Use of Electronic 

Informed Consent 

 
Questions and 

Answers 

 
Guidance for Institutional 

Review Boards, Investigators, 

and Sponsors 

 
 
 
 
   
 
U.S. Department of Health and Human Services 

Office for Human Research Protections (OHRP) 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 
 
Office of Good Clinical Practice (OGCP) 

Center for Biologics Evaluation and Research (CBER)
  
Center for Devices and Radiological Health (CDRH)
  
 
December 2016 

Procedural
 
   
Use of Electronic Informed Consent  

Questions and Answers
  
Guidance for Institutional Review Boards, Investigators, and Sponsors 
 
 
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and/or 

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http://www.hhs.gov/ohrp/newsroom/rfc/index.html 

 
U.S. Department of  Health and Human Services 

Office for Human Research Protections (OHRP) 

Food and  Drug Administration 
 
Center for Drug Evaluation and Research (CDER) 
 
Office of Good Clinical  Practice (OGCP) 

Center for Biologics Evaluation and Research (CBER) 
 
Center for Devices and Radiological Health (CDRH) 
 
 
December 2016 

Procedural 
 
  Contains Nonbinding Recommendations 
 
 
 
TABLE OF CONTENTS 
 
 
 
 
I.   INTRODUCTION............................................................................................................. 1
  
II.   BACKGROUND ............................................................................................................... 3
  
III.   INSTITUTING AN ELECTRONIC INFORMED CONSENT PROCESS ................ 4  

QUESTIONS AND ANSWERS................................................................................................... 4 
 
Q1.   How should information in the eIC be presented to the subject? .............................................. 4 
 
Q2.   How and where may the eIC process be conducted? .................................................................. 5
  
Q3.   How and when should questions from subjects be answered? .................................................. 5 
 
Q4.   What steps may be taken to facilitate the subjects understanding of the information being 

presented? ............................................................................................................................................... 6
  
Q5.   What steps may be taken to convey additional information, including significant new 

findings, to the subject during the course of the research?  ................................................................ 6
  
Q6.   How can electronic signatures be used to document eIC?  ......................................................... 7 
 
Q7.   What methods may be used to verify the identity of the subject who will be electronically 

signing an eIC for FDA-regulated clinical investigations? ................................................................. 8
  
Q8.   What special considerations should be given to the use of eIC for pediatric studies? ............. 8
  
Q9.   Should subjects receive a copy of their eIC and have easy access to the materials and 

information presented to them in their eIC?  ....................................................................................... 9
  
Q10.  What steps can be taken to help ensure privacy, security, and confidentiality of the eIC 

information?............................................................................................................................................ 9
  
Q11.  Can HIPAA authorizations for research, which are frequently combined with informed 

consent documents, be obtained electronically? ................................................................................ 10
  
Q12.  What eIC materials should the investigator submit to the IRB? ............................................. 11 
 
Q13.  What are the IRBs responsibilities in the eIC process?  .......................................................... 11 
 
Q14. What eIC documentation does FDA require for submission with applications? ................... 11
  
Q15.  What steps can be taken to ensure the system archives the eIC materials appropriately for 

FDA-regulated clinical investigations?............................................................................................... 12 
 
Q16. What materials or documents will FDA require during an inspection? ................................. 13 
 
  Contains Nonbinding Recommendations 
Use of Electronic Informed Consent  

Questions and Answers 

Guidance for Institutional Review Boards, Investigators, and 

1
 
Sponsors  
 
This guidance represents the current thinking of the Office for Human Research Protections 
(OHRP) and the Food and Drug Administration (FDA) on this topic. It does not establish any 
rights for any person and is not binding on OHRP, FDA, or the public.  You can use an 
alternative approach if it satisfies the requirements of the applicable statutes and regulations.  To 
discuss an alternative approach, contact OHRP or the FDA office responsible for this guidance 
as listed on the title page.  
 
 
 
I.  INTRODUCTION  
 
This guidance has been prepared jointly by the Department of Health and Human Services 
(HHS) Office for Human Research Protections (OHRP) and the Food and Drug Administration 
(FDA). This guidance is intended for institutional review boards (IRBs), investigators, and 
sponsors engaged in or responsible for oversight of human subject research under HHS and/or 
FDA regulations. 
 
