Guidance for Industry 

Presenting Risk Information in 

Prescription Drug and Medical 

Device Promotion 

 
 
 
DRAFT GUIDANCE
 
 
 
  This guidance  document is being distributed for comment purposes only.  
 
Comments and suggestions regarding this draft document should be  submitted within 90 days of 
publication in the  Federal Register of the notice announcing the  availability of the draft 
guidance. Submit 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) Kristin Davis at 301-796-1200, 
(CBER) Ele Ibarra-Pratt at 301-827-3028, (CVM) Martine Hartogensis at 240-453-6833, or 
(CDRH) Ann Simoneau at 240-276-0100.   
 
 
 
 
 
 
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) 

Center for Devices and Radiological Health (CDRH) 

 
May 2009 
 
     
Guidance for Industry 

Presenting Risk Information in 

Prescription Drug and Medical 

Device Promotion 

 
 
Additional copies are available from: 
 
 Office of Communication, Training  and  
 Office of  Communication, Education and Radiological 
 
Manufacturers Assistance, HFM-40 
  Programs 
 
Center for Biologics Evaluation and Research
  Division  of Small Manufacturers, International and 

 Food and Drug Administration 
  Consumer Assistance (HFZ-220) 
 
1401 Rockville Pike, Rockville, MD 20852-1448
   Center for Devices and Radiological  Health 

 http://www.fda.gov/cber/guidelines.htm.   
 Food  and Drug Administration 

(Tel)  at 800-835-4709 or  301-827-1800  
 1350 Piccard Drive 

  Rockville, MD 20850-4307 U.S.A. 

http://www.fda.gov/cdrh/ggpmain.html 
 
Email: dsmica@cdrh.fda.gov 
 
Fax: 240.276.3151  

(Tel) 800-638-2041  or 240-276-3150 
 
* 

Office of  Training and Communication 
  Communications Staff,  HFV-12  

Division of  Drug Information, HFD-240 
  Center  for Veterinary Medicine 

Center for Drug Evaluation and Research 
  Food  and Drug Administration 

Food  and Drug Administration 
 7500 Standish Place, 

5600 Fishers Lane  
 Rockville, MD  20855 

Rockville, MD  20857 
 (Tel) 301-594-1755  

(Tel) 301-827-4573
  http://www.fda.gov/cvm/guidance/guidance.html  

 http://www.fda.gov/cder/guidance/index.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) 

Center for Devices and Radiological Health (CDRH) 

May 2009 

 
  Contains Nonbinding  Recommendations  
Draft  Not for Implementation  
TABLE OF CONTENTS 
 
 
 
I.   INTRODUCTION............................................................................................................................1 
 
II.   BACKGROUND............................................................................................................................... 2 
 
A.   LEGAL OVERVIEW ...................................................................................................................... 3 
 
B.   POLICY OVERVIEW..................................................................................................................... 4 
 
III.   FACTORS CONSIDERED  IN  THE REVIEW  OF RISK COMMUNICATION ................... 6  

A.   GENERAL CONSIDERATIONS .................................................................................................. 7  

1.  Consistent Use of Language .............................................................................................................. 7  

2.  Use of Signals..................................................................................................................................... 7  

3.  Framing Risk  Information..................................................................................................................8  

4.  Hierarchy of  Risk Information ........................................................................................................... 9  

B.   CONSIDERATIONS  OF CONTENT.......................................................................................... 10  

1.  Quantity ............................................................................................................................................ 10  

2.  Materiality and Comprehensiveness................................................................................................ 11  

C.   CONSIDERATIONS  OF FORMAT............................................................................................ 14  

1.  Print Promotion................................................................................................................................ 15  

2.  Non-Print Promotion........................................................................................................................ 18  

IV.   CONCLUSION...............................................................................................................................21  

ATTACHMENT: STATUTORY AND REGULATORY REQUIREMENTS FOR LABELING 

AND ADVERTISING ................................................................................................................................. 22  

    Contains Nonbinding  Recommendations  
Draft  Not for Implementation 
 
Guidance for Industry 
1 
Presenting Risk Information in Prescription Drug and Medical 
2 
Device Promotion 
3 
 
4 
5   
6   
7  This draft guidance, when finalized, will represent the Food and Drug Administrations (FDAs) current 
8  thinking on this topic.  It does not create or confer any rights for or on any person and does not operate to 
9  bind FDA or the public.  You can use an alternative approach if the approach satisfies the requirements of  
10  the applicable statutes and regulations.  If you want to discuss an alternative approach, contact the FDA 
11  staff responsible for implementing this guidance.   If you cannot identify the appropriate FDA staff, call 
12  the appropriate number listed on the title page of this guidance.  
13   
14   
15   
16  I.  INTRODUCTION   
17   
18  This draft guidance describes factors FDA considers  when evaluating advertisements (ads) and 
19  promotional labeling for prescription drugs,1 ads  for restricted medical devices,2 and promotional labeling 
20  for all medical devices for their compliance with the Federal Food, Drug, and Cosmetic Act (the FD&C 
21  Act or the Act) and relevant regulations.3   The draft guidance discusses factors that are relevant to the 
22  disclosure of risk information and provides numerous examples to illustrate FDAs thinking on these 
23  factors.  This guidance responds to stakeholder requests for specific guidance on  how FDA evaluates 
24  prescription drug and medical device promotional pieces to determine whether they adequately present 
25  risk information.   The recommendations contained in  this draft guidance apply to promotional materials 
26  directed to both consumers and healthcare professionals.    
27   
28   
                                                       
1  This draft guidance does not address over-the-counter (OTC) drug promotional labeling, which FDA also  
regulates.  FDA encourages all manufacturers to ensure  that  their  promotional  labeling is truthful and non-
misleading.  FDA recognizes that the marketing status of animal drugs may  vary, depending upon  the intended  
species.  For example, several anthelmintics on the market are available only  by  prescription for dogs and cats,  yet 
very similar products are available OTC for horses and food animals.  OTC drugs intended for food animals, in  
particular, may carry significant risks that may affect not only the  intended  food animal, but also other animal 
species and humans.  OTC promotional  labeling for animal drugs should convey  the serious risks associated with  
use of the products, especially those affecting the public health.   
2 Devices may  become restricted,  either by  regulation issued  under  section 520(e) of the Act (21 U.S.C. 360j(e),  or  
by order approving an application for premarket approval (PMA), pursuant  to section 515(d)(1)(B)(ii) (21 U.S.C.  
360e(d)(1)(B)(ii)).  
3 This  draft guidance  also does not apply to those reminder promotions (labeling or advertising  that calls attention to  
the  name  of  a drug or device but does  not  include indications,  dosage recommendations, or  other information)  that  
are exempted by regulation from the requirements under  the FD&C Act for the disclosure  of risk information. See 
21  CFR 200.200, 201.100(f), 201.105(d)(2), 202.1(e)(2)(i), 801.109(d).  But see 21 U.S.C. 352(r) (requiring  certain  
risk information in  all restricted device advertisements).  
 
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29  Although this draft guidance focuses on the presentation of risk information in prescription drug and 
30  medical device promotion, the factors relating to effective communication outlined below  are also 
31  applicable to  the presentation of benefit  information in promotion.  Indeed, when FDA evaluates 
32  promotional pieces  for compliance  with the Act and relevant regulations, it determines  whether claims  
33  about both risk and benefit  of the product are accurate  and non-misleading, and it also looks at whether  
34  risks and benefits are presented in a comparably prominent manner.  Thus,  considerations involving the 
35  content and format of benefit information are an inherent part of FDAs evaluation of risk presentations in 
36  promotional pieces.  FDA recommends that companies take the factors outlined in this document into 
37  account when developing both risk and benefit presentations in their promotional pieces, as the public 
38  health is best served when risk and effectiveness information about drug and device products is clearly 
39  and accurately communicated. 
40   
41  FDAs guidance documents, including this draft guidance, do not establish legally enforceable  
42  responsibilities.  Instead, guidances describe FDAs  current thinking on a topic and should be viewed 
43  only as recommendations, unless specific regulatory or statutory requirements are cited.  The use of the 
44  word  should in  Agency guidances means that something is suggested or recommended, but not required.  
45   
46   
47  II.  BACKGROUND    
48   
49  The regulation of prescription drug and medical device promotion to healthcare professionals and 
50  consumers is a broad and complex topic.4   This document addresses one key aspect of this topic  the 
51  presentation of risk information.  FDA believes it is critically important to disclose risk information in 
52  prescription drug and medical device promotion appropriately and effectively to healthcare professionals 
53  and consumers.5  This information helps consumers know whether drugs or devices may be appropriate 
54  for them as  well as  what they should tell their healthcare professionals about before taking or using or 
55  while taking or using a product.  It also lets consumers know what risks they might experience and what 
56  steps they need to take for  safety reasons (e.g., no driving) because of taking or using a product.  
57  Appropriate risk disclosures help healthcare professionals by giving them some of the information they 
58  need to know about the product that will enable them to safely use or prescribe it. Recently published 
59  industry guidelines encourage manufacturers to develop prescription medicine promotion that is 
                                                       
