Key Information and 
Facilitating Understanding in 
Informed Consent 
Guidance for Sponsors, Investigators, and 
Institutional Review Boards 
 
 
DRAFT GUIDANCE 
 
  This guidance document is being distributed for comment purposes only.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publication in the Federal Register of the notice announcing the availability of the draft 
guidance.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) Alyson Karesh, 
Alyson.Karesh@fda.hhs.gov; (CBER) Office of Communication, Outreach and Development, 
800-835-4709 or 240-402-8010; (CDRH) Office of Clinical Evidence and Analysis, 
CDRHClinicalEvidence@fda.hhs.gov; (OCLiP) Office of Clinical Policy, 301-796-8340, 
gcpquestions@fda.hhs.gov; or (OHRP) Division of Policy and Assurances, 240-453-6900 or 
866-447-4777, ohrp@hhs.gov. 
 
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) 
Office of Clinical Policy (OCLiP) 
 
U.S. Department of Health and Human Services 
Office for Human Research Protections (OHRP) 
 
 
March 2024 
Procedural 
 
10468178dft.docx 
   
Key Information and Facilitating Understanding in Informed Consent 
Guidance for Sponsors, Investigators, and Institutional Review Boards 
 
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and-radiation-emitting-products  
and/or 
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and/or 
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Rockville, MD 20852 
Phone: 240-453-6900 or 866-447-4777 
https://www.hhs.gov/ohrp/regulations-and-policy/guidance/alphabetical-list/index.html 
 
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) 
Office of Clinical Policy (OCLiP) 
 
U.S. Department of Health and Human Services 
Office for Human Research Protections (OHRP) 
 
 March 2024 
Procedural 
 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  KEY INFORMATION SECTION .................................................................................. 3 
A.  Flexible Approaches to Providing Key Information ................................................................... 4 
B.  Identifying Key Information About Basic and Additional Elements of Informed Consent ... 5 
1. Voluntary Participation and Right to Discontinue Participation .................................................... 6 
2. Purpose of the Research, Expected Duration, and Procedures To Be Followed ............................ 6 
3. Reasonably Foreseeable Risks and Discomforts ............................................................................. 7 
4. Reasonably Expected Benefits ......................................................................................................... 8 
5. Appropriate Alternative Procedures ................................................................................................ 9 
6. Compensation and Medical Treatments for Research-Related Injuries .......................................... 9 
7. Costs Related to Subject Participation .......................................................................................... 10 
C.  Supplemental Information That Could Be Included Within Key Information ..................... 10 
D.  Example of Key Information Section ......................................................................................... 11 
IV.   FACILITATING UNDERSTANDING ........................................................................ 12 
A.  Using Bubbles for the Key Information Section ....................................................................... 12 
B.  Organization and Presentation of the Entire Consent Form ................................................... 13 
1. Providing Content in Sufficient Detail ........................................................................................... 13 
2. Organization .................................................................................................................................. 13 
3. Understandable Language ............................................................................................................. 14 
APPENDIX:  A HYPOTHETICAL CLINICAL TRIAL ...................................................... 15 
 
 
 
  Contains Nonbinding Recommendations 
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1  Key Information and Facilitating Understanding  
2  in Informed Consent 
3  Guidance for Sponsors, Investigators, and  
4  Institutional Review Boards1 
5   
6   
7  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
8  Administration (FDA or Agency) and the Office for Human Research Protections (OHRP) on this topic.  
9  It does not establish any rights for any person and is not binding on FDA, OHRP, or the public.  You can 
10  use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  To 
11  discuss an alternative approach, contact the FDA or OHRP staff responsible for this guidance as listed on 
12  the title page.   
13   
14   
15   
16   
17  I.  INTRODUCTION  
18   
19  This guidance provides recommendations on provisions of the Department of Health and Human 
20  Services (HHS) regulations on the protection of human subjects as well as certain proposed 
21  revisions to FDAs current regulations for the protection of human subjects.2  Specifically, this 
22  guidance addresses the presentation of key information and includes recommendations for the 
23  content, organization, and presentation of informed consent3 information in FDA-regulated 
24  clinical investigations of drugs, devices, and biologics (collectively medical products) and in 
 
1 This guidance has been prepared by 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, and the Office of Clinical Policy at the Food and Drug Administration, and the HHS Office for Human 
Research Protections.  
   
2 This guidance uses the term human subject or subject to describe individuals who participate in clinical 
investigations as defined by FDAs human subject protection regulations in 21 CFR 50.3(g) and 56.102(e), or who 
participate in human subjects research as defined by HHSs human subjects protection regulations in 45 CFR 
46.102.  We acknowledge that some interested parties may prefer other terms, such as trial participant and research 
volunteer, but we believe it is important to use the regulatory term in this guidance.  
 
3 The term consent is subsequently used in this guidance in place of informed consent for brevity and plain language, 
unless quoting regulatory language. 
 