This guidance provides recommendations on the use of electronic systems and processes that 
may employ multiple electronic media to obtain informed consent for both HHS-regulated 
human subject research and FDA-regulated clinical investigations of medical products, including 
human drug and biological products, medical devices, and combinations thereof.  FDAs 
requirements for electronic records/electronic signatures, informed consent, and IRBs are set 
forth in 21 CFR parts 11, 50, and 56, respectively. HHS requirements regarding the protection of 
human subjects are set forth in 45 CFR part 46.  The information presented to the subject, 
processes used for obtaining informed consent, and documentation of the electronic informed 
consent (eIC) must meet the requirements of these and other applicable regulations. 
 
If the study is conducted or supported by HHS and involves an FDA-regulated product, the study 
is subject to both 45 CFR part 46 and 21 CFR parts 50 and 56, meaning that both sets of 
regulations must be followed. Where the regulations differ, the regulations that offer the greater 
protection to human subjects should be followed.  Research not subject to 21 CFR parts 50 and 
                                                 
1  This guidance has been prepared by the Office of Medical  Policy in the Center for Drug  Evaluation and Research  
and the Office of Good Clinical Practice in the Office of Medical Products and Tobacco in coordination with the  
Center for Biologics Evaluation Research and the Center for Devices and Radiological Health at the Food and Drug 
Administration.  This  guidance was developed jointly with the Department for Health and Human Services Office 
for Human Research Protections. 
 
  1
  Contains Nonbinding Recommendations 
56 is also not generally subject to 21 CFR part 11 (FDA regulations regarding electronic records 
and electronic signatures).   
 
For the purposes of this guidance, electronic informed consent refers to the use of electronic 
systems and processes that may employ multiple electronic media, including text, graphics, 
audio, video, podcasts, passive and interactive Web sites, biological recognition devices, and 
card readers, to convey information related to the study and to obtain and document informed 
consent.  
 
This guidance clarifies that when implementing an eIC, a variety of approaches may be used to 
fulfill HHS and FDA regulatory requirements for informed consent and IRB review (45 CFR 
part 46 and 21 CFR parts 50 and 56) and FDA regulations for electronic records and electronic 
signatures (21 CFR part 11). 
 
This guidance provides recommendations on procedures that may be followed when using an 
eIC to help:  
 
	   Ensure protection of the rights, safety, and welfare of human subjects 
 
	   Facilitate the subjects comprehension of the information presented during the eIC 
process 
 
	   Ensure that appropriate documentation of consent is obtained when electronic systems 
and processes that may employ multiple electronic media are used to obtain informed 
consent2   
 
	   Ensure the quality and integrity of eIC data3 included in FDA applications and made 
available to FDA during inspections   
 
Although both OHRP and FDA affirm that the informed consent process begins with subject 
recruitment,4 recommendations on using electronic media and processes for subject recruitment 
are outside the scope of this guidance.  
                                                 
2 Investigators are required to prepare and maintain  records as described in  21 CFR  312.62 and 812.140(a).  
Similarly, sponsors are required to maintain records relating to an investigation as described in  21 CFR  312.57 and  
812.140(b).  
 
3 For the purposes of this guidance, eIC data includes the template and site-specific versions of eIC, materials 
submitted to IRBs for review and approval, all amendments  to the template and site-specific eICs, required informed  
consent elements presented to the subject during the eIC process, and the electronic signature of the subject, 
including the date when the subject or the subjects legally authorized representative (LAR) signed the eIC. 
 
4 For additional information on subject recruitment, see the guidance for institutional review boards and clinical 
investigators  Recruiting Study  Subjects  Information Sheet, available at 
http://www.fda.gov/RegulatoryInformation/Guidances/ucm126428.htm. We update guidances periodically.  To 
make sure you have the most recent version of a guidance, check the FDA guidance Web page  at 
www.fda.gov/RegulatoryInformation/Guidances/default.htm. 
 
  2
  Contains Nonbinding Recommendations 
 
In general, OHRP and FDA guidance documents do not establish legally enforceable 
responsibilities. Instead, guidances describe the current thinking on a topic and should be 
viewed only as recommendations, unless specific regulatory or statutory requirements are cited.  
The use of the word should in guidances means that something is suggested or recommended, 
but not required. 
 
To enhance human subject protection and reduce regulatory burden, OHRP and FDA have been 
actively working to harmonize the Agencies regulatory requirements and guidance for human 
subject research.  This guidance document was developed as a part of these efforts.  
 
