[Federal Register Volume 76, Number 243 (Monday, December 19, 2011)]
[Notices]
[Pages 78663-78667]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-32275]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-N-0230]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Examination of Online 
Direct-to-Consumer Prescription Drug Promotion

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 January 
18, 2012.

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, Examination of Online Direct-to-Consumer Prescription Drug 
Promotion. Also include the FDA docket number found in brackets in the 
heading of this document.

FOR FURTHER INFORMATION CONTACT: Juanmanuel Vilela, Office of 
Information Management, Food and Drug Administration, 1350 Piccard Dr., 
PI50-400B, Rockville, MD 20850, (301) 796-7651, 
juanmanuel.vilela@fda.hhs.gov..

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.

Examination of Online Direct-to-Consumer Prescription Drug Promotion--
(OMB Control Number 0910--New)

I. Background

    Pharmaceutical products are launched and marketed in a number of 
new modalities and venues that did not exist a short time ago. 
Increasingly, prescription products are promoted to consumers online in 
such formats as banners, Web sites, and videos. The interactive nature 
of the Internet allows for features not possible with traditional media 
(i.e., print, radio, and television), such as scrolling information, 
popup windows, linking to additional information, and embedded videos. 
FDA regulations require that prescription drug advertisements include a 
``fair balance'' of information about the benefits and risks of 
advertised products, both in terms of the content and presentation of 
the information (21 CFR 202.1(e)(5)(ii)). All prescription drug 
promotion that makes claims about a product must, therefore, also 
include risk information in a ``balanced'' manner. Currently, there are 
a number of questions surrounding how to achieve ``fair balance'' in 
online direct-to-consumer (DTC) promotion.
    A few studies have examined how well online DTC Web sites 
communicate benefit and risk information. Although content analyses 
demonstrate that most Web sites include information on side effects and 
contraindications (Ref. 1), risk information is often presented less 
prominently and in fewer locations on the Web site (Refs. 2, 3, and 4). 
Content analyses also suggest that risk information on DTC prescription 
drug Web sites is often incomplete (Ref. 5) and written at very high 
literacy levels (Ref. 6).
    One study examined how users interact with prescription drug Web 
sites (Ref. 7). This study found that the placement of risk and benefit 
information on a Web site is an important factor in whether it achieves 
``fair balance.'' Specifically, participants' ability to find and 
accurately recall risk information was enhanced when risk and benefit 
information were presented separately and when risk information was 
presented on a higher order page (i.e., on a second-level page clearly 
linked from the homepage, or on the homepage).
    This project is designed to test different ways of presenting 
prescription drug risk and benefit information on branded drug Web 
sites. This research is relevant to current policy questions and debate 
and will complement qualitative research we plan to conduct on issues 
surrounding social media. The series of studies described in this 
document will provide data that, along with other input and 
considerations, will inform the development of future guidance.

[[Page 78664]]

