Contains Nonbinding Recommendations 
Guidance for 
Institutional Review Boards, 
Clinical Investigators, and 
Sponsors
 
 
Exception from Informed 
Consent Requirements for 
  
Emergency Research
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Office of Good Clinical Practice 
Center for Drug Evaluation and Research 
Center for Biologics Evaluation and Research 
Center for Devices and Radiological Health 
 
March 2011 
Updated April 2013 
 
   Contains Nonbinding Recommendations 
 
Guidance for 
Institutional Review Boards, Clinical 
Investigators, and Sponsors 
Exception from Informed Consent 
Requirements for Emergency Research
 
 
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U.S. Department of Health and Human Services 
Food and Drug Administration 
Office of Good Clinical Practice 
Center for Biologics Evaluation and Research 
Center for Drug Evaluation and Research 
Center for Devices and Radiological Health 
March 2011 
Updated April 2013   Contains Nonbinding Recommendations 
 Guidance for 
Institutional Review Boards, Clinical 
Investigators, and Sponsors 
Exception from Informed Consent 
Requirements for Emergency Research
 
 
 
 
 
 
NOTE:   FDA made the following updates to the guidance in April 2013:   
 
  In Question #18, the phrase unless a waiver from FDA is prospectively 
applied for and granted has been deleted.  FDA made this change to 
clarify that there are no waiver provisions applicable for 21 CFR 50.24.   
  In Section XI and various other places, FDA made minor changes to 
clarify the provision regarding the establishment of an independent data 
safety monitoring committee (DMC).  FDA interprets this regulatory 
provision to permit a sponsor to either establish an independent DMC or to 
secure the services of an already established DMC to exercise oversight of 
the clinical investigation.  FDA is making this clarification to provide 
flexibility to sponsors in meeting the regulatory requirements.  
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Office of Good Clinical Practice 
Center for Biologics Evaluation and Research 
Center for Drug Evaluation and Research 
Center for Devices and Radiological Health 
 