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25  HHS-supported or -conducted nonexempt human subjects research.4,5  The recommendations in 
26  this guidance should inform the communication of consent information to subjects, including 
27  prospective subjects or their legally authorized representatives, and may be conveyed by written, 
28  oral, or electronic means. 
29   
30  This guidance is intended to assist institutional review boards (IRBs), investigators, and sponsors 
31  engaged in or responsible for oversight of human subject research subject to FDA and/or HHS 
32  regulations with the development of consent information that would comply with 45 CFR 
33  46.116(a)(5) and FDAs proposed revisions to 21 CFR 50.20(e), if finalized as proposed.6  FDA-
34  regulated clinical investigations conducted or supported by HHS are subject to both HHS and 
35  FDA regulations, per 45 CFR 46.101, 21 CFR 50.1, and 21 CFR 56.101. 
36   
37  In general, FDAs and OHRPs guidance documents do not establish legally enforceable 
38  responsibilities.  Instead, guidances describe the Agencys current thinking on a topic and should 
39  be viewed only as recommendations, unless specific regulatory or statutory requirements are 
40  cited.  The use of the word should in Agency guidances means that something is suggested or 
41  recommended, but not required.   
42   
43   
44  II.  BACKGROUND 
45   
46  FDAs regulations in 21 CFR parts 50 and 56 for the protection of human subjects are intended 
47  to protect the rights, safety, and welfare of human subjects participating in FDA-regulated 
48  clinical investigations and include requirements for informed consent and IRB review.   
49   
50  On January 19, 2017, HHS announced revisions to 45 CFR part 46, subpart A (the Common 
51  Rule), which are known as the revised Common Rule.7  The revised Common Rule is intended to 
 
4 This guidance applies to FDA-regulated clinical investigations of drugs, biologics, or devices that are subject to 21 
CFR parts 50 and 56, including investigations under 21 CFR parts 312 and 812.  This guidance also applies to HHS-
supported or -conducted nonexempt human subjects research that is subject to 45 CFR part 46.  As used in this 
guidance, an investigational medical product is an investigational drug or biological product as defined in 21 CFR 
part 312 or an investigational device as defined in 21 CFR part 812.   
 
5 In this guidance, the terms investigation, trial, study, and research are used interchangeably and refer to clinical 
investigations regulated by FDA under 21 CFR parts 50 and 56 and to human subjects research subject to regulation 
by HHS under 45 CFR part 46, as applicable, unless otherwise noted. 
 
6 See FDAs notice of proposed rulemaking Protection of Human Subjects and Institutional Review Boards (87 
FR 58733, September 28, 2022), available at https://www.federalregister.gov/documents/2022/09/28/2022-
21088/protection-of-human-subjects-and-institutional-review-boards.  As stated in the preamble, FDA intends to 
exercise enforcement discretion with respect to the proposed revisions to 21 CFR 50.20(d) through (e), 50.25(a)(9) 
and (b)(7) through (9), and 50.27(b)(2) for FDA-regulated studies that are ongoing when the proposed new 
requirements would become effective.  In the event the proposed rule is not finalized as proposed, FDA intends to 
address any differences in future guidance. 
 
7 In this guidance, the phrase revised Common Rule refers to the final rule (82 FR 7149, January 19, 2017) codified 
in 45 CFR part 46, subpart A.  It is also referred to as the 2018 Requirements.  The term harmonize as used in 
 
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52  better protect human subjects involved in research, while facilitating research and reducing 
53  burden, delay, and ambiguity for the regulated community.8  Prior to the most recent revisions to 
54  the Common Rule, FDAs regulations were largely consistent with the requirements in the 
55  Common Rule, with a few exceptions generally arising from differences in FDAs mission or 
56  statutory authority.   
57   
58  Section 3023 of the Cures Act9 directs the Secretary of HHS to harmonize differences between 
59  HHSs and FDAs human subject protection regulations to the extent practicable and consistent 
60  with other statutory provisions.  FDA has issued a notice of proposed rulemaking (the proposed 
61  rule) proposing to amend 21 CFR parts 50 and 5610 in accordance with the harmonization 
62  requirement in the Cures Act.   
63   
64   
65  III.  KEY INFORMATION SECTION  
66   
67  The revised Common Rule requires consent information to begin with a concise and focused 
68  presentation of the key information that is most likely to assist a prospective subject or legally 
69  authorized representative in understanding the reasons why one might or might not want to 
70  participate in the research (45 CFR 46.116(a)(5)(i)).  FDAs proposed regulations would add 
71  identical language to 21 CFR 50.20(e)(1).   
72   
73  The presentation of key information at the beginning of the consent process can help facilitate 
74  discussions between a prospective subject and an investigator about whether the prospective 
75  subject should participate in the trial.  This information also may be useful to enrolled subjects as 
76  a resource and to facilitate any further discussions with investigators.  We recommend that the 
77  key information section of a consent document11 be relatively short (e.g., generally no more than 
78  a few pages).  A sample key information section of a consent form for a hypothetical clinical trial 
79  is included in the appendix of this guidance.  The format of the sample is based, in part, on 
80  research regarding how the presentation of information may affect consumers understanding of 
 
FDAs proposed rule and in this guidance means harmonize to the extent practicable and consistent with other 
statutory provisions, consistent with section 3023 of the 21st Century Cures Act (Cures Act) (Public Law 114-255).  
Some HHS-supported or -conducted research is not subject to the revised Common Rule per 45 CFR 46.101(l)(3) 
and is not required to address the provisions of the revised Common Rule addressed in this guidance.   
 
8 82 FR 7149 (January 19, 2017). 
 
9 Public Law 114-255. 
 
10 See footnote 6.  FDA previously has indicated in guidance that the provisions in the revised Common Rule related 
to the content, organization, and presentation of information included in the consent form and process are not 
inconsistent with FDAs current policies and guidances.  See the guidance for sponsors, investigators, and 
institutional review boards Impact of Certain Provisions of the Revised Common Rule on FDA-Regulated Clinical 
Investigations (October 2018).  We update guidances periodically.  For the most recent version of a guidance, check 
the FDA guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents.    
 
