Brief Summary and Adequate Directions for Use: Disclosing Risk Information in Consumer-Directed Print Advertisements and Promotional Labeling for Prescription Drugs

Administrative draft guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

Brief Summary and Adequate Directions
for Use: Disclosing Risk Information in
Consumer-Directed Print Advertisements
and Promotional Labeling for
Prescription Drugs
Guidance for Industry
REVISED DRAFT GUIDANCE
This guidance document is being distributed for comment purposes only.
Comments and suggestions regarding this draft document should be submitted within 60 days of
publication in the Federal Register of the notice announcing the availability of the draft
guidance. Submit electronic comments to http://www.regulations.gov. Submit written
comments to the Division of Dockets Management (HFA-305), Food and Drug Administration,
5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with
the docket number listed in the notice of availability that publishes in the Federal Register.
For questions regarding this draft document contact (CDER) Julie Chronis at 301-796-1200;
(CBER) Office of Communications, Outreach and Development, at 800-835-4709 or 240-402-
7800; or (CVM) Thomas Moskal at 240-402-6251.
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
Center for Veterinary Medicine (CVM)
August 2015
Advertising
Revision 2

Brief Summary and Adequate Directions for
Use: Disclosing Risk Information in Consumer-
Directed Print Advertisements and Promotional
Labeling for Prescription Drugs
Guidance for Industry
Additional copies are available from:
Office of Communications, Division of Drug Information
Center for Drug Evaluation and Research
Food and Drug Administration
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor
Silver Spring, MD 20993-0002
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353
druginfo@fda.hhs.gov
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
and/or
Office of Communication, Outreach and Development
Center for Biologics Evaluation and Research
Food and Drug Administration
10903 New Hampshire Ave., Bldg. 71, rm. 3128,
Silver Spring, MD 20993-0002
Phone: 800-835-4709 or 240-402-7800
ocod@fda.hhs.gov
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
and/or
Policy and Regulations Staff
Center for Veterinary Medicine
Food and Drug Administration
7519 Standish Pl., Rockville, MD 20855
Phone: (240) 402-7075
Http://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/default.htm
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
Center for Veterinary Medicine (CVM)
August 2015
Advertising
Revision 2

Contains Nonbinding Recommendations
Draft — Not for Implementation
TABLE OF CONTENTS
I. 	INTRODUCTION............................................................................................................. 1
II. 	BACKGROUND ............................................................................................................... 2
A. 	Legal Overview .............................................................................................................................. 2
B. 	Policy Overview.............................................................................................................................. 4
III. 	OPTIONS FOR DISCLOSING RISK INFORMATION IN CONSUMER-
DIRECTED PRESCRIPTION DRUG PRINT ADVERTISEMENTS AND
PROMOTIONAL LABELING ....................................................................................... 5
A. 	Language and Readability ............................................................................................................ 6
B. 	Content............................................................................................................................................ 6
C. 	Format........................................................................................................................................... 10
1. Prescription Drug Facts Box ......................................................................................................... 10
2. Question and Answer ..................................................................................................................... 10
REFERENCES............................................................................................................................ 12

Contains Nonbinding Recommendations
Draft — Not for Implementation
1 	Brief Summary and Adequate Directions for Use: Disclosing Risk
2 	Information in Consumer-Directed Print Advertisements and
3 	Promotional Labeling for Prescription Drugs
4
5 	Guidance for Industry1
6
7
8 	This revised draft guidance, when finalized, will represent the current thinking of the Food and Drug
9 	Administration (FDA or Agency) on this topic. It does not create any rights for any person and is not
10 	binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the
11 	applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible
12 	for this guidance as listed on the title page.
13
14
15
16 	I. 	INTRODUCTION
17
18 	This revised draft guidance provides recommendations on the disclosure of risk information in
19 	prescription drug product advertisements and promotional labeling in print media directed
20 	toward consumers with respect to the brief summary requirement and the requirement that
21 	adequate directions for use be included with promotional labeling.2 The recommendations
22 	describe an alternative disclosure approach that FDA refers to as a consumer brief summary.
23 	This revised draft guidance does not focus on the presentation of risk information in the main
24 	body of promotional labeling or advertisements and does not apply to promotional materials
25 	directed toward health care professionals.
26
27 	This revised draft guidance responds to stakeholder requests for specific guidance on the
28 	disclosure of risk information to consumers and incorporates recent social science research
29 	results (Aikin, O’Donoghue, et al. 2011). This revised draft guidance revises the draft guidance
30 	entitled Brief Summary: Disclosing Risk Information in Consumer-Directed Print
31 	Advertisements (issued January 2004). Additionally, this revised draft guidance (Revision 2) has
32 	been reissued to incorporate animal prescription drugs; there are no other revisions to the revised
33 	draft guidance for industry issued February 9, 2015 (80 FR 6998).
1 This guidance has been prepared by the Office of Prescription Drug Promotion (OPDP) in the Center for Drug
Evaluation and Research (CDER) in consultation with the Center for Biologics Evaluation and Research (CBER)
and the Center for Veterinary Medicine (CVM) at the Food and Drug Administration.
2 The recommendations of this revised draft guidance also apply to biological products that are approved for
marketing under section 351 of the Public Health Service Act (PHS Act). Because each biological product also
meets the definition of “drug” under the Federal Food, Drug, and Cosmetic Act (FD&C Act), it is also subject to
regulation under provisions of the FD&C Act applicable to drugs, as well as the regulations implementing these
provisions, except that a biological product licensed under section 351 of the PHS Act is not required to have an
approved new drug application under section 505 of the FD&C Act (21 U.S.C. 355). See PHS Act section 351(j)
(42 U.S.C. 262(j)). References to “drugs” in this guidance therefore also include biological products for use in
humans that fall within the definition, as well as both human and animal prescription drugs.
1