4 Although  beyond the scope of this document,  the complexity  of the topic can be demonstrated by  past studies that  
have shown potential positive and negative effects of direct-to-consumer (DTC) advertising for prescription  drugs.   
For example, FDA research suggests that DTC advertising seems to increase awareness  of conditions and 
treatments, to  motivate questions for  the healthcare provider, and to help  patients ask better questions.  Yet this  
research also suggests that almost half of  physicians feel some pressure to  prescribe as a result of  DTC advertising,  
and patients and physicians report a belief that these ads  overstate the drug products efficacy and do not present a 
fair balance of  benefit and risk  information.  For the complete study results, see K. Aikin, J. Swasy & A. Braman, 
Patient and Physician Attitudes and Behaviors Associated  With  DTC Promotion of Prescription  Drugs   Summary  
of FDA Survey Research Results, Final Report, November 19, 2004, available at: 
http://www.fda.gov/cder/ddmac/Final%20Report/FRfinal111904.pdf.  
5   Effectively disclosing  risk  information also  requires a consideration of whether an advertisement or promotional  
material  over  warns.  For example, a drug  advertisement that includes a listing of side effects that are  not included  in 
the  drug's  approved labeling may lead to under-emphasis  of  the most important and serious risks.  FDA takes care to  
ensure  that important  risk information is  included  in the drug's approved  labeling, and sponsors have an obligation to  
update  their  labeling with appropriate new  safety  information.   21 CFR 201.57(c)(6); 201.80(e).  Nothing in  this  
guidance  should be construed as  recommending  that the  sponsor of  a drug include in  advertising or promotional 
materials risk  information not in  the product's approved labeling  or appropriate for  inclusion in  the labeling.  See  73  
Fed. Reg. 2848, 2851 (January  16, 2008).  
  2
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60  designed to achieve a balanced presentation of both the benefits and the risks associated with the 
61  advertised product.6    
62   
63  However, omission or minimization of risk information is the most frequent violation of the regulations  
64  cited in advertising and promotion enforcement letters sent to sponsors, and illustrative research in one of  
65  the areas this  guidance covers, direct-to-consumer prescription drug  advertising,  has shown that 60 
66  percent of patients believe ads directed at them do not provide enough information about risks, 60 percent 
67  of physicians believe that patients have little or no understanding from these ads about what the possible 
68  risks and negative effects of the products are, and 72 percent of physicians believe that patients have little 
69  or no understanding from these ads about who should not use the product.7    
70   
71  FDA is issuing this draft guidance to aid sponsors in effectively communicating risk information in their 
72  promotion to both healthcare professionals and consumers.  This draft guidance describes how FDA 
73  reviews prescription drug and medical device promotional pieces to determine  whether they adequately 
74  present risk information.  The document begins with some background information, including a brief 
75  overview of legal requirements and a discussion of policy considerations related to drug and device 
76  promotional materials.  The draft guidance then describes factors FDA considers when  reviewing risk 
77  communication in promotional materials.  Because the principles within this guidance are based on 
78  universal concepts of communication and understanding of risk information, the guidance will address 
79  promotion aimed at both lay consumer and healthcare professional audiences.    
80   
81  A.  LEGAL  OVERVIEW 
82   
83  Under the  FD&C  Act  and FDA's implementing regulations, promotional pieces  (such as promotional  
84  labeling for drugs and devices and advertisements for  prescription drugs and restricted devices) making 
85  claims about a product are deemed misleading if they  fail to disclose certain information about the 
86  product's risks.8  Generally, to comply with  the FD&C Act and FDAs implementing regulations, such 
87  promotional pieces:9  
88   
89     Cannot be false or misleading in any particular10  
90     Must reveal material facts about the product being promoted, including facts about the 
91  consequences that can result from use of  the product as suggested in the promotional piece11  
                                                       
6 PhRMA, PhRMA Guiding Principles Direct  to Consumer Advertisements About Prescription Medicines, Principle 
11, November  2005, available at:   http://www.phrma.org/files/DTCGuidingprinciples.pdf. 
7 K. Aikin, J. Swasy & A. Braman, Patient and Physician Attitudes and Behaviors Associated With DTC Promotion  
of Prescription Drugs  Summary  of FDA Survey Research Results, Final Report, November 19, 2004, available at:  
http://www.fda.gov/cder/ddmac/Final%20Report/FRfinal111904.pdf.  
8  The relevant statutory provisions and regulations are discussed in more detail in  the Attachment to  this guidance.   
9 The  terms  promotional piece, promotional materials, and promotional communications are used in this guidance to 
refer generally to both advertising and promotional labeling, regardless of format. Promotional materials include,  
among others, television ads, brochures,  booklets, detailing pieces, internet web sites, print ads, exhibits, and sound 
recordings  or radio ads.   As noted in  the  introduction, this guidance applies to all types  of promotion for prescription  
drugs, advertisements for restricted  devices  and promotional labeling for  all devices.  
10 Drugs and devices are misbranded under the Act if their labeling  is false or misleading in  any particular (21  
U.S.C. 352(a)).   Similarly, prescription drugs  and restricted  devices are misbranded if their advertising is false or 
misleading  in any particular (21 U.S.C. 352(n) & (q)(1); 21 CFR 202.1(e)(5)(i)). 
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92  and 
93     Should present information about effectiveness and information about risk in a balanced 

94  manner12
  
95   
96  This draft guidance document describes factors FDA considers when evaluating risk disclosure in  
97  prescription drug and medical device promotional materials to determine whether these materials comply 
98  with the statutory and regulatory requirements.  The draft guidance also makes recommendations about 
99  how manufacturers can develop the content and format of promotional communications to comply  with 
100  these requirements. The examples and recommendations provided are intended  to provide guidance and 
101  illustrate possible approaches; manufacturers are free to use alternative approaches if these approaches 
102  satisfy the requirements of the statute and regulations.   Unless otherwise specified in this draft guidance, 
103  the principles set forth below apply to all promotional pieces, regardless of the  medium used or the target  
104  audience. 
105   
106  B.  POLICY OVERVIEW 
107   
108  Section III of this guidance highlights several factors, including those related to content and format, that 
109  FDA uses to  evaluate the risk communication in a promotional piece.  We recommend that manufacturers 
110  consider these factors  when trying to achieve effective risk communication.  It is important to  emphasize  
111  that when  FDA evaluates the risk communication in a promotional piece, FDA looks not just at specific 
112  risk-related statements, but at the net impression  i.e., the  message communicated by all elements of the 
113  piece as a  whole.  The purpose of the  evaluation is to determine whether the piece as a whole conveys an 
114  accurate and non-misleading impression of the benefits and risks of the promoted product.  Manufacturers 
115  should therefore focus not just on individual claims  or presentations, but on the promotional piece as a 
116  whole.13   A promotional communication that conveys a deceptive net  impression of the product could be 
117  misleading, even if specific individual claims or presentations are not misleading.    
118   
119  FDAs consideration of the net impression of risk information is based on well-developed social science 
120  principles supported by decades of scientific research14  and is consistent with the approach of other 
121  agencies and organizations.  For example, the Federal Trade Commission (FTC) uses the interpretation of 
122  the net impression of the piece to determine whether a promotional piece is likely to mislead a 
123  consumer.15   Pharmaceutical industry members have also conducted social science research showing that, 
124  when evaluating a promotional piece, the net impression conveyed by the piece as a whole is an important 
125  element to consider, independent of individual statements within the piece.   
                                                                                                                                                                               
11 21  U.S.C. 321(n); 21 CFR 1.21 & 202.1(e)(5)(iii). 
12  See 21  CFR 202.1(e)(5)(ii).   
13 Manufacturers should  note that, although this guidance focuses on risk  disclosures in  promotional pieces, any  
claims in a promotional piece  that are misleading, whether risk-related  or not, can cause the product being promoted 
to become  misbranded ( 21  U.S.C. 352(a), (n) & (q)(1); 21 CFR 202.1(e)(5)(i)). 
14 For reviews of this field, see Kimble, G.A.  (1985)  The psychology  of  learning enters its second century.  In  
Hammonds, B.L. (Ed.),  Psychology and learning.  Washington, DC:  American Psychological Association  (pp. 5-47)  
and Mayer, R.E. (2003) Memory and information processes.  In Reynolds,  W.M., & Miller, G.E. (Eds.), Handbook 
of Psychology: Educational Psychology, 7. New York: John  Wiley & Sons, Inc. (pp.  47-57).   
15 See  Federal Trade Commission, FTC Policy Statement on Deception, (Oct. 14, 1983), appended to FTC v.  
Cliffdale Associates, Inc., et  al.,  103 F.T.C. 110, 170  (1984) (hereinafter FTC Policy Statement on Deception with 
page references to  103 F.T.C. 110).  
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126   
127  Section III of the guidance contains examples of how various aspects of content and format can contribute 
128  to a misleading net impression in promotional pieces.  The following  two examples also illustrate this. 
129   
130  Example 1: A broadcast television ad for a cholesterol-lowering drug contains a factually 
131  accurate  audio risk statement that discloses the drugs  major side effects and contraindications.  
132  This audio presentation is accompanied  by quick scene changes showing comforting visual 
133  images of patients benefiting from the drug.  It is also accompanied by loud, upbeat music. In  
134  this case, the  audio disclosure may not adequately communicate risks because of the  
135  accompanying discordant visuals and distracting music. 
136   
137  Example 2:   A one-page prescription drug ad for an arthritis drug, run in a medical journal, 
138  prominently presents the following headline claims in large bolded font and with abundant 
139  surrounding white space: 
140     Benefits!   DrugX is proven safe and effective for the relief  of arthritis  pain and 
141  stiffness, 
142     Difference!   DrugXs unique gel formulation is convenient and easy to  use, and  
143     Reason to Believe!   Drug  X is the most frequently  prescribed arthritis  drug in the  
144  United States   
145  The bottom of the page contains an inconspicuous statement in small, non-bolded font and 
146  without surrounding white space:  Like all arthritis medications, Drug X  has  been associated 
147  with a risk of serious infection.  The emphasis on benefit information in this piece  in terms  of 
148  the way the information is formatted and framed  overwhelms the risk information and may 
149  cause readers to receive  an erroneous impression that the drug is safer than it has proven to be, 
150  even though the statements themselves may be factually accurate.  
151   
152  Using the factors explained in Part III of this draft guidance, trained professionals at FDA with expertise 
153  in areas including communication, drug information, medicine and law, apply these factors and evaluate 
154  claims in promotional pieces  from the perspective of  a reasonable consumer.  As FDA has stated,16 the 
155  agency believes that the reasonable consumer standard is the appropriate standard to use in determining 
156  whether a claim in the labeling of a dietary supplement or conventional food is misleading.  The agency 
157  confirms that the reasonable consumer standard will be used to evaluate communications covered by this 
158  guidance document.  The reasonable  consumer  standard used by FDA in evaluating promotional 
159  materials is similar to the FTC standard:  
160   
161  [W]e examine the practice from the perspective of a consumer acting reasonably in the  
162  circumstances.  If the representation or practice affects or is directed  primarily to a 
163  particular  group, the Commission examines reasonableness from the perspective of  that  
164  group.17  
165     
                                                       