March 2011 
Updated April 2013 
 
TABLE OF CONTENTS   Contains Nonbinding Recommendations 
 
NOTE:   IN QUESTION #18, THE PHRASE UNLESS A WAIVER FROM FDA IS 
PROSPECTIVELY APPLIED FOR AND GRANTED HAS BEEN DELETED.  FDA 
MADE THIS CHANGE TO CLARIFY THAT THERE ARE NO WAIVER PROVISIONS 
APPLICABLE FOR 21 CFR 50.24.............................................................................................3 
APPENDIX C  SUGGESTED FLOW CHART FOR 50.24 STUDIES ........................54
  9 
GUIDANCE FOR INSTITUTIONAL REVIEW BOARDS, CLINICAL 
INVESTIGATORS AND SPONSORS.......................................................................................1 
I.  GENERAL................................................................................................................................2 
1.  Where are the regulations involving an exception from informed consent for emergency research 
studies found?..........................................................................................................................................2 
2.  Why did FDA issue the regulations at 21 CFR 50.24?.....................................................................2 
3.  How are emergency research studies unique?..................................................................................2 
4.  What are the additional responsibilities imposed on parties involved with studies conducted under 
21 CFR 50.24?.........................................................................................................................................2 
5.  When did the emergency research regulations take effect?..............................................................3 
6.  Why did FDA issue this guidance?....................................................................................................3 
7.  What must the IRB find and document in order for a study involving an exception from informed 
consent to proceed?.................................................................................................................................3 
8.  Can an emergency research study be subject to both FDAs regulations at 21 CFR 50.24 and 
HHS regulations at 45 CFR Part 46?.....................................................................................................4 
9.  Does 21 CFR 50.24 pre-empt state law?............................................................................................4 
10.  Do studies conducted under 21 CFR 50.24 need a separate Investigational New Drug 
Application (IND) or Investigational Device Exemption (IDE)?..........................................................4 
11.  What information must be submitted to FDA for a study conducted under 21 CFR 50.24?.........4 
12.  How are emergency research studies involving investigational drugs processed?........................5 
13. Can Phase 1, Phase 2, and Phase 3 safety and efficacy studies proceed under 21 CFR 50.24?....5 
14.  Can feasibility/pilot trials for devices be conducted under 21 CFR 50.24?....................................5 
15.  Can emergency research studies involving investigational drugs be placed on clinical hold?.....5 
16.  How are emergency research studies involving devices processed?...............................................6 
17.  May studies involving in vitro diagnostic devices be conducted under 21 CFR 50.24?.................6 
18.  Will FDA accept data from emergency research studies conducted at non-US sites?...................6 
19.  Must studies conducted under 21 CFR 50.24 be registered?..........................................................7 
II. QUALIFICATIONS FOR A STUDY TO BE CONDUCTED UNDER 21 CFR 50.24.....7   Contains Nonbinding Recommendations 
20.  What conditions must be present for a study to be eligible to be conducted under 21 CFR 50.24?
  7 
21.  What is meant by prospect of direct benefit?...............................................................................8 
22.  Are trials with morbidity endpoints allowed under this regulation?...............................................8 
23.  What is meant by available treatments are unproven or unsatisfactory?...................................9 
24.  What is meant by unproven?........................................................................................................9 
25.  What is meant by unsatisfactory?................................................................................................9 
III.  STUDY DESIGN.................................................................................................................10 
26.  What information should sponsors include in the proposed investigational plan (protocol) for an 
emergency research study?...................................................................................................................10 
27.  May placebo-controlled trials be conducted under 21 CFR 50.24?..............................................10 
28.  What is a non-inferiority trial?  Under what circumstances can a non-inferiority trial be 
conducted under 21 CFR 50.24?...........................................................................................................11 
29.  One of the requirements of 21 CFR 50.24 is that a study could not be practicably carried out 
without the waiver from informed consent (21 CFR 50.24(a)(4)).  What does this mean?..............11 
30.  Is it possible for researchers or first responders to identify individuals who do not want to 
participate?.............................................................................................................................................12 
31.  May studies in pediatric subjects be conducted under 21 CFR 50.24?........................................12 
32.  What is a Special Protocol Assessment (SPA)?.............................................................................13 
33.  Do Special Protocol Assessments (SPAs) apply to device studies?...............................................13 
IV.  THERAPEUTIC WINDOW..............................................................................................13 
34.  What is meant by the term, therapeutic window?......................................................................13 
35.  How can a sponsor determine the appropriate therapeutic window?...........................................13 
36.  How does the term, therapeutic window, apply to in vitro diagnostic device (IVD) studies?..14 
37.  Is it possible for an individual to indicate that he/she does not want to participate in an 
emergency research study?...................................................................................................................14 
38.  What is a legally authorized representative?.................................................................................14 
39.  Who may serve as a legally authorized representative (LAR)?.....................................................14 
40.  If an emergency research study involves pediatric subjects, who may serve as a childs legally 
authorized representative (LAR)?.........................................................................................................15 
41.  What is the purpose of contacting a subjects legally authorized representative (LAR)?............15 
42.  What is the purpose of contacting a subjects family member?....................................................15 
43.  Must attempts to contact a subjects legally authorized representative or family member exhaust 
the entire therapeutic window before the test article may be administered to the subject?................15   Contains Nonbinding Recommendations 
V.  IRB RESPONSIBILITIES...................................................................................................16 
44.  What is the IRBs role in reviewing emergency research?...........................................................16 
45.  What information should the clinical investigator or sponsor provide to the IRB related to a 
research protocol involving an exception from informed consent under 21 CFR 50.24?..................16 
46.  What does the IRB do with the submitted information?...............................................................17 
47.  Is the IRB responsible only for finding and documenting that the plans for community 
consultation and public disclosure exist, or does the IRB have additional responsibilities for 
ensuring that these activities are implemented?...................................................................................18 
48.  If an IRB determines that it needs additional input from the community about the study, what 
should the IRB do?................................................................................................................................18 
49.  Must an emergency research study be reviewed only by IRBs that are affiliated with 
institutions?............................................................................................................................................19 
50.  How should an IRB document its review of an emergency research study?................................20 
51.  What is meant by licensed physician concurrence?..................................................................20 
VI.  SPONSORS RESPONSIBILITIES..............................................................................21 
52.  What are the sponsors responsibilities under 21 CFR 50.24?.....................................................21 
VII.  CLINICAL INVESTIGATORS RESPONSIBILITIES............................................23 
53.  What are the clinical investigators responsibilities under 21 CFR 50.24?.................................23 
VIII.  COMMUNITY CONSULTATION...............................................................................24 
54.  What is meant by community consultation and what are its goals?.........................................25 
55.  What is meant by the community in which the research will be conducted?...........................25 
56.  What is meant by the community from which subjects will be drawn?....................................25 
57.  Is community consultation the same as community consent for the study?  Is community 
consent a substitute for individual informed consent?.......................................................................25 
58.  What should happen during community consultation?................................................................26 
59.  What information should be included in community consultation?............................................26 
60.  Why is community consultation important?..................................................................................27 
61.  What is meant by the phrase, representatives of the community (21 CFR 50.24(a)(7)(i)?  Must 
a representative of the community be an elected official?...................................................................28 
62.  How does community consultation differ from public disclosure?......................................28 
63.  Who should bear the costs associated with community consultation and public disclosure 
activities?................................................................................................................................................28 
64.  May IRBs review the study protocol separately from the community consultation and public 
disclosure plans?....................................................................................................................................28   Contains Nonbinding Recommendations 
65.  How can clinical investigators identify who belongs to the community from which subjects will 
be drawn?...............................................................................................................................................29 
66.  What is the IRBs role in the community consultation process?..................................................29 
67.  Where should the sponsor and clinical investigator obtain information about the study for 
inclusion during community consultation?..........................................................................................29 
68.  Must opt-out mechanisms be provided?.....................................................................................30 
69.  What is the difference between opting-out and providing a family member with an 
opportunity to object to a subjects participation in the study?........................................................30 
70.  How much community consultation activity is necessary?...........................................................31 
71.  Should sites, sponsors, or IRBs evaluate the effectiveness of community consultation and public 
disclosure activities?..............................................................................................................................31 
72.  Who is responsible for conducting community consultation activities? What are the respective 
roles of the sponsor, clinical investigator, and IRB in conducting community consultation activities?
  31 
73.  How can the sponsor and clinical investigator identify the communities that should be included 
in community consultation activities?...................................................................................................31 
74.  What should the IRB do with information received during community consultation activities?32 
75.  How can the IRB accomplish its review of community consultation plans?...............................32 
76.  What types of activities can sponsors and clinical investigators engage in to carry out 
community consultation?......................................................................................................................33 
77.  How many community consultation meetings should be held?....................................................34 
IX.  PUBLIC DISCLOSURE.....................................................................................................34 
78.  What is meant by public disclosure and what are its goals?.....................................................34 
79.  When must public disclosure occur?.............................................................................................35 
A.  PUBLIC DISCLOSURE BEFORE THE STUDY BEGINS...................................................35 
80.  Who is responsible for public disclosure activities before the study begins?...............................35 
81.  What information must be publicly disclosed?..............................................................................35 
82.  How should public disclosure be carried out?...............................................................................36 
83.  What does the IRB do with the information that has been publicly disclosed?...........................37 
84.  What does the sponsor do, upon receiving from the IRB the information that has been publicly 
disclosed?...............................................................................................................................................37 
B.  PUBLIC DISCLOSURE AFTER THE STUDY IS COMPLETED OR TERMINATED...38 
85.  What must be disclosed following completion of the clinical investigation?...............................38 
86.  What is meant by completion of the clinical investigation?......................................................39 
87.  What is meant by termination of the clinical investigation?.....................................................39   Contains Nonbinding Recommendations 
88.  Does FDA expect sponsors to publicly disclose information about studies that have been 
terminated/discontinued?......................................................................................................................39 
89.  Who is responsible for disclosing information about the study after it is completed or 
terminated?............................................................................................................................................39 
90.  When should the sponsor disclose the results of the study?.........................................................39 
91.  Would reporting results of the investigation in the ClinicalTrials.gov database be sufficient for 
purposes of meeting the public disclosure requirements under 21 CFR 50.24 after the study is 
completed?...........................................................................................................................................40 
92.  How should the information be disclosed to the community in which the clinical investigation 
was conducted and the community from which the subjects were drawn (21 CFR 50.24(a)(7)(iii))?40 
93.  How can information about the results of the study be disclosed to other researchers?.............40 
94.  Must information that is disclosed after the study is completed or terminated be submitted to 
FDAs Public Docket?...........................................................................................................................40 
X.  CONTACT OF LEGALLY AUTHORIZED REPRESENTATIVES OR FAMILY 
MEMBERS..................................................................................................................................40 
A.  PRIOR TO ADMINISTRATION OF THE TEST ARTICLE...............................................40 
95.  What procedures for contacting a subjects legally authorized representative (LAR) or family 
member prior to administration of the test article are required by 21 CFR 50.24?............................41 
96.  How can IRBs ensure that investigators make every attempt to contact the subjects legally 
authorized representative (LAR) or family member within the therapeutic window?........................41 
97.  These studies involve an exception from informed consent requirements.  Why must an 
informed consent document be prepared?............................................................................................42 
98.  What is the purpose of contacting the subjects family member?.................................................42 
99.  If a legally authorized representative (LAR) is available, what must the investigator do?..........42 
100.  If the LAR is not available, but a family member is, what must the investigator or first 
responder do?.........................................................................................................................................42 
101.  If the subjects legally authorized representative (LAR) is available, and the LAR agrees to 
allow the subject to participate in the study, must the clinical investigator also contact the subjects 
family member?.....................................................................................................................................42 
102.  Must a family members objection to the subjects participation in the study be in writing?....43 
B.  AFTER ADMINISTRATION OF THE TEST ARTICLE.....................................................43 
103.  How should a subjects family be told about the subjects participation in the study?..............43 
104.  If a subject is enrolled in a study under 21 CFR 50.24, what information must be provided to 
the subject, the subjects legally authorized representative (LAR) or family member?......................43 
105.  What is meant by feasible?.......................................................................................................43   Contains Nonbinding Recommendations 
106.  If a subject regains consciousness, or his legally authorized representative (LAR) is found, 
must consent be obtained from the subject or the subjects LAR in order to continue participation in 
the study?...............................................................................................................................................44 
107. In the event of a subjects death, must information about the subjects enrollment in the study 
be provided to the subjects legally authorized representative (LAR) or family member?..................44 
108.  When must information about the subjects enrollment in the study be provided to the subjects 
legally authorized representative (LAR) or family member?...............................................................45 
109.  What records must the clinical investigator maintain with respect to efforts to contact the 
legally authorized representative (LAR) or a subjects family member?.............................................45 
110.  What access do clinical investigators have to the medical records of research subjects?.........45 
111.  If a subject, legally authorized representative (LAR), or family member discontinues the 
subjects participation in the study, to what records would the researcher still have access?............46 
112.  Why is access to subjects data (e.g., medical and study records) important?  Can a subject 
withdraw use of his or her data that have already been collected, or results in the research database?
  46 
113.  Can information about a subjects death be collected even if the subject has discontinued 
participation in the study?.....................................................................................................................46 
114.  Do FDAs regulations require that informed consent be obtained from a deceased subjects 
family members before public records can be accessed?.....................................................................47 
115. For emergency research under 21 CFR 50.24, involving an exception from informed consent, 
may an IRB or Privacy Board waive the authorization requirement that would otherwise apply 
under 45 CFR 164.508 of the HIPAA Privacy Rule?..........................................................................47 
XI.  DATA MONITORING COMMITTEE (DMC)...............................................................48 
XII.  FOR FURTHER INFORMATION..................................................................................48 
A.  CONTACTS................................................................................................................................48 
B.  FDAs WEBSITES......................................................................................................................48 
 
APPENDIX A  21 CFR 50.24 ...........................................................................49 
APPENDIX B  DEFINITIONS ........................................................................52 
APPENDIX C  SUGGESTED FLOW CHART FOR 50.24 STUDIES ........................54   Contains Nonbinding Recommendations 
Guidance for Institutional Review Boards, Clinical Investigators and 
1
Sponsors  
Exception from Informed Consent Requirements for Emergency 
Research 
 
 
This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic.  It does not 
create or confer any rights for or on any person and does not operate to bind FDA or the public.  You can use an 
alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you 
want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance.  If you 
cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance.  
 
 
 
This guidance is intended to assist Institutional Review Boards (IRBs), clinical investigators and 
sponsors in the development, conduct, and oversight of investigations to determine the safety and 
effectiveness of FDA regulated products (e.g., drugs, including biological drug products,2 devices) in 
emergency settings when an exception from the informed consent requirements is requested under Title 
21, Code of Federal Regulations, Section 50.24 (21 CFR 50.24).  The term emergency research is 
used throughout this guidance to refer to these investigations.  These investigations involve human 
subjects who have a life-threatening medical condition that necessitates urgent intervention (for which 
available treatments are unproven or unsatisfactory), and who, because of their condition (e.g., traumatic 
brain injury) cannot provide informed consent.  The research must have the prospect of direct benefit to 
the patient and must involve an investigational product that, to be effective, must be administered before 
informed consent from the subject or the subjects legally authorized representative can be obtained and 
in which there is no reasonable way to identify prospectively individuals likely to become eligible for 
participation.  This guidance finalizes the draft guidance entitled, Guidance for Institutional Review 
Boards, Clinical Investigators, and Sponsors: Exception from Informed Consent for Emergency 
Research, dated July 2006 (published on August 29, 2006).3 
 
FDA's guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidance documents describe the Agency's 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 Agency guidance documents means that something is suggested 
or recommended, but not required.  
 