II. Comments

    In the Federal Register of April 28, 2011 (76 FR 23821), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. Seven statements were received, some of 
which included several comments.
    (Comment 1) One comment expressed the opinion that DTC advertising 
will never present risk and benefit information in a balanced manner 
and therefore the government should take a stronger stand against DTC 
advertising.
    (Response) This is outside the scope of this project, but we note 
that the overall purpose of the research is to improve consumer 
understanding of prescription drug advertising.
    (Comment 2) The comment describes Web archiving technology and how 
it can be used to capture information from Web sites. They recommended 
we use their company's Web archiving services for regulatory activities 
and to conduct the study.
    (Response) The sections of this comment that relate to how the 
company's services can be used for regulatory activities are beyond the 
scope of this project. The sections that relate to the research suggest 
that we could use Web archiving technology to create Web sites for the 
study; however, we plan to create new, unique, fictitious Web sites for 
the study to ensure familiarity with a particular Web site or brand 
does not have any influence on our findings.
    (Comment 3) Two statements suggested additional information should 
be collected from participants. One statement suggested we use some of 
this additional information (prescription drug use) as a covariate.
    (Response) Some of the additional information suggested is already 
included in the questionnaire (e.g., age, ethnicity, education level, 
and prescription drug use for the medical condition of interest). 
Although native language and whether participants are hearing or vision 
impaired are not directly assessed, participants must be capable of 
completing an intake questionnaire and core adult profile survey, both 
of which are written at an eighth grade reading level. Other additional 
information suggested will be included. Specifically, we will include 
level of Internet use and length of time from diagnosis with the 
medical condition of interest. In addition, we will use prescription 
drug use for the medical condition of interest as a covariate in our 
analyses.
    (Comment 4) One comment addressed the recruitment process, 
requesting that we disclose how participants will be recruited and 
recommending online recruitment.
    (Response) We plan to recruit and conduct the study online.
    (Comment 5) One comment recommended that caregivers also be 
included as participants.
    (Response) To ensure that our participants are motivated to 
consider the information presented in the study and to conserve 
resources, we will limit our sample to people who have the medical 
condition of interest.
    (Comment 6) One comment requested that we not apply the results of 
these studies to social media and mobile technology, as Web sites 
differ in a number of ways from other online contexts.
    (Response) These studies are designed to address questions 
surrounding branded prescription drug Web sites and therefore the 
results will not be applied to social media and mobile technology.
    (Comment 7) One comment requested that FDA publish the study design 
for the qualitative study mentioned in the Federal Register notice.
    (Response) FDA plans to conduct 10 focus groups to investigate how 
consumers, patients, and caregivers use online health communities and 
social media sites to make health decisions, especially regarding 
prescription drugs. These focus groups received OMB approval on April 
28, 2011 (``Examination of Online Direct-to-Consumer Prescription Drug 
Promotion,'' OMB control number 0910-0677). FDA will share the results 
of these focus groups when they become available.
    (Comment 8) One comment suggested that the proposed samples sizes 
may not result in adequate statistical power.
    (Response) We have conducted power analyses and will have 
sufficient sample to detect small to medium size effects with an alpha 
level of 0.05 and power of 0.90.
    (Comment 9) One statement suggested that the proposed 2 x 2 + 1 
design in Study 2 may limit an objective assessment of the effect of 
the variables in the control group. Another questioned the presence of 
the control group in Study 2, suggesting that it may confound the 
interpretation of results regarding the ``prominence'' manipulation. 
This statement suggested evaluating prominence in a separate part of 
the study.
    (Response) Study 2 is designed to test two research questions: (1) 
To what extent does the presence of special features (e.g., personal 
testimonials, animated visuals) on a branded drug Web site influence 
consumer perceptions of a prescription drug and (2) to what extent does 
the prominence of risk information in special features on a branded 
drug Web site influence consumer perceptions of a prescription drug? 
Both research questions can be addressed within the same design without 
having to evaluate prominence in a separate design. The first research 
question will be tested by comparing responses of participants exposed 
to a Web site with a special feature to those who were not (the control 
group). The second research question will be tested by comparing 
responses of participants exposed to more prominently displayed risk 
information to those exposed to less prominently displayed risk 
information (i.e., the control condition would not be included in these 
analyses).
    (Comment 10) One comment stated that the study outcome measures 
were not clear and recommended using validated measures.
    (Response) The key outcome measures are risk comprehension, benefit 
comprehension, risk perceptions, and benefit perceptions. Where 
validated measures exist we will use them. Because the comprehension 
measures by necessity will be based on the information particular to 
each fictitious drug, these will be new measures; however, they will 
take the form of similar comprehension measures used by FDA and others 
in past research.
    (Comment 11) One comment noted that we planned to conduct the 
studies with participants diagnosed with medical conditions like high 
cholesterol, seasonal allergies, depression, acid reflux, and high 
blood pressure, but suggested we also include participants with other 
medical conditions such as HIV and cancer and replicate the studies 
across different therapeutic areas.
    (Response) As noted in the comment, we plan to conduct the studies 
with patients diagnosed with a range of medical conditions that differ 
in diagnosis, symptomatology, patient population, and treatment 
options. Because it is difficult to recruit participants from low-
incidence samples such as those recommended, we do not plan to include 
these other medical conditions in the study. However, we will consider 
this for future studies and encourage replication across medical 
conditions by other researchers.
    (Comment 12) One comment recommended that FDA not delay issuing 
draft Internet guidance until the results of the studies are known.

[[Page 78665]]