16 Guidance for Industry:   Qualified Health Claims in the Labeling  of Conventional Foods and Dietary Supplements  
(Dec. 2002) (replaced by Guidance for Industry and  FDA: Interim Procedures for Qualified Health Claims in the 
Labeling  of Conventional Food and Human Dietary Supplements (July 2003)); see 70 Fed. Reg. 824 (Jan. 5, 2005)  
(noting  that, although the Guidance for Industry  on  Qualified  Health Claims in  Labeling of Conventional Foods and 
Dietary Supplements (Dec. 2002) has been  replaced by subsequent  guidance, the agency  has not abandoned the  
position in the 2002 guidance regarding  reasonable consumer standard). 
17  See FTC Policy Statement on Deception at 170.  
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166  This standard does not preclude multiple  interpretations of a claim, as long as they are reasonable.  As the 
167  FTCs Policy Statement provides:  
168   
169  To be considered reasonable, the  interpretation  or reaction does not have to be the  only 
170  one.  When a sellers representation conveys more than one meaning to reasonable 
171  consumers, one of  which is false, the seller  is liable for the misleading  interpretation.18  
172   
173  In applying the reasonable consumer standard,  FDA, like FTC, takes into account the different levels of 
174  expertise of lay consumers and healthcare professionals.   Due to their training and experience, healthcare  
175  professionals develop a level of  knowledge related to scientific concepts and medical conditions and 
176  products that lay consumers do not possess.  FDA takes this difference in knowledge and experience into 
177  account when assessing promotional materials directed at healthcare professionals versus those directed at 
178  lay audiences.  However, research has shown that experts (in this case, healthcare professionals) are  
179  subject to the same cognitive biases and processing limitations as non-experts.19    
180   
181  Cognitive science research has demonstrated that all people, regardless of  expertise, are only able to think 
182  through and process a limited amount of information at one time.20  However, our ability to process 
183  information can be greatly  improved by considering and controlling for the factors that affect attention 
184  and comprehension.   This guidance discusses those factors, how we apply them to our review of 
185  promotional materials, and what  manufacturers can do to ensure that their  materials comply with the  
186  regulations.   
187   
188   
189  III.   FACTORS CONSIDERED  IN  THE REVIEW  OF RISK COMMUNICATION  
190   
191  FDA relies on a vast scientific body of knowledge regarding human cognition in assessing which factors 
192  to consider in evaluating promotional pieces and making regulatory decisions about the presentation of 
193  risk information.  The following sections highlight factors that FDA considers when determining whether 
194  risk information is communicated in a fashion consistent with the regulations. 
195   
                                                       
18  Id.  at 177. 
19  Although physicians  generally  do not  believe that they  are  influenced by advertising, (Spiller  & Wymer, 2001),  
research has shown that physicians are influenced by  promotional activities (e.g., advertising:  Avorn et al., 1982;  
sales representatives:  Gonul et al., 2001).   Avorn, J., Chen, M. & Hartley, R. (1982) Scientific versus commercial 
sources  of influence  on the prescribing behavior of  physicians.   American  Journal of Medicine, 73, 4-8.  Gonul, F.F.,  
Carter, F., Petrova, E., & Srinivasan, K. (2001) Promotion of prescription drugs and its impact on physicians  choice 
behavior.   Journal of Marketing, 65, 79-90.  Spiller, L.D., & Wymer,  W.W. (2001) Physicians perceptions  and uses  
of commercial drug information sources: An examination of pharmaceutical marketing to physicians.   Health  
Marketing Quarterly, 19, 91-106.   
20 See, e.g., Lavie, N. (2001) Capacity  limits in selective attention: Behavioral evidence and implications for neural  
activity. In Braun, J., Koch, C., et al. (Eds.), Visual  attention and cortical circuits. Cambridge, MA:  The MIT 
Press (pp.  49-68); Miller, G.A. (1994)  The magical number seven, plus or  minus two:   Some limits on  our capacity  
for processing information.   Reprinted in Gutfreund,  H., & Toulouse, G.  (Eds.),  Biology and  computation: A 
physicists choice.  River  Edge, NJ:   World Scientific Publishing Co. (pp. 207-233); Shapiro, K. (Ed.) (2001)  The 
limits  of attention: Temporal  constraints in  human information processing.  London: Oxford University Press.  
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196  A.  GENERAL CONSIDERATIONS 
197   
198  This section explores some  important factors that relate to both the content and the format of  a 
199  promotional piece.  FDA will consider the use of  language and signals and how information is framed and  
200  ordered.  
201   
202  1.   Consistent Use of Language Appropriate for Target Audience 
203   
204  Both language used to communicate benefits and language used to communicate risks should be 
205  comprehensible to the same audience for a piece to  be considered accurate and non-misleading.  Thus, 
206  promotional materials directed to professionals can reasonably describe benefits and risks in medical  
207  language, but promotional materials directed to consumers should convey benefits and risks in language 
208  understandable to consumers.21   
209   
210  Example 3:  A consumer-directed ad for a drug that presents benefit claims in consumer friendly 
211  language should mention a risk of fainting, not syncope.    
212   
213  With respect to consumer-directed materials,  FDA encourages  manufacturers to present both benefit and 
214  risk information in clear, understandable, and non-technical language for consumer audiences.22     
215   
216  2.   Use of Signals 
217   
218  Signaling is an important component of information communication.23   In written materials, signaling has 
219  been defined as the use of writing devices designed to emphasize aspects of a texts structure or content 
220  without altering the information in the text.24   Headlines and subheads are examples of commonly used 
221  signals.25   Depending on the circumstance, accurate information in the text may not remedy a false 
222  headline [or signal] because reasonable consumers  may only glance  at the headline and skip the 
                                                       
21 See Root, J., & Stableford, S. (1999) Easy-to-read consumer communications:  A missing link in Medicaid  
managed care.  Journal of  Health Politics, Policy, &  Law, 24, 1-26. 
22 Although  not a true measure of understandability,  text  reading level,  often expressed as grade level, is one 
way to assess text difficulty.  Text that  scores  at a higher grade level (e.g., 12th  grade)  is considered more complex 
than  text scoring at a lower grade level (e.g., 8th grade).  Several validated  reading level measures  are available to 
provide an approximate  measure of  text complexity.  See, e.g., Kincaid, J.P., Fishburne, R., Rogers, R.L., Chissom,  
B.S. (1975)  Derivation of  New Readability Formulas  (Automated Reliability Index, Fog Count, and Flesch  Reading  
Ease Formula)  for  Navy Enlisted Personnel.  Research Branch Report 8-75.  Memphis:  Naval Air Station;  
McLaughlin, G.H. (1969) SMOG grading: A new  readability  formula.  Journal of Reading, 12, 639-646; Mosenthal,  
P.B. (1998) A new measure of assessing document  complexity: The PMOSE/IKIRSCH document readability 
formula.  Journal of Adolescent and Adult Literacy, 41, 620-638.  We  encourage manufacturers to  test text  
comprehensibility as  well. 
23 Loman, N.L., & Mayer, R.E.  (1983) Signaling techniques that increase the understandability of expository  prose.  
Journal of Educational Psychology, 75, 402-412; Meyer, B.J.F. (2003)  Text coherence and readability.  Topics in  
Language Disorders, 23, 204-224; Spyridakis, J.H., & Standal,  T.C.  (1987) Signals in expository  prose:  Effects on 
reading comprehension.  Reading Research Quarterly, 22, 285-298. 
24 Lorch, R.F., Lorch, E.P., & Inman,  W.E. (1993) Effects of  signaling structure on text recall.  Journal of  
Educational Psychology, 85, 281-290,  p. 281.  
25 Hyona, J., &  Lorch, R.F. (2004) Effects of topic headings  on text processing: Evidence from adult readers eye 
fixation patterns.  Learning and Instruction, 14, 131-152.  
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223  remainder of  the text.26   Signals are also used in broadcast situations, such as when an announcer draws 
224  attention to different items of information, when a word on the screen identifies a new topic, or when 
225  headlines emphasize some messages but not others.   
226   
227  When reviewing promotional materials,  FDA looks to see if the use of signals is consistent across benefit 
228  and risk information, so that the materials provide accurate and non-misleading impressions of a drug or 
229  device.  
230   
231  Example 4: If a piece contains headlines that signal benefit information,  (e.g., Drug X Provides 
232  Highly Effective Control), some sort of headline should also signal risk information (e.g., Side 
233  Effects for Drug X).    
234   
235  However, the  mere presence of similar signals for both benefit and risk information is not necessarily 
236  sufficient to make a piece accurate and non-misleading.  The content of the signals is also important.  
237  Certain headlines  may  frame (see next section) subsequent risk information in ways that emphasize or 
238  minimize its importance.    
239   
240  Example 5:  The headline Important Risk Information about Device X is preferable to  
241  Important Information about Device X because the  former headline indicates  what type of 
242  information follows.  Similarly, Common Side Effects Seen with Drug  X, is preferable to 
243  Other Information about Drug X.  Specific and clear signals are preferable because they are 
244  more effective than vague or abstract terms.    
245   
246  Presenting risk information with no signal, or beginning the presentation of risk information with  
247  unrelated information (e.g. presenting risk information in a paragraph that begins with information on 
248  indication or dosing) can also minimize the risks of the product and  mislead the audience.  For example, 
249  the headlines in the following example convey additional benefit information, potentially misleading the 
250  audience about the overall risk-benefit profile of the product.  
251   
252  Example 6:  Placing risk information under headlines such as Now  Approved for Epilepsy or 
253  Safe Enough for Children Under 5 minimizes the risk information that follows, particularly if 
254  individuals only look at the headlines.  Instead, headlines preceding risk presentations should 
255  signal that a risk presentation follows, for example, Important Risk Information About Drug X. 
256   
257  In videos, broadcast ads, and other promotional pieces with  audio components, a change of announcer or 
258  a statement in the audio portion of the piece to signal to the audience that risk information follows can aid  
259  effective communication.  However, manufacturers should consider comparable voice characteristics, as 
260  discussed in Section III.C.2.  Risk information may also be signaled graphically or visually.  Similar to 
261  print pieces, specific and straightforward audio signals are most likely to adequately convey risk 
262  information.    
263   
264  3.  Framing Risk Information 
265   
266  FDA evaluates how risk information is framed because framing can affect  the  presentation of risks and 
267  benefits in  a promotional piece.  Framing commonly refers to how a particular piece of information is 
268  stated or conveyed, such as by emphasizing either the positive or negative aspects of the information or 
269  by presenting the information in vague versus specific terms.  Research consistently shows that framing 
                                                       