                                                 
1 This guidance has been prepared by the Office of Good Clinical Practice (OGCP) in the Office of the Commissioner (OC), 
Food and Drug Administration (FDA), in consultation with FDA's Center for Biologics Evaluation and Research (CBER), 
Center for Devices and Radiological Health (CDRH), and the Center for Drug Evaluation and Research (CDER). 
2 Wherever the term drug is used in this guidance, it should be understood to include all drugs, including biological drug 
products. 
3 71 Fed. Reg. 51143 (August 29, 2006) 
  1  Contains Nonbinding Recommendations 
I.  GENERAL 
1.  Where are the regulations involving an exception from informed consent for emergency research 
studies found? 
 
The regulations at 21 CFR 50.24 and the conforming amendments contained in 21 CFR Parts 56, 312, 
314, 601, 812, and 814 provide a narrow exception to the requirement that the investigator obtain 
informed consent from each subject, or the subject's legally authorized representative, prior to 
enrollment in emergency research.  The regulations also provide additional protections for subjects 
enrolled in these studies.  For example, the regulations require consultation with representatives of and 
public disclosure to the communities in which the clinical investigation will be conducted and from 
which the subjects will be drawn, prior to initiation of the clinical investigation. They also require public 
disclosure of sufficient information following completion of the clinical investigation to apprise the 
community and researchers of the study.  As well, the regulations require that an independent data 
monitoring committee exercises oversight of the clinical investigation. (See Appendix A for the text of 
21 CFR 50.24.) 
 
2.  Why did FDA issue the regulations at 21 CFR 50.24? 
 
FDA issued the regulations at 21 CFR 50.24 to permit the study under the Federal Food, Drug, and 
Cosmetic Act (the FD&C Act) of potential treatments or improvements in the treatment of life-
threatening conditions where current treatment is unproven or unsatisfactory, in order to improve patient 
outcomes.   
 
Because of ethical concerns involved in studying subjects who cannot provide consent, much of what 
has become standard, accepted, medical therapy for use in emergency settings has not been evaluated by 
adequate and well-controlled trials that demonstrate the treatment is either safe or effective.  Controlled 
clinical trials have subsequently demonstrated that some therapies that have become standard medical 
practice are ineffective or even harmful.  Other standard therapies, although shown to be effective in 
clinical trials, have significant limitations (e.g., they only work in a small percentage of those 
individuals who receive the therapies).  FDA expects that permitting certain emergency research trials to 
proceed will (1) provide individuals in life-threatening situations access to potentially life-saving 
therapies; (2) advance knowledge through collection of information about effectiveness and safety; and 
(3) improve therapies used in emergency medical situations that currently have poor clinical outcomes.  
 
3.  How are emergency research studies unique? 
 
Emergency research involves the most vulnerable population of study subjects, i.e., a population with no 
capacity to control what happens to them and no capacity to consent, in a setting where the emergency 
circumstances require prompt action and generally provide insufficient time and opportunity to locate 
and obtain consent from each subjects legally authorized representative.  In order to protect these 
vulnerable subjects, 21 CFR 50.24 places additional responsibilities on parties involved with such 
research, including sponsors, clinical investigators, and IRBs.   
 
4.  What are the additional responsibilities imposed on parties involved with studies conducted under 
21 CFR 50.24? 
 
  2  Contains Nonbinding Recommendations 
These additional responsibilities include consultation with representatives of the community(ies) in 
which the research will take place and from which the subjects will be drawn, public disclosure of 
information before the start of the study and following its completion, a commitment by the investigator 
to try to locate the subjects legally authorized representative or contact a family member to determine 
whether the family member objects to the subject's participation, and study oversight by an independent 
data monitoring committee. (See Appendix A for the text of 21 CFR 50.24.) 
 
5.  When did the emergency research regulations take effect? 
 
The emergency research regulations became effective November 1, 1996.4  
 
6.  Why did FDA issue this guidance? 
 
FDA determined that guidance is needed to assist sponsors, IRBs, and clinical investigators in 
interpreting and complying with these regulations, particularly in the areas of planning and conducting 
community consultation and public disclosure activities, and establishing informed consent procedures 
to be used when feasible.5  This document also provides guidance related to other aspects of the 
emergency research regulations, such as the requirement for the concurrence of a licensed physician, use 
of data monitoring committees, use of independent IRBs, and the documentation of efforts to contact a 
subjects legally authorized representative or family member regarding the subjects participation in the 
study. 
 
7.  What must the IRB find and document in order for a study involving an exception from informed 
consent to proceed? 
 
The IRB must find and document that the research involves subjects unable to consent and that the 
research is subject to FDAs regulations5 and will be carried out under an FDA Investigational New 
Drug Application (IND) or an FDA Investigational Device Exemption (IDE).  The IRB must also find 
and document that the requirements for exception from informed consent for emergency research 
detailed in 21 CFR 50.24 have been met.  (See Appendix A for the text of 21 CFR 50.24.)  In addition, 
the IRB must find that the study meets the relevant requirements of 21 CFR Parts 50 and 56. 
 
If the IRB finds that the research is not subject to FDAs regulations, then the IRB should determine 
whether the research is subject to the Department of Health and Human Services (HHS) Secretarial 
waiver for emergency research studies, and report this finding to HHS Office for Human Research 
Protections.6 
                                                 
4 Protection of Human Subjects; Informed Consent and Waiver of Informed Consent Requirements in Certain Emergency 
Research; Final Rule, 61 Fed. Reg. 51498 (Oct. 2, 1996). 
http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ucm118960.htm 
5 In drafting this guidance, FDA considered comments received on two earlier published drafts of the guidance document, 
questions received by agency staff related to implementation of the regulations, and information presented at the October 11, 
2006, public meeting on emergency research studies (Docket #2006D-0331; 
http://www.regulations.gov/search/Regs/home.html#home.) 
6 The Secretary of Health and Human Services published a waiver of the general requirements for informed consent at 45 
CFR 46.116(a) and (b), and at 46.408, for emergency research if (a) the IRB responsible for the review, approval, and 
continuing review of the research activity has approved both the activity and a waiver of informed consent and found and 
documented (1) that the research activity is subject to regulations codified by the FDA at Title 21 CFR Part 50, and will be 
  3  Contains Nonbinding Recommendations 
 
8.  Can an emergency research study be subject to both FDAs regulations at 21 CFR 50.24 and HHS 
regulations at 45 CFR Part 46? 
 
Yes.  If the study involves an FDA-regulated product, and is conducted or supported by HHS, both the 
FDA regulations and HHS human subject protection regulations apply.  In order for an exception from 
the informed consent requirements to be granted for a study that is subject to both FDA and HHS 
regulations, the study may not involve pregnant women or prisoners as subjects7, and the provisions of 
21 CFR 50.24 must be satisfied.  When an exception from the informed consent requirements for such a 
study is granted, all other applicable requirements of 21 CFR Parts 50 and 56, and 45 CFR 46 must be 
satisfied. 
 
9.  Does 21 CFR 50.24 pre-empt state law? 
 
No.  Section 50.24 is not intended to preempt any applicable Federal, State, or local laws.8  Those 
conducting emergency research should understand their obligations under the laws of the States in which 
the research will be conducted.  
 
10.  Do studies conducted under 21 CFR 50.24 need a separate Investigational New Drug Application 
(IND) or Investigational Device Exemption (IDE)? 
 
Yes.  If an IND or IDE already exists, protocols involving an exception to the informed consent 
requirement must be performed under a separate IND or IDE that clearly identifies such protocols as 
protocols that may include subjects who are unable to consent (21 CFR 50.24(d)).  Studies involving an 
exception from the informed consent requirements may proceed only after a sponsor has submitted an 
IND or IDE9 and received prior written authorization from FDA10 and IRB approval (i.e., the IRB must 
find and document that specific conditions in the regulations have been met11).  (See Appendix A for the 
text of 21 CFR 50.24.) 
 