Contains Nonbinding Recommendations
Draft — Not for Implementation
34 	In general, FDA’s guidance documents do not establish legally enforceable responsibilities.
35 	Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only
36 	as recommendations, unless specific regulatory or statutory requirements are cited. The use of
37 	the word should in Agency guidances means that something is suggested or recommended, but
38 	not required.
39
40 	II. 	BACKGROUND
41
42 	A. 	Legal Overview
43
44 	Under the Federal Food, Drug, and Cosmetic Act (FD&C Act), the Agency has responsibility for
45 	regulating the manufacture, sale, and distribution of drugs in the United States. This authority
46 	includes oversight of the labeling of drugs (21 U.S.C. 352(a)) and the advertising of prescription
47 	drugs (21 U.S.C. 352(n)).
48
49 	A print advertisement3 for a prescription drug must contain a true statement of the product’s
50 	established name; quantitative composition; information in brief summary relating to side
51 	effects, contraindications, and effectiveness; and, for published direct-to-consumer
52 	advertisements, a statement encouraging consumers to report negative side effects to FDA (21
53 	U.S.C. 352(n)). FDA implementing regulations provide further clarification on the information
54 	to include in brief summary: “a true statement of information in brief summary relating to side
55 	effects, contraindications ([to] . . . include side effects, warnings, precautions, and
56 	contraindications and include any such information under such headings as cautions, special
57 	considerations, important notes, etc.) and effectiveness” (21 CFR 202.1(e)(1)). This information
58 	“shall disclose each specific side effect and contraindication . . . contained in required, approved,
59 	or permitted labeling for the advertised drug dosage form(s) . . .” (21 CFR 202.1(e)(3)(iii)). For
60 	purposes of this guidance, the requirement under these provisions that an advertisement for a
61 	prescription drug disclose each side effect, warning, precaution, and contraindication from the
62 	labeling will be referred to as the brief summary requirement.
63
64 	FDA also has responsibility for regulating labeling for prescription drugs, including promotional
65 	labeling. Section 201(m) of the FD&C Act defines labeling as “all labels and other written,
66 	printed, or graphic matter (1) upon any article or any of its containers or wrappers, or (2)
67 	accompanying such article” (21 U.S.C. 321(m)).4 The U.S. Supreme Court has explained that
68 	the language “accompanying such article” in the “labeling” definition is interpreted broadly, to
69 	include materials that supplement or explain an article. No physical attachment between the
70 	materials and the article is necessary; rather, it is the textual relationship between the items that
71 	is significant (Kordel v. United States, 335 U.S. 345, 350 (1948)). FDA generally recognizes
2
3 The FD&C Act does not define what constitutes an “advertisement,” but FDA regulations provide several
examples, including “advertisements in published journals, magazines, other periodicals, and newspapers, and
advertisements broadcast through media such as radio, television, and telephone communication systems” (21 CFR
202.1(l)(1)). Broadcast advertisements, such as radio and television advertisements, are not the subject of this
guidance.
4 See also 21 CFR 1.3(a).