26 FTC Policy Statement on Deception at  182.  
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270  the same information in different ways can change the way audience members respond to that 
271  information.27   Thus, the way information is phrased can significantly influence the message the audience 
272  receives  from a promotional piece. 
273   
274  Framing risk information in non-specific terms can undermine the effective communication of that 
275  information to the audience.  Risk information should be presented in the same  terms or with the same  
276  degree of specificity as benefit information.   For example, if a promotional piece refers to the product by 
277  name in presenting efficacy information, it should refer to the product by name in presenting risk 
278  information, rather than by referring to the products device or drug class.   
279   
280  Example 7: If the benefit information refers to the brand name, Drug X, then Common side 
281  effects  associated with  Drug  X  would be preferable to Common side effects associated with 
282  [the generic name].   
283   
284  Moreover, within the risk information presentation, phrases such as  Like all medicines, Drug X has some  
285  side effects, may have the effect of  minimizing the risks that follow.  Framing risk information in a way  
286  that minimizes the severity of a risk event may also cause a promotional piece to be considered false or 
287  misleading.   
288   
289  Example 8: If a drugs package insert contains a boxed warning about the risk of life-threatening 
290  fevers associated with its use and reports that 55 percent of patients taking the drug experience 
291  dizziness, a statement such as Adverse events associated with drug X include  fevers.  Some  
292  patients experienced dizziness misleadingly describes the risk profile of the drug by failing to 
293  convey the seriousness of the fevers and the frequency of the dizziness.   Statements like Life-
294  threatening fevers have been reported with the use of  Drug  X  and More than half of patients 
295  taking Drug X experienced dizziness would convey the seriousness and frequency of the two  
296  risks appropriately.  
297   
298  In addition, the risks conveyed in the piece should be framed in a way that accurately reflects their nature.  
299   
300  Example 9:  A statement such as  continuation of therapy may  necessitate certain monitoring is 
301  too vague for a product that requires monthly blood tests to check  for liver damage.  This 
302  statement fails to convey the risk of liver damage and also misleadingly suggests that routine 
303  monitoring may not be necessary for some patients.  A statement like Monthly blood tests 
304  should be performed to check for liver damage would accurately convey the type of  monitoring 
305  needed and the risk involved.  
306   
307  4.   Hierarchy of Risk Information 
308   
309  FDA considers the ordering of risks within a presentation an important factor in determining the risk 
310  profile conveyed by a piece, regardless of whether it is directed toward healthcare professionals or 
                                                       
27  See Armstrong, K., Schwartz, J.S., Fitzgerald, G.,  Putt, M., &  Ubel, P.A. (2002) Effect of  framing as  gain versus  
loss on understanding and  hypothetical treatment choices: survival and mortality curves.   Medical Decision Making, 
22, 76-83; Dunegan, K.J.  (1993)  Framing, cognitive modes, and  imagery theory: Toward  an understanding of  a glass  
half full.  Journal of Applied Psychology, 78, 491-503; Rothman, A.J., & Salovey, P. (1997) Shaping perceptions to  
motivate healthy behavior:   The role of message framing.   Psychological Bulletin, 121,  3-19; Smith, S.M., & Petty,  
R.E. (1996) Message framing and persuasion: A message processing analysis.  Personality  and Social Psychology 
Bulletin, 22, 257-268; Tversky, A., & Kahneman, D. (1981) The framing of decisions  and the psychology of  choice.  
Science, 211, 453-458.    
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311  consumers.  As discussed in Section III.B.2 (below) and reflected in the format  of the package insert for  
312  prescription drugs and medical devices, risks associated with a specific product are assigned a hierarchy 
313  of importance.   
314   
315  Memory research consistently shows that, in an experimental setting,  when people process an entire list or 
316  text, they are  better able to  recall items at the beginning and the end than items in the  middle.28   
317  Consequently, in a broadcast ad, where viewers do not have the opportunity to control the speed at which 
318  information is presented to help them to process it, the beginning or end, or both,  should be reserved  for 
319  the most important risk information.  On the other hand,  when reading a print promotional piece under 
320  normal circumstances, readers may lose interest toward the end of  a lengthy paragraph,  and it is not likely 
321  that the information at the end will be as well-comprehended as the information at the beginning.  If a 
322  products most important risks are located in the middle of  a list of less important risks, the important 
323  risks may not be effectively communicated.  FDA therefore recommends that the most important risk  
324  information, including relevant warnings and contraindications, be placed or stated first, especially in 
325  print materials.  As  discussed in Section III.C.1  (below), manufacturers should also note, however, that 
326  risk information should not  just be presented in one location in a piece, but should, like benefit 
327  information, appear as an integral part of the piece.     
328   
329  FDA also considers the order in  which risk information is presented to determine whether this ordering 
330  suggests that certain risks apply only to certain populations or only under certain conditions when this is 
331  not the case.   
332   
333  Example 10:  A statement in a broadcast ad that Patients should not drink alcohol when taking 
334  Drug  X.  Common side effects are drowsiness and nausea may suggest that these side effects 
335  occur only if alcohol is consumed when taking the drug.  Instead, the sponsor should consider 
336  adding intervening information or changing the order of the presentation so that it is clear the side 
337  effects listed are not caused by drinking alcohol while taking the drug.  
338   
339  B.  CONSIDERATIONS OF CONTENT   
340   
341  This section discusses how FDA evaluates the content of risk presentations in determining whether a 
342  promotional piece is accurate and non-misleading.  
343   
344  1.  Quantity  
345   
346  One content factor FDA considers is the amount or quantity of information conveyed by a promotional 
347  piece.   For example, a 30-second broadcast ad is likely to present less information than a 60-second 
348  broadcast ad.  As the amount of benefit information conveyed increases, the amount of risk information 
349  conveyed should similarly  increase.   
350   
351  The quantity of information presented can affect the net impression of the piece.  The amount of  
352  information presented is one component that, together with choice of  words, color, graphics, voiceover, 
353  and other aspects of the piece,  can affect  cognitive load, the mental effort required to understand the 
                                                       
28 See Botvinik, M.M., & Plaut, D.C. (2006) Short-term  memory for serial order: A recurrent neural network model.  
Psychological Review, 113, 201-233; Capitani, E.; della Sala, S.;  Logie, R.H.; & Spinnier, H. (1992) Recency, 
primacy, and memory: Reappraising and standardizing the serial position curve.  Cortex, 28, 315-342; Murdock, 
B.B. (1962)  The serial position effect of free recall.  Journal of Experimental Psychology, 64, 482-488. 
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354  various components of information in the piece.29  If the benefit information is easily understood and 
355  maintained through repetition or other reinforcing techniques, and the risk information is not similarly 
356  reinforced, the net impression may not be appropriately balanced.   
357   
358  To ensure comparable benefit and risk presentations, manufacturers should consider the space or time 
359  devoted to benefits and risks, the comprehensibility of the language used, and the information provided 
360  on benefits and risks.   FDA will look to see that promotional communications allot sufficient time and 
361  space to convey the important benefits and risks of the product being promoted  to ensure that, as a whole, 
362  the communication provides an accurate and non-misleading impression of the product.  
363   
364  A promotional piece with several paragraphs of information regarding benefits differs  from a piece 
365  consisting mainly of one-line benefit claims.  The treatment of risk information in each piece should be 
366  comparable to the treatment of benefit information, including how it is conveyed.    
367   
368  Promotional pieces do not have to convey an identical  number of benefits and risks, and a given drug or 
369  device may  have few or many risks.30  FDA considers these factors when determining the comparability 
370  of benefits and risks in a piece:   
371   
372     The number of statements about benefits and risks 
373     The completeness and depth of detail given about benefits and risks 
374     The amount of time (in both the audio and visual portions) devoted to benefits and risks in a 
375  video, audio, or broadcast communication 
376     The amount of space devoted to benefits and risks in a print communication 
377     The use of audio or visual components that enhance or distract from the presentation of risk 
378  or benefit information   
379   
380  As stated in the Background and discussed above, FDA evaluates the net impression created by  
381  promotional communications.  This evaluation includes considering the above factors as well as the 
382  differences in the inherent risks associated with various drugs or devices.   Simply satisfying one of the 
383  above factors (e.g., devoting the same amount of time or space to risk and benefit information) will not 
384  necessarily make a promotional piece accurate and non-misleading.  Furthermore, certain important risk 
385  information should be in all promotional pieces regardless of their length (see Section III.B.2 below). 
386   
387  2.   Materiality and Comprehensiveness  
388   
389  Generally speaking,  materiality is determined by the degree to  which information is objectively 
390  important,  relevant, or substantial to the target audience.  A promotional piece that omits material 
391  information about a products risks could be considered misleading even if the piece devotes similar 
392  space or time  to risk and effectiveness presentations.31    
                                                       
