Communications From Firms to 
Health Care Providers Regarding 
Scientific Information on 
Unapproved Uses of 
Approved/Cleared Medical 
Products  
 Questions and Answers 
Guidance for Industry 
 
DRAFT GUIDANCE
 
 
  This guidance document is being distributed for comment purposes only. 
 
Comments and suggestions regarding this draft document should be submitted within 60 days of 
publication in the Federal Register of the notice announcing the availability of the draft 
guidance.  Submit electronic comments to https://www.regulations.gov.  Submit written 
comments to the Dockets Management Staff (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) Kathleen David 301-796-1200; 
(CBER) Office of Communication, Outreach and Development, 800-835-4709 or 240-402-8010; 
(CDRH) Ana Loloei 301-796-8774; (CVM) Office of Surveillance and Compliance, 240-402-
7082; or (OC) Julie Finegan, 301-827-4830.    
 
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 Devices and Radiological Health (CDRH) 
Center for Veterinary Medicine (CVM) 
Office of the Commissioner (OC) 
 
October 2023
 
Procedural 
Revision 2 
 54578796dftrev2.docs 
10-19-2023   
Communications From Firms to Health Care Providers Regarding Scientific Information on 
Unapproved Uses of Approved/Cleared Medical Products   
 Questions and Answers 
Guidance for Industry 
 
Additional copies are available from: 
Office of Communications, Division of Drug Information 
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD  20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353; Email: druginfo@fda.hhs.gov 
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs 
and/or 
Office of Communication, Outreach, and Development  
Center for Biologics Evaluation and Research 
Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 71, rm. 3128 
Silver Spring, MD  20993-0002 
Phone: 800-835-4709 or 240-402-8010; Email: ocod@fda.hhs.gov  
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances 
and/or 
Office of Communication and Education 
CDRH-Division of Industry and Consumer Education 
Center for Devices and Radiological Health 
Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 66, rm. 4621 
Silver Spring, MD  20993-0002 
Phone: 800-638-2041 or 301-796-7100 
Fax: 301-847-8149, Email: DICE@fda.hhs.gov 
https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/guidance-documents-medical-devices-
and-radiation-emitting-products 
and/or 
Policy and Regulations Staff, HFV-6 
Center for Veterinary Medicine 
Food and Drug Administration 
7500 Standish Place, Rockville, MD 20855 
Phone: 240-276-9300 
https://www.fda.gov/animal-veterinary/guidance-regulations/guidance-industry  
and/or 
Office of Policy 
Office of the Commissioner 
Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 32, Room 4252 
Silver Spring, MD 20993-0002 
Phone: 301-827-4830 
 
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 Devices and Radiological Health (CDRH) 
Center for Veterinary Medicine (CVM) 
Office of the Commissioner (OC) 
 
October 2023 
Procedural 
Revision 2 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
TABLE OF CONTENTS 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  SCOPE ............................................................................................................................... 4 
III.  BACKGROUND ............................................................................................................... 7 
IV.  QUESTIONS AND ANSWERS ..................................................................................... 10 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
1  Communications From Firms to Health Care Providers Regarding 
2  Scientific Information on Unapproved Uses of Approved/Cleared 
3  Medical Products 
4  Questions and Answers 
5  Guidance for Industry1 
6   
7   
8  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
9  Administration (FDA or Agency) on this topic.  It does not establish any rights for any person and is not 
10  binding on FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
11  applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible 
12  for this guidance as listed on the title page.   
13   
14   
15   
16  I.  INTRODUCTION 
17   
18  This revised draft guidance, when finalized, will provide FDAs current thinking on common 
19  questions regarding certain communications by firms to health care providers (HCPs) of 
20  scientific information on unapproved use(s) (SIUU) of approved/cleared medical products.2   
21  Specifically, this guidance relates to firms sharing the following types of communications with 
22  HCPs:  
23   
24    Published scientific or medical journal articles (reprints) 
25     
26    Published clinical reference resources, as follows: 
27   
28    Clinical practice guidelines (CPGs) 
-
29     
30    Scientific or medical reference texts (reference texts) 
-
31   
32    Materials from independent clinical practice resources  
-
33   
34    Firm-generated presentations of scientific information from an accompanying published 
35  reprint  
 
1 This guidance has been prepared by the Office of Prescription Drug Promotion in the Office of Medical Policy in 
the Center for Drug Evaluation and Research in cooperation with the Center for Biologics Evaluation and Research, 
the Center for Devices and Radiological Health, the Center for Veterinary Medicine, and the Office of the 
Commissioner at the Food and Drug Administration. 
 
2 The scope of the italicized terms, for the purposes of this guidance, is further explained in section II of this 
guidance.     
 
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36  These communication types are further described in Q4 of this guidance. 
37   
38  For the purposes of this guidance, these specific types of communications from firms to HCPs of 
39  scientific information on unapproved uses of approved/cleared medical products in combination 
40  with the disclosures recommended in this guidance are referred to as SIUU communications.   
41  Other communications by firms are not specifically addressed by this draft guidance, and we do 
42  not intend to convey any views on such communications in issuing this draft guidance. 
43   
44  The Federal Food, Drug, and Cosmetic Act (FD&C Act), the Public Health Service Act (PHS 
45  Act), and their implementing regulations (collectively, the FDA Authorities) prohibit, among 
46  other things, the introduction (or causing the introduction) into interstate commerce of a medical 
47  product that fails to comply with applicable premarket requirements or is otherwise misbranded 
48  or adulterated.3  This prohibition includes introducing (or causing the introduction) into interstate 
49  commerce a medical product that is intended for a use that has not been approved or cleared by 
50  FDA, even if that same product is approved or cleared for a different use.  These premarket 
51  requirements further multiple important government interests and distributing approved/cleared 
52  medical products for unapproved uses can undermine these interests.   
53   
54  In certain circumstances, however, HCPs may be interested in scientific information about 
55  unapproved uses of approved/cleared medical products to inform clinical practice decisions for 
56  the care of an individual patient.  In developing this draft guidance, FDA has sought to strike a 
57  careful balance between supporting HCP interest in scientific information about unapproved 
58  uses of approved/cleared medical products to inform clinical practice decisions for the care of an 
59  individual patient, and mitigating the potential that the government interests advanced by these 
60  statutory requirements will be undermined.   
61   
62  In light of those goals, FDA believes it is critical that SIUU communications be truthful, non-
63  misleading, factual, and unbiased and provide all information necessary for HCPs to interpret the 
64  strengths and weaknesses and validity and utility of the information in the SIUU communication.  
65  In addition, any study or analysis described in a source publication that serves as the basis for an 
66  SIUU communication should be scientifically sound.  The study or analysis should also provide 
67  information that is relevant to HCPs engaged in making clinical practice decisions for the care of 
68  an individual patient (as used in this guidance, clinically relevant).4  The manner of presentation 
69  of SIUU communications is also critical to consider.  This guidance provides recommendations 
70  addressing all of these considerations.  
71   
 
3 See FDA Memorandum:  Public Health Interests and First Amendment Considerations Related to Manufacturer 
Communications Regarding Unapproved Uses of Approved or Cleared Medical Products (January 2017 
Memorandum) (available at https://www.regulations.gov/document/FDA-2016-N-1149-0040).  Appendix A of that 
document provides an overview of legal frameworks relevant to firms communications regarding unapproved uses 
of medical products, which include provisions directly governing the premarket review processes as well as certain 
related adulteration and misbranding provisions (collectively, premarket requirements).  In addition, we note that, 
since FDA issued the January 2017 Memorandum, Congress has amended the relevant authorities in certain 
respects, see, e.g., sections 505G, 502(a), and 502(gg) of the FD&C Act, 21 U.S.C. 355h, 352(a), and 352(gg).   
 
4 The term clinically relevant is further explained in Q1 of this guidance. 
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72  If a firm shares an SIUU communication with HCPs in a manner that is consistent with the 
73  recommendations in this guidance, FDA does not intend to use such communication standing 
74  alone as evidence of a new intended use.   For the purposes of this guidance, we refer to this 
75  enforcement policy for SIUU communications as the enforcement policy outlined in this 
76  guidance.  In addition, we note that this guidance does not describe the only circumstances in 
77  which FDA does not intend to consider a firms dissemination of information about an 
78  unapproved use of its approved/cleared medical product to be evidence of the firms intent that 
79  the medical product be used for an unapproved use.  For example, FDA has issued other 
80  guidance documents that address circumstances when FDA would not consider a firms 
81  dissemination of information regarding an unapproved use of its approved/cleared medical 
82  product to be evidence of intended use.5  We also note that nothing in this draft guidance is 
83  intended to convey new policy regarding a firms existing obligations under the FDA Authorities 
84  to update FDA-required labeling to accurately reflect what is known about the safety profile of 
85  the drug, to ensure that the FDA-required labeling is not false or misleading, or for other 
86  reasons.6   
87   
88  This guidance includes examples to illustrate some of the recommendations and general 
89  considerations for firms engaged in sharing SIUU communications with HCPs.  The examples in 
90  this guidance do not describe every aspect of the SIUU communication.  
91   
92  In developing this draft guidance, FDA considered stakeholder feedback from ongoing efforts, 
93  including comments received on the guidance entitled Distributing Scientific and Medical 
 