11.  What information must be submitted to FDA for a study conducted under 21 CFR 50.24? 
 
For an emergency research study involving an exception from informed consent, the separate IND or 
IDE submission should be completed as described in the applicable regulation.  Information previously 
submitted to FDA may be incorporated by reference.  The location of information incorporated by 
reference should be specifically identified, for example, by application number, date of submission, 
                                                                                                                                                                         
carried out under an FDA investigational new drug application (IND) or an FDA investigational device exemption (IDE), the 
application for which has clearly identified the protocols that would include subjects who are unable to consent, and (2) that 
the requirements for exception from informed consent for emergency research detailed in 21 CFR 50.24 have been met; or 
(b) the IRB responsible for the review, approval, and continuing review of the research has approved both the research and a 
waiver of informed consent and has found and documented that the research is not subject to regulations codified by the FDA 
at Title 21 CFR Part 50 and found and documented and reported that conditions for emergency research contained in the 
Secretarial waiver document have been met.  [61 Fed. Reg. at 51531. www.hhs.gov/ohrp/documents/100296.pdf ] 
7 61 Fed. Reg. 51531 
8 61 Fed. Reg. 51502 (October 2, 1996, Comment #10) 
9 21 CFR 312.2(b)(6) and 312.20(c); 21 CFR 812.20(a)(1).  Sponsors should contact FDA if they have questions as to 
whether an IND or IDE is needed.  Points of contact are listed in section "XII. For Further Information".  
10 21 CFR 312.20(c); 21 CFR 812.20(a)(4)(i) 
11 21 CFR 56.103(a); 21 CFR 50.24   
  4  Contains Nonbinding Recommendations 
volume, page and section.  If the information was submitted by someone other than the current 
applicant, a letter from the person who holds the files authorizing reference to the information must be 
provided.  In addition, the submission should address the specific requirements for studies conducted 
under 21 CFR 50.24 (e.g., plans for community consultation, plans for public disclosure).  Sponsors 
should contact FDA directly if they have questions about the submission process.  
 
12.  How are emergency research studies involving investigational drugs processed? 
 
If the protocol involves an investigational drug, the sponsor is required to submit a separate 
Investigational New Drug Application (IND)12 that clearly identifies the study as including subjects who 
are unable to consent (21 CFR 50.24(d)).  After the IND is submitted, FDA will review the study 
protocol under the applicable IND regulations and 21 CFR 50.24.  Such a study is not permitted to 
proceed without the prior written authorization of FDA13 and IRB approval (i.e., the IRB must find and 
document that specific conditions have been met14).  A copy of the prior authorization from FDA may 
be submitted to the IRB(s) reviewing the study. (See Appendix A for the text of 21 CFR 50.24.) 
 
13. Can Phase 1, Phase 2, and Phase 3 safety and efficacy studies proceed under 21 CFR 50.24?  
 
The phase of a trial is not the focus of this regulation and there is no requirement that a study be a 
Phase 1, Phase 2, or Phase 3 study in order to proceed.  Rather, the intervention that is being studied 
must hold out the prospect of direct benefit for the individual subjects.  FDA expects that Phase 1 
studies, including pharmacokinetic studies, would be conducted in consenting subjects and not in a trial 
conducted under 21 CFR 50.24, because such studies would generally not meet the criteria for the 
prospect of direct benefit required by 21 CFR 50.24(a)(3).  To establish potential benefits, Phase 2 
controlled trials in consenting subjects may be needed to explore dose response for safety or biomarkers 
before an investigation proceeds under 21 CFR 50.24.  Sponsors should consult with FDA if there are 
questions as to whether a particular study meets the requirements of this regulation.  (See Question 22 
for discussion of appropriate endpoints of trials conducted under 21 CFR 50.24.) 
 
14.  Can feasibility/pilot trials for devices be conducted under 21 CFR 50.24? 
 
Yes.  FDA believes that feasibility/pilot studies involving devices15 may be performed in individuals 
having the emergency condition provided that the study holds out the prospect of direct benefit.  
Sponsors should consult with FDA if there are questions as to whether a particular study meets the 
requirements of this regulation.  (See Question 22 for discussion of endpoints of trials conducted under 
21 CFR 50.24.) 
 
15.  Can emergency research studies involving investigational drugs be placed on clinical hold? 
 
Yes.  When appropriate, FDA will place a proposed or ongoing emergency research investigation IND 
(or study site) on clinical hold if (1) any of the conditions in 21 CFR 312.42(b)(1) or (b)(2) apply, or (2) 
                                                 
12 21 CFR 312.20(c)  
13 21 CFR 312.20(c) 
14 21 CFR 56.103(a); 21 CFR 50.24  
15 http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm081405.htm 
  5  Contains Nonbinding Recommendations 
the pertinent criteria in 21 CFR 50.24 for such an investigation to begin or continue are not submitted or 
satisfied (See 21 CFR 312.42(b)(5)).  
 
16.  How are emergency research studies involving devices processed? 
 
A sponsor is usually required to complete and submit an IDE application describing the proposed study 
(See 21 CFR 812.20(a)(1)).  However, if the device would otherwise meet the criteria of the abbreviated 
requirements under 21 CFR 812.2(b), or the proposed protocol involves a device that has already been 
cleared or approved for marketing and is being used in accordance with its cleared/approved labeling, 
the sponsor or investigator should contact FDA for clarification regarding requirements for the 
submission of an IDE application.  FDA recommends that this contact occur prior to IRB submission, 
particularly for multi-site studies, as this will facilitate IRB review.   
 
If an IDE is required, FDA will review the study protocol under the IDE regulations and 21 CFR 50.24.  
The study is not permitted to proceed without the prior written authorization of FDA and IRB approval 
(i.e., the IRB must find and document that specific conditions have been met)16.  FDA may disapprove 
the IDE or may withdraw approval if there is a failure to comply with any requirement of the IDE 
regulation, the Federal Food, Drug, and Cosmetic Act, any other applicable regulation or statute, or any 
condition of approval imposed by an IRB or FDA, including requirements related to the conduct of 
50.24 studies (See 21 CFR 812.30).  (See Appendix A for the text of 21 CFR 50.24.) 
 
(See also Question 10.)   
 
17.  May studies involving in vitro diagnostic devices be conducted under 21 CFR 50.24? 
 
Yes.  An in vitro diagnostic device (IVD) study may be conducted provided that it meets the 
requirements of 21 CFR 50.24.  IVD studies falling within the scope of section 50.24 would include, for 
example, studies in which diagnosis of a life-threatening condition cannot be confirmed by an approved 
product or well-established procedure (e.g., research involving an investigational test for a neurotoxin 
that when inhaled or in contact with skin, can cause patients to become sick within minutes, and at high 
doses, to lose consciousness, develop seizures and die).  The regulations use of language usually 
associated with therapeutic products does not exclude IVDs because the administration of therapy in a 
life-threatening situation can depend upon a diagnostic intervention.  Sponsors should contact FDA if 
they have questions as to whether a particular IVD study may be conducted under 21 CFR 50.24.  
 
18.  Will FDA accept data from emergency research studies conducted at non-US sites? 
 
Yes, provided appropriate regulatory requirements are satisfied.  For drug/biological drug studies, if the 
non-U.S. sites are under an IND, all 21 CFR 50.24 requirements must be met, as well as other provisions 
of 21 CFR Part 312.   
 
If the sites operate as non-IND sites, but the data are included in a marketing application, then 21 CFR 
312.120 would apply.  21 CFR 312.120(a)(1)(i) does not require informed consent in life-threatening 
situations when the [International Ethics Committee] reviewing the study finds, before initiation of the 
study, that informed consent is not feasible and either that the conditions present are consistent with 
                                                 
16 21 CFR 812.20(a)(4)(i); 21 CFR 56.103(a); 21 CFR 50.24  
  6  Contains Nonbinding Recommendations 
those described in 50.23 or 50.24(a)...or that the measures described in the study protocol or 
elsewhere will protect the rights, safety, and well-being of subjects...  FDA will accept data from non-
IND emergency research studies/sites provided the emergency research is conducted in accordance with 
both internationally accepted standards for good clinical practice (e.g., ICH E6) and applicable national 
laws.   
 
For devices, under 21 CFR 814.15(b), FDA will accept foreign studies submitted in support of a Pre-
Market Approval (PMA) application if the data are valid and the investigator has conducted the studies 
in conformance with the Declaration of Helsinki or the laws and regulations of the country in which 
the research is conducted, whichever accords greater protection to the human subjects.   
 
Note that some countries laws may allow expedited appointment of legally acceptable representatives17 
(e.g., judge, independent physician), who can provide consent, removing the need to waive informed 
consent.  (See 21 CFR 312.120 and 814.15 for FDAs requirements for acceptance of data from non-US 
studies that are not conducted under an IND or IDE, respectively.)  
 