Contains Nonbinding Recommendations
Draft — Not for Implementation
72 	two types of labeling for drugs: (1) FDA-required labeling5 and (2) promotional labeling.
73 	Promotional labeling is generally any labeling, other than the FDA-required labeling, that is
74 	devised for promotion of the product. Examples of materials that may be considered
75 	promotional labeling pieces for prescription drugs are described in 21 CFR 202.1(l)(2).
76
77 	While drug labeling generally must bear “adequate directions for use” (21 U.S.C. 352(f)(1),
78 	prescription drugs are exempt from this requirement if certain conditions are met. These
79 	conditions include, among others, that “any labeling” (as defined in section 201(m) of the FD&C
80 	Act) that is “distributed by or on behalf of the manufacturer, packer, or distributor of the drug,
81 	that furnishes or purports to furnish information for use or which prescribes, recommends, or
82 	suggests a dosage for the use of the drug” contains “adequate information for such use” (21 CFR
83 	201.100(d) and 21 CFR 201.105(d)). “Adequate information for such use” includes, among
84 	other things, “relevant warnings, hazards, contraindications, side effects, and precautions, under
85 	which practitioners licensed by law to administer the drug can use the drug safely and for the
86
87
purposes for which it is intended, including all conditions for which it is advertised or
represented . . .” (21 CFR 201.100(d)(1); see also 21 CFR 201.105(d)(1)). 6 The regulations also
88 	require that if the article is subject to section 505, 512, or 572 of the FD&C Act, the parts of the
89 	labeling providing such information for use are the same “in language and emphasis” as labeling
90 	approved or permitted under the provisions of sections 505, 512, or 572. (Id.)
91
92 	In addition, in order to be exempt from the “adequate directions for use” requirement in 21
93 	U.S.C. 352(f), any labeling for human prescription drugs described in 21 CFR 201.100(d) must
94 	contain the “information required, and in the same format specified by” 21 CFR 201.56, 201.57,
95 	and 201.80 (21 CFR 201.100(d)(3)). Generally, the requirements in 21 CFR 201.100(d) have
96 	been fulfilled by including the full FDA-approved package insert (PI) with promotional labeling
97 	materials. For purposes of this guidance, the requirement under these provisions that a
98 	prescription drug promotional labeling piece include the information set forth in 21 CFR
99 	201.100(d) for prescription human drugs and 21 CFR 201.105(d) for prescription animal drugs,
100 	which is generally fulfilled by inclusion of the full PI, will be referred to as the adequate
101 	directions for use requirement.
102
103 	To fulfill the brief summary requirement, consumer-directed print advertisements for
104 	prescription drugs frequently include the complete risk-related sections of the PI (also known as
105 	the “traditional approach” or “traditional format”). To fulfill the adequate directions for use
106 	requirement for promotional labeling pieces, the full PI has generally been used. As discussed
107 	more fully in section II.B, FDA believes these approaches are not optimal for consumer-directed
108 	prescription drug print advertisements and promotional labeling pieces because many consumers
5 Much FDA-required labeling is subject to FDA review and approval. For example, after drafting by the
manufacturer, labeling is reviewed and approved by FDA as part of the new drug application (NDA), new animal
drug application (NADA),biologics license application (BLA), or premarket approval application (PMA) review
(see 21 CFR 314.50(c)(2), 514.1(b)(3), and 601.2(a)). For a prescription drug to be exempted from the FD&C Act’s
requirement of adequate directions for use (21 U.S.C. 352(f)(1)), its FDA-required labeling must contain, among
other information, information addressing product hazards and other risk information, as specified in FDA
regulations (21 CFR 201.100(d)(1), (3), and 201.105(c)(1)).
6 “Adequate information for use” under 21 CFR 201.100(d)(1) and 201.105(d)(1) also includes indications, effects,
dosages, routes, methods, and frequency and duration of administration.
3

Contains Nonbinding Recommendations
Draft — Not for Implementation
109 	lack the technical background to understand some of the information as described in the PI.
110 	Additionally, information that may be of limited use to consumers (e.g., clinical pharmacology)
111 	is included. For these reasons, if manufacturers, packers, and distributors, or anyone acting on
112 	their behalf (firms) include the appropriate information discussed in this guidance, FDA does not
113 	intend to object for failure to include each side effect from the PI in the brief summary in
114 	consumer-directed print advertisements. Furthermore, if firms include the appropriate
115 	information discussed in this guidance, FDA does not intend to object for failure to include the
116 	entire PI to fulfill the requirements of 201.100(d) or 201.105(d) for consumer-directed
117 	promotional labeling pieces.
118
119 	In other words, this revised draft guidance recommends alternative approaches firms may use to
120 	develop content that can be used to fulfill both the brief summary requirement for consumer-
121 	directed prescription drug print advertisements and the requirements in 201.100(d) or 201.105(d)
122 	for consumer-directed prescription drug print promotional labeling pieces. Suggested research-
123 	tested formats for this information are also provided in this revised draft guidance. The
124 	examples included throughout are intended to provide guidance and illustrate possible
125 	approaches; firms may use alternative approaches if these approaches satisfy the requirements of
126 	the statute and regulations.
127
128 	B. 	Policy Overview
129
130 	To provide better and more actionable information for consumers, FDA believes that the brief
131 	summary should focus on the most important risk information rather than an exhaustive list of
132 	risks and that the information should be presented in a way most likely to be understood by
133 	consumers. Thus, FDA strongly recommends against the use of the traditional approach to fulfill
134 	the brief summary requirement in consumer-directed advertisements, an approach in which risk-
135 	related sections of the PI are presented verbatim, often in small font. Because the target audience
136 	of the PI is health care providers, it is written in highly technical medical terminology, which is
137 	potentially of limited value to consumers who may not have the medical or scientific background
138 	to understand this information. In an FDA survey, few respondents reported reading half or
139 	more of the brief summary presented in the traditional format. Of those who read at least some
140 	of the brief summary, 55 percent described it as hard to read. Over 40 percent of respondents in
141 	the survey reported they do not usually read any of the brief summary in direct-to-consumer
142 	prescription drug print advertisements (Aikin, Swasy, et al. 2004).
143
144 	Furthermore, the risk information in the PI sometimes includes lengthy lists of all possible
145 	adverse events. In general, FDA believes that exhaustive lists that include even minor risks
146 	detract from, and make it difficult for, consumers to comprehend and retain information about
147 	the more important risks. While remaining an important source of information for consumers,
148 	even the volume of material in excerpted sections of the PI, along with the format (i.e., a smaller
149 	font with limited white space) and the technical language, may serve to detract from consumers’
150 	comprehension of the information or from the likelihood of consumers reading the material in its
151 	entirety. Research has demonstrated that people process only a limited amount of information at
152 	one time both in general communications (Lavie 2001; Miller 1994; Shapiro 2001) and in direct-
153 	to-consumer prescription drug advertising specifically (Stotka, Rotelli, et al. 2007). Past
154 	research has shown that alternative formats for the brief summary outperform the traditional,
4