29 See Mayer, R.E., & Moreno, R. (2003) Nine ways  to reduce cognitive load  in multimedia learning. Educational  
Psychologist, 38, 43-52; Pass, F., Renkl, A.,  & Sweller, J.  (2004)  Cognitive load theory: Instructional implications  
of the interaction between information structures and cognitive architecture.  Instructional Science, 32, 1-8.   
30  If  the drug or device being  promoted is  associated with  a minimal number of  risks,  and  all of these risks are 
conveyed in a format that  is comparably  prominent to the presentation of benefit information, then the risk  
presentation in such an ad  or promotional labeling piece  would be considered accurate, non-misleading and balanced  
even if the ad  presented several more benefit than  risk claims. 
31 21  U.S.C. 321(n); see also  21 CFR 1.21  & 202.1(e)(5)(iii).  Please see the Attachment to  this document for a full  
description  of the relevant  requirements. 
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393   
394  Material facts are those that would influence reasonable consumers (or healthcare professionals when 
395  they are the intended audience) about a product.  Material facts include those that influence such peoples 
396  understanding of the following: 
397   
398     The relevant properties of  a product 
399     Whether or not the product is appropriate for them or their patients 
400     Whether or not they are  willing to accept the  risks or burdens associated with using or 
401  prescribing a product 
402   
403  Some drug and device risks are material regardless of the amount or type of benefit claims in a piece.   
404  The most serious risks set forth in a products labeling are generally material to  any presentation of 
405  efficacy.  A promotional piece that communicates a products benefits should similarly communicate the 
406  most serious risks involved in using the product.   Similarly, the most frequently occurring risks would 
407  usually be material to consumers and healthcare professionals in promotion, particularly if a product is 
408  only associated with a small number of more serious risks, because of the likelihood that they will affect 
409  patients taking the drug or using the device.  
410   
411     Consideration of Target Audience 
412   
413  FDA considers the target audience of a promotional piece to be critical in determining what risk 
414  information is material.  FDA evaluates  the promotion from the perspective of a reasonable member of  
415  the targeted population (e.g.,  consumers, specific patient populations,  healthcare professionals).  As  is 
416  explored in more detail below (e.g.,  Examples 11 and 13),  different information can be material to 
417  different audiences.  For example, in a piece promoting use of a product in a selected class of patients,  
418  risks especially applicable  to that selected class of patients are  material (see The  Nature of Benefit  
419  Claims, below).32  
420   
421  Generally speaking, communications directed to healthcare professionals should convey the most critical 
422  information they need to know about the product to help them decide whether it is appropriate for their 
423  patients and to help enable them to safely use the product or counsel patients on the safe use of the 
424  product.   Consumer-directed communications should generally convey the following: 
425   
426     What the drug or device is used for 
427     Who should or should not take a drug or use a device 
428     What can be  expected from  a drug or device 
429     What patients should ask their healthcare professionals about a drug or device 
430     What patients should tell their healthcare professionals about before or while taking a drug or 
431  using a device 
432   
433  Example 11:  A drugs package insert includes a warning for healthcare professionals about dosing 
434  adjustments in patients with kidney disease.  This information is material  for healthcare professionals, 
435  both because  of the seriousness indicated by its  warning status and because of its relevance to safe  
436  prescribing.   However, although this information is important to the safe use of the drug and should 
437  be considered by prescribers, it is not material to consumers, although the reasons for such care in  
438  dosing (e.g., the consequences of  inappropriate dosing) could be.   
439   
                                                       
32 See 21 CFR 202.1(e)(7)(x). 
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440     Importance of Package Insert 
441   
442  In determining the materiality of the risks associated with a drug or device, FDA refers to the products 
443  package insert. FDA is more likely to consider as important or material a products most serious or most 
444  frequently occurring risks than a products less serious or less commonly occurring risks.33   FDA 
445  characterizes the risks associated with a specific product along a hierarchy of importance reflected by 
446  placement in  a risk-related  section of the products package insert  traditionally , the Contraindications,  
447  Warnings or Hazards,  Precautions, Adverse Reactions or Side Effects sections, as well as the  
448  Overdosage, and Drug Abuse and Dependence sections in the case of prescription drugs  and in the use 
449  of various means to emphasize certain risks, such as boxed warnings and bolded statements.  For labeling 
450  that complies  with the new formatting requirements in the recently finalized Physician Labeling Rule for 
451  prescription drugs,34 the risk-related sections include Boxed Warning, Contraindications, Warnings and 
452  Precautions, Adverse Reactions, Drug Interactions, Use in Specific Populations, Drug Abuse & 
453  Dependence, and Overdosage.  
454   
455  For prescription drug physician labeling that follows the new requirements, the risks included in the 
456  Highlights section of labeling are the most important risks associated  with the drug.   For other labeling,  
457  contraindications and warnings or hazards are considered to contain the most serious and material risk  
458  information associated with a drug or device and convey information that must be understood before the 
459  product is prescribed or used.  Contraindications and boxed warnings are generally considered the most 
460  important.  Precautions also convey important risk information that can help healthcare professionals and 
461  patients use a drug or device more safely.  These include ways to avoid adverse effects and information 
462  about important differences in individual response and,  for drugs,  about interactions with other drugs or 
463  food.  Risks conveyed only in the adverse events or side effects section are generally less serious or less 
464  well-documented than those in the preceding three categories.  They are often  the most commonly 
465  experienced risks associated with a product, however, and they therefore may constitute important 
466  information for both healthcare professionals and consumers.  
467    
468     The Nature of Benefit Claims  
469   
470  Promotional pieces should reveal risk information that is material in light of the specific benefit claims  
471  made in the piece.   
472   
473  Example 12:  If a piece claims convenience because the promoted drug is dosed once-weekly, 
474  information about risks directly related to the regimens convenience is material.  Such risk 
475  information might include, for example, that inflammatory reactions such as swelling have been 
476  reported at the application site for a topical product, or that patients must restrict their activities 
477  for some time after taking an oral medication because  of a risk of fainting.  
                                                       
33 As indicated above, the most  serious risks set forth  in a products labeling are generally  material  to any  
presentation of efficacy.  Frequently occurring, less  serious risks  (e.g., those reflected in Adverse Reactions) can be 
material, particularly for a  product  that  is not associated with serious risks, but these less serious risks may  not  be  
material for a product that  has many serious risks that  need  to  be disclosed in promotion,  or whose most frequently  
occurring risks occur at a very  low rate.  In  general, FDA believes that exhaustive lists of minor risks distract from  
and make it  difficult to comprehend and retain  information  on the more important risks.  To this end, we  have issued 
a draft guidance for prescription drugs entitled  Brief  Summary Disclosing  Risk Information in Consumer-Directed  
Print Advertisements, which suggests approaches to communicating less, but better, information in consumer brief  
summaries.  Once finalized, this  guidance  will represent the Agency's thinking on  this  topic. 
34  See 71 Fed. Reg. 3922 (Jan. 24, 2006).  The rule became effective June 30, 2006. 
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478   
479  Similarly, as  stated above, for promotional pieces that  promote a products benefits in a selected class of 
480  patients, the significant risks applicable to that class of patients are material.35    
481   
482  Example 13:  If a Web site for a product approved to treat high blood pressure presents 
483  information about a products benefits in postmenopausal women, any risks specific to  
484  postmenopausal women are particularly material.  
485   
486     Accuracy and Comprehensiveness of Risk Information 
487   
488  When it evaluates the content of  a promotional pieces risk information, FDA assesses the quality as well 
489  as the quantity of the information.  Both consumer  and professional audiences  expect that certain 
490  information will be present in promotions for prescription drugs and medical devices.  This expectation 
491  results from schemas,36 or mental frameworks, about these promotional pieces that have developed from  
492  previous exposures (i.e., preconceived expectations based on past experience).  Consumers have 
493  preconceived ideas about the amount of scrutiny these ads undergo.  Many believe FDA exercises tight 
494  regulatory control over the content of these ads and to some extent, believe that all ads have been pre-
495  reviewed prior to airing.37   As a result, consumers are likely to expect that the most relevant risks have 
496  been included in the ad.  Because people expect to see risk information, there is no reason for them to  
497  imagine that the product has important risks that have been omitted.   Instead, the audience is likely to 
498  believe that all significant risks are included, especially if some risks are included.   This missing risk 
499  information can have serious effects; it  may cause consumers to fail to inform their healthcare 
500  professionals of important considerations, and healthcare professionals to prescribe inappropriately or 
501  even dangerously.  
502   
503  Example 14:  A product is associated with the rare but serious risk of a heart attack.  FDA is likely 
504  to consider an ad misleading if it devotes a certain amount of time or space to the presentation of  
505  claims  about the products efficacy in treating migraines and then devotes a similar amount of  
506  time or space to describing only the frequently occurring, least serious adverse events, or only 
507  one of several significant risks.    
508   
509  Even though a similar quantity of risk and benefit information may be conveyed, a promotional piece that 
510  presents information on the benefits of the product but then communicates only its least serious risks, or 
511  an inadequate set of its serious risks,  will not have conveyed an accurate understanding of the products 
512  relevant properties. 
513   
514  C.  CONSIDERATIONS OF FORMAT  
515   
516  FDA also considers formatting factors  when assessing whether a piece is  false or  misleading.  Format  
517  includes the shape, size, and general  layout of all portions of a print promotional piece,  as well as the 
                                                       
35  See 21 CFR 202.1(e)(7)(x). 
36  See Kardash,  C.A.M., Royer, J.M., & Greene, B.A. (1988)  Effects of schemata on  both  encoding and retrieval of  
information from prose.  Journal of Educational Psychology, 80, 324-329;  Smith, E.E., & Swinney, D.A. (1992)  
The role of  schemas  in reading text: A real-time examination.  Discourse Processes,  15, 303-316.  
37 See, e.g., K. Aikin, J.  Swasy  & A. Braman, Patient and Physician Attitudes and Behaviors Associated  With  DTC  
Promotion of Prescription Drugs  Summary  of FDA Survey Research Results, Final Report, November 19, 2004, 
available at: http://www.fda.gov/cder/ddmac/Final%20Report/FRfinal111904.pdf;  Prevention Magazine (2004)  5th  
Annual Survey: Consumer Reaction to DTC Advertising of Prescription Medicines. Emmaus, PA: Rodale. 
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518  general plan  of organization, arrangement, and theme in non-print promotional pieces such as videos and 
519  broadcast ads.  
520   
521  To process information, a person must first pay attention to it.  Several factors contribute to whether 
522  people will pay attention to information.  These factors also may help or hinder peoples understanding of 
523  information once it has drawn their attention.  When evaluating whether a promotional piece 
524  appropriately communicates risk information, FDA considers several formatting factors.38   Because these 
525  factors apply to information processing in general, prescription drug  and medical device manufacturers 
526  should keep them in  mind  when developing promotional pieces.   
527    
528  As a general matter, risk and benefit information should be comparably noticeable or conspicuous in 
529  promotional pieces, and audiences should be able to  read both risk and benefit  information with similar  
530  ease (e.g., comparably legible and understandable; see Section III.A.1 above).39  Manufacturers should 
531  note that any one of the  following formatting factors could make a  piece  false or  misleading and that each  
532  factor could interact  with others to increase this problem or to create a false or  misleading impression 
533  when there might not be one if a factor were considered in isolation.  
534   
535  1.  Print Promotion 
536   
537  The layout of a print promotional piece (generally, its plan, design,  or arrangement) influences readers 
538  ability to pay attention to and process specific features of the piece.40  FDA considers the following 
539  selected aspects of the layout of a print promotional piece when assessing the comparable  prominence and 
540  readability of risk and efficacy information.   This is not an exhaustive list; other issues, such as language 
541  comprehension and the risk hierarchy, are covered in other sections.  
542   
543     Overall  Location of Risk Information  
544   
545  For a piece to be accurate and non-misleading, risk information should be included in the main part of a 
546  piece.  If the omission of risk information in any part  of a piece makes that part of the piece false or 
547  misleading, the problem cannot be corrected simply  by including the risk information in a separate part of  
548  the piece.41   To be comparably prominent to benefit information, risk information should generally appear 
549  in the same parts of the piece as the benefits.  
                                                       