    (Response) FDA does not intend to delay issuing draft guidance 
because of this research.
    (Comment 13) One comment suggested that FDA policy should not 
categorically prohibit the use of hyperlinks to provide risk 
information.
    (Response) Because this comment addresses issues of policy and not 
the current research, this comment is outside the scope of this 
project.
    (Comment 14) One comment suggested that, rather than focus on a 
single branded drug Web site, the studies should take into account the 
multiple executional elements of Internet drug promotion and how online 
promotional executions are affected by the broader health information 
environment. The comment argues that this is necessary because risk and 
benefit comprehension is affected not only by the specifics of one 
branded drug Web site but also by other health information found online 
and elsewhere.
    (Response) The regulations these studies address do not apply to 
the broader online health information environment; rather, each 
individual branded drug Web site needs to achieve fair balance. The 
fictitious branded drug Web sites used in the studies will include 
multiple executional elements; however, only one variable will be 
manipulated at a time in order to maintain experimental control.
    (Comment 15) One comment recommended we take advantage of other 
researchers who can help revise the study design.
    (Response) We obtained comments from peer reviewers and 
incorporated their suggestions in the new design.
    (Comment 16) One comment noted that there are numerous issues that 
this research does not address, including online data mining by 
pharmaceutical companies, techniques of personalization for targeted 
digital pharmaceutical and health marketing, and pharmaceutical 
marketing's ``exploitative'' approach to social media. The comment 
criticized the focus on branded drug Web sites, as the online marketing 
environment encompasses newer technology.
    (Response) Although there are several other issues surrounding 
prescription drug advertising online, such as privacy concerns, this is 
not the purview of the current research. This research is not designed 
to ``assess the full impact of digital drug marketing'' or document 
pharmaceutical marketing practices but rather to address specific 
issues regarding implementation of ``fair balance'' regulations for 
branded prescription drug Web sites. We note that no one study can 
address all relevant questions and encourage others to pursue research 
in this area to supplement the proposed research.
    Although the online landscape is much broader than Web sites, Web 
sites continue to be a major source of information for consumers (e.g., 
a recent survey found that 49 percent of respondents who went online 
for prescription drug information reported seeking this information on 
a specific brand's Web site (Ref. 8)) and, as noted previously in this 
document, there is not much relevant research on branded prescription 
drug Web sites.
    (Comment 17) One comment suggested that the study use eye tracking 
and neuromarketing methods.
    (Response) Because the comment does not specify why eye tracking 
and neuromarketing should be used in this research beyond noting that 
the pharmaceutical industry employs these methods, it is difficult to 
understand how the current research would benefit from these methods. 
Neuromarketing, for instance, may tell us that participants prefer one 
Web site over another. While this is relevant information from a 
marketing perspective, from a regulatory perspective it is 
comprehension, and not preference, that is the important outcome to 
assess.
    (Comment 18) One comment requested additional information on the 
study. Issues not already addressed previously in this document include 
hypotheses, how the risk information will be portrayed, whether the Web 
site will be viewed under controlled conditions, how the participants' 
perceptions and understanding of the risks and benefits will be 
assessed, and the statistical analyses to be performed.
    (Response) As noted in the 60-day Federal Register notice, the 
questionnaire is available upon request; this demonstrates how 
participants' perceptions and understanding will be assessed. We intend 
to manipulate how the risk information will be portrayed; please see 
the study design. Participant will complete the study online, not under 
controlled conditions. We will ask about the type of device they are 
using to view the Web site and can control for this if necessary. 
Hypotheses and statistical analyses are included in this document.
    (Comment 19) One comment recommends testing the use of hyperlinks 
to risk information in the first study. The comment states that this 
would be useful in developing guidance for social media as well.
    (Response) We have revised the design in Study 1 so that the risk 
visibility manipulation now tests the use of hyperlinks to risk 
information. We note that this study focuses on prescription drug Web 
sites aimed at consumers. As discussed in a previous comment, the 
results of these studies will be applied in this context only and not 
to social media.
    (Comment 20) One comment asks for more detail regarding the 
checklist and animated spokesperson to be used in the first study.
    (Response) The Study 1 risk formats were chosen based on the risk 
communication literature. Risk communication studies have found that 
making risk information less dense (e.g., bulleted lists), more visual 
(e.g., checklists), and audible (e.g., spokesperson) might increase 
comprehension. Thus, we want to test formats that are consistent with 
risk communication best practices. The checklist will be more visual 
and pronounced than a typical bulleted list. The animated spokesperson 
will include an audio component.
    (Comment 21) One comment recommended that FDA follow FDA's 2009 
Draft Guidance on Presenting Risk Information when deciding which risk 
information should be included in the special features in Study 2.
    (Response) FDA will consider this guidance when designing the study 
stimuli.
    (Comment 22) One comment questioned the usefulness of the Study 3 
design.
    (Response) We have redesigned the third study to ensure it 
addresses relevant questions in online prescription drug promotion. 
Please see the revised study design in this document.