 
II.  BACKGROUND 
 
The term  informed consent is often mistakenly viewed as synonymous with obtaining a 
handwritten signature from the subject or the subjects legally authorized representative (LAR)5  
on a written informed consent form.  However, obtaining a subjects oral or written informed 
consent is only part of the overall informed consent process.  Informed consent involves 
providing a potential subject with adequate information about the research to allow for an 
informed decision about the subjects voluntary participation in a research study.  Informed 
consent must include a process that facilitates the subjects comprehension of the information 
and allows adequate opportunity for the subject to ask questions and consider whether or not to 
participate (45 CFR 46.116 and 21 CFR 50.20). Furthermore, this process often continues 
beyond obtaining the subjects initial consent at the time of enrollment and may involve 
providing additional information as the research progresses or as the subject or situation 
requires.6  The elements of informed consent for human subjects and the requirements for 
documentation of informed consent are discussed in 45 CFR 46.116 and 46.117 and 21 CFR 
50.25 and 50.27, respectively. 
 
The research community is showing increasing interest in using electronic media to supplement 
or replace paper-based informed consent processes.  An eIC may be used to provide information 
usually contained within the written informed consent document, evaluate the subjects  
comprehension of the information presented, and document the consent of the subject or the 
subjects LAR.  Electronic processes to obtain informed consent may use an interactive interface, 
which may facilitate the subjects ability to retain and comprehend the information.  
Furthermore, these electronic processes may allow for rapid notification to the subjects of any 
amendments pertaining to the informed consent that may affect their willingness to continue to 
participate. Electronic processes may also promote timely entry of any eIC data into a study 
                                                 
5  Legally authorized representative (LAR)  means an individual or judicial or other body authorized under applicable  
law to consent  on behalf of a prospective subject to the subjects participation in the procedure(s) involved in the 
research  (45 CFR 46.102(c) and 21 CFR 50.3(l)). 
 
6 See also the draft guidance for IRBs, clinical investigators, and sponsors Informed Consent Information Sheet, 
available at http://www.fda.gov/RegulatoryInformation/Guidances/ucm404975.htm.   When final, this guidance will 
represent FDAs current thinking  on  its informed consent regulations. 
  3
  Contains Nonbinding Recommendations 
database and allow for timely collection of the subjects informed consent data from remote 
locations.  
 
 
III.   INSTITUTING AN ELECTRONIC INFORMED CONSENT PROCESS 
 
QUESTIONS AND ANSWERS  
 
Q1.  How should information in the eIC be presented to the subject?  
 
The eIC must contain all elements of informed consent required by HHS and/or FDA regulations 
(45 CFR 46.116 and 21 CFR 50.25). The information must be in language understandable to the 
potential subject or the subjects LAR and conveyed in a manner that minimizes the possibility 
of coercion or undue influence regarding the subjects decision to participate in a study (45 CFR 
46.116 and 21 CFR 50.20).7   Understandable means that the information presented to subjects is 
in a language and at a level the subject can comprehend, including an explanation of scientific 
and medical terms.  To ensure that the eIC is presented appropriately and that subjects will have 
enough time to dedicate to the eIC process, the subjects should be informed of approximately 
how long the process will take and what information will be presented to them. 
 
Any eIC should be easy to navigate, allowing the user to proceed forward or backward within the 
system and to stop and continue at a later time.  Hyperlinks may be provided where helpful.  The 
eIC may also incorporate electronic strategies to encourage subjects to access all of the consent 
material before documenting their consent. 
 
Electronic informed consent may be used to either supplement or replace paper-based informed 
consent processes in order to best address the subjects needs throughout the course of the study.  
For example, some subjects may prefer one method over another.  Other subjects may have 
difficulty navigating or using electronic systems because of, for example, a lack of familiarity 
with electronic systems, poor eyesight, or impaired motor skills.  In such cases, the eIC process 
may not be appropriate for these subjects.8  Therefore, subjects should have the option to use 
paper-based or electronic informed consent methods completely or partially throughout the 
informed consent process.  Moreover, in some circumstances, it may be appropriate for 
investigators or study personnel to assist subjects in using the eIC technology.  For example, 
study personnel may help the subject navigate the consent by clicking on links for the subject. 
 
 
                                                 
7 For additional information, see section III.A.2  of the draft guidance for IRBs, clinical investigators, and sponsors 
Informed Consent Information  Sheet, available at 
http://www.fda.gov/RegulatoryInformation/Guidances/ucm404975.htm.    
 
8 For additional information, see section V.D of the draft  guidance for IRBs, clinical investigators, and sponsors 
Informed Consent Information  Sheet, available at 
http://www.fda.gov/RegulatoryInformation/Guidances/ucm404975.htm.  
  4
  Contains Nonbinding Recommendations 
Q2.  How and where may the eIC process be conducted? 
 