38 See, e.g.,  21 CFR 202.1(e)(7)(viii) for a list  of implementing factors FDA takes  into consideration when  
evaluating the balance between benefit and risk information in an ad.  See generally 21 CFR 202.1(e)(6)-(7). 
39  See 21  U.S.C.  352(c). 
40 See Adams, A.S., & Edworthy, J. (1995)  Quantifying and  predicting  the effects of basic text display variables on  
the perceived urgency of warning labels:  Tradeoffs involving font size, border weight, and color.  Ergonomics, 38, 
2221-2237; Brundage, M., Feldman-Stewart, D., Leis, A., Bezjak, A.,  Degner, L., Velji, K.,  et al. (2005) 
Communicating quality of life information to  cancer  patients:  A study  of six presentation formats.  Journal of  
Clinical Oncology, 23, 6949-6956; Frantz, J.P. (1993)  Effect  of location and presentation format on attention to and  
compliance with product warnings  and instructions.  Journal of  Safety Research, 24, 131-154;  Morrow, D., Leirer, 
V., Altieri, P. (1995) List formats improve medication instructions  for older adults. Educational Gerontology, 21, 
151-166; Niemela, M., & Saariluoma, P. (2003)  Layout attributes and recall.  Behaviour and Information  
Technology, 22, 353-363;  Wogalter, M.S., & Vigilante, W.J., Jr. (2003)  Effects of label format on  knowledge  
acquisition and perceived readability  by  younger and  older adults.  Ergonomics, 46, 327-344.  
41  See 21  CFR 202.1(e)(3)(i).  The prescription drug  regulations  allow the presentation of  risk information in  a 
particular part of  a promotional piece to  be  concise if it is  supplemented  by  a prominent  reference on  each page  to  
the presence and location of a more complete discussion  of such information  elsewhere in the  piece.  Id. However,  
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550   
551  Complete separation of benefit and risk information (e.g., presenting several pages of benefits before any  
552  risks) is one example of a lack of appropriate prominence.42   FDA will also look to see that risk 
553  information is not placed in such a  way  as to interfere  with readers perceptions of the relative importance  
554  or utility of the information.   
555   
556     Location of Risk Information within a Part of the Promotional Piece 
557   
558  In addition to appearing with or near benefit presentations, risk information should appear as an integral 
559  part of the piece,  just as benefit information does.   For example,  a prescription drug ad should not present 
560  risks only on a brief summary page.   
561   
562  Example 15:  A products logo and a tagline are often  used to signal the end of a piece.  Readers 
563  may assume that any risk information placed below the logo and tagline is there only for liability 
564  purposes or to fulfill a regulatory requirement and is  unrelated to the main message, especially if 
565  the information is presented in small type or otherwise lacking in emphasis.  
566   
567  Example 16:  A seven-page sales aid devotes the first six pages to effectiveness claims, which are 
568  prominently presented with colorful graphics, abundant white space, and large, colorful headers.  
569  Three of these pages also include a footnote referring readers to Important Information on page 
570  7.   The seventh page summarizes some risk information from the  PI in single-spaced paragraph 
571  format without headers or other presentation elements to emphasize to the reader that it is 
572  important risk information.  Such a presentation creates problems regarding the adequate 
573  presentation of risk.   The important risk information about the drug should instead be integrated 
574  into the piece and presented with similar prominence to the effectiveness claims. 
575   
576  Similarly, problems can arise when parts of  a print promotional piece appear so unrelated that the risks do 
577  not look to be part of the piece.   
578   
579  Example 17:  Risk information is placed in a thin column  along the side of an ad in a different  font 
580  and color scheme, so that the visuals and benefit information form a complete whole, separate  
581  from the risk information.  This is not likely to be considered an adequate presentation of risk 
582  information.   
583   
584     Font Size and Style 
585   
586  Font size and type style are format factors that can affect the prominence and readability of information.43  
587  FDA does not object to a presentation on the basis of minor differences in font size alone, depending on 
                                                                                                                                                                               
although  the regulations allow for the concise presentation of such information, the nature  and importance of this  
information should  be accurately conveyed.   For example, if a drug contains a boxed warning with  information on  
the risk  of elevations in  potassium levels  that can lead  to life-threatening complications in some patients, a statement 
in a part  of a promotional piece that Drug X may increase your  potassium levels; see Prescribing Information (PI)  
for more information is  not likely  to convey to  consumers or healthcare professionals the magnitude (i.e., life-
threatening nature) of the risk.   
42 21 CFR 202.1(e)(3)(i); see also 21 U.S.C.  321(n), 21 CFR 202.1(e)(5)(iii).  
43 Adams, A.S., & Edworthy, J. (1995) Quantifying and predicting  the effects of basic text  display variables on the 
perceived urgency of  warning labels:  Tradeoffs involving font size, border weight, and color.  Ergonomics, 38, 
2221-2237;  Arditi, A., & Cho, J. (2005)  Serifs and font legibility.  Vision Research, 45, 2926-2933; Baker, S.  
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588  other factors used to achieve emphasis (e.g., bolded lettering, bullets).  However, FDA may  object to  
589  substantial differences in  font size or the presentation of risk information in a difficult to read  font size, 
590  irrespective of the font size of benefit information, because this may seriously reduce the ability to see or 
591  comprehend the risk information.  
592   
593  Even  with identical risk and benefit font sizes, differences in type styles can render some information 
594  easier to read  than other information.44   To be comparably prominent  and readable,  FDA recommends  that 
595  risk and benefit information be presented in type styles that are similar in the use of capitalization, serifs, 
596  the weight of the type-face, the angle of the letters, the degree of  flourishes and scripting, and other 
597  typographical factors such as spacing (e.g., leading and kerning).45    
598   
599     Contrast 
600   
601  Contrast between text and background should not highlight the benefit information more than the risk 
602  information.   
603   
604  Example 18:  If benefit information in a piece is presented in white letters on a black background,  
605  risk information should be presented with similar contrast.  If the piece presents risk information 
606  in a way that would make it difficult to discern (e.g., using white letters on a light gray 
607  background or gray letters on a black background), the presentation may be considered false or 
608  misleading.    
609   
610  Even if the background is a color designed to attract attention, the contrast influences the prominence of  
611  the words once attention has been gained.  In  fact, printing words in some  attention-grabbing colors (e.g.,  
612  red) may make the words difficult to read.46  Similarly, the placement  of  risk information over pictures or 
                                                                                                                                                                               
(2006).  Provision  of effective information.   British Dental Journal, 201, 100; Sheedy, J.E., Subbaram, M.V., 
Zimmerman, A.B., & Hayes, J.R. (2005)  Text legibility and the letter superiority effect.  Human Factors,  47, 797-
815; Tantillo, J., Di Lorenzo-Aiss, J., & Mathisen, R.E. (1995) Quantifying  perceived differences in  type styles: An  
exploratory study.  Psychology and Marketing, 12, 447-457; Wogalter, M.S., & Vigilante, W.J. (2003) Effects of  
label format on knowledge acquisition and perceived readability  by  younger and older adults.  Ergonomics, 46, 327-
344.    
44 English, E.  (1944)  A  study of  the  readability of  four newspaper headline types.   Journalism Quarterly, 21, 217-
229; Mansfield, J.S., Legge, G.E., & Bane, M.C. (1996) Psychophysics of reading.   XV: Font effects in normal and  
low vision.  Investigative Opthamology and Visual Science, 37, 1492-1501; Sheedy, J.E., Subbaram, M.V., 
Zimmerman, A.B., & Hayes, J.R. (2005)  Text legibility and the letter superiority effect.  Human Factors,  47, 797-
815; Tantillo, J., Di Lorenzo-Aiss, J., & Mathisen, R.E. (1995) Quantifying  perceived differences in  type styles: An  
exploratory study.  Psychology and Marketing, 12, 447-457.  
45  See Arditi, A., & Cho, J. (2005) Serifs and  font  legibility.  Vision Research, 45, 2926-2933; Baker, S. (2006)  
Provision of  effective information.   British Dental  Journal, 201, 100; Moriarty, S.E., & Scheiner, E.C.  (1984) A 
study of close-set text type.  Journal of Applied Psychology, 69, 700-702; Paterson,  D.G., & Tinker,  M.A. (1947)  
Influence of  leading upon readability of  newspaper type.  Journal of Applied Psychology, 31, 160-163; Smither, 
J.A., & Braun, C.C. (1994) Readability  of prescription  drug  labels  by older and  younger adults.  Journal of  Clinical  
Psychology in Medical Settings, 1, 149-159; Tinker, M.A., & Paterson, D.G. (1946) Effect of  line width and leading 
on readability  of newspaper type.  Journalism Quarterly, 23, 307-309.  
46 See Pearson,  R., & van Schaik, P.  (2003)  The effect of spatial layout and link colour in  web pages on  performance 
in a visual search task and an interactive search task.  International Journal  of Human-Computer Studies, 59, 327-
353; but  see  Adams, A.S., & Edworthy, J.  (1995) Quantifying and predicting  the effects of basic text  display 
variables on  the perceived urgency of  warning labels: Tradeoffs involving font size, border weight, and  color.  
Ergonomics, 38, 2221-2237. 
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613  other visual elements with  multiple colors can cause this information or portions of this information to 
614  lack prominence and be difficult to read.47   Furthermore, a print piece that superimposes risk information 
615  over a visual image could compromise the accuracy  of the piece as a whole by drawing attention away  
616  from the risk information.48  
617   
618     White Space 
619   
620  Background space (often called white space) between  and around letters can influence the prominence 
621  and readability of text.49   Presenting benefit information in multiple paragraphs with double spaces 
622  between each paragraph,  while presenting risk information in one block paragraph without spacing or 
623  indentation could reduce the comparability of the risk and benefit  presentations.  Moreover, if a 
624  promotional piece uses headings, bullets, and other attention-getting symbols to emphasize product 
625  benefits, FDA recommends that it use similar techniques to present product risks.50  
626   
627  2.  Non-Print Promotion 
628   
629  Some print formatting issues also apply to non-print promotion such as videos, broadcast ads, and similar 
630  audio and visual pieces. However, the unique features of non-print  media add complexity.   As  with print,  
631  FDA considers factors such as location, proximity, type size, type style,  and contrast when evaluating 
632  these materials.   These factors are especially important  with regard  to text that is  superimposed on other 
633  images in videos or broadcast ads (SUPERs) and other visual components, such as graphics, within the 
634  scene.  In non-print pieces, FDA also evaluates other formatting factors in addition to those described 
635  above to determine whether a particular piece is considered false or misleading (e.g.,  audio components, 
636  motion within the visual component, the juxtaposition of visual and audio components, and duration of 
637  exposure).    
638   
639     Textual Elements 
640   
641  Prescription drug broadcast ads must present major product risks in the audio or audio and visual parts of  
642  the ad.51   Thus, broadcast ads and videos often use SUPERs and other text to present risk-related 
643  qualifying information.  When used to disclose risk, SUPERs can pose particular problems of  readability, 
644  comprehensibility, and proximity to benefit information.  For example, the FTC, which  requires that 
                                                       