5 FDA issued a draft guidance with recommendations for firms on responding to unsolicited requests for information 
about unapproved uses of approved medical products (see the draft guidance for industry Responding to Unsolicited 
Requests for Off-Label Information About Prescription Drugs and Medical Devices (December 2011)).  When final, 
that guidance will represent FDAs current thinking on this topic.  We update guidances periodically.  To make sure 
you have the most recent version of a guidance, check the FDA guidance web page at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents.  FDA has also provided 
recommendations for industry support of scientific or educational activities (such as Continuing Medical Education 
programs) without being subject to FDA regulation (see the guidance Industry-Supported Scientific and Educational 
Activities (December 1997)).  In June 2018, FDA issued a final guidance that provides recommendations for firms 
communications with payors and similar entities (see the guidance Drug and Device Manufacturer Communications 
With Payors, Formulary Committees, and Similar Entities  Questions and Answers (June 2018) (superseded in part 
by section 502(gg) of the FD&C Act enacted in December 2022 as part of the Consolidated Appropriations Act, 
2023 (Public Law No. 117-328)).  Furthermore, in amending FDAs regulations regarding evidence of intended use 
in 20202021, FDA provided several examples of evidence that, standing alone, are not determinative of intended 
use.  See Proposed Rule (NPRM): Regulations Regarding Intended Uses (2020 Intended Use NPRM) (85 FR 
59718 at 5972526, September 23, 2020); Final Rule: Regulations Regarding Intended Uses (2021 Intended Use 
Final Rule) (86 FR 41383, 41397, August 2, 2021).  In addition, it has long been FDA policy not to consider a 
firms presentation of truthful and non-misleading scientific information about unapproved uses at the planned 
sessions and presentations at medical or scientific conferences to be evidence of intended use when the presentation 
is made in non-promotional settings and not accompanied by promotional communications.  (See January 2017 
Memorandum (cited in footnote 3 of this guidance) at 2021).   
 
6 See, e.g., section 502(a) of the FD&C Act; 21 CFR 201.56(a)(2) (labeling must be updated when new information 
becomes available that causes the labeling to become inaccurate, false, or misleading), 21 CFR 314.70 and 601.12 
(concerning supplements and other changes to an approved application, including labeling), and 21 CFR 514.8(c) 
(concerning supplements and other changes to an approved application for a new animal drug, including labeling). 
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Draft  Not for Implementation 
 
94  Publications on Unapproved New Uses  Recommended Practices (2014 revised draft guidance).  
95  This draft guidance will supersede the 2014 revised draft guidance.  Changes include a revised 
96  title, a question-and-answer format, and certain changes in scope. 
97   
98  In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
99  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
100  as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
101  the word should in Agency guidance means that something is suggested or recommended, but 
102  not required.  
103   
104   
105  II.  SCOPE 
106   
107  As previously noted, the SIUU communications addressed by this draft guidance relate to 
108  scientific information on an unapproved use of an approved/cleared medical product.  This is 
109  one of several important aspects of the scope of this guidance that are further described in this 
110  section.  We begin by describing the scope of unapproved use, approved/cleared medical 
111  product, and related terms as those terms are used in this guidance:  
112   
113    The term medical product refers to a medical device for human use (including one that is 
114  a biological product), a human drug (including one that is a biological product), or an 
115  animal drug.  
116   
117    The term approved/cleared medical product7 refers only to certain medical products that 
118  may be introduced into interstate commerce for at least one use under the FDA 
119  Authorities as a result of having satisfied applicable premarket requirements, as follows:  
120   
121    With respect to a device, the term refers only to a device that is the subject of an 
-
122  approved premarket application (PMA) under section 515 of the FD&C Act, a 510(k) 
123  clearance, or a De Novo classification; to a device that is licensed under PHS Act 
124  section 351; or to a device that is exempt from premarket notification.  
125   
126    With respect to a human drug, the term refers only to a drug that is the subject of an 
-
127  approved application under section 505 of the FD&C Act or section 351 of the PHS 
128  Act, or it is marketed in compliance with section 505G of the FD&C Act.  
129   
130    With respect to an animal drug, the term refers only to a drug that is the subject of an 
-
131  approved application under section 512 of the FD&C Act; it does not include a 
132  conditionally approved or indexed animal drug. 
 
7 This term has been chosen for ease of reference within this guidance and its use in this guidance is not intended to 
indicate that every medical product covered by this term is referred to as approved or cleared under the 
language of the FDA Authorities.  For example, nonprescription drugs that satisfy requirements for marketing under 
Section 505G of the FD&C Act are not approved under Section 505.  The use of the term approved/cleared 
medical product also does not convey that the introduction of the medical product into interstate commerce for an 
unapproved use would be legal.   
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133  Note, this guidance does not apply to communications about a use that is an unapproved 
134  use of an approved product for the purposes of section 564 of the FD&C Act and that is 
135  an authorized emergency use under that section (see sections 564(a)(2)(B) and (a)(4)(E) 
136  of the FD&C Act).8  
137   
138    The term approved use9 refers to a use that is lawfully included as an indication or use in 
139  the FDA-required labeling of an approved/cleared medical product (as that term is 
140  defined in this guidance) as a result of having satisfied applicable premarket 
141  requirements. 
142   
143    The term unapproved use refers to a use that is not lawfully included as an indication or 
144  use in the FDA-required labeling of an approved/cleared medical product (as that term is 
145  defined in this guidance).  
146   
147    The term FDA-required labeling includes, but is not necessarily limited to, the labeling 
148  reviewed and approved by FDA as part of the medical product premarket review process.  
149  FDA-required labeling includes, for example:  
150   
151    for a prescription human drug (including a drug that is licensed as a biological 
-
152  product), the FDA-approved prescribing information that meets the requirements of 
153  21 CFR 201.100 
154   
155    for a nonprescription human drug that is the subject of an approved drug application 
-
156  under section 505 of the FD&C Act, the FDA-approved Drug Facts labeling that 
157  meets the requirements of 21 CFR 201.66  
158   
159    for a nonprescription drug that is not the subject of an approved drug application 
-
160  under section 505 of the FD&C Act but instead is marketed under section 505G of the 
161  FD&C Act, the labeling that must be provided in order for that drug to comply with 
162  section 505G  
163   
164    for an animal drug, the FDA-approved prescribing information 
-
165   
166    for a device, the labeling approved during the review of a premarket approval 
-
167  application or De Novo classification 
168   
 
8 In addition, this guidance does not apply to any communications about a medical product that is an unapproved 
product as that term is used in section 564 of the FD&C Act, including communications about a use that is an 
authorized emergency use under that section.  (See sections 564(a)(2)(A) and (a)(4)(D) of the FD&C Act.) 
 
9 This term is chosen for ease of reference within this guidance.  We note that for certain categories of medical 
products, the FDA Authorities use terms other than approved to describe satisfaction of applicable premarket 
requirements. 
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169    for a device subject to premarket notification (510(k)) requirements or exempt from 
-
170  premarket review, the labeling that provides indications for use and adequate 
171  directions for use and other information required to appear on the label or in labeling  
172   
173  We next describe the meaning, as used in this guidance, of additional key terms that relate to the 
174  scope of this draft guidance:    
175    
176    The term firm or firms refers to the persons legally responsible for the labeling of medical 
177  products, and includes applicants, sponsors, requestors,10 manufacturers, packers, and 
178  distributors of medical products, and licensees of such persons, and any persons 
179  communicating on behalf of these entities.   
180   
181    The term health care providers (HCPs) refers to individuals such as physicians, 
182  veterinarians, dentists, physician assistants, nurse practitioners, pharmacists, or registered 
183  nurses who are licensed or otherwise authorized by law to prescribe, order, administer, or 
184  use medical products in a professional capacity.  The recommendations in this guidance 
185  are specific to communications by firms to HCPs engaged in making clinical practice 
186  decisions for the care of an individual patient.11   
187   
188    The term SIUU communications refers to specific types of communications (see section I 
189  of this guidance) from firms to HCPs of scientific information on unapproved uses of 
190  approved/cleared medical products in combination with the disclosures recommended in 
191  this guidance.  We acknowledge that firms share these communications through different 
192  media (e.g., paper, digital).  The recommendations in this guidance apply regardless of 
193  the medium of the communication.  We also acknowledge that firms communicate with 
194  other audiences, and we do not intend to convey any views on communications with 
195  other audiences in issuing this draft guidance.   
196   
197    The term source publication refers to the published reprint, CPG, reference text, or 
198  material from an independent clinical practice resource that serves as the basis of a firms 
199  SIUU communication. 
200   
201  This draft guidance does not cover a firms communications of scientific information in response 
202  to unsolicited requests, which are addressed in the draft guidance for industry Responding to 
 