The investigator is responsible for ensuring that legally effective informed consent is obtained 
before that subject takes part in the study (see 45 CFR 46.116 and 21 CFR 50.20, 312.60, and 
812.100). If the investigator delegates this responsibility, the responsibility should be delegated 
to an individual qualified by education, training, and experience to perform this activity.9   
Whether part or all of the eIC process takes place on-site or remotely, the responsibility for 
obtaining informed consent remains with the investigator and the study personnel to which 
responsibility has been appropriately delegated.  The investigator cannot delegate authority to 
obtain informed consent to the electronic system. 
 
The consent process may take place at the study site when both the investigator and subject are at 
the same location, or it may take place remotely (e.g., at the subjects home or another 
convenient venue) where the subject reviews the consent document in the absence of the 
investigator.  The eIC materials may be provided for both on-site and remote access.  
 
If the entire process takes place at the study site, the study personnel can personally verify the 
subjects identification, review the eIC content, answer questions about the material, have 
follow-up discussions, and witness the signing of the eIC. 
 
If any or all of the consent process takes place remotely and is not personally witnessed by study 
personnel, the electronic system must include a method to ensure that the person electronically 
signing the informed consent is the subject who will be participating in the research study or is 
the subjects LAR (see 21 CFR 11.100(b)). Examples of various methods that could be used 
include verification of a state-issued identification or other identifying documents or use of 
personal questions, biometric methods, or visual methods (see Q7).    
 
For Research Under the Sole Authority of 45 CFR Part 46 
 
OHRP recognizes that it may not be possible or necessary for all types of research covered by 45 
CFR part 46 to verify that the person signing the informed consent is the subject or the subjects 
LAR who will be participating in the research study.  OHRP encourages investigators to apply a 
risk-based approach to the consideration of subject identity.  For example, social behavioral 
minimal risk research will not typically warrant such verification.  In addition, informed consent 
may be waived for minimal risk research meeting the requirements at 45 CFR 46.116(d).  
 
 
Q3.  How and when should questions from subjects be answered? 
 
Whether the eIC is obtained from the subject on-site or remotely, the eIC process must provide 
sufficient opportunity for the subject to consider whether to participate (see 45 CFR 46.116 and 
21 CFR 50.20). The investigator should have methods in place to ensure that the eIC process 
allows subjects the opportunity to consider whether or not to participate and to ask questions 
                                                 
9 See the guidance for industry Investigator Responsibilities  Protecting the Rights, Safety, and Welfare of Study 
Subjects (available at http://www.fda.gov/regulatoryinformation/guidances/ucm122046.htm).  
  5
  Contains Nonbinding Recommendations 
about the study before signing consent as well as at any time during the subjects involvement in 
the research.  This may be accomplished by in-person discussions with study personnel or 
through a combination of electronic messaging, telephone calls, video conferencing, or a live 
chat with a remotely located investigator or study personnel.  When live chat or video 
conferencing is used during the eIC process, investigators and study personnel should remind 
subjects to conduct the eIC discussion in a private location to help ensure privacy and 
confidentiality.   
 
Subjects should be given a description of how and when they will receive answers to their 
questions, and they must be provided information on how to contact an appropriate individual for 
pertinent questions about the research and their rights and whom to contact in the event that they 
sustain a research-related injury (see 45 CFR 46.116(a)(7) and 21 CFR 50.25(a)(7)).  
 
 
Q4. 	 What steps may be taken to facilitate the subjects understanding of the 
information being presented? 
 
To assist the subject in understanding the material, the eIC may use interactive electronic-based 
technology, which may include diagrams, images, graphics, videos, and narration.  The eIC 
should be appropriate for the intended audience, taking into consideration the subjects age, 
language, and comprehension level.   
 
The eIC may contain various methods to help an investigator assess the subjects understanding 
of the information being presented during the eIC process.  For example, the eIC may include 
optional questions at any time during the eIC discussion that can be used to help educate the 
subject about the information presented, as well as assess the subjects understanding of the 
informed consent materials.  Such optional questions and other methods may be used as tools to 
gauge subject comprehension of key study elements and highlight areas where the subject might 
need further explanation and discussion before signing the informed consent to enter the study. 
 
 
Q5. 	 What steps may be taken to convey additional information, including 
significant new findings, to the subject during the course of the research? 
 