11 In this guidance, the terms informed consent form and informed consent document are used interchangeably.  
 
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81  information found in labeling for prescription drugs.12  Our recommendations in this guidance 
82  are not requirements, but are intended to provide considerations for how to present key 
83  information to prospective subjects. 
84   
85  For studies using a short form written consent in conjunction with an oral presentation of 
86  informed consent, the revised Common Rule at 45 CFR 46.117(b)(2) requires, and FDAs 
87  regulation at 21 CFR 50.27(b)(2) (if the rule is finalized as proposed) would require, that the key 
88  information be presented to a prospective subject or their legally authorized representative at the 
89  beginning of the informed consent process, before other information.  Additionally, consent 
90  documents developed for FDA-regulated clinical investigations allowed to proceed under 21 
91  CFR 50.24 (Exception From Informed Consent Requirements for Emergency Research) would 
92  also be required to begin with a key information section.13  Similarly, consent documents 
93  developed for expanded access use of an investigational drug would be required to begin with a 
94  key information section (21 CFR 312.305(c)(4)).   
95   
96  A.  Flexible Approaches to Providing Key Information  
97   
98  There are multiple strategies for providing key information to prospective research subjects that 
99  would be consistent with the provisions of the revised Common Rule and FDAs proposed rule.  
100  Interested parties may consider developing an approach that encompasses principles from a 
101  variety of sources for the key information section, depending on the distinctive attributes and 
102  design of the study, the prospective subject population, the condition being examined, and other 
103  relevant factors.  We encourage interested parties to develop innovative ways and utilize 
104  available technologies to provide key information that will help prospective subjects better 
105  understand the reasons why one might or might not want to participate in the research.  
106  Interested parties could consider developing alternate ways to present key information that would 
107  facilitate understanding by prospective subjects by, for example, consulting in advance with 
108  patient advocacy groups or prospective subjects about their views on key information.  The key 
109  information section could also be presented using alternative media, such as illustrations, video, 
110  and electronic tablets, to meet the goals of improving clarity and increasing prospective subjects 
111  understanding of consent information.   
112   
 
12 Boudewyns, V, AC ODonoghue, B Kelly, SL West, O Oguntimein, CM Bann, and LA McCormack, 2015, 
Influence of Patient Medication Information Format on Comprehension and Application of Medication Information:  
A Randomized, Controlled Experiment, Patient Educ Couns, 98(12):15921599, doi: 10.1016/j.pec.2015.07.003.  
 
13 Proposed 21 CFR 50.24(a)(6) (87 FR 58733 at 58749, September 28, 2022) would require an IRB to approve a 
consent document that meets the requirements of part 50 (including the key information provision) as a condition of 
authorizing an exception from informed consent requirements.  See also the guidance for institutional review boards, 
clinical investigators, and sponsors Exception From Informed Consent Requirements for Emergency Research (April 
2013).  For research that is not FDA-regulated and is carried out under OHRPs Emergency Research Consent 
Waiver provisions (61 FR 51531-51533, October 2, 1996) for research where obtaining informed consent from 
subjects or their legally authorized representatives is not feasible, there is no key information requirement.  Where 
consent is feasible, the consent process and documents must satisfy the key information requirement. 
 
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113  B.  Identifying Key Information About Basic and Additional Elements of 
114  Informed Consent 
115   
116  We recommend that the key information section of the consent form begin with an introductory 
117  statement to frame the key information included in the consent form and to guide prospective 
118  subjects when reading the entire document.  We do not recommend that the key information 
119  section of the consent form necessarily include each element of informed consent contained in 45 
120  CFR 46.116(b) and (c) or in 21 CFR 50.25(a) and (b), including the proposed revisions to that 
121  section.14   
122   
123  One approach to developing the content of the key information section is for prospective subjects 
124  and other interested parties to advise on which basic and additional elements of informed consent 
125  may be considered key from the perspective of prospective subjects for a particular study.  We 
126  recommend that the most important elements for a particular study be included at the beginning 
127  of the key information section. 
128   
129  Which basic and additional consent elements should be included in the key information section 
130  may vary based on factors such as the study attributes and its design; the condition(s), 
131  behavior(s), or outcome(s) being examined; and the prospective subject population.  Basic and 
132  additional elements (or parts of such elements) of informed consent that are not addressed (or not 
133  fully addressed) in the key information section would need to be included elsewhere in the 
134  consent form as required (21 CFR 50.25(a) and (b) and 45 CFR 46.116(b) and (c)).   
135   
136  If appropriate, the elements of informed consent that are addressed in the key information section 
137  can also be repeated in other parts of the consent form.  For instance, information about the most 
138  important reasonably foreseeable risks (e.g., most serious and/or most common adverse events) 
139  could be addressed in the key information section and could also be repeated with 
140  comprehensive risk information later in the consent form.  Appropriate repetition of key 
141  information, particularly for longer and more-complex consent forms, can help clarify concepts 
142  and ensure that the entire consent form remains understandable to prospective subjects.  We 
143  suggest using page numbers (or hyperlinks for electronic consent forms) to cross-reference 
144  information from the key information section to other sections of the consent form.15  When the 
145  key information section encompasses all information for a required consent element (21 CFR 
146  50.25(a) and (b) and 45 CFR 46.116(b) and (c)), further discussion regarding that element may 
147  not be needed in the remainder of the consent form.     
148   
149  Certain studies, such as those involving no more than minimal risk, may have relatively brief 
150  consent forms.  In such cases, the key information section could constitute the majority of or 
 
14 For a full discussion of how to address the elements of informed consent during the informed consent process, see 
the FDA guidance for IRBs, clinical investigators, and sponsors Informed Consent (August 2023). 
 
