[Federal Register Volume 72, Number 49 (Wednesday, March 14, 2007)]
[Notices]
[Pages 11889-11892]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-4556]



[[Page 11889]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2006N-0133]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Experimental 
Evaluation of Variations in Content and Format of the Brief Summary in 
Direct-to-Consumer Print Advertisements for Prescription Drugs

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 (the PRA).

DATES: Fax written comments on the collection of information by April 
13, 2007.

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: 202-395-6974.

FOR FURTHER INFORMATION CONTACT: Elizabeth Berbakos, Office of the 
Chief Information Officer (HFA-250), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-1482.

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

Experimental Evaluation of Variations in Content and Format of the 
Brief Summary in Direct-to-Consumer Print Advertisements for 
Prescription Drugs--(OMB Control Number 0910-0591)

    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 903(b)(2)(c) of the Federal Food, Drug, and 
Cosmetic Act (the act) (21 U.S.C. 393(b)(2)(c)) authorizes FDA to 
conduct research relating to drugs and other FDA-regulated products in 
carrying out the provisions of the act. Under the act, a drug is 
misbranded if its labeling or advertising is false or misleading. In 
addition, section 502(n) of the act (21 U.S.C. 352(n)) specifies that 
advertisements for prescription drugs and biological products must 
provide a true statement of information ``in brief summary'' about the 
advertised product's ``side effects, contraindications, and 
effectiveness.'' The prescription drug advertising regulations (Sec.  
202.1(e)(3)(iii) (21 CFR 202.1(e)(3)(iii))) specify that the 
information about risks must include ``each specific side effect and 
contraindication'' from the advertised drug's approved labeling. The 
regulation also specifies that the phrase ``side effect and 
contraindication'' refers to all of the categories of risk information 
required in the approved product labeling written for health 
professionals, including the warnings, precautions, and adverse 
reactions sections. Thus, every risk in an advertised drug's approved 
labeling must be included to meet these regulations.
    In recent years, FDA has become concerned about the adequacy of the 
brief summary in Direct-to-Consumer (DTC) print advertisements. 
Although advertising of prescription drugs was once primarily addressed 
to health professionals, increasingly consumers have become a target 
audience, as DTC advertising has dramatically increased in the past few 
years.
    Because the regulations do not specify how to include each risk, 
sponsors can use discretion in fulfilling the brief summary requirement 
under Sec.  202.1(e)(3)(iii). Frequently, sponsors print in small type, 
verbatim, the risk-related sections of the approved product labeling 
(also called the package insert, professional labeling, or prescribing 
information). This labeling is written for health professionals, using 
medical terminology. FDA believes that while this is one reasonable way 
to fulfill the brief summary requirement for print advertisements 
directed toward health professionals, this method is difficult for 
consumers to understand and therefore may not be the best approach to 
communicate this important information to them.
    In 2004, FDA published a draft guidance entitled ``Brief Summary: 
Disclosing Risk Information in Consumer-Directed Print Advertisements'' 
(available at http://www.fda.gov/cder/guidance/5669dft.htm). This 
guidance outlined possible options for improving the communication of 
risk information to consumers in specific promotional pieces. When 
discussing the current professional prescribing information format, the 
guidance states that the ``volume of the material, coupled with the 
format in which it is presented... discourages its use and makes the 
information less comprehensible to consumers.'' The draft guidance 
suggested three possible presentations for the brief summary, including 
the current prescribing information format, an approved patient package 
insert, or highlights from the physician labeling rule.
    In the content study, FDA plans to investigate the role of context 
in providing useful risk information to consumers. It has been 
theorized that long lists of minor risks may detract from the 
understanding of more serious risks, as stated in the draft guidance. 
Nonetheless, if the risk information is presented with proper 
supporting context, people may find the information facilitates rather 
than distracts from the understanding of the risk information. One of 
the two proposed studies in this notice will investigate the context 
that may contribute to this facilitation.
    In addition to context, format also plays a role in the clarity and 
understanding of the brief summary. FDA proposes to collect information 
on the usefulness of different formats suggested in the draft guidance. 
In addition to the patient package insert, which is usually presented 
in a question and answer format, FDA proposes to test a consumer-
friendly highlights format, as well as a format based on the drug facts 
labeling used for over-the-counter drugs.
    Data from these two studies will converge to allow a better 
assessment of various ways to present risk information in a print 
advertisement for a prescription drug.
    FDA estimates that 1,800 individuals will need to be screened to 
obtain a respondent sample of 900 for the content study and that 600 
individuals will need to be screened to obtain a respondent sample of 
300 for the format study. The screener is expected to take 30 seconds, 
for a total screener burden of 41 hours. The 1,200 respondents in the 
two studies will then be asked to respond to a series of questions 
about the advertisement. We estimate the response burden for each of 
the two studies to be 20 minutes, for a burden of 396 hours. The 
estimated total burden for this data collection effort is 437 hours.
    In the Federal Register of April 25, 2006 (71 FR 23921), FDA 
published a 60-day notice requesting public comment on the information 
collection provisions. Seven comments were received, and none were PRA 
related.
    Five comments were from individual citizens, one comment was from 
AstraZeneca, a member of industry, and