When appropriate, the eIC must contain a statement that significant new findings developed 
during the course of the research that may affect to the subjects willingness to continue 
participation will be provided to the subject or the subjects LAR (see 45 CFR 46.116(b)(5)  and 
21 CFR 50.25(b)(5)).  If an update or amendment to an eIC is necessary and could affect the 
subjects willingness to continue participation in the study, the eIC process must provide 
sufficient opportunity for the subject to consider whether to continue participation (see 45 CFR 
46.116 and 21 CFR 50.20). If the eIC is updated or amended, the subject should be given 
sufficient opportunity to ask questions about the amended contents (see Q3).  In such cases, the 
subject or the subjects LAR must sign the amended eIC before the subject continues in the study 
(see 45 CFR 46.117(a) and 21 CFR 50.27).  OHRP and FDA regulations permit the flexibility of  
using electronic and paper informed consent methods independently or in combination 
throughout the course of the study.  Thus, amendments to the eIC do not need to be electronic in 
  6
  Contains Nonbinding Recommendations 
nature and can instead rely on more traditional means, such as paper-based amendments or postal 
mail, for conveying and transmitting the information to the subject (see Q1). 
 
 
Q6.  How can electronic signatures be used to document eIC?  
 
The procedure for eIC may include an electronic method to capture the signature of the subject 
or the subjects LAR. OHRP and FDA regulations permit the use of electronic signatures when 
written informed consent is required.  OHRP permits electronic signatures if such signatures are 
legally valid within the jurisdiction where the research is to be conducted.  
 
For FDA-Regulated Clinical Investigations  
 
FDA regulations found at 21 CFR part 11 set forth the criteria under which FDA considers 
electronic records, electronic signatures, and handwritten signatures executed to electronic 
records to be trustworthy, reliable, and generally equivalent to a handwritten signature executed 
on paper (see 21 CFR 11.1(a)). In order to be considered equivalent to full handwritten 
signatures, electronic signatures must comply with all applicable requirements under 21 CFR 
part 11.10  The electronic system must also capture and record the date that the subject or  
subjects LAR provides consent (see 21 CFR 50.27(a)).   
 
The regulations found at 21 CFR part 11 permit a wide variety of methods to create electronic 
signatures, including using computer-readable ID cards, biometrics,11 digital signatures,12 and 
user name and password combinations.  FDA does not mandate or specify any particular 
methods for electronic signatures, including any particular biometric method upon which an 
electronic signature may be based.   
 
Electronic signatures based on biometrics must be designed to ensure that they cannot be used by 
anyone other than their genuine owners (21 CFR 11.200(b)).  Therefore, suitable biometrics 
should be uniquely identified with the individual and should not change with time.  In addition, 
electronic signatures based upon biometrics are accepted provided they meet the requirements 
found in 21 CFR part 11 (i.e., they must contain pertinent information associated with the 
signing (see 21 CFR 11.50(a)); they are subject to the same controls as electronic records and 
must be included as part of any human readable form of the electronic record (see 21 CFR 
11.50(b)); and they must be linked to their respective electronic records (see 21 CFR 11.70).  
                                                 
10 See 21 CFR part 11.  For additional information,  see the guidance for industry Part 11, Electronic Records; 
Electronic Signatures  Scope and  Application,  available at  
http://www.fda.gov/RegulatoryInformation/Guidances/ucm125067.htm. 
 
11  Biometrics means a method of verifying an  individuals identity based on measurements of the individuals 
physical feature(s) or repeatable action(s)  where those features and/or actions are both  unique to that individual and  
measurable (21 CFR 11.3(b)(3)).   
 
12  Digital signature means an electronic signature based upon cryptographic methods of  originator authentication, 
computed  by using a set of rules and a set of parameters such that the identity of the signer and the integrity of the 
data can be verified (21 CFR 11.3(b)(5)). 
  7
  Contains Nonbinding Recommendations 
IRBs, investigators, and sponsors should consider such issues as how the electronic signature is 
created and whether the informed consent or permission document can be produced in hard copy 
for review by the subject upon request. IRBs, investigators, and sponsors may rely on a 
statement from the vendor of the electronic system used for obtaining the electronic signature 
that describes how the signature is created and that the system meets the relevant requirements 
contained in 21 CFR part 11. 
 
A copy of the informed consent must be provided to the person signing the form (see 21 
CFR 50.27(a)) (see Q9). 
 
 
Q7. 	 What methods may be used to verify the identity of the subject who will be 
electronically signing an eIC for FDA-regulated clinical investigations? 
 
Compliance with the requirements in Part 11 is meant in part to prevent fraudulent use. 
Therefore, the regulations found at 21 CFR part 11 require that an organization verify the 
identity of an individual before it establishes, assigns, certifies, or otherwise sanctions an 
individuals electronic signature or any element of such electronic signature (see 21 CFR 
11.100(b)). 
 