Contains Nonbinding Recommendations
Draft — Not for Implementation
155 	non-consumer-friendly brief summary on measures of consumer risk comprehension (Riggs,
156 	Holdsworth, et al. 2004; Schwartz, Woloshin, et al. 2009; Stotka, Rotelli, et al. 2007; Thumma
157 	1997).
158
159 	Occasionally, sections taken from the PI to fulfill the brief summary requirement are rewritten in
160 	a manner that is meant to be more understandable to consumers. However, this approach does
161 	not necessarily solve the problems with the traditional approach. In research conducted by FDA,
162 	participants who viewed the brief summary information in a format similar to the over-the-
163 	counter (OTC) “Drug Facts” box had better risk recall than those who viewed a traditional, but
164 	consumer-friendly, version of the brief summary. Two additional alternative formats (a Question
165 	and Answer (Q&A) format and a Highlights version from the content and format rule of 2006 7)
166
167
did not differ from the consumer-friendly traditional format on risk recall or confidence (Aikin,
O’Donoghue, et al. 2011).8
168
169 	For similar reasons that are further exacerbated by the length and complexity of the full approved
170 	professional labeling, FDA also strongly recommends against providing the full PI to satisfy the
171 	adequate directions for use requirement for consumer-directed print promotional labeling pieces
172 	for prescription drugs. While the Agency recognizes that 21 CFR 201.100(d) and 21 CFR
173 	201.105(d) identify the PI as a source for furnishing adequate directions for use, FDA believes
174 	that following the content and format recommendations in this guidance will better communicate
175 	information and help consumers make informed decisions about the medication being promoted.
176 	By adopting the content and format recommendations in this guidance, firms can also provide
177 	consumers with the same information in both advertising and promotional labeling pieces.
178
179 	III. 	OPTIONS FOR DISCLOSING RISK INFORMATION IN CONSUMER-
180 	DIRECTED PRESCRIPTION DRUG PRINT ADVERTISEMENTS AND
181 	PROMOTIONAL LABELING
182
183 	FDA does not intend to object if a firm does not include “each specific side effect and
184 	contraindication” from the PI in the brief summary in consumer-directed print advertisements
185 	(21 CFR 202.1(e)(3)(iii)), or does not supply the entire PI to fulfill the requirements in 21 CFR
186 	201.100(d) or 21 CFR 201.105(d) for consumer-directed print promotional labeling pieces, so
187 	long as the firm follows the recommendations and examples in this guidance. These alternate
188 	approaches will not become a part of FDA-approved labeling.
189
190 	For purposes of this guidance, in the text and examples below, the consumer-directed
191 	document recommended by FDA as an alternative to the full PI or the risk portions of the
192 	PI in consumer-directed prescription drug print promotional labeling pieces and the brief
7 See 21 CFR 201.56, 201.57, 201.58, and 201.80.
8 Participants who viewed the brief summary information in a format similar to the OTC Drug Facts box had better
risk recall, greater confidence in their ability to perform tasks related to the brief summary, more positive attitudes
toward the ad, and greater preference for the format than did those who viewed a traditional, but consumer-friendly,
version of the brief summary. Participants had more positive attitudes toward the Q&A format and the Highlights
format than toward the traditional format, and participants who viewed the Q&A format had more positive attitudes
toward the ad than those who viewed the traditional format.
5