19.  Must studies conducted under 21 CFR 50.24 be registered? 
 
The Food and Drug Administration Amendments Act of 2007 (FDAAA)18, Title VIII, Section 801 
mandates that a responsible party (i.e., the sponsor or designated principal investigator) register an 
applicable clinical trial in the registry database, Clinicaltrials.gov,19 and defines an applicable clinical 
trial.20  In addition, the statute describes the responsible partys obligation to report results of certain 
applicable clinical trials.21  Results must be reported if the trial conducted under 21 CFR 50.24 meets 
the criteria for an applicable clinical trial as described at ClinicalTrials.gov.   
 
 
II. QUALIFICATIONS FOR A STUDY TO BE CONDUCTED UNDER 21 CFR 50.24 
 
20.  What conditions must be present for a study to be eligible to be conducted under 21 CFR 50.24? 
 
All of the following conditions must be present: 
   
  The human subjects are in a life-threatening situation that necessitates urgent intervention; 
  Available treatments are unproven or unsatisfactory (See also Questions 23, 24, and 25);  
  Collection of valid scientific evidence is necessary to determine the safety and effectiveness 
of the intervention;   
  Obtaining informed consent is not feasible because the subjects are not able to give their 
informed consent as a result of their medical condition;   
                                                 
17 FDAs regulations define the term, legally authorized representative as 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.  ICH E6 defines the term legally acceptable representative in almost identical language.  See 
ICH E6, 1.37 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073122.pdf). 
18 U.S. Public Law 110-85 
19 http://clinicaltrials.gov/ 
20 http://grants.nih.gov/ClinicalTrials_fdaaa/definitions.htm   
21 http://prsinfo.clinicaltrials.gov/fdaaa.html 
  7  Contains Nonbinding Recommendations 
  The intervention must be administered before consent can be obtained from the subjects 
legally authorized representative; 
  There is no reasonable way to identify prospectively individuals likely to become eligible for 
participation; 
  Participation in the research holds out the prospect of direct benefit to the subjects (See also 
Question 21); and 
  The clinical investigation could not practicably be carried out without the waiver (See also 
Question 29).  
 
(See Appendix A for the complete text of 21 CFR 50.24.) 
 
21.  What is meant by prospect of direct benefit? 
 
The information from animal and preclinical studies, other clinical data (e.g., use of the product in 
another setting or for another diagnosis or in a different study population) or other evidence should 
support the potential for the investigational product to provide a direct benefit to the individual subjects.  
 
Under 21 CFR 50.24(a)(3), the IRB must find and document that participation in an emergency research 
study holds out the prospect of direct benefit to the subjects because 
 
(1) the subjects are in a life-threatening situation that necessitates intervention;  
(2) information from appropriate animal and other preclinical studies support the potential for the 
intervention to provide a direct benefit to the individual subjects; and  
(3) the risks associated with the investigation are reasonable in relation to what is known about 
the medical condition of the potential class of subjects, the risks and benefits of standard therapy, 
if any, and what is known about the risks and benefits of the proposed intervention or activity.  
 
22.  Are trials with morbidity endpoints allowed under this regulation? 
 
Trials that have morbidity endpoints (e.g., multiple organ failure free days), rather than mortality 
endpoints, can meet the requirements of 21 CFR 50.24(a)(3) if the study is evaluating severe morbidity 
that is closely associated with mortality, and therefore clinically relevant.  For example, patients with 
stroke or head injury are at risk of both death and severe disability.  A study of an intervention to 
improve stroke outcome would always consider survival, but could also examine functional status, 
which might be the primary endpoint of the trial.22  Similarly, a study intended to improve treatment of 
status epilepticus, a life-threatening condition, might focus on reduced time to seizure control, a benefit 
likely to affect survival, even if the study itself is not large enough to show improved survival.   
 
FDA recognizes that it may be important to obtain preliminary information on dose tolerability or effect 
on a critical biomarker (e.g., measurement of brain infarcted area, degree and extent of acidosis) before 
proceeding to a study that evaluates effectiveness.  Considered from the point of view of the individual 
study subject, the study intervention could hold out the prospect of direct benefit even if the overall 
study were not large enough to prove this.  Such a study would be acceptable only if it could not be done 
in subjects capable of consenting, and all the other requirements of 21 CFR 50.24 are satisfied.  In such 
                                                 
22 61 Fed. Reg. 51508 (Comment #38) 
  8  Contains Nonbinding Recommendations 
cases, FDA would expect sponsors to provide a clear rationale for conducting these studies in non-
consenting subjects.  
 
FDA will consider all proposed morbidity endpoints on a case-by-case basis.  Early discussions with the 
appropriate FDA review divisions are encouraged.  
 
23.  What is meant by available treatments are unproven or unsatisfactory? 
 
21 CFR 50.24(a)(1) requires IRBs to document that available treatments are unproven or unsatisfactory...  
For studies involving drugs, FDA has interpreted the term available therapy to mean therapy that is specified 
in the approved labeling of regulated products, with only rare exceptions.  For example, a treatment that is not 
FDA-regulated (e.g., surgery) or a drug that is not labeled for a specific use but which is nevertheless supported 
by compelling evidence in the medical literature23 may be considered an available treatment.   
 
For studies conducted under 21 CFR 50.24, sponsors, investigators, and IRBs should consider the following: 
 
  What is the current standard of care? 
  What treatments are available? 
  Are available treatments (including standard of care treatments) unproven? (See also Question 24) 
  If a product is not approved, but widely used, could a study be done to support approval?  
  Are available treatments unsatisfactory, and if so, how? (See also Question 25) 
 
24.  What is meant by unproven? 
 
In general, unproven means that there is not substantial evidence that a treatment is effective for the condition 
of interest.  This may reflect the absence of any data or the absence of studies of acceptable quality.  The term 
unproven therapy includes: 
 
a.  Treatment that is considered standard of care but which has never been subjected to rigorous 
scientific testing or submitted to FDA for approval; 
b.  Treatment for which there are no or insufficient clinical or pre-clinical data to support safety or efficacy 
of the product; 
c.  Treatment for which existing studies and data are insufficient to serve as the basis of approval even if 
the data were submitted to FDA; 
d.  A product that is not approved for, nor does the labeling for the product contain, the specific indication 
under study; and 
e.  An available product or therapy that is not labeled for use in a specific patient population (e.g., pediatric 
use). 
 
25.  What is meant by unsatisfactory? 
 
                                                 
23 See Guidance for Industry, Available Therapy 
(http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm126637.pdf ) issued July 2004, by CBER and CDER. 
  9  Contains Nonbinding Recommendations 
Although a treatment may be approved and available, it may be unsatisfactory.  Unsatisfactory includes 
situations in which the available product or therapy is effective, but there are other drawbacks to its use, such 
as: 
a.  Safety issues (e.g., high incidence of adverse effects; exacerbation of an adverse effect for the 
relevant subject population); 
b.  Efficacy issues, including: 
  Poor survival rate; 
  The treatment is only partially effective; 
  The treatment fails to prevent a significant permanent disability; 
  Established efficacy is low; 
c.  The time for the treatment to be effective is too long (e.g., time to cessation of seizures); 
d.  The treatment has limitations related to the setting in which it is needed (e.g., should be administered 
in the field but needs refrigeration; is not portable; may be difficult to use (must be administered 
intravenously, requires surgical intervention)). 
 
III.  STUDY DESIGN 
 
The regulations for emergency research (21 CFR 50.24) do not specify study designs for conducting 
emergency research.  The study design should be adequate to evaluate whether the investigational drug 
or device has the hypothesized effect.  FDA advises study sponsors to consult with the appropriate FDA 
review division if they have questions about specific study designs or whether conducting a study under 
21 CFR 50.24 is appropriate.    
 
26.  What information should sponsors include in the proposed investigational plan (protocol) for an 
emergency research study? 
 
In addition to the information that sponsors customarily provide, the sponsor should also include 
justification for conducting the study in subjects who cannot consent, justification as to why the 
investigational intervention may be better than existing, available treatment, and a description as to why 
existing, available treatments are unproven or unsatisfactory.  In addition, the sponsor must include a 
rationale for selecting the therapeutic window in which the investigational product is to be used, and a 
description of the investigators commitment to attempting to contact a legally authorized representative 
for each subject within that window of time (21 CFR 50.24(a)(5)) or to contact a family member to 
provide an opportunity to object to the subjects participation (21 CFR 50.24(a)(6)). 
 
27.  May placebo-controlled trials be conducted under 21 CFR 50.24? 
 
Yes.  Placebo-controlled trials may be conducted, when appropriate (21 CFR 50.24(a)(1)).  In virtually 
all cases, when a placebo is used, standard care (if any) would be given to all subjects, with subjects 
randomized additionally to receive either a test treatment or a placebo.  An exception to this would be 
the situation in which the study objective is to determine whether some aspect of the standard treatment 
is in fact useful.  In that case, there would be a group that does not receive that aspect of the standard 
treatment.  Sponsors designing trials that include subjects who neither receive some aspect of the 
standard treatment nor a test article should provide a sound rationale for this type of study design.  
Choosing an appropriate design for these studies may be particularly challenging.  FDA recommends 
that sponsors consult with the appropriate FDA office or division about the proposed study design. 
  10  Contains Nonbinding Recommendations 
 
28.  What is a non-inferiority trial?  Under what circumstances can a non-inferiority trial be 
conducted under 21 CFR 50.24?  
 