FDA regulations do not specify any particular method for verifying the identity of an individual 
and accepts many different methods.  For example, verifying someones identity can be done by 
using information from some form of official identification, such as a birth certificate, 
government-issued passport, or a drivers license.  In addition, use of security questions to 
confirm an individuals identity can also be considered.  
 
 
Q8. 	 What special considerations should be given to the use of eIC for pediatric 
studies? 
 
The eIC process can be used to obtain assent from pediatric subjects (when required) and 
parental permission from their parent(s) or guardian.  The general requirements for informed 
consent, found in 45 CFR 46.116 and 46.117 and 21 CFR 50.20, 50.25, and 50.27, apply to 
parental permission, in addition to the requirements for permission by parents or guardians and 
for assent by children found at 45 CFR 46.408 and 21 CFR 50.55.13  Therefore, parental 
permission may be obtained and documented using the same eIC procedures as would be used 
for informed consent.  
 
Absent a waiver of the assent requirement (see 45 CFR 46.408(a) and 21 CFR 50.55(d)), or a 
determination that assent is not necessary (see 45 CFR 46.408(a) and 21 CFR 50.55(c)), the IRB 
                                                 
13  We  note that  while  45 CFR  46.408(c) permits a waiver of  parental permission under certain circumstances, 21  
CFR part 50  does not contain such a waiver  provision.  There may, however, be certain circumstances under which 
parental permission is  not  required  by 21 CFR part  50  for research conducted in mature or emancipated minors 
because those minors do not  meet the definition of children  found at 21  CFR 50.3(o).  See 78 FR 12937 at 12945 
and 12946.  
  8
  Contains Nonbinding Recommendations 
must determine that there are adequate provisions for soliciting the assent of children when, in 
the IRBs judgment, the children are capable of providing assent (see 45 CFR 46.408(a) and 21 
CFR 50.55(a)).  When approving an eIC assent process, an IRB should consider whether the 
capability of a child to assent may be affected by the method used to obtain and/or document 
child assent. For example, if assent would otherwise be required, the method used to obtain eIC 
assent should not impede the childs capability to provide assent.  The language and presentation  
of information must be understandable to the child.  In addition, when the IRB determines that 
assent is required, it must also determine whether and how assent must be documented (see 45 
CFR 46.408(e) and 21 CFR 50.55(g)).   
 
For FDA-Regulated Clinical Investigations  
 
Depending on the method of identity verification used to satisfy the regulations in 21 CFR part 
11 for electronic signatures in FDA-regulated clinical investigations, a child may lack the 
documentation necessary to verify their identity for the purposes of preventing fraudulent use of 
electronic signatures (e.g., drivers license) (see Q7).  If so, depending on the clinical 
investigation, it may be reasonable for the parent to initially document the childs assent, which 
can then be verified when the investigator first sees the child.  
 
 
Q9. 	 Should subjects receive a copy of their eIC and have easy access to the 
materials and information presented to them in their eIC?  
 
Yes. HHS and FDA regulations require that the person signing the informed consent (i.e., the 
subject or the subjects LAR or the parents or guardians of subjects who are children) be given a 
copy of the written informed consent form  (45 CFR 46.117(a) and 21 CFR 50.27(a)), unless the 
requirement for documentation of informed consent has been waived under 45 CFR 46.117(c) 
and 21 CFR 56.109(c)). Although FDA regulations do not require that the subjects copy 
include a signature, FDA recommends that a copy of the signed informed consent form that 
includes the date when the eIC was signed be provided to the subject.  
 
The copy provided to the subject can be paper or electronic and may be provided on an 
electronic storage device or via email.  If the copy provided includes one or more hyperlinks to 
information on the Internet, the hyperlinks should be maintained and information should be 
accessible until study completion.  Note that if the eIC uses hyperlinks or other Web sites or 
podcasts to convey information specifically related to the research, the information in these 
hyperlinks should be included in any printed paper copy, if one is provided.  
 
 
Q10. 	 What steps can be taken to help ensure privacy, security, and confidentiality 
of the eIC information? 
 
For FDA-regulated clinical investigations, the electronic system  that supports the eIC must be 
secure with restricted access (see 21 CFR 11.10 and 11.30) and should include methods to ensure 
  9
  Contains Nonbinding Recommendations 
confidentiality regarding the subjects identity, study participation, and personal information 
after informed consent has been obtained.14   
 
If the entity holding the subjects personal information is a covered entity under the Health 
Insurance Portability and Accountability Act of 1996 (HIPAA) (Public Law No. 104-191)15 or 
acting as a business associate of a HIPAA-covered entity, the requirements in the HIPAA 
Privacy, Security, and Breach Notification Rules apply (see 45 CFR parts 160 and 164).  For 
example, the subjects information within an electronic system must be encrypted, unless the 
entity documents why encryption is not reasonable and appropriate in their specific 
circumstances and implements a reasonable and appropriate equivalent measure. 
 