15 The terms form and document are not intended to discourage the use of electronic media and other innovative 
approaches to improving the consent form and process.  For more information on electronic informed consent, see 
the FDA and OHRP joint guidance for institutional review boards, investigators, and sponsors Use of Electronic 
Informed Consent:  Questions and Answers (December 2016).   
 
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151  even the entire consent document.  This approach may be acceptable as long as the entire consent 
152  document provides sufficient information to help prospective subjects make an informed 
153  decision about participation and the document includes all of the required elements of informed 
154  consent described in 21 CFR 50.25(a) and (b) and 45 CFR 46.116(b) and (c).  If the entire 
155  consent form is the key information section, it does not need to be labeled key information. 
156   
157  Our recommendations on how to address basic and additional elements of informed consent in 
158  the key information section are discussed in the topics that follow.  These specific topics were 
159  selected because, in our view, these topics are likely to be considered key information for FDA-
160  regulated clinical investigations and HHS-supported or -conducted nonexempt human subjects 
161  research.  Some elements of informed consent, such as information regarding confidentiality of 
162  subject records under 21 CFR 50.25(a)(5) and 45 CFR 46.116(b)(5), are not addressed in this 
163  guidance, although they may be considered key information for some study designs.   
164   
165  The following topics, including the sample approach in the appendix, are intended to provide 
166  suggestions that we believe can help interested parties conducting research present key 
167  information in a concise and focused way that facilitates comprehension.16   
168   
169  1.  Voluntary Participation and Right to Discontinue Participation17 
170   
171  A statement that consent for research is being sought and that participation is voluntary is a 
172  required element of informed consent, and we recommend that this element be included as key 
173  information.  We recommend including a statement as part of key information that a prospective 
174  subjects decision not to participate in the study or to discontinue participation at any time will 
175  involve no penalty or loss of benefits to which the prospective subject is otherwise entitled.  In 
176  some circumstances, interested parties may consider including a statement that assures 
177  prospective subjects that any decision not to participate in or to withdraw their consent from a 
178  study will not adversely affect their relationship(s) with or medical care received from health 
179  care providers.   
180   
181  2.  Purpose of the Research, Expected Duration, and Procedures To Be Followed18 
182   
183  The key information section should convey information that is most likely to provide prospective 
184  subjects with a clear understanding of the purpose of the study and relevant details of the 
185  protocol (e.g., explaining in language understandable to prospective subjects that the study 
186  design is a randomized investigation with a placebo component).  This approach to key 
187  information may include a simple description of why the research is being conducted and why 
188  the prospective subject is being asked to participate (e.g., due to the subjects diagnosis, the stage 
 
16 See, e.g., Freer, Y, N McIntosh, S Teunisse, KJS Anand, and EM Boyle, 2009, More Information, Less 
Understanding:  A Randomized Study on Consent Issues in Neonatal Research, Pediatrics, 123(5):1301, doi: 
10.1542/peds.2007-3860.  
 
17 21 CFR 50.25(a)(8) and 45 CFR 46.116(b)(8). 
 
18 21 CFR 50.25(a)(1) and 45 CFR 46.116(b)(1). 
 
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189  or status of their health condition, their lack of response to previous treatments, or other factors, 
190  such as inclusion of prospective subjects from different racial groups, ethnicities, gender 
191  identities, or socioeconomic status).  The information should be explained in a way that promotes 
192  understanding of why a person might want or not want to participate.   
193   
194  Given the variability in the study design, the design details that are presented as key information 
195  will also vary.  In many cases, key details of the design would include (1) the expected duration 
196  of the prospective subjects participation, (2) a high-level description of the major procedures 
197  involved, (3) a brief description of any investigational medical product and its marketing 
198  authorization status, and (4) identification of any experimental procedures, which for HHS-
199  regulated research could include research procedures outside of a clinical research context (e.g., 
200  educational research).19  It could be helpful to also include a discussion emphasizing the number 
201  of visits and time duration per visit so that prospective subjects understand the total time 
202  commitment involved with participating in the study.   
203   
204  When the key information section presents details about investigational medical products or  
205  other investigational interventions, interested parties should consider including information on 
206  whether the study design will include a placebo or whether a sham procedure (e.g., a procedure 
207  with a non-working device to blind the study design to avoid biasing results) will be used, how 
208  subjects will be assigned to a particular regimen (e.g., randomization), and what treatment or 
209  intervention options are available following the study (if any).  Interested parties should also 
210  consider providing information on how an investigational medical product and/or participation in 
211  the study is similar to or different from the care the prospective subject would receive if not 
212  enrolled in the study.   
213   
214  3.  Reasonably Foreseeable Risks and Discomforts20 
215   
216  The discussion of risks and discomforts is generally among one of the most important and 
217  complex required elements of informed consent, and we recommend that this topic be addressed 
218  in the key information section.  We recommend providing information about the most common 
219  and serious risks and discomforts in the key information section to inform a prospective subjects 
220  decision about participation.21  Key information about risks and discomforts of research 
221  participation should be included on the first page of the key information section, if possible.  If 
222  the key information section does not include all risk-related information, the key information 
223  section should note that fact and include a page cross-reference (or hyperlink for electronic 
224  documents) that directs prospective subjects to the appropriate section of the consent form where 
225  complete information is located.   
 