Contains Nonbinding Recommendations
Draft — Not for Implementation
193 	summary requirement in consumer-directed prescription drug advertisements will be
194 	referred to as the “consumer brief summary.”
195
196 	A. 	Language and Readability
197
198 	FDA strongly encourages the use of consumer-friendly language in all consumer-directed
199 	materials. The consumer brief summary should be written in language designed for
200 	understanding by a broad target audience with various levels of literacy skills. Technical
201 	language, scientific terms, and medical jargon should be avoided. A conversational tone or
202 	language designed to engage the reader may be useful, such as in the following examples.
203
204 	 	“do not use if you have . . .” or “who should not use . . .” rather than
205 	“contraindications”
206 	 	“what is [drug name]” rather than “indication”
207 	 	“drowsiness” not “somnolence”
208 	 	“fainting” not “syncope”
209
210 	The information in the consumer brief summary must be presented in a readable format (21
211 	U.S.C. 352(c); 21 CFR 202.1(e)(7)(viii)). Different techniques can be used to assist consumers
212 	with comprehension of information. For example, signals,9 such as headlines and subheadings,
213 	help communicate important information (Loman and Mayer 1983; Meyer 2003; Spyridakis and
214 	Standal 1987). Consumers are influenced by the layout of print information in their ability to
215 	pay attention to and process specific features of a document (Adams and Edworthy 1995;
216 	Brundage, Feldman-Stewart, et al. 2005; Frantz 1993; Morrow, Leirer, et al. 1995; Niemela and
217 	Saariluoma 2003; Wogalter and Vigilante 2003). Font size and type style can affect the
218 	readability of information (Adams and Edworthy 1995; Arditi and Cho 2005; Baker 2006;
219 	Sheedy, Subbaram, et al. 2005; Tantillo and Mathisen 1995; Wogalter and Vigilante 2003).
220
221 	Therefore, the consumer brief summary should be presented visually in a manner designed for
222 	ease of use by consumers. Carrying over elements of the main body of the ad (such as logos and
223 	branded colors) may help the reader understand the connection between the consumer brief
224 	summary and the promotional piece. Font size and style should be selected or designed for
225 	readability. Using double spacing between paragraphs and indentations, as opposed to plain
226 	block paragraphs, helps maximize background space (also called white space) and improves
227 	readability. Arranging information in text boxes (i.e., paragraphs of information on a similar
228 	topic surrounded by borders) with headings (Hyona and Lorch 2004) and other attention-drawing
229 	symbols (e.g., bullets, capitalization of select words or phrases) may also be useful to consumers.
230
231 	B. 	Content
232
233 	FDA’s current thinking is that the consumer brief summary should provide clinically significant
234 	information on the most serious and the most common risks associated with the product and omit
9 “Signaling” has been defined as the use of “writing devices designed to emphasize aspects of a text’s structure or
content without altering the information in the text” (Lorch, Lorch, et al. 1993).
6

Contains Nonbinding Recommendations
Draft — Not for Implementation
235 	less pertinent information. FDA recommends that firms look to available standards to determine
236 	which risks should be included. For example, FDA-approved patient labeling and Medication
237 	Guides, or, for animal drugs, a client information sheet, if available for the drug at issue, may be
238 	an appropriate starting point to determine which risks should be included in the consumer brief
239 	summary and, in fact, may contain the same risk information that should appear in the consumer
240 	brief summary. However, some information in patient labeling—such as information found in
241 	the Directions for Use section (for human prescription drugs) or the client information sheet (for
242 	animal drugs)—is not necessary to include in the consumer brief summary. Additionally,
243 	information not contained in patient labeling, such as information about certain relevant drug
244 	risks, might need to be added to the consumer brief summary.
245
246 	Under the final rule for Requirements on the Content and Format of Labeling for Human
247 	Prescription Drug and Biological Products (the “Physician Labeling Rule” or PLR),10 the
248 	labeling of new and recently approved products11 must include Highlights of Prescribing
249 	Information (Highlights). FDA believes the criteria used for selecting risk information for the
250 	Highlights section are an appropriate reference for firms to use when determining which risk
251 	information topics to address in the consumer brief summary. See 21 CFR 201.57(a). In
252 	addition, information in the consumer brief summary should be placed in an order similar to
253 	information in the Highlights section (Boxed Warning followed by Contraindications, Warnings
254 	and Precautions, etc.). However, since information in the Highlights section is intended for use
255 	in conjunction with information in the full PI and the full PI is not being provided, generally the
256 	information in the consumer brief summary should be more detailed and provide more material
257 	information than what is contained in the Highlights. For drugs for which the PLR is not
258 	applicable (i.e., new animal drugs and some human drugs), similar information can be taken
259 	from the analogous sections of each drug’s PI.
260
261 	For each of the formats discussed below, or for alternative formats, information addressing the
262 	following should be included:
263
264 	 	Boxed Warning12
265 	 	All Contraindications
266 	 	Certain information regarding Warnings and Precautions:
267 	o 	the most clinically significant information from the Warnings and Precautions
268 	section(s) of the PI;
269 	o 	information that would affect a decision to prescribe or take a drug;
270 	o 	monitoring or laboratory tests that may be needed;
271 	o 	special precautions not set forth in other parts of the PI; and
272 	o 	measures that can be taken to prevent or mitigate harm.
273
10 Requirements on the Content and Format of Labeling for Human Prescription Drug and Biological Products (71
FR 3922, Jan 24, 2006).
11 The PLR applies to human prescription drugs that were approved after, on, or 5 years prior to the effective date of
the rule, and to older drugs for which certain supplements are submitted (21 CFR 201.56(b)).
12 Certain recommendations will not apply to all drugs. For example, not all drugs have a Boxed Warning. If a
recommendation is not applicable, the information should be omitted.
7