[[Page 11890]]

one comment was from a health care coalition, the Clear Language Group. 
Most of the comments addressed the proposed content study.
    The five comments from individual citizens were identical. They 
stated, ``Deny the drug industry petition. Show all side effects.'' 
These comments show a lack of understanding of the relevant issues. 
This proposed information collection is not a pharmaceutical industry 
petition; it is a research project supported by funds received from the 
Office of Medical Policy within the Center for Drug Evaluation and 
Research, part of FDA. The goal of this research is to further the 
public health by improving the readability and functionality of the 
brief summary in print ads, an easily accessed forum for information. 
Research in cognitive psychology overwhelmingly suggests that people 
have limited capacity for information and cannot process endless 
lists.\1\ Recent research has suggested that providing a small number 
of the more minor side effects may actually improve the understanding 
of the benefit-risk tradeoff of the drug as a whole.\2\ FDA wants to 
ensure that the presentation of risk information is in the best 
interests of consumers. This research will provide empirical evidence 
to support the optimal presentation of side effects.
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    \1\ Lavie, N. (2001). Capacity limits in selective attention: 
Behavioral evidence and implications for neural activity. In Braun, 
J., Koch, C., et al. (Eds.), Visual attention and cortical circuits. 
Cambridge, MA: The MIT Press (pp. 49-68); Shapiro, K. (Ed.) (2001). 
The limits of attention: Temporal constraints in human information 
processing. London: Oxford University Press.
    \2\ See, e.g., Stotka, J.L., Rotelli, M.D., Dowsett, S.A., 
Elsner, M.W., Holdsworth, S.M., et al. (2007). A new model for 
communicating risk information in direct-to-consumer print 
advertisements. Drug Information Journal, 41, 111-127.
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    In the sixth comment, AstraZeneca supported the proposed research 
as a method to create more consumer-friendly brief summaries. They 
requested that the research be delayed, however, until the data from 
study 1 is collected. If this were not possible, they requested that 
the comment period remain open until commenters have the ability to 
look at the questionnaire materials. Study 1 is currently in the field 
and we expect to have data available by the midpoint of the year. These 
results will be analyzed in the next several months. Given the interest 
in the finalization of the brief summary guidance,\3\ which in part 
relies on information from these studies, we cannot delay the 
development of studies 2 and 3 until data from study 1 are analyzed and 
interpreted. Questionnaire materials are available for public comment 
through FDA's Office of Information Review Management. Comments may be 
submitted to the docket at any time, even after the docket has closed.
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    \3\ See, e.g., http://www.fda.gov/ohrms/dockets/dockets/05n0354/05N-0354-EC444-Attach-1.pdf; Washington Legal Foundation response to 
the Division of Drug Marketing, Advertising, and Communications 
regarding WellSpring Pharmaceutical Corp. at http://www.wlf.org/Resources/DDMAC/default.asp. (FDA has verified the Web site address, 
but FDA is not responsible for any subsequent changes to the Web 
site after this document publishes in the Federal Register.)
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    The final comment was submitted by Sarah Furnas as a representative 
of the Clear Language Group, a consortium of plain language 
consultants, and involved two primary concerns. The first concern 
regarded our plan to recruit and divide respondents into education 
groups of completed college or some college or less. This division may 
limit our ability to make finer distinctions among educational groups. 
Moreover, Furnas suggests that people who struggle with obesity fall 
disproportionately into the lower education groups. If FDA chose a 
division point that represents a fairly high level of education, they 
may recruit more people from the highest education group, thus leaving 
out an appropriate proportion of lower education individuals. Furnas 
suggests using the educational breakdown used by the American Obesity 
Association: 4+ years of college, some college, high school graduate, 