10 See section 505G(q)(3) of the FD&C Act. 
 
11 FDA has separate recommendations for a firms communications with the payor audience, which could include 
HCPs serving on formulary committees or other entities carrying out responsibilities for medical product selection 
or acquisition, formulary management, and/or coverage and reimbursement decisions on a population basis (payors). 
(See the guidance for industry Drug and Device Manufacturer Communications With Payors, Formulary 
Committees, and Similar Entities  Questions and Answers.  See also section 502(a) and (gg) of the FD&C Act, 21 
U.S.C. 352(a) and (gg).)  Additionally, while HCPs may serve as researchers, a firms communications with HCPs 
in their capacities as researchers are not within the scope of this guidance.  The Agency is separately soliciting 
public comment on the topic of a firms communications with researchers.  
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203  Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices 
204  (December 2011).12 
205   
206   
207  III.  BACKGROUND 
208   
209  The evolution of medical product regulation in the United States has been shaped by experience 
210  with the real and substantial risks to the public from uses of medical products not shown to be 
211  both safe and effective.  Congress developed the premarket review frameworks for medical 
212  products in response to public health tragedies, realizing that (1) safety and effectiveness for 
213  each intended use needs to be appropriately studied by firms and then independently evaluated 
214  by FDA before a medical product is introduced into interstate commerce for that use because the 
215  evidence that demonstrates effectiveness and safety for one use of a product provides no 
216  guarantee of the effectiveness or safety of additional uses; and (2) exclusive reliance on post-
217  market remedies (e.g., enforcement actions for false or misleading labeling) is unacceptable as a 
218  public health strategy because it does not prevent consumers from experiencing harm from 
219  unsafe and/or ineffective treatments.13   
220   
221  Accordingly, the FDA Authorities prohibit the introduction (or causing the introduction) into 
222  interstate commerce of a medical product that fails to comply with applicable premarket 
223  requirements.14  This prohibition includes the introduction (or causing the introduction) into 
224  interstate commerce of a medical product that is intended for a use that has not been approved 
225  (an unapproved use), even if that same medical product is approved by FDA for a different use.15  
226   
227  The intended use of a medical product can be established from, among other things, its label, 
228  accompanying labeling, promotional claims, advertising, and any other relevant source.16  For 
229  example, claims or statements made by or on behalf of a firm that explicitly or implicitly 
 
12 When final, that guidance will represent FDAs current thinking on this topic.   
 
13 See January 2017 Memorandum (cited in footnote 3 of this guidance) at 1, 4, and footnote 8. 
 
14 For a more detailed discussion of many relevant statutory provisions and implementing regulations related to 
premarket review of medical products, see Appendix A of the January 2017 Memorandum.  
 
15 The concept of intended use is fundamental to the regulatory approach for medical products embodied in the FDA 
Authorities.  Intended use is an element in the definitions of drug and device, helping to define the scope of FDAs 
authority over medical products and subjecting the medical products to the drug or device provisions of the FDA 
Authorities, as applicable.  In addition, intended use may affect the appropriate premarket review pathway for a 
medical product and is a separate element in establishing certain violations under the FDA Authorities.  (See, 
generally, 2020 Intended Use NPRM, 85 FR 59718 at 59724; 2021 Intended Use Final Rule, 86 FR 41383 at 
41385.)  
 
16 See, e.g., 2021 Intended Use Final Rule, 86 FR 41383 at 41386-41388 (citing cases). 
 
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230  promote a medical product for a particular use may be taken into account.17  Accordingly, a 
231  firms communications may be relevant to establishing whether its medical product is subject to 
232  the FDA Authorities and whether particular statutory or regulatory provisions apply to the 
233  medical product.    
234   
235  The premarket requirements of the FDA Authorities advance substantial government interests 
236  that include increasing the availability of medical products that have been shown to be safe and 
237  effective for a particular use and in preventing direct and indirect harm from uses of medical 
238  products that have not been shown to be safe and effective.  Maintaining the premarket review 
239  process for safety and effectiveness of each intended use advances these and other interests, 
240  including protecting against fraud, misrepresentation, and bias, and preventing the diversion of 
241  health care resources toward ineffective treatments.   
242   
243  The premarket requirements of the FDA Authorities advance further substantial government 
244  interests, including motivating the development of robust scientific data on safety and 
245  effectiveness; ensuring that the FDA-required labeling is accurate and informative; protecting the 
246  integrity and reliability of promotional information regarding medical product uses; protecting 
247  human subjects receiving experimental treatments; ensuring informed consent; maintaining 
248  incentives for clinical trial participation; protecting innovation incentives, including statutory 
249  grants of exclusivity; and promoting the development of products for underserved patients.18 
250   
251  Generally, FDAs premarket review process focuses on determining whether a medical product 
252  is safe and effective for the specified use(s) in an identified population.  However, after the 
253  premarket review process is complete and a product is approved/cleared, questions may arise in 
254  clinical practice relating to the use of the medical product for a particular patient.   
255   
256  HCPs prescribe and use approved/cleared medical products for unapproved uses when they judge 
257  that the unapproved use is medically appropriate for their particular patientwhose 
258  characteristics and needs may differ from the characteristics of the population(s) reflected in the 
259  approved use(s).19  This practice may be most common in patients with diseases for which there 
260  is no medical product that is a proven treatment or in patients who have exhausted all approved 
261  uses of medical products.20  In such instances, HCPs may be interested in communications about 
262  unapproved uses of approved/cleared medical products.  However, especially because such 
263  communications may be used to inform clinical practice decisions for the care of an individual 
264  patient, it is critical that these communications be truthful, non-misleading, factual, and unbiased 
265  and include all information necessary for HCPs to interpret the strengths and weaknesses and 
 
17 See, e.g., 21 CFR 201.128 (drugs); 21 CFR 801.4 (devices); 2020 Intended Uses NPRM, 85 FR 59718 at 59721; 
2021 Intended Use Final Rule, 86 FR 41383 at 4138641397, footnote 3. 
 
18 See January 2017 Memorandum at 316. 
 
19 The extra-label use of approved veterinary or human drugs in animals is permitted only if it complies with section 
512(a)(4) and (a)(5) of the FD&C Act, 21 U.S.C. 360b(a)(4) and 360b(a)(5), and 21 CFR part 530. 
 
20 See January 2017 Memorandum at 17. 
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266  validity and utility of the information about the unapproved use.  It is also critical that such 
267  communications be based on studies and analyses that are scientifically sound and provide 
268  clinically relevant information.  In contrast, patient harm could result from communicating 
269  information about unapproved uses of approved/cleared medical products to HCPs who are 
270  engaged in prescribing or administering those medical products to an individual patient if that 
271  information is false, misleading, biased, or not based on studies and analyses that are 
272  scientifically sound and able to provide clinically relevant information.21  And where firms 
273  choose to use persuasive marketing techniques (as that term is described below)  in 
274  communications regarding unapproved uses, this suggests an improper intent to market the 
275  relevant products for unapproved uses. 
276   
277  Cognizant of all these factors, FDA, in implementing the premarket requirements of the FDA 
278  Authorities and, more specifically, in developing this draft guidance, has sought to strike a 
279  careful balance, supporting HCP interest in scientific information about unapproved uses of 
280  approved/cleared medical products to inform clinical practice decisions for the care of an 
281  individual patient, but without undermining the other government interests described elsewhere 
282  in this guidance document.  This includes the government interest in incentivizing the 
283  development of and satisfaction of applicable premarket requirements for medical products, 
284  which reduces the need to rely on unapproved use(s), and in protecting patients from medical 
285  product uses that have not been shown to be safe and effective.  
286   
287  This draft guidance represents a continuation of FDAs ongoing efforts to consider, develop, and 
288  refine its policies and recommendations relating to communications by firms about unapproved 
289  uses of their approved/cleared medical products.  In 2009, FDA issued the guidance for industry 
290  Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or 
291  Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or 
292  Cleared Medical Devices to provide guidance to firms on distributing journal articles and 
293  scientific or medical reference publications.  Then, FDA issued the 2014 revised draft 
294  guidance to clarify the Agencys position on a firms dissemination of scientific or medical 
295  reference texts and CPGs that include information on unapproved uses of the firms medical 
296  products and to provide additional explanation on these topics.  
297   
298  In 2016, FDA held a public hearing and requested comments on the topic of Manufacturer 
299  Communications Regarding Unapproved Uses of Approved or Cleared Medical Products (2016 
300  public hearing) (81 FR 60299, September 1, 2016).  In response to comments at the hearing, 
301  FDA developed and placed in the docket (FDA-2016-N-1149-0040) a memorandum to provide 
302  additional background on the issues it is considering as part of its review of its rules and policies 
303  relating to communications by firms regarding unapproved uses of approved or cleared medical 
304  products.  (See FDA Memorandum:  Public Health Interests and First Amendment 
305  Considerations Related to Manufacturer Communications Regarding Unapproved Uses of 
 
21 As an example, FDA generally does not consider preliminary scientific data to be clinically relevant because 
[w]hen what exists is preliminary scientific data, the ultimate relevance and utility of that data is often unknown.  
That is, one might truthfully summarize the data generated by a preliminary study without being able to determine 
whether any inferences or conclusions drawn from the data would ultimately be shown to be correct . . . . (See 
January 2017 Memorandum (cited in footnote 3 of this guidance) at 7.)  
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306  Approved or Cleared Medical Products (January 2017 Memorandum), cited at footnote 3 of this 
307  guidance; see also 82 FR 6367, January 19, 2017 (announcing the addition of the January 2017 
308  Memorandum to the 2016 public hearing docket and extending the comment period).)  FDA also 
309  revised its intended use regulations, publishing the final rule in 2021.  See 2021 Intended Use 
310  Final Rule, 86 FR 41383 (August 2, 2021), codified at 21 CFR 201.128 and 801.4.  The 
311  preambles to the proposed and final rules address some related topics.  In addition, the guidance 
312  for industry Drug and Device Manufacturer Communications With Payors, Formulary 
313  Committees, and Similar Entities  Questions and Answers (June 2018) and subsequent 
314  legislation address related topics (see footnote 5 of this guidance).   
315   
316   
317  IV.  QUESTIONS AND ANSWERS 
318   
319  Q1.  What should firms consider when determining whether a source publication is 
320  appropriate to serve as the basis for an SIUU communication?  
321    
322  Source publications that serve as the basis for SIUU communications should describe studies or 
323  analyses that are scientifically sound and provide clinically relevant information.  To be 
324  scientifically sound, the studies or analyses, at a minimum, should meet generally accepted 
325  design and other methodological standards for the particular type of study or analysis performed, 
326  taking into account established scientific principles and existing scientific knowledge.22  To be 
327  clinically relevant, the studies or analyses, in addition to being scientifically sound, should 
328  provide information that is pertinent to HCPs engaged in making clinical practice decisions for 
329  the care of an individual patient.      
330   
331  For human and animal drugs, randomized, double-blind, concurrently controlled superiority 
332  trials are usually regarded as the most rigorous design and informative to clinical practice, and 
333  therefore the most likely to provide scientifically sound and clinically relevant information; 
334  however, other well-designed and well-conducted trials are also able to generate scientifically 
335  sound and clinically relevant information.  For medical devices, the types of studies, information, 
336  and analyses that are considered valid scientific evidence are described in 21 CFR 860.7 and may 
337  include well-controlled investigations, partially controlled studies, studies and objective trials 
338  without matched controls, well-documented case histories conducted by qualified experts, and 
339  reports of significant human experience with a marketed device.  For medical devices, these 
340  types of studies, information, and analyses are most likely to be scientifically sound and 
341  clinically relevant.  
342   
343  Real-world data and associated real-world evidence about medical products may be scientifically 
344  sound and clinically relevant depending on the characteristics of the data and the nature of the 
 