Contains Nonbinding Recommendations
Draft — Not for Implementation
274
275
FDA also recommends that the most frequently13 occurring Adverse Reactions be included in the
consumer brief summary. 14 If a product has more than one indication, the most common
276 	Adverse Reactions for each indication being promoted should be included, if included in the PI,
277 	rather than pooled results for all indications (which could include indications that are not being
278 	promoted). Adverse Reactions should be listed in the same order as in the PI.
279
280 	Other important Adverse Reactions, such as those that are serious 15 or those that lead to
281 	discontinuation of the drug or dosage adjustment, should be included unless they are repeated
282 	elsewhere in the PI (e.g., risks included in Warnings and Precautions).
283
284 	Material information regarding any of these risks may also include the severity of the risks, such
285 	as whether they are debilitating, life-threatening, irreversible, or whether stopping the medication
286 	will alleviate or mitigate the risks. If early warning signs of risks are known, consumers should
287 	be given information about these signs and the importance of informing their health care
288 	provider about the signs. Firms may also include information regarding the need for monitoring
289 	or testing during treatment. Other material information may be relevant depending on the drug
290 	and its risk profile.
291
292
293
FDA also believes that the consumer brief summary should include the indication for the use
being promoted, any clinically significant drug interactions,16 and information regarding topics
294 	or issues consumers should discuss with their health care providers (e.g., other drugs they are
295 	taking or pre-existing conditions). Other types of information may be included if relevant to the
296 	drug or specific indication referred to in the promotion (e.g., that a drug is not indicated for use
297 	for more than 4 weeks for the indication being advertised even if a different indication allows for
298 	a longer use). Information relating to special populations (e.g., children or young animals, the
299 	elderly or geriatric animals, pregnant or nursing women or animals, people or animals with liver
300 	or renal impairment, food-producing animals) should be included if they are of particular
13 The list of Adverse Reactions identified as most frequently occurring or most common is usually generated from a
table of Adverse Reactions from clinical trials in the approved labeling. Rates of most common Adverse Reactions
vary, but should be appropriate to the nature of a drug’s Adverse Reactions profile and the size and composition of
the safety database. See the guidance for industry entitled Labeling for Human Prescription Drug and Biological
Products—Implementing the PLR Content and Format Requirements (Feb 2013), available on the Internet at
http://www.fda.gov/Drugs/default.htm under Guidances (Drugs).
14 This recommendation comports with the information required in the Highlights section (21 CFR 201.57(a)(11)),
and is also applicable to drugs to which the PLR does not apply.
15 Serious Adverse Reaction refers to any reaction occurring at any dose that results in any of the following
outcomes: death, a life-threatening adverse experience, inpatient hospitalization or prolongation of existing
hospitalization, a persistent or significant disability or incapacity, or a congenital anomaly or birth defect. Important
medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious
Adverse Reactions when, based upon appropriate medical judgment, they may jeopardize the patient or subject, and
may require medical or surgical intervention to prevent one of the outcomes listed in this definition. See the
guidance for industry entitled Adverse Reactions Section of Labeling for Human Prescription Drug and Biological
Products—Content and Format (Jan 2006). For animal drugs, the term “serious adverse drug experience” is defined
as “an adverse event that is fatal, or life-threatening, or requires professional intervention, or causes an abortion, or
stillbirth, or infertility, or congenital anomaly, or prolonged or permanent disability, or disfigurement” (21 CFR
514.3).
16 For example, for a drug with PLR labeling, typically the most clinically significant drug interactions appear in the
Contraindications or Warnings and Precautions sections.
8

Contains Nonbinding Recommendations
Draft — Not for Implementation
301 	concern based on the drug’s known or potential safety profile (e.g., not recommended for use in
302 	children based on adverse events; not for use in nursing women due to the potential for harm to
303 	the infant; drug withdrawal periods in different animal populations).
304
305 	In general, certain information found in the PI or in FDA-approved patient labeling can be
306 	excluded from the consumer brief summary. This information might include dosage and
307 	administration, how the drug is supplied, clinical pharmacology, specific directions regarding use
308 	of the drug (such as how to perform an injection or how to use a patch), or how long the drug
309 	takes to work. However, excluding certain information from the consumer brief summary does
310 	not mean that the same information can be omitted from other parts of the promotional piece
311 	(e.g., information that a drug is administered via an injection versus orally might be material
312 	information that is required in the main body of the promotional piece, while detailed
313 	instructions for use may be omitted from the consumer brief summary).
314
315 	FDA also recommends that, because the risk information in the consumer brief summary is not
316 	comprehensive, the consumer brief summary should include a statement (1) reminding
317 	consumers that the information presented is not comprehensive; (2) suggesting that consumers
318 	speak to their health care provider, veterinarian, or pharmacist; and (3) containing a toll-free
319 	telephone number or website address (uniform resource locator or URL) where consumers can
320 	obtain the FDA-approved product labeling.17 For example:
321
322 	 	The risk information provided here is not comprehensive. To learn more, talk
323 	about [drug name] with your health care provider or pharmacist [veterinarian].
324 	The FDA-approved product labeling can be found at www.drugnamePI.com or 1-
325 	800-555-DRUG.
326
327 	 	This information is not comprehensive.
328 	 	How to get more information:
329 	 	Talk to your health care provider or pharmacist [veterinarian]
330 	 	Visit www.drugnamePI.com to obtain the FDA-approved product labeling
331 	 	Call 1-800-555-DRUG
332
333 	The consumer brief summary may also contain a title such as “Important Facts” or “Summary of
334 	Information about . . .” along with the drug’s name.18
335
336 	When the PI is revised, the consumer brief summary for the drug must be reviewed and revised
337 	promptly if pertinent information has been changed (21 CFR 314.70(a)(4), 514.8(c)(2), and
338 	601.12(a)(4)).
339
17 This recommendation is distinct and separate from the “adequate provision” requirement for broadcast
advertisements found at 21 CFR 202.1(e)(1). This guidance only covers print advertisements and print promotional
labeling and does not apply to broadcast advertisements.
18 See the revised draft guidance for industry entitled Product Name Placement, Size, and Prominence in Advertising
and Promotional Labeling (Nov 2013). When final, this guidance will represent the FDA’s current thinking on this
topic.
9