19 21 CFR 50.25(a)(1) and 45 CFR 46.116(b)(1).  For FDA-regulated clinical investigations, see the FDA guidance 
for IRBs, clinical investigators, and sponsors Informed Consent. 
 
20 21 CFR 50.25(a)(2) and 45 CFR 46.116(b)(2).    
 
21 See, e.g., the Informed Consent Discussion Tool in Lentz, J, M Kennett, J Perlmutter, and A Forrest, 2016, Paving 
the Way to a More Effective Informed Consent Process:  Recommendations from the Clinical Trials Transformation 
Initiative, Contemp Clin Trials, 49:6569, p. 67, doi: 10.1016/j.cct.2016.06.005.  
 
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226   
227  To help prospective subjects assess risks, interested parties should consider prioritizing key risks 
228  from any investigational medical products, research procedures, or other aspects of the study, at 
229  the beginning of the information about risks.  It may be appropriate in the key information 
230  section to present only the most important risks or discomforts based on frequency or magnitude, 
231  rather than listing all reasonably foreseeable risks.22  In clinical studies involving investigational 
232  medical products, the possibility that the product may present unknown risks to prospective 
233  subjects should generally be included as key information.  Information about any potential risks 
234  should be explained in detail when possible, including, as applicable, the possibility that 
235  participation may not improve or could exacerbate a prospective subjects condition. 
236   
237  We recommend that interested parties clearly delineate between risks and discomforts associated 
238  with an investigational medical product or other investigational procedures (e.g., educational or 
239  behavioral health interventions) and the risks and discomforts associated with other research 
240  interventions or procedures (e.g., additional imaging studies that would not ordinarily be part of 
241  clinical care).  Also, the degree to which the risks and potential benefits in the study are likely to 
242  differ from the risks and benefits of clinical care should be included as key information when 
243  appropriate.   
244   
245  In some cases, the key information section may include actions that will be taken to monitor and 
246  mitigate risks, such as planned safety monitoring, dose adjustments, or discontinuation of a 
247  subjects participation in the research.   
248   
249  4.  Reasonably Expected Benefits23 
250   
251  Any reasonably expected benefits of participating in research, either to prospective subjects or 
252  others, are likely to be considered key information and could be a major determinant of whether 
253  a prospective subject decides to participate in a study.  If there is no potential for direct benefit to 
254  the prospective subject, this point should be clearly stated.  In general, for clinical research, it is 
255  important that prospective subjects understand that research is not the same as clinical care and 
256  that there may be considerable uncertainty about any potential benefits.24  Details about any 
257  potential benefits of participation in a study should be presented in a manner that does not 
258  convey an inappropriate or overly optimistic representation of the facts.  Potential benefits 
259  should be explained in terms of any direct impact to the prospective subject, in addition to the 
 
22 See Office for Human Research Protections, Attachment C  New Key Information Informed Consent 
Requirements:  SACHRP Commentary on the New Key Information Informed Consent Requirements, October 
17, 2018, available at https://www.hhs.gov/ohrp/sachrp-committee/recommendations/attachment-c-november-13-
2018/index.html.  The recommendations in this draft guidance concerning reasonably foreseeable risks in key 
information are consistent with SACHRPs recommended approaches.   
 
23 45 CFR 46.116(b)(3) and proposed 21 CFR 50.25(a)(3), 87 FR 58733 at 58749 (September 28, 2022).   
 
24 The assumption of research subjects that decisions about their care are being made solely with their benefit in 
mind is termed therapeutic misconception.  See Appelbaum, PS, LH Roth, and C Lidz, The Therapeutic 
Misconception:  Informed Consent in Psychiatric Research, International Journal of Law and Psychiatry, 1982, 
5:319329.   
 
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260  anticipated societal benefit of the research.  Any reasonably expected benefits of research 
261  participation should also be described in simple and straightforward terms.  When appropriate, 
262  the description of the potential benefits should include an explanation of any potential impact on 
263  a prospective subjects health condition or illness.  For example, if a clinical trial is being 
264  conducted to assess whether an investigational medical product may reduce tumor size, the key 
265  information section should indicate that it is unknown whether the investigational medical 
266  product will result in a change in tumor size and that if there is a change, it is not known if that 
267  change would affect the prospective subjects quality or length of life.    
268   
269  When evaluating potential benefits for inclusion in the key information section, we recommend 
270  that interested parties consider only those benefits that may result from the research (as 
271  distinguished from benefits of therapies or other interventions outside of a research setting (e.g., 
272  some behavioral interventions) that prospective subjects would receive even if not participating 
273  in research). 
274   
275  5.  Appropriate Alternative Procedures25  
276   
277  In many circumstances, key information should include a clear and concise description of 
278  alternative procedures or courses of treatment, if any, that might be appropriate for the 
279  prospective subject.  For clinical studies, consider first informing prospective subjects about care 
280  they would likely receive if not involved in the study and then providing them with information 
281  to help them understand how the care they would receive in the study differs.  The emphasis 
282  should be on increasing awareness of alternatives because the choice between available 
283  alternatives is expected to vary based on individual values and preferences.   
284   
285  When conveying appropriate alternative procedures or courses of treatment, we recommend 
286  providing a description of any reasonably foreseeable risks or discomforts and potential benefits 
287  associated with these alternatives.  However, a lengthy and detailed description of the risks and 
288  benefits of all alternatives may not be appropriate to include in the key information section 
289  because such information is likely to vary based on a prospective subjects health condition and 
290  past treatment experience as well as the type of study.  All of this information need not appear in 
   
291  the key information section but should be included in the remainder of the consent document and
292  as part of the discussion during the consent process.   
293   
294  6.  Compensation and Medical Treatments for Research-Related Injuries26 
295   
296  For research involving more than minimal risk, we recommend addressing as key information 
297  details related to any medical treatments and compensation available to prospective subjects if 
298  injury occurs as a result of participation.  Including this information as part of the key 
 
25 21 CFR 50.25(a)(4) and 45 CFR 46.116(b)(4).  
 