A non-inferiority trial compares a test treatment to a control treatment of established effectiveness and 
seeks to show that the test treatment is not materially worse than or inferior to the control treatment.  A 
non-inferiority trial seeks to show that any difference between the two treatments is small enough to 
allow a conclusion that the test treatment has at least some effect or, in many cases, an effect that is not 
significantly less than the active control.  A non-inferiority trial may proceed under 21 CFR 50.24 if it 
meets the requirements of the regulation.  
 
For a non-inferiority trial to be informative, there would need to be clear data about the effectiveness of 
the control treatment (to make the non-inferiority study interpretable) and about known safety or other 
problems associated with the control treatment.  Non-inferiority trials are generally used in situations 
where a placebo-controlled trial would be unethical and where there are no data to suggest the new 
treatment would be more effective than the standard treatment.   
 
A non-inferiority design trial might be used, for example, in a situation in which available treatment is 
effective, but is potentially damaging to other organ systems.  The non-inferiority design could be used 
to establish effectiveness of the new therapy, while searching for a demonstrable advantage over 
available therapy (e.g., fewer side effects).  In addition to being rigorously designed to show non-
inferiority, the study should also be designed to show any safety advantage. 
 
(For more information about clinical trial design, see ICH E10, Choice of Control Group and Related 
Issues in Clinical Trials.24) 
 
29.  One of the requirements of 21 CFR 50.24 is that a study could not be practicably carried out 
without the waiver from informed consent (21 CFR 50.24(a)(4)).  What does this mean? 
 
If (1) the results obtained in consenting subjects could be generalized to subjects who are unable to 
provide consent, or (2) the research would not be unduly delayed by restricting it to consenting subjects, 
then FDA would expect the research to be performed in consenting subjects.  
 
In the first case, if the research can be carried out in subjects who can give consent (e.g., people with a 
stroke who are not comatose), and the results can be generalized to the subjects who cannot give consent 
(e.g., comatose patients), then the study would not meet the requirements of 21 CFR 50.24.  It may not 
be reasonable, however, to extrapolate results from a less ill population.  Subjects who are able to 
provide consent may have better prospects for full recovery than subjects who are unable to consent, or 
may be less susceptible to the risks of the treatment.  
 
In the second case, it might be possible to obtain consent in advance from a patient who does not have 
the condition that will be treated, but who suffers from a particular disease or condition that places 
him/her at an extremely high risk for the event to be treated (e.g., surgical patients at high risk for intra-
operative stroke, cardiac patients at high risk for cardiac arrest, already hospitalized and acutely ill 
patients).  However, even if the population at risk can be identified (e.g., cardiac patients entering a 
                                                 
24 www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm125912.pdf 
  11  Contains Nonbinding Recommendations 
hospital), it may be impracticable to obtain consent from all of them because the event (e.g., a specific 
life-threatening cardiac arrhythmia) may only occur in a very small fraction of those patients; therefore, 
subject enrollment would take too long to conduct the study in a reasonable amount of time.   
 
Sponsors may consult with the FDA on whether an investigation meets this criterion. 
 
30.  Is it possible for researchers or first responders to identify individuals who do not want to 
participate? 
 
Study protocols may describe situations in which emergency care personnel could reasonably infer that 
some incapacitated individuals would not agree to participate in a research study, even if the individuals 
meet the inclusion criteria.  For example, members of some religious groups object to blood transfusions 
and other medical interventions.  The plan should encourage the first responder to examine, as time 
permits, easily accessible sources of information, such as the medical identification bracelet, for 
evidence that may indicate the individual's willingness or unwillingness to participate in research.  The 
investigational plan should also ask first responders to determine if an LAR is present, and if present and 
there is adequate time within the therapeutic window, to ask the legally authorized representative for 
consent within that window.  If an LAR is not available, the first responder should ask a family member 
who may be present, if there is an objection to enrolling the subject in the study. (See also Questions 37, 
68, and 69.) 
 
31.  May studies in pediatric subjects be conducted under 21 CFR 50.24? 
 
Yes.  Pediatric studies may be conducted under 21 CFR 50.24.  In addition to the requirements of 21 
CFR 50.24, the IRB must find and document that the study meets the requirements of 21 CFR 50, 
Subpart D.25  21 CFR 50.52 applies to pediatric studies that involve greater than minimal risk, but hold 
out the prospect of direct benefit to subjects.  A study that meets the criteria in 21 CFR 50.24 would be 
likely to meet the criteria in 21 CFR 50.52.  However, IRBs may encounter complicated issues related to 
emergency research studies involving pediatric subjects.  21 CFR 50.54 applies to pediatric studies that 
are not otherwise approvable, but which present an opportunity to understand, prevent, or alleviate a 
serious problem affecting the health or welfare of children.  Section 50.54 provides a mechanism for an 
IRB to request a determination by the Commissioner of Food and Drugs (after consultation with a panel 
of pertinent experts) on whether a study is approvable.26  
 
FDA recommends that community consultation and public disclosure activities for emergency research 
studies involving pediatric subjects include parents of children having the condition under study, and the 
children, too, if appropriate.  
 
                                                 
25 21 CFR 50.51 applies to pediatric studies that involve no more than minimal risk.  Because emergency research studies 
conducted under 21 CFR 50.24 would involve greater than minimal risk, 21 CFR 50.51 would not be applicable to these 
studies.  21 CFR 50.53 applies to pediatric studies that involve greater than minimal risk, but which provide no prospect of 
direct benefit; because 21 CFR 50.24 requires that the research hold out the prospect of direct benefit, studies that could be 
pursued under 21 CFR 50.53 would not meet the requirements of 21 CFR 50.24. 
26 See Guidance for Clinical Investigators, Institutional Review Boards and Sponsors: Process for Handling Referrals to FDA 
under 21 CFR 50.54 (http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126577.pdf ). 
  12  Contains Nonbinding Recommendations 
32.  What is a Special Protocol Assessment (SPA)27?  
 
In general, a sponsor may request an SPA prior to initiating a study in order to address and resolve 
substantial scientific issues related to clinical trials, when that clinical trials results are likely to form 
the primary basis of an efficacy claim in a marketing application for an investigational drug.  An SPA 
allows FDA and the sponsor to reach agreement on the design, size, conduct, and analysis or other 
aspects of one or more such clinical trials.   
 
Should it be necessary to change the protocol as a result of community consultation activities, sponsors 
may need to consult with FDA to determine whether principles and expectations agreed to as part of the 
SPA process are pertinent to the revised study.   
 
Sponsors who wish to make non-scientific changes to a study protocol that is subject to both 21 CFR 
50.24 and an SPA may do so.  If a protocol is changed, the sponsor, IRB, and clinical investigator may 
subsequently need to conduct additional community consultation or public disclosure activities to ensure 
that the communities in which the research will be conducted and from which subjects will be drawn are 
aware of the changes.  
 
33.  Do Special Protocol Assessments (SPAs) apply to device studies? 
 
No.  However, the Center for Devices and Radiological Health (CDRH) does provide consultations with 
device sponsors called early collaboration meetings.  (For more information, see Early Collaboration 
Meetings Under the FDA Modernization Act (FDAMA); Final Guidance for Industry and for CDRH 
Staff.28) 
 
IV.  THERAPEUTIC WINDOW 
 
34.  What is meant by the term, therapeutic window? 
 
The therapeutic window for an investigational product is the time period after onset of the event, based 
on available scientific evidence, within which the investigational product must be used or administered 
to have its potential clinical effect (diagnostic or therapeutic).     
 
FDA recognizes that the therapeutic window for some emergency research studies may be very brief or, 
in some cases, almost non-existent (e.g., studies involving resuscitative devices that must be used 
immediately).  
 
35.  How can a sponsor determine the appropriate therapeutic window?  
 
While the therapeutic window cannot be fully known until the relationship between time of treatment 
and treatment outcome is formally studied, the sponsor must use available data (e.g., pathophysiologic 
data, animal data) to identify, to the extent possible, the therapeutic window (21 CFR 50.24(a)(5)).  The 
                                                 
27 See Federal Food, Drug, and Cosmetic Act, Section 505(b)(5)(B) and (C); Guidance for Industry: Special Protocol 
Assessment  
(http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM080571.pdf). 
28 http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm073604.htm 
  13  Contains Nonbinding Recommendations 
therapeutic window should be specified in the study protocol and explained in relation to the amount of 
time to be devoted to seeking informed consent.  (See also Question 43.) 
 