and some high school. FDA agrees and will incorporate this suggestion 
into the questionnaire.
    This commenter also expressed concern that the options in our 
research design require high numeracy and document literacy skills. 
Furnas suggested that FDA omit some of the design options and perhaps 
add other, easier options. First, although FDA shares the goal of 
making documents easier to read and would like to make the brief 
summary accessible to the greatest number of people possible, at some 
level, people who have difficulty reading will not seek out a written 
explanation of risks. In its guidance Consumer Directed Broadcast 
Advertisements,\4\ the agency suggested a number of ways complete risk 
information could be obtained by consumers, including a toll-free 
telephone number, making this option a good choice for those who have 
difficulty reading health information.
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    \4\ Available at http://www.fda.gov/cder/guidance/1804fnl.htm. 
(Last accessed March 8, 2007.)
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    Consumers who have difficulty reading may not seek out medical 
information in a print advertisement, especially in its current form. 
However, the very nature of the information in the brief summary is the 
communication of risk information which is at its heart probability-
based. By limiting their options, FDA not only fails to empirically 
determine the best option for the greatest number of people, but they 
may fail to appropriately inform the people who are most likely to read 
the advertisement and the brief summary. Therefore, FDA is testing ways 
to better communicate this information.
    Second, FDA does not agree that table formats are more difficult to 
read than lists of information in paragraph format. The over-the-
counter labeling change of 1999 (21 CFR 201.66), requiring a 
presentation of Drug Facts in a table format, has received positive 
reviews for its improvement over older labels.\5\ Moreover, the 
Nutrition Facts label required as part of the Nutrition Labeling and 
Education Act of 1990 has also received praise for its easier-to-
understand format.\6\ These two table-based formats have been in the 
public domain for several years now, making them familiar to consumers. 
Nonetheless, FDA has changed its design based on other factors and will 
not be examining a chart or table format.
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    \5\ For example, the Association of Clinicians for the 
Underserved states, ``These new labels should assist consumers in 
the selection of Over the Counter (OTC) products by enabling them to 
assess drugs' risks and benefits more easily.'' (http://www.clinicians.org/programsandservices/rxfiles/patient_education_safety.html) (FDA has verified the Web site address, but FDA is not 
responsible for any subsequent changes to the Web site after this 
document publishes in the Federal Register.)
    \6\ Marietta, A.B., Welshimer, K.J., and Anderson, S.L. (1999). 
Knowledge, attitudes, and behaviors of college students regarding 
the 1990 Nutrition Label Education Act food labels. Journal of the 
American Dietetic Association, 99, 445-449.
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    FDA acknowledges that placebo may be a fairly complex concept for 
many people. One of the research goals is to determine whether the 
addition of context may improve the understandability or usefulness of 
the brief summary as a whole. The value of an experimental design is 
that FDA will be able to empirically test whether or not their 
manipulations have an effect. Therefore, FDA has chosen two other forms 
of context, the frequency of side effects, and the temporal nature of 
side-effects, in place of placebo rate. FDA will be able to determine 
which groups have more or less difficulty with each condition. It is 
likely that at least some people will value the addition of this 
information.
    In the interest of communicating to as many people as possible, FDA 
has changed the format of the rate information. Instead of providing 
this

[[Page 11891]]

information in percentages, FDA will provide this information as, ``x 
out of 100.'' FDA thanks this commenter for bringing these issues to 
their attention.
    As a result of the comments, the agency received and some further 
thought on the design of the studies, FDA has altered the designs 
somewhat. The following are the revised designs.