26 21 CFR 50.25(a)(6) and 45 CFR 46.116(b)(6).   
 
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299  information may be especially important when there are no plans to compensate prospective 
300  subjects for the costs related to the treatment of research-related injuries.27   
301   
302  7.  Costs Related to Subject Participation28  
303   
304  We recommend that interested parties consider whether the key information section should also 
305  address costs the prospective subject may incur when participating in a study.  If the sponsor or 
306  investigator intends to charge for the cost of tests, procedures, products, and/or interventions 
307  (including interventions outside of a clinical setting) used during the study, information about 
308  costs that may be incurred by a prospective subject or whether the prospective subjects health 
309  insurance could be charged (along with information on how to determine whether health 
310  insurance will cover costs) should be included in the key information section.  The key 
311  information section could also inform prospective subjects about whether they will be 
312  reimbursed for study-related expenses (e.g., mileage, parking, airfare, lodging, childcare) 
313  because such information may influence a prospective subjects decision to participate.  
314  Similarly, incentives to encourage participation, as well as payments for a prospective subjects 
315  time, inconvenience, and/or discomfort, may be appropriate to include as key information.  
316   
317  C.  Supplemental Information That Could Be Included Within Key Information 
318   
319  While not required, supplemental information beyond the basic and additional consent elements 
320  may be included in the key information section when it is likely to be important to the 
321  prospective subjects decision about research participation.  For example, an investigator 
322  conducting a study that could involve risks to others not participating in research (e.g., 
323  radioactive interventions, potential shedding of a virus in gene therapy studies) may want to 
324  highlight in the key information section the potential risks to these third parties.   
325   
326  Identifying information beyond the basic and additional elements of informed consent that an 
327  investigator might want to include with the key information can be complex.  The Secretarys 
328  Advisory Committee on Human Research Protections (SACHRP)29 has provided 
329  recommendations on approaches to providing key information consistent with the provision 
330  included in the revised Common Rule.30  For example, SACHRP addresses several approaches, 
331  including preparing the key information section from a prospective subjects perspective by 
 
27 For ways to address compensation, medical treatments, and information for research-related injuries, see the FDA 
guidance for IRBs, clinical investigators, and sponsors Informed Consent.  
 
28 21 CFR 50.25(b)(3) and 45 CFR 46.116(c)(3).   
 
29 See footnote 22. 
 
30 Ibid.  See also 45 CFR 46.116(a)(5)(i). 
 
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332  keeping certain questions about the research in mind.  The following list of questions is 
333  consistent with, but not limited to, SACHRPs recommendations:31   
334   
335  (1) What aspects of research participation or this particular study are likely to be unfamiliar 
336  to a prospective subject, to diverge from their expectations, or to require special 
337  attention? 
338  (2) What information about prospective subjects is being collected as part of the research? 
339  (3) What are the plans to share and protect data that may be of concern to a prospective 
340  subject? 
341  (4) What impact will participating in this research have on a prospective subject outside of 
342  the research?  For example, will it reduce options for standard treatments, prevent 
343  prospective subjects from accessing future care or from participating in other studies, or 
344  impact personal activities such as driving or sun exposure? 
345  (5) How will a prospective subjects experience in this study differ from treatment outside of 
346  the study? 
347  (6) How is this research novel? 
348  (7) What investigators conflict of interest (if any) may be of interest to prospective subjects? 
349  (8) How can prospective subjects access any investigational medical products or other 
350  interventions examined in the study following completion of the study?  
351  The answers to these and similar questions can be used to help identify information that could be 
352  appropriate to include with the key information for a given study.  We note that this list is not 
353  exhaustive and should not be used as a checklist.   
354   
355  D.  Example of Key Information Section 
356   
357  The appendix to this guidance presents one example of an approach to key information that may 
358  be considered by interested parties when developing a key information section and may be 
359  considered by IRBs when reviewing consent forms.  The language and formatting used are 
360  offered as suggestions only, and other language and formatting may be used where appropriate.  
361  Depending on the study, it may be appropriate for the key information section to include other 
362  informed consent elements from those selected for the example. 
363   
364   
 
31 See appendix I in the Office for Human Research Protections, Attachment C  New Key Information Informed 
Consent Requirements:  SACHRP Commentary on the New Key Information Informed Consent Requirements, 
October 17, 2018, available at https://www.hhs.gov/ohrp/sachrp-committee/recommendations/attachment-c-
november-13-2018/index.html. 
 