Contains Nonbinding Recommendations
Draft — Not for Implementation
340 	C. 	Format
341
342 	Various formats may be used when conveying information in the consumer brief summary.
343 	Although other formats may be acceptable, the following two sections describe recommended
344 	formats that have been tested in research.
345
346 	1. 	Prescription Drug Facts Box
347
348 	Ever since the labeling rule for OTC human drugs was finalized more than a decade ago,19 OTC
349 	products have contained a Drug Facts box on each product. For the consumer brief summary, a
350 	layout similar to the OTC Drug Facts box may be familiar to consumers and may offer
351 	advantages over other formats. In a study testing various brief summary formats, the Drug Facts
352 	box format resulted in better recall of the risk information when compared to the traditional
353 	format (which was written in consumer-friendly language). Consumers in the same study who
354 	saw the Drug Facts box also reported that they felt more confident in their ability to use the
355 	information when compared to consumers who saw the traditional format. In addition,
356 	consumers had more positive attitudes toward the Drug Facts box format than toward two other
357 	formats: the traditional format and a format that is structured like the Highlights section of the
358 	PI (Aikin, O’Donoghue, et al. 2011).
359
360 	Under a prescription Drug Facts box format, information could appear within a box similar to the
361 	OTC Drug Facts box. Standardized headings may assist consumers in locating and
362 	comprehending important drug information. For example:
363
364 	 	Uses
365 	 	Do not use if you
366 	 	Warnings
367 	 	Ask a health care provider before use if
368 	 	When using this product you may have
369
370 	The recommended content for this format is set forth in section III.B above, and the
371 	recommendation to use consumer-friendly language also applies.
372
373 	2. 	Question and Answer
374
375 	A Question and Answer (Q&A) format simulates a dialogue using personal pronouns, thus
376 	increasing consumer interest in, and comprehension of, the information. The study testing brief
377 	summary formats found that consumers had more positive attitudes toward a Q&A format than
378 	the traditional brief summary (which was written in consumer-friendly language). However, this
379 	study did not find a difference in risk recall or confidence between the Q&A format and the
380 	traditional format. Because consumers preferred the Q&A format and the format did not
19 See Food and Drug Administration, “Final Rule; Over-The-Counter Human Drugs, Labeling Requirements” (64
FR 13254, Mar 17, 1999).
10

Contains Nonbinding Recommendations
Draft — Not for Implementation
381 	decrease risk recall (Aikin, O’Donoghue, et al. 2011), this format is recommended over the
382 	traditional brief summary.
383
384 	Under the Q&A format, information in the consumer brief summary could appear in columns or
385 	a similar layout. Headings would be framed in the form of questions, for example:
386
387 	 	What is [drug] used for?
388 	 	When should I not take [drug]?
389 	 	What Warnings should I know about [drug]?
390 	 	What should I tell my health care provider?
391 	 	What are the side effects of [drug]?
392 	 	What other medications might interact with [drug]?
393
394 	The recommended content for this format is set forth in section III.B above, and the
395 	recommendation to use consumer-friendly language also applies.
396
11