22 Statistical robustness is generally necessary, but not sufficient, to determine if a study or analysis is appropriate 
for an SIUU communication.  Although statistical robustness factors into the rigor of the design and methodology, 
statistical robustness does not assure that the study or analysis relates to outcomes of clinical relevance to HCPs. 
 
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345  analyses.23  Other types of well-designed and well-conducted studies and analyses can also be 
346  informative to HCPs, but any study or analysis described in a source publication should be 
347  evaluated in light of its limitations to determine whether the study or analysis is scientifically 
348  sound and provides clinically relevant information.   
349   
350  Certain studies without an adequate comparison or control group, isolated case reports about 
351  medical products, and other reports that lack enough detail to permit scientific evaluation would 
352  generally not be scientifically sound or clinically relevant and, therefore, use of such reports 
353  alone as the basis for an SIUU communication would not be consistent with the enforcement 
354  policy outlined in this guidance.  
355   
356  Similarly, communications that distort studies as well as communications based on publications 
357  that distort studies24 or include fraudulent data would not be consistent with the enforcement 
358  policy outlined in this guidance and may also violate provisions of the FDA Authorities, such as 
359  section 502(a) of the FD&C Act.  In situations where flaws of a study or analysis render the data 
360  unreliable,25 such study or analysis should also be excluded from serving as the basis of an SIUU 
361  communication as even full disclosure of the limitations of such study or analysis would not 
362  permit interpretation of results or attribution of the results to an effect of the medical product.  
363   
364  Of note, scientific data generated in early stages of medical product development can produce 
365  results that are not borne out in later studies, as demonstrated by the failure of some clinical 
366  studies26 to support the use of a medical product for the treatment of a disease or condition for 
 
23 For example, analyses of real-world data should be prespecified, protocols and statistical analysis plans should be 
finalized prior to conducting the prespecified analyses, and data integrity should be carefully monitored and 
maintained.  For more information on considerations relevant to real-world data and real-world evidence, see, for 
example, the guidance for industry and Food and Drug Administration staff Use of Real-World Evidence to Support 
Regulatory Decision-Making for Medical Devices (August 2017) and the guidance for industry Considerations for 
the Use of Real-World Data and Real-World Evidence To Support Regulatory Decision-Making for Drug and 
Biological Products (August 2023).   
 
24 Studies may be distorted by, for example, inaccurately describing or interpreting results. 
 
25 For example, studies or analyses that fail to control for confounding factors, fail to enroll the appropriate spectrum 
of patients, or fail to include clear definitions of study endpoints are unlikely to produce reliable results.  
Additionally, studies or analyses based on, for example, poorly extracted data or data that is transferred with errors, 
is not source verified, or is inaccurately collected and documented would not provide reliable information.  For 
further discussion of common weaknesses in study design, see, e.g., Appendix D, Common Weaknesses in Study 
Designs. Institute of Medicine (US) and National Research Council (US) Committee on New Approaches to Early 
Detection and Diagnosis of Breast Cancer; Joy JE, Penhoet EE, Petitti DB, editors. (2005). Saving Women's Lives: 
Strategies for Improving Breast Cancer Detection and Diagnosis. Washington (DC): National Academies Press 
(US). Available from https://www.ncbi.nlm.nih.gov/books/NBK22323/.  
 
26 For example, the failure rate during the process of new prescription drug development exceeds 95 percent (see 
National Center for Advancing Translational Sciences. About New Therapeutic Uses. U.S. Department of Health 
and Human Services, National Institutes of Health. Retrieved August 14, 2023, from 
https://ncats.nih.gov/ntu/about).  Similarly, medical devices have a very high failure rate in their first prototype tests, 
with a reported 90 percent of medical devices failing in their first prototype tests (see Intertek (2010). The Top 10 
 
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367  which the medical product initially appeared promising.27,28  Such scientific data generated in 
368  early stages of product development are unlikely to be sufficiently reliable by themselves to 
369  allow for a determination of clinical relevance.  As a result, a communication based on this type 
370  of data alone is unlikely to be within the scope of the enforcement policy outlined in this 
371  guidance.   
372   
373  Finally, it would not be consistent with the enforcement policy outlined in this guidance to 
374  continue to share an SIUU communication that is based on a study or analysis that is no longer 
375  clinically relevant.  A study or analysis may no longer be clinically relevant because, for 
376  example, subsequent research has established that the findings from the study or analysis are not 
377  reliable.  Accordingly, when a firm has shared on the internet an SIUU communication that is 
378  based on a study or analysis that is later determined to no longer be clinically relevant and the 
379  firm has the ability to remove their SIUU communication, we recommend the firm remove their 
380  SIUU communication.29   
381   
382  Q2.  What information should firms include as part of SIUU communications?  
383   
384  It is critical that SIUU communications be truthful, non-misleading, factual, and unbiased and 
385  provide all information necessary for HCPs to interpret the strengths and weaknesses and 
386  validity and utility of the information in the SIUU communication.  Accordingly, FDA 
 
Reasons Medical Devices Fail Product Certification Testing the First Time. Available at 
https://www.intertek.com/medical/10-reasons-medical-devices-fail-testing-paper/).  
27 One report evaluated 22 case studies of drugs, vaccines, and medical devices from 1999 to 2017 in which 
promising phase 2 clinical trial results were not confirmed in phase 3 clinical trials.  Phase 3 studies did not confirm 
phase 2 findings of effectiveness in 14 cases, safety in 1 case, and both safety and effectiveness in 7 cases.  These 
unexpected results could occur even when the phase 2 study was relatively large and even when the phase 2 trials 
assessed clinical outcomes.  In two cases, the phase 3 studies showed that the experimental product increased the 
frequency of the problem it was intended to prevent (see U.S. Food and Drug Administration Report. (2017). 22 
Case Studies Where Phase 2 and Phase 3 Trials Had Divergent Results. Available at 
https://www.fda.gov/media/102332/download).   
 
28 Further study is often needed to demonstrate safety and effectiveness for an intended use because the ultimate 
relevance and utility of scientific data generated in early stages of product development often cannot be ascertained 
from that early-stage data alone.  See, e.g., Echt DS, Liebson PR, Mitchell LB et al. (1991). Mortality and Morbidity 
in Patients Receiving Encainide, Flecainide, or Placebo: The Cardiac Arrhythmia Suppression Trial. New Eng. J. 
Med., 324(12): 781-88.  The Cardiac Arrhythmia Suppression Trial (CAST) was a well-controlled study that 
examined the widely held belief (in the absence of well-controlled studies showing this to be true) that treating 
minor rhythm abnormalities (frequent ventricular premature beats) with anti-arrhythmics after an acute myocardial 
infarction would improve survival.  To test this belief, the National Institutes of Health conducted the CAST study 
which demonstrated that, although the drugs did indeed treat minor rhythm abnormalities, the patients who took 
those drugs had a 2 12 fold increase in mortality.  See also National Academy of Sciences (1969), Drug Efficacy 
Study: Final Report to the Commissioner of Food and Drugs, Food and Drug Administration, which found that 
approximately one-third of all pre-1962 marketed drugs did not have a single effective use.   
 