Content Study

    Design Overview: This study will employ a between-subjects crossed 
factorial design using a mall-intercept protocol. We will manipulate 
the minor side effect section, varying the presence of frequency 
information and the presence of framing, and the efficacy section, 
varying the presence of frequency information. We are interested in how 
these changes influence the understanding of the risks of the product 
as a whole, particularly the more serious risk sections. If these 
changes enhance or, at the very least, do not detract from the major 
risks, then these additions of context may be something to include in 
future brief summaries. In the best case scenario, we find context that 
enhances the total picture of the drug and does not interfere with the 
processing of the major risks.
    Primary Research Questions
    a. Will the presence of information on the frequency of minor side 
effects influence the readers' comprehension of the major risks? Will 
the comprehension of major risks vary depending on whether the 
frequencies are high or low?
    b. Will the presence of information on the temporal duration of 
minor side effects influence the comprehension of the major risks?
    c. Will the presence of clinical efficacy information influence 
readers' comprehension of the major risks? Will the comprehension of 
the major risks vary depending on whether clinical efficacy is high or 
low?
    d. Will clinical efficacy and frequency of minor side effects 
interact to influence comprehension of major risks? Will clinical 
efficacy and temporal duration interact to influence comprehension of 
major risks?
    Procedure: Participants will be shown one advertisement. Then a 
structured interview will be conducted with each participant to examine 
a number of important perceptions about the brief summary, including 
perceived riskiness of the drug, comprehension of information in the 
brief summary, and perceived usefulness of brief summary information. 
Finally, demographic and health care utilization information will be 
collected. Interviews are expected to last approximately 20 minutes. A 
total of 900 participants will be involved. This will be a one-time 
(rather than annual) collection of information.

Format Study

    Design Overview: This study will employ a between-subjects crossed 
factorial design using a mall-intercept protocol. Four print 
advertisements will be created using four different formats: 
Traditional long format, Question and Answer, Highlights (71 FR 3922, 
January 24, 2006), and Drug Facts (21 CFR 201.66). As much as possible, 
the information in the formats will be constant across conditions. 
Participants who self-identify as being in the target market for the 
condition will be asked to read a single print advertisement for a new 
prescription drug. After reading the advertisement, they will be asked 
questions about their comprehension and evaluation of the information 
presented in the advertisement. Lastly, participants will be shown all 
four versions and asked to rate them relative to one another on 
measures assessing visual appeal, preference, and information 
accessibility.
    Primary Research Questions
    a. Will alternative formats influence the comprehension of major 
risks, behavioral intentions, and/or self-efficacy?
    b. Which format will consumers prefer?
    Procedure: Participants will be shown one advertisement. Then a 
structured interview will be conducted with each participant to examine 
a number of important perceptions about the brief summary, including 
perceived riskiness of the drug, comprehension of information in the 
brief summary, and perceived usefulness of brief summary information. 
Finally, demographic and health care utilization information will be 
collected. Interviews are expected to last approximately 20 minutes. A 
total of 300 participants will be involved. This will be a one-time 
(rather than annual) collection of information.
    FDA estimates the burden of this collection of information as 
follows:
    FDA estimates that 1,800 individuals will need to be screened to 
obtain a respondent sample of 900 for the Content study, and 600 
individuals will need to be screened to obtain a respondent sample of 
300 for the Format study. The screener is expected to take 30 seconds 
in each study, for a total screener burden of 41 hours. The 1,200 
respondents in the two studies will then be asked to respond to a 
series of questions about the advertisement. We estimate the response 
burden for each of the two studies to be 20 minutes, for a burden of 
396 hours. The estimated total burden for this data collection effort 
is 437 hours. The respondent burden is listed in table 1 of this 
document.

                                 Table 1.--Estimated Annual Reporting Burden\1\
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                                       Annual Frequency     Total Annual        Hours per
         No. of Respondents              per Response        Responses           Response         Total Hours
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1,800 (content study: screener)                       1              1,800               .017                 31
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900 (content study: questionnaire)                    1                900               .33                 297
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600 (format study: screener)                          1                600               .017                 10
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300 (format study: questionnaire)                     1                300               .33                  99
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Total                                                                                                        437
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.



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    Dated: March 7, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-4556 Filed 3-13-07; 8:45 am]
BILLING CODE 4160-01-S