology prescription 
drugs to increase the generalizability of the results (one solid tumor 
indication and one hematology indication). The ads will include audio 
claims about overall survival, overall response rate with and without a 
disclosure, or progression-free survival with and without a disclosure 
(see table 1 for the Study 1 design).
    Some current television ads for oncology products include 
disclosures that are intended to help consumers differentiate surrogate 
endpoints like progression-free survival and overall response rate from 
overall survival. Examples include ``At the time of analysis, overall 
survival comparison was not yet available'' and ``Clinical trials are 
ongoing to determine if there is an overall survival benefit.'' The 
disclosure we use in the study will be based on disclosures currently 
in use and will be informed by consumer feedback elicited in focus 
groups conducted prior to the cognitive testing (approved under OMB 
control number 0910-0695). For example, the study disclosure may 
include language such as ``We currently do not know if Drug X helps 
people live longer.''
    Participants will be randomly assigned to view one prescription 
drug television ad and then complete a questionnaire that assesses 
whether participants noticed the disclosure, their interpretations of 
the disclosure, their retention of the endpoint, and their perceptions 
of the drug's benefits and risks. We will also measure covariates such 
as demographics, cancer history, and literacy. Without a disclosure, we 
hypothesize that participants will not differentiate between overall 
survival, overall response rate, and progression-free survival. We 
hypothesize that a disclosure will help participants understand the 
surrogate endpoints (i.e., overall response rate and progression-free 
survival) and thus will lead to greater understanding of the drug's 
efficacy compared with conditions without the disclosure. We will 
explore unintended effects of the disclosure, such as whether the 
disclosure lowers perceived efficacy compared with the overall survival 
condition.
    For the second objective, in Study 2 we will vary the presentation 
of the products' indication, such that material information related to 
the indication will appear in superimposed text only, in the audio 
only, in both superimposed text and audio, or in neither (the control 
condition; see tables 2 and 3 for the Study 2 design). Participants 
will be randomly assigned to view a prescription drug television ad and 
then complete a questionnaire that assesses their retention and 
comprehension of the information. Following previous research on dual-
modality presentations, we hypothesize that participants who view an ad 
with the material information in the audio and text will have greater 
retention of that information than participants in any other condition. 
We also hypothesize that participants who view an ad with the material 
information in the audio only will have greater retention of that 
information than participants in the superimposed text condition and 
the control condition. To test Study 1 and

[[Page 5215]]

2 hypotheses, we will conduct inferential statistical tests such as 
logistic regression and analysis of variance.
    The questionnaires are available upon request from 
DTCresearch@fda.hhs.gov.
    For all phases of this research, we will recruit a general 
population sample of adult volunteers 18 years of age or older. We will 
exclude individuals who work for the Department of Health and Human 
Services or work in the healthcare, marketing, or pharmaceutical 
industries. We will use literacy quotas to ensure that our sample 
includes participants with a range of literacy skills. We will also 
exclude pretest participants from the main studies, and participants 
will not be able to participate in both Studies 1 and 2. With the 
sample sizes described below, we will have sufficient power to detect 
small-sized effects in Studies 1 and 2 (table 4).

                                             Table 1--Study 1 Design
----------------------------------------------------------------------------------------------------------------
                                                                      Overall                      Progression-
                                      Overall         Overall      response rate   Progression-    free survival
           Indication                survival      response rate       with        free survival       with
                                                                    disclosure                      disclosure
----------------------------------------------------------------------------------------------------------------
Solid Tumor.....................  ..............  ..............  ..............  ..............  ..............
Hematology......................  ..............  ..............  ..............  ..............  ..............
----------------------------------------------------------------------------------------------------------------
Note: The solid tumor condition will be non-small cell lung cancer. The hematology condition will be multiple
  myeloma. Claims and disclosures are TBD, based on focus group feedback. Overall survival and progression-free
  survival claims will be the same for both indications. Study 1 will use the control ad from Study 2.


                                      Table 2--Study 2 Design: Solid Tumor
----------------------------------------------------------------------------------------------------------------
                                                                Material information in    Material information
 Material information in superimposed  Material information in    superimposed text +      not in superimposed
              text only                       audio only                 audio           text or audio (control)
----------------------------------------------------------------------------------------------------------------
                                             Indication presentation
----------------------------------------------------------------------------------------------------------------
Audio: Drug X is for adults with       Audio: Drug X is for     Audio: Drug X is for     Audio: Drug X is for
 advanced non-small cell lung cancer.   adults with advanced     adults with advanced     adults with advanced
Superimposed text: Drug X is for        non-small cell lung      non-small cell lung      non-small cell lung
 adults with advanced non-small cell    cancer previously        cancer previously        cancer.
 lung cancer previously treated with    treated with platinum-   treated with platinum-  Superimposed text: Drug
 platinum-based chemotherapy, who       based chemotherapy,      based chemotherapy,      X is for adults with
 have a certain type of ALK gene..      who have a certain       who have a certain       advanced non-small
                                        type of ALK gene.        type of ALK gene.        cell lung cancer.
                                       Superimposed text: Drug  Superimposed text: Drug
                                        X is for adults with     X is for adults with
                                        advanced non-small       advanced non-small
                                        cell lung cancer..       cell lung cancer
                                                                 previously treated
                                                                 with platinum-based
                                                                 chemotherapy, who have
                                                                 a certain type of ALK
                                                                 gene..
----------------------------------------------------------------------------------------------------------------
Note: Study 2 will use the overall survival ad from Study 1.