29 While it would not be consistent with the enforcement policy outlined in this guidance for a firm to continue to 
share a communication based solely on a study or analysis that is no longer clinically relevant, a communication that 
includes some discussion of or reference to a source publication containing historical information, such as to 
describe the historical context and evolution of clinical knowledge in a subject area, would be consistent with the 
recommendations of this guidance if it makes clear that the historical information is no longer clinically relevant. 
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387  recommends that firms include all of the following information as part of SIUU 
388  communications:30 
389   
390    A statement that the unapproved use(s) of the medical product has not been approved by 
391  FDA and that the safety and effectiveness of the medical product for the unapproved 
392  use(s) has not been established 
393    For example, a statement that [Medical Product X] has not been approved by FDA 
-
394  for use in [Condition Y] and the safety and effectiveness of [Medical Product X] for 
395  [Condition Y] has not been established. 
396    A statement disclosing the FDA-approved use(s) of the medical product, including any 
397  limitations of use specified in the FDA-required labeling  
398    A statement disclosing any limitations, restrictions, cautions, or warnings described in the 
399  FDA-required labeling about the unapproved use(s) 
400    A copy of the most current FDA-required labeling (or a mechanism for obtaining this 
401  labeling, as appropriate) 
402    A statement describing any contraindication(s) in the FDA-required labeling for the 
403  medical product 
404    A statement describing any serious, life-threatening, or fatal risks posed by the medical 
405  product that are in the FDA-required labeling for the medical product or known by the 
406  firm and that are relevant to the unapproved use(s)31 
407    A statement identifying any authors, editors, or other contributors to publication(s) 
408  included in the SIUU communication who were employees of or consultants to or who 
409  received compensation from the firm32 at the time of writing, editing, or contributing to 
410  the publication, to the extent a firm acting reasonably would know of such relationship  
 
30 See item 2 in Q4 of this guidance for information on limited exceptions to the recommendations in this section 
when SIUU communications in the form of certain unabridged CPGs or reference texts in their entirety are shared. 
 
31 If a risk evaluation and mitigation strategy (REMS) has been established under 21 U.S.C. 355-1, the statement 
should disclose that fact and should describe the goal(s) of the REMS.  
 
32 Systematic reviews of studies funded and/or conducted by the firm or its representatives demonstrate bias 
favoring a firms medical product.  See, e.g., Lexchin, J., Bero, L. A., Djulbegovic, B., & Clark, O. (2003). 
Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ (Clinical research 
ed.), 326(7400), 11671170. https://doi.org/10.1136/bmj.326.7400.1167 (reviewing 30 studies finding that 
[s]ystematic bias favours products which are made by the company funding the research.); Lundh, A., Lexchin, J., 
Mintzes, B., Schroll, J. B., & Bero, L. (2017).  Industry sponsorship and research outcome. The Cochrane database 
of systematic reviews, 2(2), MR000033. https://doi.org/10.1002/14651858.MR000033.pub3 (reviewing 48 studies 
 
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411    In the case of an SIUU communication that is based on a source publication that is 
412  primarily focused on a particular scientific study or studies,33 for each such study34 where 
413  the following information is not included in the publication, provide a description of:35 
414    All material aspects of study design, methodology, and results  
-
415    All material limitations related to the study design, methodology, and results36  
-
416    Any conclusions from other relevant studies, when applicable, that are contrary to or 
-
417  cast doubt on the results shared, including citations for any such studies  
418    The publication date of any referenced or included publication(s) (if not specified in the 
419  publication or citation)   
420  Q3.  What presentational considerations should firms take into account for SIUU 
421  communications?  
422   
423  As noted above, the premarket requirements of the FDA Authorities further multiple important 
424  government interests.  In developing this draft guidance, FDA has sought to strike a careful 
425  balance between supporting HCP interest in scientific information about unapproved uses of 
426  approved/cleared medical products to inform clinical practice decisions for the care of an 
427  individual patient, and mitigating the potential that the government interests advanced by these 
428  statutory requirements will be undermined.  There are several presentational considerations that 
429  can help achieve the appropriate balance, in part by helping to ensure that SIUU communications 
430  are conveyed in a manner that enhances and does not interfere with HCP understanding and 
431  evaluation of the underlying scientific information, including its limitations.  In addition to the 
432  information being truthful and non-misleading, it is critical that the presentation is factual and 
433  unbiased.  To that end, FDA recommends the following:   
434   
435  1.  SIUU communications should clearly and prominently present all disclosures 
436  recommended in this guidance. 
437   
438  All recommended disclosures should be clearly and prominently presented.  This helps to ensure 
439  that HCPs have the information necessary to interpret the scientific information and the SIUU 
 
showing that [s]ponsorship of drug and device studies by the manufacturing company leads to more favorable 
results and conclusions than sponsorship by other sources).   
 
33 FDA anticipates that most SIUU communications of CPGs or reference texts would not be subject to this 
recommendation because they are not focused primarily on a specific study or studies.  
 
34 For example, if an SIUU communication includes a reprint that describes two studies in detail, this 
recommendation applies to each study, even if the SIUU communication does not address them in identical detail.  
 
35 See item 3 in Q4 for specific recommendations for the presentation of such material information in firm-generated 
presentations of scientific information from an accompanying reprint.  
 
36 See Q1 for further discussion of limitations of studies and analyses.  
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440  communication as a whole.  Factors FDA considers when determining whether information is 
441  clearly and prominently presented may include type size, font style, layout, contrast, graphic 
442  design, headlines, spacing, volume, articulation, pace, and any other techniques to achieve 
443  emphasis or notice.37  For SIUU communications that have both audio and visual components, to 
444  help HCPs notice and comprehend the information, FDA recommends that disclosures be 
445  presented in both the audio and in text at the same time using the same words (key terms and 
446  phrases or a full transcript).38  Note, for SIUU communications that have both audio and visual 
447  components, it would be consistent with the disclosure recommendations of this guidance for 
448  both the audio and visual components to include a statement about how to obtain a copy of the 
449  most current FDA-required labeling for the medical product that is the subject of the SIUU 
450  communication. 
451   
452  2.  SIUU communications should not use persuasive marketing techniques. 
453   
454  When communicating about the approved uses of their medical products, firms often use 
455  marketing techniques to influence the views of their audience.  Some of these marketing 
456  techniques influence use of the products based on elements other than the scientific content of 
457  the communication (as used herein, persuasive marketing techniques).  Examples of these 
458  persuasive marketing techniques include the use of celebrity endorsements, premium offers, and 
459  gifts.39  In the context of a firms communications to HCPs in support of an unapproved use, a 
460  firms choice to use persuasive marketing techniques suggests an effort to convince the HCP to 
461  prescribe or use the product for the unapproved use, and FDA therefore considers such 
462  communications to be evidence of an intended use of the product for purposes of relevant 
463  requirements of the FDA Authorities.40  And because such communications attempt to influence 
464  HCPs to reach positive conclusions about the unapproved use based on elements other than the 
465  scientific content, such communications are outside the scope of the enforcement policy outlined 
466  in this guidance.  
467   
 
37 FDA assesses disclosure clarity and prominence on a case-by-case basis.   
 
38 For example, if a firm posts a reprint on a web page and also includes a firm-generated video presentation of 
scientific information from the accompanying reprint on that web page (see item 3 in Q4), the firm should present 
recommended disclosures in the video in both the audio and in text at the same time, using the same words.  
 
39 See, e.g., Datta, A., & Dave, D. (2017). Effects of physiciandirected pharmaceutical promotion on prescription 
behaviors: longitudinal evidence. Health economics, 26(4), 450-468; Meffert, J. (2009). Key opinion leaders: where 
they come from and how that affects the drugs you prescribe. Dermatol Ther, 22, 262-268; Naylor, C., Chen, E., 
Strauss, B. (1992). Measured enthusiasm: does the method of reporting trial results alter perceptions of therapeutic 
effectiveness? Ann Intern Med. 117(11): 916-21; Price, S., ODonoghue, A., Rizzo, L., Sapru, S., Aikin, K. (2021). 
What influences healthcare providers prescribing decisions? Results from a national survey. Research in Social and 
Administrative Pharmacy, 17(10), 1770-1779; Sismondo, S. (2015). How to make opinion leaders and influence 
people. CMAJ: Canadian Medical Association journal = journal de l'Association medicale canadienne, 187(10), 
759760. 
 
40 See 2021 Intended Use Final Rule, 86 FR at 41388 (Courts have repeatedly held that . . . promotional claims are 
one source of evidence of intended use).   
 
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468  Because an SIUU communication may be used to inform clinical practice decisions about 
469  whether to use an approved/cleared medical product for an unapproved use in an individual 
470  patient, it is also important that the communication be presented in a manner that is unlikely to 
471  lead HCPs to base those decisions on conclusions about the safety or effectiveness of the 
472  unapproved use that are not in alignment with, or that go beyond what is justified by, the 
473  underlying scientific information.41  Research demonstrates that promotional communications 
474  about medical products often employ marketing techniques that are effective at influencing 
475  attitudes and behaviors of HCPs,42 and that how information is presented can impact HCP 
476  impressions of that information.43  These marketing techniques can influence attitudes and 
477  behavior, independent of the quality of the information, even among highly educated medical 
478  professionals.44   
 
41 See, e.g., Eguale, T., Buckeridge, D. L., Verma, A., Winslade, N. E., Benedetti, A., Hanley, J. A., & Tamblyn, R. 
(2016). Association of Off-label Drug Use and Adverse Drug Events in an Adult Population. JAMA internal 
medicine, 176(1), 5563; Radley, D. C., Finkelstein, S. N., & Stafford, R. S. (2006). Off-label prescribing among 
office-based physicians. Archives of internal medicine, 166(9), 10211026. See also the January 2017 Memorandum 
at 13 (Marketing activities and communications regarding the safety and effectiveness of a medical product for a 
particular use that are not properly supported by scientific evidence may thus create a false or misleading impression 
about the safety and efficacy of the medical product for that use, which can lead to prescribing or use decisions that 
harm patients.  Examples of some marketing activities that caused such harm are described in Appendix C.). 
 