47  See, e.g., Hillstrom,  A.P., & Chai, Y. (2006)  Factors that guide or disrupt attentive visual processing.  Computers 
in Human Behavior, 22, 648-656; Petty, R.E., Wells, G.L., & Brock, T.C. (1976)  Distraction can enhance or reduce 
yielding to propaganda: Thought disruption versus  effort  justification.   Journal of Personality  and Social  
Psychology, 34, 874-884;  Zimbardo, P.G., Snyder, M., Thomas, J., Gold, A., & Gurwitz, S. (1970) Modifying  the 
impact of  persuasive communications with  external distraction.  Journal of Personality and Social Psychology, 16, 
669-680. 
48 See Shiffrin, R.M., & Schneider, W. (1977) Controlled and automatic  human information processing  II:  
Perceptual  learning, automatic attending, and a general theory.   Psychological Review, 84, 127-190.  
49 Adams, A.S., & Edworthy, J. (1995) Quantifying and predicting  the effects of basic text  display variables on the 
perceived urgency of  warning labels:  Tradeoffs involving font size, border weight, and color.  Ergonomics, 38, 
2221-2237; Pracejus, J.W., Olsen, G.D., & OGuinn, T.C. (2006) How nothing became something: White space, 
rhetoric, history, and meaning.   Journal  of Consumer Research, 33, 82-90.  
50 See Luckiesh, M., & Moss, F.K.  (1940) Boldness as a factor in  type-design and  typography.  Journal of  Applied 
Psychology, 24, 170-183. 
51 21 CFR 202.1(e)(1).  
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645  [q]ualifying disclosures...be legible and understandable, recognizes that,  in many circumstances 
646  reasonable consumers do not read the entirety of an ad or are directed away from the importance of the  
647  qualifying phrase by acts or statements of the seller.52  FDA  has similar concerns.   
648   
649  FDA assesses the temporal location of SUPERs within  a broadcast ad or video  when evaluating whether 
650  it is false or misleading.  If claims  must be qualified to avoid misleading the audience,  we recommend 
651  that the qualifier be vocalized, presented through visual images, or placed in a prominent SUPER that  
652  runs concurrently  with the claim.53   If SUPERs do  not appear close enough to the claim or risk 
653  information requiring qualification, a misleading impression of the product may result.54   In addition,  if 
654  qualifying information is complex  and requires more than one line of text, we recommend that 
655  manufacturers use other means to convey this information.    
656   
657  Other issues FDA considers important that manufacturers should keep in mind include the following: 
658   
659     SUPERs, if used, should be reasonably visible to a person under typical viewing conditions.    
660     All SUPERs should be on screen long enough to allow the audience to read and understand their 
661  full content.  
662     Graphics that distract from the presentation of risk information, including from risk-related 
663  SUPERs (e.g., busy scenes,  frequent scene changes, vivid and compelling visuals55 and moving 
664  camera angles) can misleadingly minimize the risks of the product being promoted by detracting 
665  from the audiences comprehension of the risk presentation.   
666     Competition from other SUPERs (e.g., presenting a SUPER related to a particular risk while 
667  unrelated SUPERs are on the screen) hampers the audiences ability to read and understand the 
668  SUPERs and could compromise the communication of risk information and make a piece 
669  misleading.56    
670     Factors such as font size, type style, and capitalization can also affect the readability of 
671  SUPERs.57  Words presented in all upper case letters are more difficult to read than words 
672  presented in upper and lower case letters.58   
673   
                                                       
52 FTC Policy Statement on Deception at  183. 
53  See 21 CFR 202.1(e)(3)(i). 
54 Manrai,  L.A., Manrai, A.K., & Murray, N. (1994) Comprehension of info-aid supers in  television advertising for 
social ideas: Implications for public  policy.   Journal of Business  Research, 30, 75-84.   
55 Vivid visual  images are those images, pictures or other visual stimuli that are emotionally or cognitively  
interesting, attention-getting,  compelling,  provoking, or  personal in a sensory, temporal or spatial manger (after 
Nisbett, R., and Ross, L.  (1980) Human Inference: Strategies and Shortcomings of  Social Judgment. Englewood  
Cliffs, NJ: Prentice-Hall).  Background music can also  be  distracting (Furnham, A., & Strbac, L.  (2002).  Music is as 
distracting as noise: The differential distraction of  background music and noise on the cognitive test performance of  
introverts and extraverts.  Ergonomics, 45, 203-217).  
56 See, e.g., Mackie, D.M., &  Worth, L.T. (1989) Processing  deficits and the mediation of positive affect  in  
persuasion.  Journal of Personality  and Social Psychology, 57, 27-40; Manrai, L.A.,  Manrai,  A.K., & Murray, N.  
(1994) Comprehension of info-aid supers in  television advertising for social  ideas: Implications for public policy.  
Journal of Business  Research, 30, 75-84. 
57 Baker, S. (2006) Provision  of effective information.   British Dental  Journal, 201,  100; Manrai, L.A., Manrai, 
A.K., & Murray, N. (1994) Comprehension of info-aid supers in television advertising for social  ideas: Implications  
for public  policy.   Journal of  Business Research, 30, 75-84.  
58 Paterson, D.G., & Tinker, M.A.  (1941) Caps vs. lower-case in headlines.   Editor  & Publisher, 74, 51.  
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674     Contrast 
675   
676  Contrast is an important visual factor59  that FDA considers when evaluating television ads and videos.60   
677  As in print pieces, risk disclosures presented in SUPERs should be in a font color that reasonably 
678  contrasts with the background visuals.  Because important non-benefit information is often conveyed by 
679  SUPERs, any obstacle to the prominence and readability of this information, and thus to the audiences 
680  understanding of SUPERs, may result in a misleading risk presentation.    
681   
682     Dual Mode Considerations 
683   
684  The interplay of visual and audio components in pieces such as television ads and videos introduces 
685  unique factors FDA must consider when evaluating the adequacy of risk disclosure.  The issues raised  
686  above in Textual Elements about distracting visuals apply not only to the SUPER presentation but also to 
687  the audio presentation of risks.61  If visuals in a broadcast ad distract the audience  from the statement of a  
688  products risks, the ad  will  not, as a whole, convey an  accurate impression of the risks of the advertised 
689  product.   This distraction could be caused by factors including busy scenes, frequent scene changes,  
690  moving camera angles, and even inherently compelling, vivid visuals.  In addition, the overall  tone of the 
691  ad or of specific background visuals can affect the comparable prominence of the risks, particularly if the  
692  tone is contrary to the risk message.   
693   
694  Example 20:  A video or broadcast ad depicts a joyous or  exhilarating moment, contains images of 
695  people enjoying the benefits of the product, or includes otherwise compelling or distracting non-
696  risk related images  while  major risks are communicated in a voiceover.   The inconsistent tone or 
697  images may be too distracting for the audience to listen to or process the risks, causing the video 
698  or broadcast ad to communicate a false or misleading net impression of the product.   
699   
700     Audio Considerations 
701   
702  FDA considers  several audio-related factors  when  evaluating pieces  such as sound recordings, videos, or 
703  broadcast ads, including television,  radio, and telephone communications.  
704   
705     The qualities of speech should be similar across benefit and risk information for these 
706  components to be considered comparably prominent.  
707     A critical  speech consideration is  pacing. If risk information is considerably more difficult to 
708  hear and process than benefit information because it is presented at a  much faster pace, the piece  
709  will not convey an accurate impression of the product.  
710     Markedly reducing volume or being less articulate when discussing risks compared to benefits  
711  may hinder the audiences comprehension of the risks.    
712     Background music should be comparable in volume and distraction potential during both benefit 
713  and risk presentations.   
714   
                                                       