36.  How does the term, therapeutic window, apply to in vitro diagnostic device (IVD) studies? 
 
For IVD studies that meet the criteria for emergency research, the therapeutic window is the time period, 
based on available scientific evidence, during which diagnosis must occur to allow timely administration 
of appropriate therapy.   
 
In practice, the therapeutic window may be determined by the characteristics of the investigational IVD 
or by the nature of the potential therapeutic intervention(s).  For example, if available scientific evidence 
suggests that an IVD might reasonably produce accurate diagnostic results to allow administration of 
appropriate therapy only when administered within a specified interval of time, the therapeutic window 
would be that specified interval.  On the other hand, if the therapy appropriate for a particular diagnostic 
outcome must be administered within a particular interval, the therapeutic window would be that 
interval minus the amount of time necessary to administer and receive results from the IVD.  Where the 
effectiveness of both the investigational IVD and the appropriate therapy are contingent upon 
administration within specific time intervals, the therapeutic window is the shortest interval during 
which the IVD results would render a diagnosis and therapy must be administered. 
 
37.  Is it possible for an individual to indicate that he/she does not want to participate in an 
emergency research study?  
 
Yes.  The emergency situations to which 21 CFR 50.24 applies involve individuals who are typically 
unconscious or otherwise unable to communicate.  There may be some cases, however, in which an 
individual may be conscious and able to communicate.  In such cases, while full consent may be 
difficult or impossible, an individual may be able to indicate that he/she does not want to participate in 
the emergency research study, prior to administration of the test article.  If the individual declines to 
participate in the research, his/her wishes must be honored (21 CFR 50.20).  There may also be other 
evidence that an individual does not wish to participate in a study (e.g., medical jewelry, wallet card), an 
LAR at the scene who declines to provide informed consent, or a family member present at the scene 
who may be able to communicate a subjects unwillingness to participate in the study.  (See also 
Questions 30, 68, and 69.)   
 
38.  What is a legally authorized representative? 
 
Legally authorized representative 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 (21 CFR 50.3(l)).   
 
39.  Who may serve as a legally authorized representative (LAR)? 
 
Some states have statutes, regulations, or common law that specifically address consent to participation 
in research by someone other than the subject, that is, the LAR.  However, if state law does not define 
who is authorized to give consent on behalf of another person to participate in research, then state law 
governing consent for clinical procedures and/or treatments may be applicable.  Institutions and IRBs 
  14  Contains Nonbinding Recommendations 
may be able to assist clinical investigators in determining if a family member is recognized under 
applicable state law as an LAR. 
 
40.  If an emergency research study involves pediatric subjects, who may serve as a childs legally 
authorized representative (LAR)? 
 
As stated above, generally the laws of the jurisdiction in which the research takes place (e.g., State law, 
court order) govern who may serve as LAR.  Under many states laws, parents generally serve as LAR 
for their children, and in such cases would provide permission for their childs participation in a clinical 
investigation, including an emergency research study (21 CFR 50, Subpart D).  Clinical investigators 
may need to verify a claim to authority (e.g., ask to see copies of court orders or other documentation) if 
someone other than the childs parent asserts responsibility for a child.   
 
41.  What is the purpose of contacting a subjects legally authorized representative (LAR)? 
 
The clinical investigator must commit to attempting to contact a subjects LAR within the therapeutic 
window.  The purpose of contacting the LAR is to ask the LAR, if feasible, for consent to enroll the 
subject in the study, rather than proceeding without consent (See 21 CFR 50.24(a)(5)).  
 
42.  What is the purpose of contacting a subjects family member?  
 
If a subjects legally authorized representative is not available, the clinical investigator must attempt to 
contact the subjects family member (21 CFR 50.24(a)(7)(v)) in order to provide an opportunity for the 
family member to object to enrolling the subject in the study.  If a family member is present or 
accompanying the subject to the emergency room, the emergency responders or investigator must ask 
the family member immediately if there is any objection to enrolling the subject in the study.  If the 
family member objects, the subject must not be enrolled in the study. There is no requirement that the 
family member be the subjects legally authorized representative. 
 
43.  Must attempts to contact a subjects legally authorized representative or family member exhaust 
the entire therapeutic window before the test article may be administered to the subject? 
 
No.  FDA does not expect attempts to contact a legally authorized representative (LAR) or a family 
member to exhaust the entire therapeutic window before the test article may be administered.  It would 
ordinarily be expected that the potential benefit of the test article will decrease as the delay in 
administering the test article increases.  Thus, the effect of delaying administration of the test article 
should be taken into account when determining the portion of the therapeutic window to be devoted to 
seeking informed consent from a LAR or providing the opportunity for a family member to object to the 
subject's participation. 
 
Before determining that a study has met the requirements in 21 CFR 50.24, the IRB must review the 
proposed plan and procedures for attempting to contact the LAR or family member and determine 
whether the specified period of time for making these attempts, before the test article may be 
administered, is appropriate (21 CFR 50.24(a)(5) and (6)).  (See section "X. Contact of Legally 
Authorized Representatives or Family Members" for more detail.)  
 
  15  Contains Nonbinding Recommendations 
V.  IRB RESPONSIBILITIES 
 
44.  What is the IRBs role in reviewing emergency research? 
 
Under 21 CFR 56.109, an IRB must review and have authority to approve, require modifications in, or 
disapprove a proposed clinical investigation.  For emergency research under 21 CFR 50.24, the IRB, 
with the concurrence of a licensed physician who is a member of or consultant to the IRB and who is not 
otherwise participating in the clinical investigation (See also Question 51), must find and document29 
whether the investigation satisfies the criteria in 21 CFR 50.24(a)(1) through (7) and whether the 
investigation may be approved under this section.   
 
For example, IRBs must review plans for community consultation and public disclosure (21 CFR 
50.24(a)(7)(i), (ii), (iii)).  Community consultation activities should be designed to help ensure that the 
communities in which the emergency research will be conducted and from which subjects will be drawn 
are adequately informed about the risks and expected benefits of the research and are given the 
opportunity to ask questions about it, and express their views prior to the IRB making a determination 
about the research.30  In reviewing community consultation activities, IRBs will need to exercise 
judgment in determining whether these activities are adequately designed to reach the broader 
communities identified in the investigational plan.   
 
Each IRB is required to ...be sufficiently qualified through the experience and expertise of its 
members, and the diversity of the members, including consideration of race, gender, cultural 
backgrounds, and sensitivity to such issues as community attitudes, to promote respect for its advice and 
counsel in safeguarding the rights and welfare of human subjects... (21 CFR 56.107(a)).  Thus, FDA 
recommends that IRB members attend community consultation activities to hear the views of these 
communities.  
 
In addition, under 21 CFR 50.24(b), the IRB must ensure that there are appropriate procedures in place 
to inform, at the earliest feasible opportunity, subjects or their legally authorized representatives or 
family members, of the subjects inclusion in the investigation, details about the investigation, each 
subjects right to discontinue participation in the research, and other information contained in the 
informed consent document.  
 
Because the activities under this rule are unique to emergency research studies, a brief description of the 
IRBs responsibilities under 21 CFR 50.24 and one possible order in which they might occur is provided 
below.  (A sample flow chart is provided in Appendix C.) 
 
45.  What information should the clinical investigator or sponsor provide to the IRB related to a 
research protocol involving an exception from informed consent under 21 CFR 50.24? 
 
The clinical investigator or sponsor should provide the following: 
  materials documenting that the criteria for the exception from informed consent requirements for 
emergency research listed in 21 CFR 50.24(a)(1) through (4) are met;  
                                                 
29 The determinations of the convened IRB must be documented in the IRBs written meeting minutes (21 CFR 
56.115(a)(2)). 
30 Fed. Reg. 61 51514, (Comment #60) 
  16  Contains Nonbinding Recommendations 
  the clinical investigator's commitment to attempt to contact the subject's legally authorized 
representative (LAR) to obtain consent, or provide the subject's family member an opportunity to 
object, if feasible, prior to administering the test article during the time allotted for this contact, 
in order to obtain consent, within the therapeutic window (21 CFR 50.24(a)(5) and (7)(v)); 
  the proposed investigational plan, including informed consent procedures and an informed 
consent document, procedures and information to be used when providing an opportunity for a 
subject, LAR, or family member to object to a subject's enrollment and/or continued 
participation in the study (21 CFR 50.24(a)(6) and (7)(v)); 
  procedures and information to be used to inform a subject's LAR or family members about the 
subject's participation in the investigation in the event of a subject's death (21 CFR 50.24(b)); 
and 
  plans for additional protections of the rights and welfare of the subjects, including, at least, plans 
for community consultation and public disclosure prior to the start of the study (21 CFR 
50.24(a)(7)). 
 