42 See e.g., Austad, K. E., Avorn, J., & Kesselheim, A. S. (2011).  Medical students exposure to and attitudes about 
the pharmaceutical industry:  a systematic review.  PLoS Med, 8(5), e1001037; Austad, K. E., Avorn, J., Franklin, J. 
M., Campbell, E. G., & Kesselheim, A. S. (2014).  Association of Marketing Interactions With Medical Trainees 
Knowledge About Evidence-Based Prescribing: Results From a National Survey.  JAMA Internal Medicine, 
174(8):1283-1290; Avorn, J., Chen, M., & Hartley, R. (1982).  Scientific versus commercial sources of influence on 
the prescribing behavior of physicians.  The American Journal of Medicine, 73(1), 4-8; and Spurling, G. K., 
Mansfield, P. R., Montgomery, B. D., Lexchin, J., Doust, J., Othman, N., & Vitry, A. I. (2010).  Information from 
pharmaceutical companies and the quality, quantity, and cost of physicians' prescribing:  A systematic review.  PLoS 
Med, 7(10), e1000352. 
 
43 See, e.g., Bobbio, M., Demichelis, B., & Giustetto, G. (1994). Completeness of reporting trial results: effect on 
physicians' willingness to prescribe. Lancet, 343(8907), 12091211; Bucher, H. C., Weinbacher, M., & Gyr, K. 
(1994). Influence of method of reporting study results on decision of physicians to prescribe drugs to lower 
cholesterol concentration. BMJ (Clinical research ed.), 309(6957), 761764; Kahwati, L., Carmody, D., Berkman, 
N., Sullivan, H. W., Aikin, K. J., & DeFrank, J. (2017). Prescribers' knowledge and skills for interpreting research 
results: a systematic review. The Journal of Continuing Education in the Health Professions, 37(2), 129136; 
Marcatto, F., Rolison, J.J., & Ferrante, D. (2013). Communicating clinical trial outcomes: effects of presentation 
method on physicians evaluations of new treatments. Judgment and Decision Making, 8(1), 29-33.  
 
44 See e.g., Chaiken, S., Liberman, A., & Eagly, A.E. (1980). Heuristic and systematic information processing within 
and beyond the persuasion context.  In Unintended Thought (ed. J.E. Uleman). New York: Guilford Press, 212-252; 
DeJong, C., Aguilar, T., Tseng, C-W., Lin, GA., Boscardin, WJ., Dudley, RA. (2016). Pharmaceutical industry
sponsored meals and physician prescribing patterns for Medicare beneficiaries.  JAMA Intern Med., 176(8):1114-
1122; Hadland, SE., Cerda, M., Li, Y., Krieger, MS., Marshall, BDL. (2018). Association of pharmaceutical 
industry marketing of opioid products to physicians with subsequent opioid prescribing. JAMA Intern Med., 
178(6):861-863; Inoue, K., Tsugawa, Y., Mangione, CM., Duru, OK. (2021). Association between industry 
payments and prescriptions of long-acting insulin: An observational study with propensity score Matching. PloS 
Med, 18(6): e1003645; Petty, R. E. & Cacioppo, J. T. (1986); Communication and Persuasion: Central and 
Peripheral Routes to Attitude Change. New York: Springer-Verlag; Sah, S., & Fugh-Berman, A. (2013). Physicians 
 
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479  As explained above, this guidance strives to balance (1) HCP interest in scientific information 
480  about unapproved uses of approved/cleared medical products to inform clinical practice 
481  decisions for the care of an individual patient and (2) the various government interests in 
482  incentivizing the development of and satisfaction of applicable premarket requirements for 
483  medical products.  A firms use of persuasive marketing techniques in communications that 
484  support unapproved uses does not appropriately serve the purpose of informing clinical practice 
485  decisions for individual patient care and therefore does not counterbalance the important 
486  government interests discussed above.  For these reasons, a firms communications that support 
487  unapproved uses and use persuasive marketing techniques are outside the scope of the 
488  enforcement policy outlined in this guidance.     
489   
490  3.  SIUU communications should be separate and distinct from promotional communications 
491  about approved uses of medical products. 
492   
493  As set forth in this guidance, the medical products that are discussed in SIUU communications 
494  are approved/cleared for at least one use, and, as such, it is likely that firms regularly disseminate 
495  promotional communications for those approved uses.  However, including information about 
496  unapproved uses in those promotional communications has the potential to undermine the 
497  government interests in the premarket requirements of the FDA Authorities.  In this guidance, 
498  FDA has sought to strike a careful balance, supporting HCPs interested in scientific information 
499  about unapproved uses of approved/cleared medical products to inform clinical practice 
500  decisions for the care of an individual patient, while mitigating the potential that the government 
501  interests advanced by these statutory requirements will be undermined.  To preserve this balance 
502  and to avoid misleading HCPs, we strongly recommend that firms avoid sharing an SIUU 
503  communication for a medical product together with a promotional communication for that 
504  product for its approved use(s) because combining these two types of communications is more 
505  likely to lead to conflation of the approved use and unapproved use information.45  This 
506  conflation may lead HCPs to conclude that the firms medical product has been demonstrated to 
507  be safe and effective for all presented uses, including the unapproved use(s), or to conclude that 
508  all presented uses of the medical product are uses for which it may be approved/cleared.  
509   
510  Additionally, FDA recommends that firms use dedicated vehicles, channels, and venues for 
511  sharing SIUU communications that are separate from the vehicles, channels, and venues used for 
512  promotional communications about approved uses of medical products to reduce the risk of 
 
under the influence: social psychology and industry marketing strategies. The Journal of law, medicine & ethics: a 
journal of the American Society of Law, Medicine & Ethics, 41(3), 665672; Yeh, JS., Franklin, JM., Avorn, J., 
Landon, J., Kesselheim, AS. (2016). Association of industry payments to physicians with the prescribing of brand-
name statins in Massachusetts. JAMA Intern Med., 176(6):763-768. 
 
45 Research indicates that combining multiple communications can prompt conflation of the messages conveyed by 
each communication.  See, e.g., Sullivan, H. W., ODonoghue, A. C., Rupert, D. J., Willoughby, J. F., Amoozegar, 
J. B., & Aikin, K. J. (2016). Are Disease Awareness Links on Prescription Drug Websites Misleading? A 
Randomized Study. Journal of health communication, 21(11), 11981207; Aikin, K. J., Sullivan, H. W., & Betts, K. 
R. (2016). Disease Information in Direct-to-Consumer Prescription Drug Print Ads. Journal of health 
communication, 21(2), 228239.    
 
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513  HCPs conflating the approved and unapproved use information.  In cases where there is only one 
514  vehicle, venue, or channel available for the sharing of information, a firm should ensure that 
515  SIUU communications are clearly identified and distinct from promotional communications 
516  about approved uses.  
517   
518  For example, firms may be interested in sharing information about both the approved and 
519  unapproved uses of their medical products online through websites.  In these cases, FDA 
520  recommends that SIUU communications be on a separate web page from the web page that hosts 
521  promotional communications about the approved uses of the medical product.  FDA also 
522  recommends that firms not include direct links from web pages that host promotional 
523  communications about approved uses to webpages that host SIUU communications.  Similarly, 
524  FDA recommends that email messages used to share SIUU communications be separate and 
525  distinct from email messages used to share promotional communications about approved uses of 
526  the medical product.  
527   
528  Medical or scientific conferences also represent a venue where information about both approved 
529  and unapproved uses of medical products is shared.  Although conference organizers generally 
530  select the content to be shared for the planned sessions and presentations at the conference (e.g., 
531  poster sessions),46 these same conferences also offer venues (e.g., booths in commercial exhibit 
532  halls) where firms can independently select and share information with conference attendees, 
533  which could include both promotional communications about approved uses of medical products 
534  and SIUU communications.  When sharing information in commercial exhibit halls and similar 
535  venues where programming is not selected and determined by the conference organizers, firms 
536  should ensure that SIUU communications are clearly identified and distinct from promotional 
537  communications about approved uses.47  For example, in commercial exhibit halls, FDA strongly 
538  recommends that firms divide booth space to allow for a dedicated space where SIUU 
539  communications can be shared, separate and distinct from promotional communications about 
540  approved uses.  
541   
542  4.  SIUU communications should be shared through media and via platforms that enable 
543  firms to implement the recommendations in this guidance. 
544    
545  Different media types and platforms are available to firms interested in sharing SIUU 
546  communications, and each medium and platform may prompt unique presentational challenges 
547  and considerations.  For example, certain online platforms may impose character-space 
 
46 FDA does not consider a firms presentation of truthful and non-misleading scientific information about 
unapproved uses in the planned sessions and presentations selected by conference organizers at medical or scientific 
conferences to be evidence of intended use when the presentation is made in non-promotional settings and not 
accompanied by promotional communications. 
 
47 This recommendation applies even to those SIUU communications that include the same substantive content as 
presented in planned sessions at the conference.  Courts have recognized that a different level of First Amendment 
scrutiny can apply to the same speech depending on how the speech is communicated.  See, e.g., Washington Legal 
Foundation v. Friedman, 13 F. Supp. 2d 51, 64 (D.D.C. 1998), vacated in part sub nom. Washington Legal 
Foundation v. Henney, 202 F.3d 331, 336-37 (D.C. Cir. 2000). 
 
