
[Federal Register Volume 75, Number 240 (Wednesday, December 15, 2010)]
[Notices]
[Pages 78252-78256]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2010-31388]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2010-N-0184]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Experimental Study of 
Patient Information Prototypes

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 
14, 2011.

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 e-mailed to oira_submission@omb.eop.gov. All 
comments should be identified with the OMB control number 0910-new and 
title ``Experimental Study of Patient Information Prototypes.'' Also 
include

[[Page 78253]]

the FDA docket number found in brackets in the heading of this 
document.

FOR FURTHER INFORMATION CONTACT: Elizabeth Berbakos, Office of 
Information Management, Food and Drug Administration, 1350 Piccard Dr., 
PI50-400B, Rockville, MD 20850, 301-792-3792, 
Elizabeth.Berbakos@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.

Experimental Study of Patient Information Prototypes--(OMB Control 
Number 0910-New)

    In order to make informed decisions about health care and to use 
their medications correctly, consumers need easy access to up-to-date 
and accurate information about the risks, benefits and safe use of 
their prescription drugs. Consumers currently receive multiple pieces 
of paper with their prescription drugs from the pharmacy, containing 
information that is developed and distributed through various sources. 
Written prescription drug information is provided through a voluntary 
effort (Consumer Medication Information) \1\ as well as through FDA 
mandated use of Medication Guides \2\ and Patient Package Inserts 
(PPI).\3\ Patients describe a wide range of experiences and varying 
degrees of satisfaction with information currently provided at the time 
medicines are received at the pharmacy. In some cases, the written 
documents are difficult to read and understand, duplicative and 
overlapping, incomplete or contradictory. FDA has held multiple public 
meetings to solicit feedback on providing balanced, comprehensive, and 
up-to-date prescription drug information to consumers.
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    \1\ Public Law 104-180, August 6, 1996, Title VI, Effective 
Medication Guides.
    \2\ Part 208 (21 CFR part 208).
    \3\ 21 CFR 310.501 and 310.515.
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    Since 1968, FDA regulations have required that PPIs written 
specifically for patients be distributed when certain prescription 
drugs or classes of prescription drugs are dispensed. PPIs are required 
for estrogens and oral contraceptives, are considered part of the 
product labeling, and are to be dispensed to the patient with the 
product. In the 1970s, FDA began evaluating the general usefulness of 
patient labeling for prescription drugs resulting in a series of 
regulatory steps to help ensure the availability of useful written 
consumer information. Other PPIs are submitted to FDA voluntarily by 
manufacturers and approved by FDA, but their distribution is not 
mandated by regulation. In the Federal Register of July 6, 1979 (44 FR 
40016), FDA proposed regulations that would have required written 
patient information for all prescription drugs, and in the Federal 
Register of September 12, 1980 (45 FR 60754), FDA finalized those 
regulations. In the Federal Register of September 7, 1982 (47 FR 
39147), the regulations were revoked based, in part, on assurances that 
the effort could be handled more efficiently within the private sector.
    In the Federal Register of August 24, 1995 (60 FR 44182), FDA 
proposed the ``Prescription Drug Product Labeling: Medication Guide 
Requirements,'' designed to set specific distribution and quality goals 
and timeframes for distributing written information to patients. In the 
Federal Register of December 1, 1998 (63 FR 66378), the Agency 
published a final rule that established a program under which 
Medication Guides would be required for a small number of drugs 
considered to pose a serious and significant public health concern (21 
CFR 208.20).
    Evidence suggests that both the content (e.g., organization) and 
format (e.g., white space) of a document will impact the comprehension 
of patient information. Research on reading behavior and document 