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365  IV.   FACILITATING UNDERSTANDING  
366    
367  The revised Common Rule at 45 CFR 46.116(a)(5)(ii) requires that informed consent as a 
368  whole must present information in sufficient detail relating to the research and be organized and 
369  presented in a way that does not merely provide lists of isolated facts, but rather facilitates the 
370  prospective subjects or legally authorized representatives understanding of the reasons why one 
371  might or might not want to participate.  This provision applies to the consent document as a 
372  whole, and the principles are also expected to be applicable to any presentation of consent 
373  information (e.g., written, oral, or electronic).32  FDAs proposed revisions to its regulations at 
374  21 CFR 50.20(e)(2) would also include this requirement.33  Our recommendations on how 
375  consent forms can be organized and presented in a way to facilitate understanding are included in 
376  the following sections.   
377   
378  A.  Using Bubbles for the Key Information Section  
379   
380  To help present key information in a simple, concise format, we recommend that interested 
381  parties consider organizing information within a defined border (e.g., rounded boxes creating a 
382  discrete unit of information), referred to here as bubbles, or another format that makes the 
383  content easy to read and understand.  (See the appendix to this guidance for an example of the 
384  bubble format for the key information section.)  Discrete bubbles addressing separate topics, 
385  such as the purpose of the research, potential risks, or alternative therapies, may facilitate a 
386  prospective subjects understanding of the information.34   
387   
388  Research has explored consumers comprehension of alternative versions of prescription drug 
389  labeling information to assess whether certain formats improved comprehension.35  The research 
390  found that consumers had better comprehension when information was provided in a simple 
391  format, with information organized or grouped together within a defined border (e.g., rounded 
392  boxes creating a discrete unit of information that can be thought of as a bubble).36   
393   
394  In addition to using the bubble format or a similar approach for the key information section, 
395  other helpful approaches to formatting and organization could be used, including formatting text 
396  into two columns, using bullet points to simplify long explanations, and including ample white 
 
32 See the FDA and OHRP joint guidance for IRBs, investigators, and sponsors Use of Electronic Informed Consent:  
Questions and Answers. 
 
33 Proposed 21 CFR 50.20(e)(2) (87 FR 58733 at 58749, September 28, 2022). 
 
34 See footnote 12.   
 
35 Ibid.  
 
36 Ibid. (See page 1597 in Boudewyns et al. (footnote 12)).  Note that this article compared three formats, including 
a bubble format in which rounded boxes were aligned in two vertical columns and a format used for over-the-
counter (OTC) medications that organized information into boxes that ran the width of the page.  A third approach 
with paragraphs followed the MedGuide format and was used as a control.   
 
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397  space or empty space around discrete bubbles.  Such formatting approaches may make 
398  documents easier to read.37   
399   
400  B.  Organization and Presentation of the Entire Consent Form  
401   
402  The revised Common Rule at 45 CFR 46.116(a)(5)(ii) requires, and 21 CFR 50.20(e)(2) of 
403  FDAs proposed rule would also require, that consent information be presented in a way that 
404  facilitates the understanding of prospective subjects, and, like the key information provision, 
405  could also be addressed in multiple ways.  We recommend following plain language principles 
406  for the entire consent form.38  Plain language principles generally involve a combination of text-
407  based and visual approaches (e.g., pictures and diagrams), including organizing information with 
408  the most important points first, breaking complex information into understandable groups, using 
409  simple language, and defining technical terms.39  The use of bubbles beyond the key information 
410  section may not be feasible.  However, we suggest that interested parties consider using other 
411  formatting suggestions discussed in section IV.A of this guidance (e.g., bulleted lists, two-
412  column format, white space), as appropriate, for the entire consent form.   
413   
414  1.  Providing Content in Sufficient Detail  
415   
416  The revised Common Rule at 45 CFR 46.116(a)(5)(ii) requires, and 21 CFR 50.20(e)(2) of 
417  FDAs proposed rule would also require, that the consent present information in sufficient detail 
418  relating to the research.  This provision applies to information that is required to be included in 
419  informed consent.  Sufficient detail about research information may be contained within a key 
420  information section or elsewhere in the consent form, depending on where it is most appropriate.  
421   
422  2.  Organization 
423   
424  The revised Common Rule at 45 CFR 46.116(a)(5)(ii) requires that informed consent as a whole 
425  be organized and presented in a way that does not merely provide lists of isolated facts, but 
426  rather facilitates the prospective subjects or legally authorized representatives understanding of 
427  the reasons why one might or might not want to participate.  FDAs proposed rule, if finalized 
428  as proposed, would include identical language in 21 CFR 50.20(e)(2).   
429   
430  Thoughtful organization of consent documents can help prospective subjects better understand 
431  the information presented in the entire consent form.  One suggestion would be to use a tiered 
432  approach, particularly for more-complex study designs.40  The first tier would provide the key 
 
37 Ibid.  
 
38 See Hadden, KB, LY Prince, TD Moore, LP James, JR Holland, and CR Trudeau, 2017, Improving Readability of 
Informed Consents for Research at an Academic Medical Institution, J Clin Trans Sci, 361365, doi: 
10.1017/cts.2017.312.  Also see footnote 21.   
 
39 See footnote 12. 
 
40 See footnote 21.   
 
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433  information.  The second tier could be divided into different topics with the remaining consent 
434  elements (or with further details of consent elements partially addressed in the key information 
435  section).  A third tier could address other information that is not required by the regulations or 
436  could provide details of required elements, such as a detailed description of the study design, a 
437  schedule of procedures at each visit, and language about how confidential information may be 
438  handled.  If appropriate for the consent form, the third tier also could include glossaries and 
439  references.  We recommend including a table of contents and page numbers (or hyperlinks for 
440  electronic documents) to cross-reference related topics. 
441   
442  3.  Understandable Language 
443   
444  Information should be presented in plain language and at a level prospective subjects would 
445  likely comprehend; explanations should be included for scientific and medical terms.41  An 
446  assessment of the needs and characteristics of the prospective subject population, including their 
447  age, any relevant medical diagnosis, level of English proficiency, education level, and cognitive 
448  abilities, can be helpful in developing consent information that facilitates understanding.  
449  Information should be provided in the primary language of a prospective subject with limited 
450  English proficiency.42  Although not required, one possible way to evaluate whether the 
451  information is presented in a way that facilitates understanding is to have the information 
452  reviewed by individuals unfamiliar with the research.  This may be particularly helpful for forms 
453  translated into additional languages.  For example, this could include review by patient advocacy 
454  groups or a sample of individuals from the subject population.    
 