Contains Nonbinding Recommendations
Draft — Not for Implementation
397 	REFERENCES
398
399 	Adams, AS and J Edworthy, 1995, Quantifying and Predicting the Effects of Basic Text Display
400 	Variables on the Perceived Urgency of Warning Labels: Tradeoffs Involving Font Size, Border
401 	Weight, and Color, Ergonomics, 38:2221-2237.
402
403 	Aikin, KJ, AC O’Donoghue, J Swasy, and HW Sullivan, 2011, A Randomized Trial of Risk
404 	Information Formats in Direct-to-Consumer Prescription Drug Advertisements, Medical
405 	Decision Making, 31:23-33.
406
407 	Aikin, K, J Swasy, and A Braman, 2004, Patient and Physician Attitudes and Behaviors
408 	Associated with DTC Promotion of Prescription Drugs—Summary of FDA Survey Research
409 	Results, Final Report, FDA (accessible at
410 	http://www.fda.gov/downloads/Drugs/ScienceResearch/ResearchAreas/DrugMarketingAdvertisi
411 	ngandCommunicationsResearch/UCM152860.pdf).
412
413 	Arditi, A, and J Cho, 2005, Serifs and Font Legibility, Vision Research, 45:2926-2933.
414
415 	Baker, S, 2006, Provision of Effective Information, British Dental Journal, 201:100.
416
417 	Brundage, M, D Feldman-Stewart, A Leis, A Bezjak, L Degner, K Velji, et al., 2005,
418 	Communicating Quality of Life Information to Cancer Patients: A Study of Six Presentation
419 	Formats, Journal of Clinical Oncology, 23:6949-6956.
420
421 	FDA guidance for industry, 2013, Product Name Placement, Size, and Prominence in
422 	Advertising and Promotional Labeling (accessible at
423 	http://www.fda.gov/downloads/Drugs/.../Guidances/ucm070076.pdf).
424
425 	Frantz, JP, 1993, Effect of Location and Presentation Format on Attention to and Compliance
426 	with Product Warnings and Instructions, Journal of Safety Research, 24:131-154.
427
428 	Hyona, J, and RF Lorch, 2004, Effects of Topic Headings on Text Processing: Evidence from
429 	Adult Readers’ Eye Fixation Patters, Learning and Instruction, 14:131-152.
430
431 	Lavie, N, 2001, Capacity Limits in Selective Attention: Behavioral Evidence and Implications
432 	for Neural Activity, J Braun, C Koch, and J Davis, eds. Visual Attention and Cortical Circuits,
433 	Cambridge, MA: The MIT Press, 49-68.
434
435 	Loman, NL, and RE Mayer, 1983, Signaling Techniques that Increase the Understandability of
436 	Expository Prose, Journal of Educational Psychology, 75:402-412.
437
438 	Lorch, RF, EP Lorch, and WE Inman, 1993, Effects of Signaling Structure on Text Recall,
439 	Journal of Educational Psychology, 85:281-290.
440
441 	Meyer, BJF, 2003, Text Coherence and Readability, Topics in Language Disorders, 23:204-224.
442
12

Contains Nonbinding Recommendations
Draft — Not for Implementation
443 	Miller, GA, 1994, The Magical Number Seven, Plus or Minus Two: Some Limits on Our
444 	Capacity for Processing Information, H Gutfreund and G Toulouse, eds. Reprinted in Biology
445 	and Computation: A Physicist’s Choice, River Edge, NJ: World Scientific Publishing Co., 207-
446 	233.
447
448 	Morrow, D, V Leirer, and P Altieri, 1995, List Formats Improve Medication Instructions for
449 	Older Adults, Educational Gerontology, 21:151-166.
450
451 	Niemela, M, and P Saariluoma, 2003, Layout Attributes and Recall, Behaviour and Information
452 	Technology, 22:353-363.
453
454 	Riggs, DL, SM Holdsworth, and DR McAvoy, 2004, Direct-to-Consumer Advertising:
455 	Developing Evidence-Based Policy to Improve Retention and Comprehension [Supplementary
456 	Web Exclusive], Health Affairs, 23:249-252.
457
458 	Schwartz, LM, S Woloshin, and HG Welch, 2009, Communicating Drug Benefits and Harms
459 	with a Drug Facts Box: Two Randomized Trials, Annals of Internal Medicine, 150:516-527.
460
461 	Shapiro, K, ed., 2001, The Limits of Attention: Temporal Constraints in Human Information
462 	Processing, London: Oxford University Press.
463
464 	Sheedy, JE, MV Subbaram, AB Zimmerman, and JR Hayes, 2005, Text Legibility and the Letter
465 	Superiority Effect, Human Factors, 47:797-815.
466
467 	Spyridakis, JH, and TC Standal, 1987, Signals in Expository Prose: Effects on Reading
468 	Comprehension, Reading Research Quarterly, 22:285-298.
469
470 	Stotka, JL, MD Rotelli, SA Dowsett, MW Elsner, SM Holdsworth, PJ Pitts, and DR McAvoy,
471 	2007, A New Model for Communicating Risk Information in Direct-to-Consumer Print
472 	Advertisements, Drug Information Journal, 41:111-127.
473
474 	Tantillo, J, J Di Lorenzo-Aiss, and RE Mathisen, 1995, Quantifying Perceived Differences in
475 	Type Styles: An Exploratory Study, Psychology and Marketing, 12:447-457.
476
477 	Thumma, C, May 1997, Consumer Engagement with Health Information, Paper Presented at the
478 	Meeting of the Marketing and Public Policy Conference, Washington, DC.
479
480 	Wogalter, MS, and WJ Vigilante, 2003, Effects of Label Format on Knowledge Acquisition and
481 	Perceived Readability by Younger and Older Adults, Ergonomics, 46:327-344.
13