 
Q11. 	 Can HIPAA authorizations for research, which are frequently combined 
with informed consent documents, be obtained electronically?16  
 
Yes. HIPAA authorizations may be obtained electronically, provided that the signature of the 
subject (or the subjects personal representative) is a valid electronic signature under applicable 
laws and regulations.17  The Electronic Signatures in Global and National Commerce Act (E-
Sign Act) (Public Law 106-229) addresses what constitutes a valid electronic signature and 
provides that a signature may not be denied legal effect because it is in electronic form.  
 
The HIPAA Privacy Rule requires that when a covered entity seeks an authorization from a 
subject (or a subjects personal representative), the covered entity must provide the individual 
with a copy of the signed authorization; this requirement also applies where a HIPAA 
authorization is obtained electronically.18   
 
 
                                                 
14 See the Health Insurance Portability and  Accountability Act of 1996 (HIPAA) Security Rule (available at 
http://www.hhs.gov/ocr/privacy/hipaa/understanding/srsummary.html) and see 45 CFR  part  160 and subparts A and  
C of part  164.  
 
15 The HHS Office for Civil Rights (OCR) administers and enforces the HIPAA Privacy Rule, which  protects the 
privacy of individually identifiable health information and establishes an array of individual rights with respect to 
health information; the Security Rule, which  sets national standards for protecting the security of electronic 
protected  health information; and the Breach Notification Rule, which  requires covered entities and business 
associates to provide notification following a breach of unsecured protected  health information.  Additional  
information about the HIPAA Rules is available on  OCRs Web site at:  http://www.hhs.gov/hipaa/. 
 
16 For additional  information, see the guidance for industry  IRB Review of  Stand-Alone HIPAA Authorizations  
Under FDA Regulations (available at http://www.fda.gov/regulatoryinformation/guidances/ucm122046.htm). 
 
17 See the Electronic Signatures in Global and National Commerce Act (E-Sign Act) (Public Law  106-229) and  21  
CFR part 11.  
 
18 See 45 CFR part 160 and subparts A and E of 45 CFR part 164. 
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  Contains Nonbinding Recommendations 
Q12. 	 What eIC materials should the investigator submit to the IRB? 
 
The investigator should submit to the IRB copies of all forms (electronic and paper forms) and 
informational materials, including any videos and Web-based presentations, which the subject 
will receive and view during the eIC process.  The investigator must obtain IRB approval for any 
subsequent modifications to the study-related information, whether electronic or in hard copy 
(see 45 CFR 46.109 and 21 CFR 56.109). OHRP and FDA recommend that an investigator 
discuss plans for using eIC with the IRB before finalizing development of the eIC to ensure that 
the IRB agrees that such a format may be used for the applicable research for obtaining informed 
consent. 
 
 
Q13. 	 What are the IRBs responsibilities in the eIC process? 
 
HHS and FDA regulations require that an IRB review and have authority to approve, require 
modifications in (to secure approval), or disapprove all research activities covered by the 
applicable regulations (see 45 CFR 46.109(a) and 21 CFR 56.109(a)).  A critical part of this 
responsibility is for the IRB to ensure there is an adequate informed consent process that protects 
the rights and welfare of subjects participating in HHS-regulated research and FDA-regulated 
clinical investigations (see 45 CFR 46.109(b) and 21 CFR 56.109(b) and 56.111(a)(4)).  
Therefore, the IRB must review and approve the eIC and any amendments to the eIC that the 
subject will receive and view (see 45 CFR 46.109(a) and 21 CFR 56.109(a)).   The IRBs must 
maintain and retain copies of materials that have been reviewed in accordance with 45 CFR 
46.115 and 21 CFR 56.115. 
 
The IRBs should also review any optional questions or methods used to gauge subject 
comprehension of key study elements. The IRB should also review the usability of the eIC 
materials to ensure that they are easy to navigate.  If the program uses hyperlinks to convey 
study-related information, IRBs should review the contents to which subjects are referred in 
order to determine if the study-related information that has been supplied is accurate and 
appropriate. Because Web sites are often modified over time, IRBs must maintain the version of 
the Web site information that contains the study-related information that the IRB reviews and 
approves, either electronically or as a hard copy (see 45 CFR 46.115 and 21 CFR 56.115).   
 
 
Q14. 	 What eIC documentation does FDA require for submission with 
applications? 
 