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548  limitations or other presentational limitations that would not enable a firm to include within their 
549  communications on that platform all of the disclosures that are recommended for an SIUU 
550  communication.  To be consistent with the recommendations in this guidance, such platforms 
551  should not be used to host SIUU communications but could be used to direct HCPs to an SIUU 
552  communication.  For example, it would be consistent with the recommendations in this guidance 
553  for a communication on a character-space limited platform to direct HCPs to an SIUU 
554  communication through a statement that does not mention the name of any specific medical 
555  product, such as New publication for Health Care Providersphase 3 trial results for an 
556  investigational treatment for [disease X], followed by a link to a website where the SIUU 
557  communication appears. 
558   
559  Firms should carefully consider the limitations of different media types and platforms to ensure 
560  that the medium and platform used for sharing an SIUU communication allows the firm to 
561  include all information consistent with the recommendations in this guidance.   
562   
563  5.  Firms should consider using plain language in the content they develop for SIUU 
564  communications to facilitate comprehension.  
565   
566  Although HCPs have specialized training and experience in evaluating scientific information, 
567  research indicates that HCPs may nonetheless have difficulty understanding some types of 
568  scientific information, including clinical trial data, and the design and methodological limitations 
569  of studies.48  To aid in comprehension and encourage careful consideration of the information 
570  shared in an SIUU communication, firms should consider using plain language for any firm-
571  generated portions of the SIUU communication, including recommended disclosures.  Plain 
572  language is language that is clear, concise, well-organized, and where possible, avoids 
573  complexities such as technical jargon, passive voice, and long sentences and paragraphs.49  
574  Clearly explaining scientific or technical terms and avoiding or appropriately introducing 
575  acronyms and abbreviations can facilitate comprehension.  
576   
 
48 See, e.g., Anderson, B.L., Schulkin, J. (2014). Numerical Reasoning in Judgments and Decision Making about 
Health. Cambridge University Press; Kahwati, L., Carmody, D., Berkman, N., Sullivan, H. W., Aikin, K. J., & 
DeFrank, J. (2017). Prescribers' Knowledge and Skills for Interpreting Research Results: A Systematic Review. The 
Journal of Continuing Education in the Health Professions, 37(2), 129136; Moynihan, C. K., Burke, P. A., Evans, 
S. A., O'Donoghue, A. C., & Sullivan, H. W. (2018). Physicians' Understanding of Clinical Trial Data in 
Professional Prescription Drug Promotion Journal of the American Board of Family Medicine. JABFM, 31(4), 645
649; Weir, I. R., Marshall, G. D., Schneider, J. I., Sherer, J. A., Lord, E. M., Gyawali, B., Paasche-Orlow, M. K., 
Benjamin, E. J., & Trinquart, L. (2019). Interpretation of time-to-event outcomes in randomized trials: an online 
randomized experiment. Annals of oncology: official journal of the European Society for Medical Oncology, 30(1), 
96102. 
 
49 See the U.S. General Services Administration (GSA) Plain Language Action and Information Network (PLAIN) 
website at https://www.plainlanguage.gov/.  
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577  Q4.  What additional recommendations apply to specific types of SIUU communications? 
578   
579  This draft guidance addresses a number of different types of SIUU communications.  This 
580  section offers specific recommendations for firms to take into account for these different types of 
581  SIUU communications, in addition to the recommendations outlined in Q1, Q2, and Q3. 
582   
583  1.  Reprints:  
584   
585  In this guidance, we use the term reprint to refer to a copy of an article originally published by a 
586  medical or scientific journal.  When firms share SIUU communications in the form of a reprint, 
587  FDA recommends that the reprint have all of the following characteristics:   
588   
589    The article is published in a journal managed by an independent organization with an 
590  editorial board comprised of persons who have demonstrated expertise in the subject of 
591  the articles under review by the organization (through education or experience), and a 
592  publicly stated policy regarding the disclosure of conflicts of interest or biases for all 
593  authors, contributors, or editors 
594    
595    The article is peer-reviewed by experts in the subject of the article, as established by 
596  education or experience 
597    
598    The article is generally available (or the journal from which the article is taken is 
599  generally available) through independent distribution channels (e.g., internet sources, 
600  book retailers, subscriptions, libraries) where periodicals and reprints are sold or are 
601  accessible 
602    
603    The article describes studies or analyses that are scientifically sound and provide 
604  information that is clinically relevant (see Q1); specifically: 
605   
606    To be scientifically sound, the scientific studies or analyses described in the article 
-
607  should meet generally acceptable design and other methodological standards for the 
608  type of study or analysis being performed (e.g., provide a clear description of the 
609  hypothesis stated and tested, acknowledge and account for potential bias, and 
610  otherwise meet generally accepted scientific standards for the type of study or 
611  analysis performed).  Meta-analyses, cohort or case-control studies, open-label 
612  studies, single-arm studies, or epidemiological studies can be scientifically sound if 
613  these studies and analyses meet generally acceptable design and other methodological 
614  standards for the type of study or analysis being performed and take into account any 
615  limitations of the selected design and methodology.  For some devices, well-
616  documented case histories conducted by qualified experts may also be scientifically 
617  sound and provide information that is clinically relevant.   
618   
619    To be clinically relevant, the scientific studies or analyses described in the article 
-
620  should, in addition to being scientifically sound, provide information that is pertinent 
621  to HCPs engaged in making clinical practice decisions for the care of an individual 
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622  patient.  Generally, sharing articles focused on a nonclinical study or analysis alone 
623  would not be consistent with the enforcement policy outlined in this guidance because 
624  this nonclinical study or analysis alone is unlikely to provide information that is 
625  clinically relevant. 
626   
627    Articles that misrepresent or overstate findings in light of the limitations of the study 
-
628  or analysis would not be consistent with the enforcement policy outlined in this 
629  guidance.   
630   
631    Reprints should be unaltered/unabridged as the sharing of unaltered/unabridged articles is 
632  less likely to introduce bias or result in the omission of material information.50 
633   
634  2.  Clinical Reference Resources: 
635   
636  In this draft guidance, we address the following clinical reference resources: 
637   
638    Clinical Practice Guidelines (CPGs):  
639   
640    In this guidance, we use the term CPG to refer to a statement or document from 
-
641  a professional or academic organization that includes recommendations focused 
642  on a specific disease or condition intended to help HCPs make decisions for 
643  individual patient care, including decisions in circumstances where there are few 
644  or no approved/cleared medical products indicated for the patients condition or 
645  the approved/cleared medical products have not proven successful for the 
646  individual patient.51  
647   
648    Reference Texts: 
649   
650    In this guidance, we use the term reference text to refer to medical or scientific 
-
651  textbooks that typically discuss a wide range of topics (e.g., medical diagnosis, 
652  pathophysiology and treatments, pharmacology, surgical techniques, and other 
653  scientific or medical information).   
654   
655    Materials from Independent Clinical Practice Resources: 
656   
657    In this guidance, we use the term independent clinical practice resource to refer 
-
658  to a digital resource that contains medical and scientific information on a wide 
 
50 A firm could develop a truthful, non-misleading, factual, and unbiased presentation of scientific information from 
an accompanying reprint and not be inconsistent with this recommendation.  See item 3 in Q4 for recommendations 
regarding firm-generated presentations of scientific information from an accompanying reprint. 
 
51 CPGs can provide a resource for HCPs who may not have the time or capacity to review the full range of primary 
source publications and make an independent, evidence-based assessment to inform their clinical practice decisions.  
CPGs provide recommendations for care for a disease or condition, in addition to offering potential alternatives for 
certain patient subgroups.   
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659  range of topics developed by subject matter experts in various medical specialty 
660  fields.  The information is typically searchable by topic or keyword and 
661  produces materials in response to the HCPs search terms.   
662   
663  These clinical reference resources often contain information about unapproved uses of medical 
664  products.  Therefore, when sharing SIUU communications in the form of CPGs, reference texts, 
665  or materials from independent clinical practice resources, FDA recommends that firms follow 
666  the recommendations in Q1, Q2, and Q3, subject to the following additions and modifications.  
667   
668  When a firm shares an SIUU communication in the form of one or more individual section(s) of 
669  any of these clinical reference resources, the SIUU communication should include all 
670  information from the clinical reference resource necessary for HCPs to interpret the strengths 
671  and weaknesses and validity and utility of the information.  This may involve the sharing of 
672  multiple sections of the clinical reference resource that contain related or linked information.  
673  When a firm shares individual section(s) from these clinical reference resources, those 
674  individual section(s) should be unaltered/unabridged and extracted directly from the clinical 
675  reference resource. 
676   
677  Because unabridged CPGs and reference texts in their entirety generally discuss a wide range 
678  of topics and medical products, FDA notes the following exceptions to the recommendations in 
679  Q2.  When a firm shares an SIUU communication in the form of an unabridged CPG or 
680  reference text in its entirety that discusses a wide range of medical products and that discussion 
681  is not primarily focused on one or more of a firms medical products, FDA does not expect a 
682  firm to include any of the following: 
683   
684    A statement disclosing the FDA-approved use(s), including any limitations of use 
685  specified in the FDA-required labeling, for each of the firms medical products 
686  mentioned in the CPG or reference text   
687   
688    A statement disclosing any limitations, restrictions, cautions, or warnings described in 
689  the FDA-required labeling about the unapproved use(s) for each of the firms medical 
690  products mentioned in the CPG or reference text 
691   
692    A copy of or mechanism to obtain the FDA-required labeling for each of the firms 
693  medical products mentioned in the CPG or reference text 
694     
695    A statement describing the contraindications in the FDA-required labeling for each of 
696  the firms medical products mentioned in the CPG or reference text 
697   
698    A description of the serious, life-threatening, or fatal risks that are in the FDA-required 
699  labeling or are known by the firm and that are relevant to the unapproved use(s) posed 
700  by each of the firms medical products mentioned in the CPG or reference text 
701  (including whether a REMS has been established for any of the firms medical 
702  products mentioned in the CPG or reference text and a description of the goal(s) of the 
703  REMS)  
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704  Instead, FDA recommends that firms include a more general statement in the SIUU 
705  communication, such as, This [CPG/reference text] describes some uses of medical products 
706  that are not approved by the FDA, and the safety and effectiveness of any unapproved use(s) 
707  have not been established.   
708   
709  a.  Specific Recommendations for CPGs:  
710   
711  CPGs are generally based on a wide range of evidence, with the goal of making treatment 
712  recommendations and describing the different levels of evidence that support those 
713  recommendations.  When firms share SIUU communications in the form of a CPG, FDA 
714  recommends that the CPG have all of the following characteristics: 
715   
716    The CPG is based on rigorous reviews of the existing evidence conducted according to 
717  a clear, established procedure and following a transparent process that minimizes biases 
718  and conflicts of interest   
719   
720    The CPG includes ratings of the recommendations to reflect the quality and strength of 
721  evidence that supports each recommendation 
722   
723    The CPG is revised when important new evidence warrants modifications of current 
724  recommendations 
725   
726    The CPG is generally available through independent distribution channels (e.g., internet 
727  sources, book retailers, subscriptions, libraries) where CPGs are sold or are accessible  
728   
729  One helpful resource when considering whether a particular CPG is appropriate to serve as the 
730  basis for an SIUU communication is the National Academy of Medicine (NAM)52 standards for 
731  CPG trustworthiness.53  CPGs that are consistent with the NAM standards would also be in 
732  alignment with the standards FDA has articulated.  The NAM standards recommend that CPGs 
 