III. Revised Study Design

    This research will be conducted in three concurrent studies. The 
design and hypotheses for each study are outlined as follows. We will 
use ANOVAs, planned comparisons, and regressions to test hypotheses.
    The purpose of Study 1 is to investigate whether the presentation 
of risk information on branded drug Web sites influences consumers' 
perceptions and understanding of the risks and benefits of the product. 
In Study 1, we will examine the format (e.g., whether the risk 
information is presented in a paragraph or as a bulleted list) and 
visibility of risk information on a prescription drug Web site. Risk 
visibility will be manipulated by having the risk information on the 
homepage; having the risk information on the homepage with a signal to 
scroll; or having a hyperlink, with a signal to

[[Page 78666]]

click on the link, on the homepage that leads to a secondary page with 
the risk information. The signal will direct participants to the 
important safety information. Participants will be randomly assigned to 
experimental conditions in a factorial design as follows:

                                                            Table 1--Study 1 Proposed Design
                                                                         [3 x 5]
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                                                                         Format
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   Risk visibility             Paragraph                 Bullet list                Checklist              Highlighted box        Animated spokesperson
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On Homepage            .........................  ........................  ........................  ........................  ........................
On Homepage with       .........................  ........................  ........................  ........................  ........................
 Signal
On Secondary Page      .........................  ........................  ........................  ........................  ........................
 with Signal
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A. Study 1 Hypotheses

    1. Locating risk information on the homepage (with or without a 
signal) will lead consumers to have greater perceived risk and greater 
risk comprehension than locating this information on a secondary page 
with a hyperlink. Locating risk information on the homepage with a 
signal will lead consumers to have greater perceived risk and greater 
risk comprehension than locating this information on the homepage 
without a signal.
    2. Presenting risk information in a bulleted list or checklist 
format will lead consumers to have greater perceived risk and greater 
risk comprehension than presenting this information in paragraph 
format.
    3. Presenting risk information in a highlighted box format will 
lead consumers to have greater perceived risk and greater risk 
comprehension than presenting this information in bulleted list, 
checklist, or paragraph format.
    4. We have competing hypotheses for the animated spokesperson. If 
the use of audio increases attention to the animated spokesperson, then 
presenting risk information via an animated spokesperson will lead 
consumers to have greater perceived risk and greater risk comprehension 
than presenting this information in any other format. If the animated 
spokesperson distracts consumers and/or the preset pace of the audio 
presentation is difficult for consumers to follow, then presenting risk 
information via an animated spokesperson will lead consumers to have 
lower perceived risk and lower risk comprehension than presenting this 
information in any other format.
    The purpose of Study 2 is to investigate how special visual 
features on branded drug Web sites influence perceptions and 
understanding of the risks and benefits of the product. The special 
features we will examine are a personal testimonial video and an 
animated mechanism of action visual. Benefit information will be 
presented in either a personal testimonial video, an animated mechanism 
of action visual, or in text (the control). We will examine these 
special features in the context of the prominence of the presentation 
of risk information in two levels; more prominent and less prominent. 
An example of a more prominent display of risk information might 
involve including the risks as part of the spoken testimonial, whereas 
a less prominent display may involve a scrolling text of the risks 
after the animated video. We will include a control condition in which 
participants view a Web page with no special features. Participants 
will be randomly assigned to experimental conditions in a factorial 
design as follows:

                    Table 2--Study 2 Proposed Design
                               [2 x 2 + 1]
------------------------------------------------------------------------
                            Special features
-------------------------------------------------------------------------
                        Personal
Risk presentation     testimonial      Animated visual    Control group
------------------------------------------------------------------------
Prominent          .................  ................  ................
Less Prominent     .................  ................  ................
------------------------------------------------------------------------

B. Study 2 Hypotheses

    1. The presence of any special feature will lead consumers to have 
lower perceived risk, greater perceived efficacy, greater benefit 
comprehension, and greater intentions to ask their doctor about the 
drug than the absence of these features.
    2. More prominently displayed risk information will lead consumers 
to have greater perceived risk and greater risk comprehension than less 
prominently displayed risk information.
    The revised Study 3 design tests whether participants are misled by 
a link from a branded prescription drug Web site to a disease awareness 
Web site with off-label information, and whether the presence of 
context attenuates this potential effect. Participants will be randomly 
assigned to experimental conditions in a factorial design as follows:

[[Page 78667]]



                     Table 3--Study 3 Revised Design
                                 [4 x 1]
------------------------------------------------------------------------
                                 Context
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                                                        External and not
No Link (control)         None          External only       sponsored
------------------------------------------------------------------------
                   .................  ................  ................
------------------------------------------------------------------------