Investigational new drug application (IND) regulations do not specifically require submission of 
informed consent documents to FDA as part of an IND application; however, the Center for 
Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research 
(CBER) may request submission of the informed consent form for review19 under certain 
circumstances (e.g., when unusual known clinical toxicity is associated with the study drug or 
class of drugs; when the study population is particularly vulnerable; when the clinical 
                                                 
19 See 21 CFR 312.23(a)(11). 
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investigation has significant potential for serious risks to human subjects; or for a postmarket 
safety clinical trial, required under section 505(o) of the Federal Food, Drug, and Cosmetic Act 
(FD&C Act)20 to assess a serious risk).21  Although all informed consent documents used in 
FDA-regulated clinical investigations must be reviewed by an IRB (see 21 CFR 56.103), there 
are situations in which CDER and CBER review of an informed consent in addition to IRB 
review is particularly important to determine whether a clinical investigation may safely proceed 
under 21 CFR part 312. 
 
Investigational device exemption (IDE) regulations state that IDE applications must include 
copies of all forms and informational materials to be provided to subjects to obtain informed 
consent (see 21 CFR 812.20(b)(11)).  When FDA approval of an IDE application is required, a 
sponsor must not begin an investigation until the IDE application and informed consent materials 
have been reviewed and approved by FDA (see 21 CFR 812.20(a) and (b)).   
 
The sponsor should submit to FDA the same eIC materials that will be presented to subjects to 
obtain eIC for their participation in the clinical  investigation.  For example, as part of an 
electronic submission to FDA, the sponsor should submit copies of all forms and informational 
materials including any videos, Web-based presentations, hyperlinks or other Web sites or 
podcasts that are used to convey information specifically related to the investigation.  The 
sponsor should also submit any written information related to the clinical investigation that is 
provided to the subject on paper. Hyperlinks or other Web sites or podcasts containing 
incidental information not related to the clinical investigation need not be submitted to FDA.  
The eIC materials should be provided in an electronic format acceptable to FDA, on an 
electronic storage device, or as a link to the eIC Web page that is accessible to FDA for viewing 
these eIC materials.22    
 
 
Q15. 	 What steps can be taken to ensure the system archives the eIC materials 
appropriately for FDA-regulated clinical investigations?  
 
FDA regulations do not specify a preferred method for archiving documents; however, the eIC 
process should incorporate procedures to ensure that electronic documents can be archived 
appropriately and that all versions of the IRB-approved eIC can be retrieved easily.  All 
procedures must be in compliance with applicable FDA regulations for electronic records.23   
                                                 
20 21  U.S.C 355(o). 
 
21 For additional information, see the draft guidance for IRBs, clinical investigators, and sponsors Informed Consent 
Information Sheet (available at  http://www.fda.gov/RegulatoryInformation/Guidances/ucm404975.htm). 
 
22 For additional  information, see the guidance for industry  Providing  Regulatory Submissions in Electronic Format  
 Certain Human Pharmaceutical  Product Applications and Related  Submissions Using the eCTD Specifications  
(available at  http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm064994.htm). 
See also the guidance for industry and Food  and Drug Administration staff  eCopy Program for Medical Device 
Submissions (available at  
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/ucm370879.htm). 
 
23  See footnote 10. 
 
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  Contains Nonbinding Recommendations 
Q16.  What materials or documents will FDA require during an inspection? 
 
During inspections of clinical investigation sites,24 FDA regulations require that FDA be granted 
access to records and reports made by the investigator, including site-specific versions of the 
eIC, the materials submitted to IRBs for review and approval, all amendments to the site-specific 
eICs, and all subject-specific signed eICs.25  These should be available at the site either in 
electronic or paper form.  FDA reserves the right to review the content of the eIC program or 
informed consent document and the corresponding informed consent of the subject or the 
subjects LAR and the signature of a witness, where applicable, along with the date that the eIC 
was signed. Any updates to the documentation should also be available for review. 
 
                                                                                                                                                             
 
24 See the information sheet  guidance for IRBs, clinical investigators, and sponsors FDA Inspections  of Clinical  
Investigators (available at  http://www.fda.gov/regulatoryinformation/guidances/ucm122046.htm) and the FDA  
Compliance Program Guidance Manual (CPGM) 7348.811:  Clinical Investigators and Sponsor-Investigators 
(December 8, 2008). 
 
25 Under the FD&C Act, FDA  may inspect and copy all  records relating to a clinical investigation  (21  U.S.C. 
374(a)(1)).  See also 21  CFR 312.58, 312.68, and 812.145(b).  
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