simplification suggests that the use of less complex terminology 
presented in shorter sentences with a more organized, or chunked, 
structure should improve consumer processing for at least three 
reasons. First, it should decrease the cognitive load engendered by the 
current physician-directed format. Second, a more structured and 
organized patient information document should present a less imposing 
processing demand, increasing consumers' willingness and self-perceived 
ability to read and understand the presented material. Research with 
the format of over-the-counter (OTC) drug labels,\4\ the nutrition 
facts label,\5\ and other information formats \6\ demonstrates that 
information presented with section headings, graphics (such as 
bullets), and other design elements is more easily read than 
information presented in paragraph format. Consumers are more likely to 
engage in behavior they believe they can successfully complete.\7\ 
Third, a patient information document that provides readers with 
clearer ``signals'' regarding the most important information should 
help readers prioritize the importance of the presented information. 
This should increase the probability that the set of information 
identified as important is subjected to more complete mental 
processing, thereby increasing the communication of that 
information.\8\
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    \4\ Aikin, K.J., ``Consumer Comprehension and Preference for 
Variations in the Proposed Over-The-Counter Drug Labeling Format, 
Final Report,'' 1998; Vigilante, W.J., M.S. Wogalter, ``The 
Preferred Order of Over-the-Counter (OTC) Pharmaceutical Label 
Components,'' Drug Information Journal, 31, 973-988, 1997.
    \5\ Levy, A.S., S.B. Fein, R.E. Schucker, ``More Effective 
Nutrition Label Formats Are Not Necessarily More Preferred,'' 
Journal of the American Dietetic Association, 92(10), 1230-1234, 
1992.
    \6\ Lorch, R., E. Lorch, ``Effects of Organizational Signals on 
Text-Processing Strategies,'' Journal of Educational Psychology, 
87(4), 537-544, 1995; Lorch, R., E. Lorch, ``Effects of 
Organizational Signals on Free Recall of Expository Text,'' Journal 
of Educational Psychology, 88(1), 38-48, 1996; Lorch, R., E. Lorch, 
W. Inman, ``Effects of Signaling Topic Structure on Text Recall,'' 
Journal of Educational Psychology, 85(2), 281-290, 1993.
    \7\ Wood, R., A. Bandura, ``Impact of Conceptions of Ability on 
Self-Regulatory Mechanisms and Complex Decision Making,'' Journal of 
Personality and Social Psychology, 56(3), 407-415, 1989.
    \8\ Lorch, R., E. Lorch, ``Effects of Organizational Signals on 
Text-Processing Strategies,'' Journal of Educational Psychology, 
87(4), 537-544, 1995; Lorch, R., E. Lorch, ``Effects of 
Organizational Signals on Free Recall of Expository Text,'' Journal 
of Educational Psychology, 88(1), 38-48, 1996; Lorch, R., E. Lorch, 
W. Inman, ``Effects of Signaling Topic Structure on Text Recall,'' 
Journal of Educational Psychology, 85(2), 281-290, 1993.
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    As part of FDA's efforts to improve the patient information 
received with prescription drugs, a Risk Communications Advisory 
Committee meeting was held on February 26 and 27, 2009. At this 
meeting, committee members discussed issues such as the ones described 
previously in this document and listened to stakeholder problems 
regarding the design and distribution of patient information. Following 
the advisory committee meeting, the working group created four 
prototypes to aid discussion at a public workshop to be held later in 
the year.
    This public workshop was held on September 24 and 25, 2009. During 
the workshop stakeholders from industry, consumer advocacy, and 
academia converged to discuss desirable features for a single-document 
patient leaflet, if that were to be developed, consumer tested, and 
distributed. Participants were divided into six groups to address the 
pros and cons of the four prototypes with the goal of deciding which 
features participants appreciated and did not appreciate. For 
additional information on the September 24 and 25, 2009, public 
workshop, go to http://www.fda.gov/Drugs/'NewsEvents/ucm168106.htm.
    Given the information obtained from workshop participants, the 
working