                                       Table 3--Study 2 Design: Hematology
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                                                                Material information in    Material information
 Material information in superimposed  Material information in    superimposed text +      not in superimposed
              text only                       audio only                 audio           text or audio (control)
----------------------------------------------------------------------------------------------------------------
                                             Indication presentation
----------------------------------------------------------------------------------------------------------------
Audio: Drug Y is used to treat         Audio: Drug Y is used    Audio: Drug Y is used    Audio: Drug Y is used
 multiple myeloma.                      to treat multiple        to treat multiple        to treat multiple
Superimposed text: Drug Y is used to    myeloma in combination   myeloma in combination   myeloma.
 treat multiple myeloma in              with dexamethasone, in   with dexamethasone, in  Superimposed text: Drug
 combination with dexamethasone, in     people who have          people who have          Y is used to treat
 people who have received at least      received at least        received at least        multiple myeloma.
 three prior medicines to treat         three prior medicines    three prior medicines
 multiple myeloma..                     to treat multiple        to treat multiple
                                        myeloma.                 myeloma.
                                       Superimposed text: Drug  Superimposed text: Drug
                                        Y is used to treat       Y is used to treat
                                        multiple myeloma..       multiple myeloma in
                                                                 combination with
                                                                 dexamethasone, in
                                                                 people who have
                                                                 received at least
                                                                 three prior medicines
                                                                 to treat multiple
                                                                 myeloma..
----------------------------------------------------------------------------------------------------------------
Note: Study 2 will use the overall survival ad from Study 1.

    In the Federal Register of June 21, 2019 (84 FR 29213), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. FDA received four submissions that were PRA-
related. Within those submissions, FDA received multiple comments, 
which the Agency has addressed below.
    (Comment 1) One comment voiced support for the current study and 
recommended future research to examine how DTC advertising addresses 
value-based care.
    (Response 1) We thank the commenter for their support for this 
study and will consider their recommendations for future research.
    (Comment 2) Two comments suggested limiting study recruitment to 
patients already diagnosed with and/or

[[Page 5216]]

treated for cancer and their caregivers and family members. The 
comments suggested that patients who have already been diagnosed and/or 
treated are likely to have a higher level of disease comprehension than 
the general population and that this would make the results more 
reflective of the population seeking cancer treatment information.
    (Response 2) We chose a general population sample for the first 
study on this topic because of concerns about being able to recruit a 
sufficient number of participants if we selected a cancer-specific 
sample. However, we agree that in the future, a small, carefully-
designed replication study with cancer patients and their caretakers 
and family members would be valuable. Prior to this study, we conducted 
both general-population focus groups and cancer-survivor focus groups. 
We will use the information gleaned from these focus groups to consider 
the ways in which these groups do and do not differ when discussing the 
limitations of the study's general-population sample. We will also ask 
participants if they have been diagnosed with cancer and whether they 
are a caregiver for someone with cancer.
    (Comment 3) One comment suggested that the duration of the study 
ads be consistent with the duration of real-life ads.
    (Response 3) The duration of the study ads will be consistent with 
the duration of real-life ads.
    (Comment 4) One comment suggested adding screening questions to 
assess whether participants watch television, whether they watch ads, 
and how they are most likely to view DTC television ads.
    (Response 4) We added questions about television viewing to the end 
of the questionnaire.
    (Comment 5) One comment agreed with the hypothesis that consumers 
who view an ad with material information in both audio and text will 
have greater retention of that information. However, they do not 
believe there is enough time in a television ad to include the full 
indication in the audio, and they do not believe it is necessary 
because they believe the primary objective of ads is to raise product 
awareness so that consumers can seek additional information about the 
drug from health care providers or adequate provision sources.
    (Response 5) The duration of the ads used in this study will be 
consistent with those currently airing on television and that duration 
will be sufficient to include all material information (Ref. 4) in the 
audio and text. While consumers may be able to find this information 
through other sources, the intent of this study is to determine what 
effect, if any, the material information has when delivered as an 
integrated part of the DTC advertisement.
    (Comment 6) One comment notes that the Study 1 results would not be 
generalizable to an ad for a drug that has overall survival data but 
advertises with claims about overall response rate or progression-free 
survival.
    (Response 6) We agree that our results would not generalize to this 
situation.
    (Comment 7) One comment suggested wording changes for the claims in 
Study 1, including deleting ``decrease the number of detectable cancer 
cells in the body'' from the multiple myeloma overall response rate, 
describing progression-free survival as ``delayed disease progression 
or live longer without cancer getting worse,'' and using the disclosure 
statement ``clinical trials are still ongoing to determine if there is 
an overall survival benefit with Drug X.''
    (Response 7) We thank the commenter for these suggestions and will 
consider them, along with the feedback from our focus group 
participants, when we finalize the language for the main study.
    (Comment 8) One comment suggested changes to the Study 1 
questionnaire, including rewording Q2 to make it clearer, adding a 
``don't know'' response to Q4, removing Q5 because it is speculative, 
and rewording Q7 from ``any side effects it may have'' to ``side 
effects described in the ad.''
    (Response 8) We revised Q2 to ask what the drug can do for people, 
added a ``don't know'' response to Q4, and edited Q7 as suggested. Q5 
will only be asked of participants who already report that the drug 
will help people live longer; its purpose is to gauge their perception 
of how much longer people will live. We plan to keep this item, but we 
will cognitively test and pretest it to determine whether it should be 
revised or deleted.
    (Comment 9) One comment suggested changes to the Study 2 
questionnaire, including changing Q2 to ask about what disease the drug 
treats rather than who it is for, so it is less similar to Q4, adding 
Q10 from the Study 1 questionnaire to measure behavioral intentions, 
and revising Q7-Q12 because they are too detailed and require the 
respondent to recall a lot of information from the ad.
    (Response 9) We agree that Questions 2 and 4 are similar; they are 
both designed to elicit responses related to the material information, 
not just the disease the drug is indicated to treat. However, Question 
4 will only be asked of participants who respond ``no'' to Question 3. 
We believe this will provide context for those participants, but we 
will ask whether this series of questions is too repetitive or 
confusing in cognitive interviews, and we will review participants' 
responses in a pretest. We will add Q10a and Q10b to the Study 2 
questionnaire. Questions 7 through 12 are designed to measure 
participants' retention and understanding of the material information. 
We will cognitively test and pretest the items to determine whether 
they should be revised or deleted.
    FDA estimates the burden of this collection of information as 
follows:

                                                      Table 4--Estimated Annual Reporting Burden 1
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                                                                  Number of
                   Activity                       Number of     responses per   Total annual         Average  burden  per response          Total hours
                                                 respondents     respondent       responses
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Cognitive Interview screener.................              30               1              30  0.08 (5 minutes).........................             2.4
Cognitive Interviews.........................              18               1              18  1 (60 minutes)...........................              18
Pretests 1 and 2 screener....................             200               1             200  0.08 (5 minutes).........................              16
Pretests 1 and 2.............................             120               1             120  0.33 (20 minutes)........................            39.6
Study 1 screener.............................           1,167               1           1,167  0.08 (5 minutes).........................           93.36
Study 1......................................             700               1             700  0.33 (20 minutes)........................             231
Study 2 screener.............................             867               1             867  0.08 (5 minutes).........................           69.36
Study 2......................................             520               1             520  0.33 (20 minutes)........................           171.6
                                              ----------------------------------------------------------------------------------------------------------
    Total....................................  ..............  ..............  ..............  .........................................          641.32
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.


[[Page 5217]]

II. References

    The following references marked with an asterisk (*) are on display 
at the Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852) and 
are available for viewing by interested persons between 9 a.m. and 4 
p.m., Monday through Friday; they also are available electronically at 
https://www.regulations.gov. References without asterisks are not on 
public display at https://www.regulations.gov because they have 
copyright restriction. Some may be available at the website address, if 
listed. References without asterisks are available for viewing only at 
the Dockets Management Staff. FDA has verified the website addresses, 
as of the date this document publishes in the Federal Register, but 
websites are subject to change over time.

    1. Kim, J., J. Gao, L. Amiri-Kordestani, et al., ``Patient-
Friendly Language to Facilitate Treatment Choice for Patients with 
Cancer.'' The Oncologist, 10.1634/theoncologist.2018-0761, 2019. 
Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693727/.
    2. Aikin, K.J., A.C. O'Donoghue, C.M. Squire, et al., ``An 
Empirical Examination of the FDAAA-Mandated Toll-Free Statement for 
Consumer Reporting of Side Effects in Direct-to-Consumer Television 
Advertisements.'' Journal of Public Policy & Marketing, 35(1):108-
123, 2016.
    3. Sullivan, H.W., V. Boudewyns, A.C. O'Donoghue, et al., 
``Attention to and Distraction from Risk Information in Prescription 
Drug Advertising: An Eye-Tracking Study.'' Journal of Public Policy 
& Marketing, 36(2):236-245, 2017.
    4. 21 U.S.C. 321(n).

    Dated: January 23, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-01555 Filed 1-28-20; 8:45 am]
BILLING CODE 4164-01-P