41 See Jefford, M, and R Moore, 2008, Improvement of Informed Consent and the Quality of the Consent Form, 
Lancet Oncol, 9(5):485493; p. 489.  Also see footnote 38 and footnote 21. 
 
42 FDA and OHRP strongly encourage stakeholders to ensure that informed consent documents are accessible to 
individuals with limited English proficiency.  To the extent an organization receives Federal financial assistance 
from HHS, the organization must comply with Title VI of the Civil Rights Act of 1964 and its implementing 
regulations.  This guidance provides information to assist IRBs, investigators, and sponsors in complying with 
OHRPs regulation and FDAs proposed regulation, if and when it is finalized, related to the key information section 
of informed consent.  This document does not provide guidance on how to comply with any regulatory obligations 
stemming from a source outside of the statutes FDA and OHRP administer and their respective regulations. 
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455  APPENDIX:  A HYPOTHETICAL CLINICAL TRIAL 
456   
457  Title:  A trial to evaluate the use of product X to treat health condition Y  
458   
459   
460    Key Information You Should Know Before Agreeing to Participate 
461     
462    The key information that follows can help you learn more about this clinical trial.  It can also help you decide 
463    whether or not to take part in the trial.  Please read the entire consent form or have someone read it with 
464    you.  If there is anything that you do not understand, please talk to the trial doctor or team to have your 
465    questions answered before signing the consent form. 
466     
467   
468   
469    Voluntary Participation and Right to Discontinue Participation 
470     
471    We are asking you to consent to participate in this research study.  Your participation is voluntary and should 
472    be based on what is important to you.  It is your choice to participate in this trial.  If you agree to participate, 
473    you may leave at any time without penalty or loss of benefits to which you are otherwise entitled.   
474     
475   
476   
Purpose of the Research  
477   
 
478   
The purpose of the trial is to find out if product X, the product that is being studied, is safe and effective in 
479   
treating adults like you who have health condition Y.  
480   
  
481   
482   
483   
484    Key Reasonably Foreseeable Risks and  Reasonably Expected Benefits (see page #)  
485    Discomforts (see page #)   
486        Prior research suggests product X may 
487     If you take product X, you have a chance of  improve condition Y.  
488    side effects, such as fever or rash.   
489        Researchers are studying product X in 
490     Nausea or vomiting may be related to your  this trial to learn more about whether 
491    health condition and is a rare but serious  product X will improve condition Y.  
492    side effect of product X.  If product X is   
493    suspected to cause these or other    If you are randomly assigned to take 
494    symptoms, product X may be stopped.  product X, product X may improve your 
495    health condition Y.  If you are randomly 
 
496    assigned to take the inactive pill, you will 
 We do not know if product X will help you.  
497    not receive product X and will not benefit 
There is a chance that product X could 
498    directly.   
worsen condition Y.  
499     
500        By participating in this trial, you will help 
501     More information on risks is available in the  researchers learn how product X may help 
502    consent form.  people with condition Y. 
503     
504     
505   
506   
507  ~ MORE ~ 
508   
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509   
510   
511   
Expected Duration and Procedures to Be  Compensation and Medical Treatments for 
512   
Followed (see pages #)  Research-Related Injuries (see page #) 
513   
   
514   
  To learn if product X makes a difference, it   If you experience an injury caused by your 
515   
is important for the trial to include people  participation in this research, the medical 
516   
who will get a placebo (inactive pill).  With  treatment of your injury will be paid for.  
517   
this information, researchers can compare   
518   
the effects of product X or the placebo on   More information on medical treatments for 
519   
your health condition.   research-related injuries is available in the 
520   
  consent form.  
521   
  A computer will assign you randomly, like   
522   
flipping a coin, to a group taking product X 
523   
or to a group taking the inactive pill.  
524   
 
525    Costs Related to Subject Participation (see 
526      You and your doctors cannot choose which  page #) 
527    group you will be assigned to. 
528       You may incur costs by participating in this 
529      This trial will take 6 months and require    trial.  
530    weekly clinic visits (24 visits total), with   
531    each visit expected to take 1 hour.  At each   The sponsor will reimburse you for any 
532    visit, you will have blood drawn and a  travel costs for mileage, parking, and other 
533    procedure to test your blood oxygen  expenses.  
534    content.    
535       In addition, the sponsor will pay you for 
 
536      your time participating in the trial. 
537     
538    Appropriate Alternative Procedures (see 
539    page #) 
540     
541     In this trial, if you are assigned to take the  Additional Information (see page #) 
542    placebo, you cannot take product X.   
543       If trials show that product X is effective in 
544     Before joining the trial, you should talk to  treating your health condition, you may be 
545    your doctor about alternative approved  able to continue to take product X in a related 
546    treatment options for your condition, and  trial. 
whether or not this trial is a good choice for 
547   
you.  
548   
   
549   
 Before agreeing to join, you should review 
550   
information in the rest of the consent form. 
551     
552   
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