    The three context conditions will include a link. For example, 
``For more information about Disease X, please visit [link].'' An 
example of the ``none'' context condition is, ``if the link is clicked, 
there is an interim page that says `Loading.' '' An example of the 
``external only'' context is, ``if the link is clicked, there is an 
interim page that says `You are leaving the Drug X Web site and 
entering an external Web site.' '' An example of the ``external and not 
sponsored'' context is ``if the link is clicked, there is an interim 
page that says `You are leaving the Drug X Web site and entering an 
external Web site not controlled or endorsed by Pharmaceutical Company 
Y.' ''

C. Study 3 Hypotheses

    1. Participants who view the link to external information, compared 
to those who do not, will have greater perceived efficacy and lower 
correct benefit comprehension.
    2. This effect may be attenuated by context, such that participants 
who view the link without context, compared to those who view the link 
with either type of context, will have greater perceived efficacy and 
lower correct benefit comprehension. We will explore whether the type 
of context (external only vs. external and not sponsored) affects 
perceived efficacy and benefit comprehension.
    In these three studies, participants will be randomly assigned to 
view one version of a (fictitious) prescription drug Web site. After 
viewing the Web site, participants will answer a series of questions 
about the drug. We will test how the manipulations affect outcomes such 
as perceived efficacy, perceived risk, behavioral intention, and 
accurate understanding of the benefit and risk information. In each 
study, the fictitious prescription drug will be for the treatment of a 
high-prevalence medical condition and modeled on an actual drug used to 
treat that condition. Participants will be consumers who have been 
diagnosed with the medical condition of interest. For instance, the 
medical conditions may be high cholesterol and seasonal allergies for 
Study 1, high blood pressure and acid reflux disease for Study 2, and 
depression for Study 3. Interviews are expected to last no more than 25 
minutes (the questionnaire is available upon request). This will be a 
one-time (rather than annual) collection of information.
    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
--------------------------------------------------------------------------------------------------------------------------------------------------------
Screener....................................          16,000               1          16,000  0.03 (2 minutes)..........................             533
Pretests....................................           1,200               1           1,200  0.33 (20 minutes).........................             400
Study 1.....................................           6,000               1           6,000  0.42 (25 minutes).........................           2,500
Study 2.....................................           2,000               1           2,000  0.42 (25 minutes).........................             833
Study 3.....................................           1,000               1           1,000  0.42 (25 minutes).........................             417
                                             -----------------------------------------------------------------------------------------------------------
    Total...................................  ..............  ..............  ..............  ..........................................           4,683
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

IV. References

    The following references have been placed on display in the 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, rm. 1061, Rockville, MD 20852, and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday.

    1. Macias, W. and L. Stavchansky Lewis, ``How Well Do Direct-to-
Consumer (DTC) Prescription Drug Web Sites Meet FDA Guidelines and 
Public Policy Concerns?'' Health Marketing Quarterly, vol. 22, pp. 
45-71, 2005.
    2. Hicks, K.E., M.S. Wogalter, and W.J. Vigilante, Jr., 
``Placement of Benefits and Risks in Prescription Drug 
Manufacturers' Web Sites and Information Source Expectations,'' Drug 
Information Journal, vol. 39, pp. 267-278, 2005.
    3. Huh, J. and B.J. Cude, ``Is the Information 'Fair and 
Balanced' in Direct-to-Consumer Prescription Drug Web Sites?'' 
Journal of Health Communication, vol. 9, pp. 529-540, 2004.
    4. Sheehan, K.B., ``Direct-to-Consumer (DTC) Branded Drug Web 
Sites Risk Presentation and Implications for Public Policy,'' 
Journal of Advertising, vol. 36, pp. 123-135, 2007.
    5. Davis, J.J., E. Cross, and J. Crowley, ``Pharmaceutical Web 
Sites and the Communication of Risk Information,'' Journal of Health 
Communication, vol. 12, pp. 29-39, 2007.
    6. Naik, S. and S.P. Desselle, ``An Evaluation of Cues, 
Inducements, and Readability of Information on Drug-Specific Web 
Sites,'' Journal of Pharmaceutical Marketing and Management, vol. 
17, pp. 61-81, 2007.
    7. Vigilante, Jr., W.J., and M.S. Wogalter, ``Assessing Risk and 
Benefit Communication in Direct-to-Consumer Medication Web Site 
Advertising,'' Drug Information Journal, vol. 39, pp. 3-12, 2005.
    8. Prevention Magazine. 14th Annual Survey of Consumer Reactions 
to DTC Advertising of Prescription Medicines, Emmaus, PA: Rodale, 
Inc., 2011.

    Dated: December 13, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-32275 Filed 12-16-11; 8:45 a.m.]
BILLING CODE 4160-01-P