59 Mitzner, T.L., & Rogers, W.A. (2006) Reading in the dark:  Effects of age and contrast  on reading speed and  
comprehension.   Human Factors,  48, 229-240. 
60  Seibert, W.F., Kasten, D.F., & Potter, J.R. (1959)  A study of  factors influencing the legibility of televised  
characters.  Journal of the Society  of Motion Picture &  Television Engineers, 68, 467-472. 
61 See, e.g, Regan,  D.T., & Cheng, J.B. (1973) Distraction and attitude change: A resolution.   Journal of  
Experimental Social Psychology, 9, 138-147. 
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715   
716  IV.  CONCLUSION  
717   
718  The FDAs regulation of prescription drug and medical device promotion to healthcare professionals and 
719  consumers is a broad and complex topic.  A vast scientific body of knowledge is available regarding 
720  human cognition, and FDA relies on this knowledge when evaluating promotional pieces and making 
721  regulatory decisions about the presentation of benefit and risk information.  The Agency hopes that by 
722  discussing the most relevant factors and by providing specific examples, manufacturers  will  gain a better  
723  understanding of what they should consider as they  develop the content and format of their promotional 
724  communications.  
725   
726  It is important to re-emphasize that, in addition to specific risk-related claims, FDA also considers the net  
727  impression conveyed by all the elements of a piece.  For this reason, manufacturers should focus not just 
728  on individual claims or presentations, but on the messages conveyed by the promotional piece as a whole. 
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729   
730  ATTACHMENT: STATUTORY AND REGULATORY REQUIREMENTS FOR 
731  LABELING AND ADVERTISING 
732   
733  FDA regulates the manufacture, sale, and distribution of drugs and devices in the United  States under the 
734  authority of  the Federal Food, Drug, and Cosmetic Act (the Act).  This authority includes oversight of 
735  labeling for all drugs and devices and of  advertising for prescription drugs and restricted devices.  21 
736  U.S.C. 352(a), (n), (q), & (r).  In regulating the labeling and advertising of drugs and devices, FDA 
737  attends to the First Amendment. 
738   
739  The Act defines label to mean a display of written, printed, or graphic matter upon the immediate 
740  container of any article . . . .   21 U.S.C. 321(k).   According to FDA regulations (21 CFR 1.3(b)): Label 
741  means any display of  written, printed, or graphic matter on the immediate container of  any article, or any 
742  such matter affixed to any  consumer commodity or affixed to or appearing upon a package containing any 
743  consumer commodity.   The Act defines labeling to mean all labels and other written, printed, or graphic 
744  matter (1) upon any article or any of  its containers or wrappers, or (2) accompanying such article.  21 
745  U.S.C. 321(m).  Similarly, FDA regulations (21 CFR 1.3(a)) provide that labeling includes all written,  
746  printed, or graphic matter  accompanying an article  at any time  while such article is in interstate  commerce 
747  or held for sale after shipment or delivery in interstate commerce. 
748   
749  According to Kordel v. United States, 335 U.S. 345, 350 (1948), the language accompanying such 
750  article in the labeling definition includes materials that supplement or explain an article,  in the 
751  manner that a committee report of the Congress accompanies a bill.  No physical attachment one to the 
752  other is necessary.  It is the textual relationship that is significant.   FDAs prescription drug advertising 
753  regulations (21 CFR 202.1(l)(2)) thus provide as examples of labeling a wide variety of  written, printed, 
754  or graphic matter that bears a textual relationship with a product.  
755   
756  FDA generally recognizes two types of labeling for drugs and devices:  FDA-required labeling and 
757  promotional labeling.  Much FDA-required labeling is subject to  FDA review and approval.  For 
758  example, after drafting by the manufacturer, required labeling is reviewed and approved by FDA as part 
759  of the new drug application (NDA), new animal drug application (NADA), biologics license application 
760  (BLA) or premarket approval application (PMA) review (21 CFR 314.50(c)(2),  514.1(b)(3), 601.2(a), and 
761  814.20(b)(10)).   
762   
763  For devices that are not subject to premarket approval, but instead are subject to premarket notification 
764  requirements or are exempt from  premarket review, there is no agency review or approval of labeling, but 
765  such devices remain subject to all of the requirements of applicable  labeling regulations, including those 
766  for adequate directions for use.  For a prescription drug or prescription device to  be exempted from the 
767  Acts requirement of adequate directions for use (21 U.S.C. 352(f)(1)), its FDA-required labeling must 
768  contain,  among other information, information addressing product hazards and other risk information, as 
769  specified  in FDA regulations.62  
770   
771  Promotional labeling is generally any labeling other than the FDA-required labeling that is devised for 
772  promotion of the product.  Promotional labeling may  include items  such as brochures, booklets,  mailing 
773  pieces, detailing pieces, file cards, bulletins, calendars, price lists, catalogs, house organs, letters, motion 
774  picture films,  film strips, lantern slides, sound recordings, exhibits, literature,  and reprints and similar 
                                                       
62 21 CFR 201.100(d)(1),  (3), 201.105(c)(1), & 801.109(d).  
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775  pieces of printed, audio, or visual matter  . . . .63  The Act specifies that a drug or device shall be deemed  
776  to be misbranded if its labeling is false or  misleading in any particular.  21 U.S.C. 352(a).  The Act further 
777  specifies that labeling or advertising may be considered misleading if it fails to reveal material facts about 
778  the product being promoted, including facts about the consequences that can result from use of the 
779  product as suggested in a promotional piece.  21 U.S.C. 321(n).  In addition, the Act specifies that a drug 
780  or device will be deemed to be misbranded if any word,  statement, or other information required under 
781  the Act to appear on the label or labeling is not prominently placed thereon  with such conspicuousness 
782  (as compared with other words, statements, designs, or devices, in the labeling) and in such terms as to  
783  render it likely to be read and understood by the ordinary individual under customary conditions of  
784  purchase and use. 21  U.S.C. 352(c).  
785   
786  Advertising64 for prescription drugs and restricted devices is also subject to requirements under the Act 
787  for the disclosure of risk and other information.  Under section 502(n) of the Act (21 U.S.C. 352(n)) and 
788  FDAs implementing regulations (21 CFR Part 202), an ad for a prescription drug  must include, in 
789  addition to the products established name and quantitative composition, a true statement of information 
790  in brief summary relating to side effects,  contraindications and effectiveness of the product with respect 
791  to the use or  uses that the message promotes.65   Advertisements for restricted devices  must include a  
792  brief statement of the intended uses of the device  and relevant warnings, precautions, side effects,  and 
793  contraindications . . . .  21 U.S.C. 352(r)(2).  For prescription drug advertisements, FDAs implementing 
794  regulations specify that, among other things, the statutory requirement of  a true statement is not 
795  satisfied if an ad  for a prescription drug product is false or misleading with respect to side effects,  
796  contraindications or effectiveness or if it fails to reveal material facts about consequences that may result 
797  from the use of the drug as recommended or suggested in the advertisement.  21 CFR 202.1(e)(5).   
798  Similarly, the  Act also specifies that restricted device advertisements must not be false or misleading (21 
799  U.S.C. 352(q)(1)) and must reveal facts that are material about the product being advertised, including 
800  facts about the consequences that can result from use of the product as suggested in an ad.  21 U.S.C. 
801  321(n).  
802   
803  The prescription drug regulations also specify that ads must  present a fair balance between information 
804  relating to risks and benefits, which is achieved when the treatment of risk and benefit information in a 
805  promotional piece is comparably thorough and complete throughout the piece.  21 CFR 202.1(e)(5)(ii).  
806  These regulations also provide illustrations of the factors FDA considers in determining whether 
807  promotional pieces comply  with the above requirements relating to risk disclosure.  Specifically, these 
808  regulations identify twenty types of  advertising communications that  FDA considers false, lacking in fair 
809  balance, or otherwise misleading.  21 CFR 202.1(e)(6).  These include,  for example, representations or 
810  suggestions that a drug is more effective or safer than has been demonstrated by substantial evidence or  
811  substantial clinical experience, the use of pictures  or graphics in a way that is misleading,  and the 
812  presentation of risk information by means of a general term for a group rather than disclosing specific 
                                                       
63 See, e.g.,  21  CFR 202.1(l)(2).  
64  The act does not define advertising or advertisement. According to FDA regulations (21 CFR  202.1(l)(1)), 
Advertisements subject to section 502(n)  of the act include advertisements in published journals, magazines,  other 
periodicals, and newspapers, and advertisements  broadcast  through media such as radio, television, and telephone  
communication systems.  
65  According to 21  CFR 202.1(e)(3)(iii), the  information in brief  summary relating to  side  effects  and 
contraindications must disclose each specific side effect and contraindication  (which  include side effects, warnings, 
precautions, and contraindications and include  any such information under such headings as  cautions,  special 
considerations, important notes, etc. . . .) contained in  required, approved, or permitted labeling for the advertised 
drug  dosage form(s) (emphasis added).    
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813  risks.  21 CFR 202.1(e)(6)(i), (xviii), & (xx).  Representing or suggesting that a drug product is safer 
814  than has been demonstrated by substantial evidence or substantial clinical experience means obscuring 
815  or failing to include the most serious risk information set forth in the drug's FDA-approved labeling,  and 
816  does not refer to a failure to include risk information that is not set forth in the drug's FDA-approved 
817  labeling.   
818   
819  In addition, these regulations identify thirteen additional types of  advertising communications that may  
820  be false, lacking in fair balance, or otherwise misleading.  21 CFR 202.1(e)(7).  These include, for 
821  example, advertising communications that fail to present information relating to side effects and 
822  contraindications with a prominence and readability reasonably comparable with the presentation of 
823  information relating to effectiveness of the drug.  21 CFR 202.1(e)(7)(viii).  
824   
825  Although the regulations discussed above were promulgated in the context of prescription drug  
826  advertising, the guidance they provide on what FDA considers false or misleading in promotion has 
827  broader applicability.  For example, promotional  pieces that fail to  present a balanced view of  the risks 
828  and benefits of a product are generally considered to be false or misleading and also generally fail to 
829  reveal  material facts about the product being promoted.  Because both labeling pieces for drugs and 
830  devices, and advertising pieces  for prescription drugs and restricted devices, are  considered to misbrand a  
831  product if they are false or misleading or fail to reveal material facts,66 drug and device manufacturers 
832  should take into account the guidance provided by these regulations when developing promotional 
833  labeling and advertising pieces for  their products.   
834   
835   
836   
                                                       
66  21 U.S.C. 352(a), (n), (q)(1) & 321(n); 21  CFR 202.1(e)(5). 
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