[[Page 78254]]

group refined several prototypes and designed a study to investigate 
the usefulness of three possible patient information formats from a 
user perspective. The results of this study will inform FDA as to the 
usefulness and parameters of various format options for the patient 
information documents.

Description of the Project

    This project is designed to test different ways of presenting 
information about prescription drugs to patients who have obtained a 
prescription. The information used will be based on a fictitious 
medication for the treatment of rheumatoid arthritis, ankylosing 
spondylitis, and plaque psoriasis. Data collection will occur via 
computer at training and testing facilities with orientation and 
debriefing conducted by interviewers. Participants will include adults 
who have been diagnosed with one of the conditions the fictitious drug 
treats. Participants will be prescreened to obtain a reasonable 
representation of health literacy, including those who score at the 
lower end of the scale. Questionnaire measures will include open- and 
closed-ended questions. Extensive pretesting of materials and stimuli 
will be conducted to refine the experimental stimuli and dependent 
measures and to ensure the stimuli meet minimum communication 
requirements and are delivering expected messages.

Proposed Study Design and Protocol

    The study is experimental and will have two independent variables 
in a 3x2 design. The independent variables are Format (3 levels: Drug 
Facts, Minimal Column, and Column Plus) and Order (2 levels: Warning 
first and Indication first).

                                                     Format
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                                                                                      Minimal
                              Order                                 Drug facts        column        Column plus
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Warning first...................................................
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Indication first................................................
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    The Order manipulation will vary the primacy of the boxed warning 
information versus the paragraph about the uses to the drug. In terms 
of Format, the Drug Facts format will follow the conventions of the 
existing OTC labeling. The Minimal Column condition will contain 
information in two columns with only basic information in the sections 
regarding information patients should tell their doctors. The Column 
Plus condition will also present information in two columns, but will 
include additional contextual information in the sections about what 
information patients should report to their doctors.
    Participants with relevant medical conditions will be randomly 
assigned to one of the six experimental conditions and each participant 
will see only one version of the patient information. Participants will 
be prescreened to represent a range of health literacy levels, 
including a portion with low literacy. Thus, all participants in the 
study will have been diagnosed with rheumatoid arthritis, ankylosing 
spondylitis, or plaque psoriasis and at least 30 percent of the sample 
will fall in the lower range of literacy. Because the average reading 
level in the United States is estimated to be 8th grade \9\ and it is 
recommended that consumer medication information be written at a 5th 
grade reading level,\10\ the low literate cohort will consist of 
consumers who have 5th to 8th grade reading skills. Education level is 
not a reliable substitute for literacy testing. At screening, the 
participants will be assessed for literacy level using a validated 
instrument.
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    \9\ Cotunga N., C.E. Vickery, K.M. Carpenter-Haefele, 
``Evaluation of Literacy Level of Patient Education Pages in Health-
Related Journals,'' Journal of Community Health, 30(3), 213-219, 
2005.
    \10\ Andrus, M.R., M.T. Roth, ``Health Literacy: A Review,'' 
Pharmacotherapy, 22(3), 282-302, 2002.
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    An additional small study will be conducted via the Internet to 
determine whether electronic prototype presentation alters the 
processing of the information in any way. Two-hundred individuals with 
the same characteristics of the original sample (e.g., medical 
condition and literacy levels) will be recruited over the Internet and 
will complete the same questionnaire as original participants.
    FDA is undertaking this study because it does not yet have 
sufficient evidence-based research relating to patient needs, or 
whether those needs are being effectively met. Research related to the 
functionality and effectiveness of written patient information 
consistently identifies the importance of performance-based testing as 
well as content based testing, which enables the evaluation of 
materials in order to assure their utility and identify issues in 
content format, or design. Development of new prescription drug patient 
materials must be based on consumer testing that focuses on utility to 
the patient and comprehension of material in the broadest audience 
possible. FDA has developed three prototypes in order to user test 
prescription drug information with consumers in order to achieve this 
goal. For further information, contact Elizabeth Berbakos (see FOR 
FURTHER INFORMATION CONTACT).
    In the Federal Register of May 4, 2010 (75 FR 23775), FDA published 
a 60-day notice requesting public comment on the proposed collection of 
information. FDA received five comments. In the following section, we 
outline the observations and suggestions raised in the comments and 
provide our responses. Four of the five comments expressed support for 
the conductance of the research to explore issues of quantitative 
benefit information. They all described the collection of data as a 
worthy endeavor which will provide useful information on how best to 
communicate information to patients about their prescription drugs.
    (Comment 1) The first comment stated that FDA's approach to 
examining the content and format of the prototypes is reasonable. This 
comment provided minor suggestions regarding how to improve the study, 
most of which are currently addressed in the questionnaire. For 
example, we have included time measurement, questions about the safe 
use of the product, and scenario-based questions in the questionnaire 
for the second phase of our study. We have incorporated other 
suggestions into the qualitative first phase of our project. In this 
phase, we will present participants with all versions of the prototypes 
to assess their preferences and will able to probe participants more 
thoroughly about their reactions and responses to the prototypes.
    (Comment 2) This comment provided a statement of support for the 
approval