52 NAM was formerly known as the Institute of Medicine (IOM) and is one of three academies that make up the 
National Academies of Sciences, Engineering, and Medicine.  
 
53 Through the Medicare Improvements for Patients and Providers Act of 2008, Congress required the Secretary of 
Health and Human Services (HHS) to contract with IOM (through the Agency for Healthcare Research and Quality) 
to undertake a study that focused on the best methods used in developing clinical practice guidelines in order to 
ensure that organizations developing such guidelines have information on approaches that are objective, 
scientifically valid, and consistent (Public Law No. 110-275, 122 Stat. 2595).  Also, in this legislation, Congress 
required IOM to submit a report to the Secretary of HHS and the appropriate committees of Congress containing the 
results of the study, together with recommendations for such legislation and administrative action as IOM 
determines appropriate.  The standards for CPG trustworthiness, as referred to in this guidance, are taken directly 
from IOMs study results (as articulated in its report, Robin Graham, et al. eds., Institute of Medicine of the National 
Academies, Committee on Standards for Developing Trustworthy Clinical Practice Guidelines, Clinical Practice 
Guidelines We Can Trust (2011)), available at https://nap.nationalacademies.org/catalog/13058/clinical-practice-
guidelines-we-can-trust.  
 
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733  (1) be based on a systematic review54 of the existing evidence; (2) be developed by a 
734  knowledgeable, multidisciplinary panel of experts and representatives from key affected 
735  groups; (3) consider important patient subgroups and patient preferences, as appropriate; (4) be 
736  based on an explicit and transparent process by which the CPG is developed and funded that 
737  minimizes distortions,55 biases, and conflicts of interest; (5) provide a clear explanation of the 
738  logical relationships between alternative care options and health outcomes, provide clearly 
739  articulated recommendations in standardized form, and provide ratings of both quality of 
740  evidence and the strength of recommendations; and (6) be reconsidered and revised when 
741  important new evidence warrants modifications of recommendations. 
742   
743  Numerous professional organizations develop and disseminate CPGs that are pertinent to their 
744  members clinical practices.  In an era of rapidly increasing amounts of scientific information 
745  about medical products, CPGs can be a tool to manage this information.  However, in light of 
746  the proliferation of professional organizations promulgating CPGs and the variations in scope 
747  and evidence used for CPG recommendations by these organizations, it is important that firms 
748  assess CPGs in a medical practice area to ensure they are consistent with the recommendations 
749  in this guidance, including that CPG recommendations have ratings to reflect the strength and 
750  quality of evidence supporting those CPG recommendations and that any CPG 
751  recommendations are updated when new evidence warrants modification. 
752    
753  b.  Specific Recommendations for Reference Texts and Independent Clinical 
754  Practice Resources: 
755   
756  When firms share SIUU communications in the form of a reference text or material from 
757  independent clinical practice resources, FDA recommends that the reference text or material 
758  from an independent clinical practice resource have all of the following characteristics:  
759   
760    It is published by an independent publisher that is in the business of publishing 
761  scientific or medical educational content56  
762   
763    It is published in a manner consistent with current standards for medical content 
764  creation and review that are generally accepted by the medical publishing industry and 
765  in accordance with any specific peer-review procedures of the publisher  
 
54 The NAM has defined a systematic review as a scientific investigation that focuses on a specific question and 
uses explicit, prespecified scientific methods to identify, select, assess, and summarize the findings of similar but 
separate studies.  Institute of Medicine, Finding What Works in Health Care: Standards for Systematic Reviews 
(Jill Eden et al. eds., The National Academies Press 2011), available at 
https://nap.nationalacademies.org/catalog/13059/finding-what-works-in-health-care-standards-for-systematic-
reviews.   
 
55 Per NAM, distortion may result from, for example, reliance on incomplete data. 
 
56 It would be consistent with this recommendation for a firm to fund the production of copies of a reference text or 
material from an independent clinical practice resource that is already generally available and to provide those 
copies to HCPs.  
 
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766    It is authored, edited, and contributed to by experts who have demonstrated expertise in 
767  the subject area(s) through education or experience  
768   
769    It is generally available or sold through independent distribution channels57 (e.g., 
770  internet sources, book retailers, subscriptions, libraries) for medical and scientific 
771  educational content   
772   
773  3.  Specific Recommendations for Firm-Generated Presentations of Scientific Information 
774  from an Accompanying Reprint  
775   
776  In addition to sharing reprints, some firms develop firm-generated presentations of scientific 
777  information from an accompanying reprint.  Consistent with the above recommendations in this 
778  guidance, an SIUU communication in the form of a firm-generated presentation of scientific 
779  information from an accompanying reprint should be truthful, non-misleading, factual, and 
780  unbiased and provide all information necessary for HCPs to interpret the strengths and 
781  weaknesses and validity and utility of the presented information, as further explained in this 
782  section.   
783   
784  First, the full reprint(s) should accompany the firm-generated presentation and should be 
785  consistent with the recommendations in item 1 in Q4.  However, firms should not rely upon the 
786  accompanying reprint(s) to provide information that is material to the representations made in 
787  the firm-generated presentation; all information material to the representations made in the firm-
788  generated presentation should be included with those representations within the firm-generated 
789  presentation, notwithstanding the recommendations in Q2.  For example, if a firm-generated 
790  presentation includes information about study results, the firm-generated presentation should 
791  include all material aspects of and limitations related to the study design, methodology, and 
792  results necessary to interpret the presented information directly with the presented information.  
793   
794  Second, firm-generated presentations should include the disclosures recommended in Q2 of this 
795  guidance58 and should also clearly disclose what portions of the communication are firm-
796  generated.  For example, a firm-generated presentation could include the following statement: 
797  This presentation was developed by FIRM X.   
798   
799  Third, firm-generated presentations should be consistent with the recommendations in this 
800  guidance regarding presentational considerations (see Q3). 
801   
 
57 FDA recognizes that individual chapters of reference texts may not be generally available through these channels; 
this language is referring to general availability of the complete reference text. 
 
58 To the extent that recommended disclosures apply to both the firm-generated presentation and the reprint, FDA 
does not generally expect that firms repeat the recommended disclosures in both the firm-generated presentation and 
separately in an attachment to the reprint(s).  However, firms should ensure that all recommended disclosures that 
are material to specific representations made in the firm-generated presentation are at a minimum included with such 
representations in the firm-generated presentation.  
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802  Fourth, to ensure that an SIUU communication in the form of a firm-generated presentation of 
803  scientific information from an accompanying reprint is truthful, non-misleading, factual, and 
804  unbiased, the firm-generated presentation should not, for example, do any of the following: 
805   
806    Imply that the study, analysis, or underlying data or information from the reprint(s) 
807  represents larger or more-general experience with the medical product than it actually 
808  does 
809   
810    Present information (e.g., excerpts, quotes, paraphrases, conclusions) from the reprint(s) 
811  out of context, without the information necessary for HCPs to interpret the strengths and 
812  weaknesses and validity and utility of the information 
813   
814    Include representations or suggestions about the safety or effectiveness of the medical 
815  product for the unapproved use(s) that are not consistent with the reprint   
816   
817    Present conclusions or representations about safety or effectiveness for the unapproved 
818  use, even if an accurate reflection of the statements in the reprint, without attributing that 
819  statement expressly to the reprint and without immediately following it with the 
820  statement identifying any authors, editors, or other contributors to the reprint(s) who were 
821  employees of or consultants to or who received compensation from the firm at the time of 
822  writing, editing, or contributing to the reprint  
823   
824    Use statistical analyses or techniques to indicate clinical significance or validity of a 
825  finding not supported by the data or information in the reprint 
826   
827    Use tables or graphs or other presentational elements to distort or misrepresent the 
828  relationships, trends, differences, or changes among the outcomes evaluated in the reprint 
  26