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of this data collection, claiming the study will have practical 
utility.
    (Comment 3) This comment provided support for the research proposed 
in this document and reported that the components identified by FDA are 
consistent with those found in their own research. The comment 
suggested the inclusion of a visual system for identifying drug 
products and the inclusion of a variety of font sizes for people with 
visual impairments. FDA fully supports the presentation of information 
for special populations. However, the scope of the present study is to 
determine one format out of several that works with a range of 
participants. After this step, we can move toward incorporating special 
features, such as pictures or large font, to accommodate patients with 
varying needs.
    (Comment 4) Part of comment 4 was outside the scope of the proposed 
data collection; i.e., regarding the proper channels for distribution 
of Patient Medication Information (PMI). Regarding the parts of the 
comment that focused on the proposed research, the comment generally 
discussed omissions in the current proposed prototypes. These 
additional pieces of information have all been discussed at length at 
various public and expert meetings, including the public workshop in 
September 2009, the Brookings Institute Expert Workshop in July 2010, 
and the Part 15 hearing in September 2010. When improving medication 
documents for patients, there is always a trade-off between the desire 
to keep it simple and the desire to provide more information. Although 
a small number of individuals reported the desire for exhaustive 
information, the great majority of the feedback FDA has received and 
the literature the Agency has reviewed suggests that the information in 
the currently proposed prototypes is a reasonable collection of the 
important information that patients need to safely use their 
medications. Moreover, research suggests that providing large amounts 
of information will not serve patients well, but may instead impede 
their understanding of the information.\11\ Finally, the proposed 
research itself is designed to address the issue of whether the 
information in the prototypes is optimal. The first phase of the 
research will involve qualitative interviews, wherein participants will 
have ample opportunity to tell us what they want and need to know. The 
second phase of the research will involve quantitative assessment of 
the comprehension of important information in the document. Thus, we 
believe our two-pronged approach will address some of the concerns 
raised in this comment and we must defer to the volumes of other 
feedback we have received regarding the limiting of information in PMI.
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    \11\ See, for example, Day, R.S, PMI: From Concept to 
Compliance, Development and Distribution of Patient Medication 
Information for Prescription Drugs: Part 15 Public Hearing, FDA 
White Oak Campus, Silver Spring, MD, (September 27, 2010).
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    (Comment 5) Comment 5 had five main concerns with the study. First, 
the comment suggested that FDA reach out to Consumer Medication 
Information (CMI) publishers as early as possible in the development of 
the prototypes. FDA concurs with the importance of doing this and, in 
fact, has already done so multiple times and in multiple venues. 
Several CMI publishers participated in the public workshop held in 
September 2009 and spoke at the Part 15 hearing in September 2010.
    Second, the comment claims that FDA has not used an evidence-based 
strategy to develop the PMI prototypes. We disagree. FDA developed the 
prototypes based on the scientific literature. As described in the 
first section of this document, the prototypes were based on 
recommendations to include chunks of information that would reduce 
cognitive load and facilitate processing by including plenty of white 
space, headings, and maintaining a readable font size. From this first 
step, public feedback was obtained and incorporated, and feedback from 
communications experts was obtained and incorporated, resulting in the 
current prototypes. At this stage, we are proposing the continuation of 
the gathering of evidence by conducting the proposed two-part study to 
examine the PMI prototypes.
    Third, the comment expresses concerns that the use of a fictitious 
drug (and only one) may limit the generalizability of the findings of 
the study. The use of a fictitious drug eliminates the confound of 
prior knowledge when asking participants about the information they 
see. Rheutopia was selected to be a very close amalgam of an existing 
class of drugs. This class was chosen because it has a complicated set 
of risks, it is given by injection (an unusual administration), and it 
has multiple indications. FDA's reasoning is that if successful PMI can 
be developed for such a complex drug, PMI for drugs with simpler 
profiles will be attainable. It is true we are investigating only one 
drug in the current study; this decision was based on resource 
constraints. One research study cannot accomplish all goals. Future 
studies may be used to assess the applicability of the results in other 
drug classes.
    Fourth, the comment expresses concern that the research will not 
include a variety of different populations and that the lack of detail 
provided in the Federal Register notice suggests that very little 
knowledge will be gained from the research. Regarding the first part, 
the revised research proposed in this document includes low literacy 
individuals with chronic disease, general population individuals, and 
individuals with one of the medical conditions that Rheutopia treats. 
FDA believes these are the populations most relevant to this particular 
type of drug, as well as other chronic diseases. In terms of the detail 
provided, the questionnaire, which provided extensive detail about the 
exact questions proposed, was available upon request during the first 
comment period and will continue to be available during the second 
comment period.
    Fifth and finally, the comment suggested that comparing variations 
of a short, one-page document limits the findings because there will be 
no comparison to a longer document, which may perform better. FDA 
concurs. In the revised research currently proposed, we have included a 
control condition. A subset of individuals will be randomly assigned to 
see the Medication Guide format for Rheutopia. Thus, we will compare 
two proposed one-page prototypes with an existing document that would 
be currently required for Rheutopia if it were a real drug.

External Reviewers

    In addition to public comment, FDA's Division of Drug Marketing, 
Advertising, and Communications discussed the prototypes and the 
research design and protocol with a panel of 19 experts convened by the 
Brookings Institution on July 21, 2010. The names of these individuals 
can be found in Appendix A. After the workshop, several experts 
provided detailed written feedback to FDA, which was incorporated into 
the design of the study.
    FDA estimates the burden of this collection of information as 
follows:

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                                 Table 1--Estimated Annual Reporting Burden \1\
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                                               Annual
          Number of respondents            frequency  per     Total annual        Hours per        Total hours
                                              response          responses         response
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540.....................................                 1               540             20/60               180
900.....................................                 1               900             25/60               375
200.....................................                 1               200             25/60                83
    Total...............................                                                                     638
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    The burden chart reflects up to 3 pretests of 180 individuals each, 
900 participants in the main study, and 200 participants in the 
followup study involving electronic administration.

    Dated: December 8, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-31388 Filed 12-14-10; 8:45 am]
BILLING CODE 4160-01-P