46.  What does the IRB do with the submitted information? 
 
The IRB reviews the submitted information, determines whether the criteria under 21 CFR 50.24 and 
56.111 (and Part 50, Subpart D for pediatric research) are satisfied, and determines whether the research 
may be approved, pending consideration of the input received from community consultation activities.  
Because of the complexity of these studies and the 50.24 process, more than one IRB meeting may be 
necessary for the IRB to complete its review.  Depending on the submitted information, the community 
consultation, and its obligations under 21 CFR 50.24, the IRB will consider a wide variety of 
determinations and actions.  The list below provides one example of how an IRB might review and 
respond to materials related to an emergency research study.31 
 
  If the criteria under 21 CFR 50.24 and 56.111 (and Part 50, Subpart D for pediatric research) are 
satisfied, the IRB reviews the community consultation plan to ensure that it is designed to reach 
the communities identified in the investigational plan, will adequately inform the communities 
about the risks and expected benefits of the research, and will provide an opportunity for 
community members to express their views and ask questions about the proposed research.  The 
IRB may require changes to the community consultation plan (21 CFR 56.109(a)).    
  The investigator and the sponsor (or the IRB where appropriate, that is, when the IRB has 
decided at its discretion to carry out community consultation activities itself) conduct the 
community consultation activities.  FDA encourages IRB members to attend community 
consultation activities in order to hear the perspectives and concerns of the communities.   
  The IRB considers concerns and objections to the research raised during community consultation 
activities.  
  Before the investigation begins, the IRB documents that the sponsor has arranged for an 
independent data monitoring committee32 to exercise oversight of the clinical investigation (21 
CFR 50.24(a)(7)(iv)).  (See also Question 116.) 
                                                 
31 Some of the activities under this rule are unique to emergency research studies; the order in which these activities occur  is 
not specified in the regulations and may vary. 
32 See Guidance for Clinical Trial Sponsors: Establishment and Operation of Clinical Trial Data Monitoring Committees 
(http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126578.pdf). 
  17  Contains Nonbinding Recommendations 
  The IRB determines whether the proposed clinical investigation can be approved and allowed to 
proceed and notifies the investigators and the institution(s) in writing of its decision.    
  If the IRB decides that it cannot approve the investigation because it does not meet all of the 
criteria under 21 CFR 50.24 and 56.111 (and Part 50, Subpart D for pediatric research), or 
because of other relevant ethical concerns, the IRB promptly notifies the investigator and the 
sponsor in writing, including a statement of the reasons for the IRBs determination (21 CFR 
50.24(e) and 56.109(e)).   
  Prior to the initiation of an investigation, the IRB reviews the information that will be publicly 
disclosed to assure that the information will reach the broader communities involved and will 
adequately inform the affected communities of the plans to conduct the investigation and its risks 
and expected benefits. 
  The IRB must find and document that the public disclosure will have or has taken place prior to 
initiation of the investigation (21 CFR 50.24(a)(7)(ii)). 
  The IRB promptly provides to the sponsor in writing a copy of the information that has been 
publicly disclosed about the initiation of the study under 21 CFR 50.24(a)(7)(ii): see 21 CFR 
56.109(g).   
  After the study is completed, the IRB reviews the plans for disclosure of sufficient information to 
apprise the community and researchers of the study, including the demographic characteristics of 
the research population and its results.  
  The IRB promptly provides to the sponsor in writing a copy of the information that has been 
publicly disclosed following completion of the study (21 CFR 50.24(a)(7)(iii); 21 CFR 
56.109(g), 312.54(a) and 812.47(a)).  
  The IRB retains records related to these studies for at least 3 years after completion of the 
clinical investigation and makes them accessible for inspection and copying by FDA (21 CFR 
50.24(c)). 
 
47.  Is the IRB responsible only for finding and documenting that the plans for community 
consultation and public disclosure exist, or does the IRB have additional responsibilities for 
ensuring that these activities are implemented?  
 
  The IRB must review the plans for community consultation and public disclosure before the 
plans are implemented (21 CFR 50.24(a)(7)(i), (ii), (iii)).  FDA also expects the IRB to consider 
the concerns and objections raised during community consultation activities when the IRB 
deliberates on whether to approve, require modifications in (to secure approval) or disapprove 
the research activity.  An IRB may decide, at its discretion, that it is appropriate for the IRB itself 
to carry out community consultation activities, for example, if it determines that the plans were 
not adequately implemented. In addition, the IRB must find and document that the public 
disclosure will have or has taken place prior to initiation of the investigation (21 CFR 
50.24(a)(7)(ii)). 
 
48.  If an IRB determines that it needs additional input from the community about the study, what 
should the IRB do?  
 
The IRB could:  
 
  18  Contains Nonbinding Recommendations 
o  Invite members of the community from which the subjects will be drawn to an IRB  meeting to 
discuss the study; 
 
o  Consistent with IRB membership requirements (see 21 CFR 56.107), enhance the membership of 
the IRB by adding members who are not affiliated with the institution and are representative of 
the community; 
 
o  Use community members as consultants to the IRB under 21 CFR 56.107(f).  Use of consultants 
would not by itself adequately substitute for the community consultation called for in 21 CFR 
50.24(a)(7)(i); 
 
o  Request that the sponsor and investigator conduct additional or other community consultation 
activities; and 
 
o  Decide, where appropriate, to conduct community consultation activities itself (21 CFR 
50.24(a)(7)(i)).  The IRB could use one or more of the activities listed in Question 76 (e.g., hold 
a public community meeting to discuss the protocol). 
 
49.  Must an emergency research study be reviewed only by IRBs that are affiliated with institutions? 
 
No.  All of the options available for IRB review of non-emergency research studies are also available for 
review of emergency research studies.  Examples include, but are not limited to, the following: 
 
  Emergency research may be reviewed by an IRB that is responsible for reviewing all studies at a 
particular institution.   
  Emergency research may be reviewed by an independent (commercial) IRB. 
  Emergency research may be reviewed using a centralized IRB process.33,  34, 35)    When a 
centralized IRB process is used: 
o  The central IRB may be responsible for reviewing all aspects of the study, including local 
issues. 
o  Review may be shared by a local IRB and central IRB who cooperate in the review of 
emergency research studies. ( 21 CFR 56.114)  For example, the central IRB may agree 
to be responsible for the scientific review of the study and the informed consent 
document; the local IRB may agree to be responsible for evaluating plans for community 
consultation and public disclosure.   
 
                                                 
33 A centralized IRB review process may be helpful in multi-site trials to improve efficiency and/or consistency in the 
scientific review, and eliminate duplication of effort. 
34 OHRP requires cooperative agreements (i.e., any designation under the Assurance of another Institution's IRB or an 
independent IRB) to be documented in writing by a written agreement between the Institution and the IRB organization 
outlining their relationship.  This requirement is derived from the provision under 45 CFR 46.103(a) which states that Each 
institution engaged in research covered by this policy...shall provide written assurance satisfactory to the department or 
agency head.  For more information about cooperative review for research covered by 45 CFR 46, see 
http://www.hhs.gov/ohrp/assurances/assurances_index.html.  
35 See Guidance for Industry: Using a Centralized IRB Review Process in Multi-Center Clinical Trials; 
http://www.fda.gov/RegulatoryInformation/Guidances/ucm127004.htm. 
  19  Contains Nonbinding Recommendations 
Any IRB that reviews an emergency research study must be able to ascertain the acceptability of the 
proposed research in terms of institutional commitments and regulations, applicable law, and standards 
of professional conduct and practice; therefore the IRB needs to include persons knowledgeable in these 
areas (21 CFR 56.107).    
 
The IRB that is responsible for finding and documenting that community consultation and public 
disclosure will take place (as required by 21 CFR 50.24(a)(7)) should be knowledgeable about local 
conditions in order to evaluate the community consultation and public disclosure plans.  A central IRB 
may want to obtain input from an IRB at the institution where the research is to be conducted, to ensure 
that local concerns are addressed.  The institutions IRB may have additional insights or knowledge 
about local or State laws or regulations pertaining to emergency research studies, the demographics of 
the area in which the study will take place, the need to translate the informed consent document, 
community consultation or public disclosure materials into other languages, practices of emergency 
medical services in the area, etc.    
 
Responsibility for these studies should not be delegated to another IRB unless the institution agrees to 
the transfer.  Any such agreements to allow review using a centralized IRB process or an IRB other than 
the institutions IRB should be in writing.36  Copies of any agreements should be provided to all parties 
involved in conducting the research (e.g., the institution, the institutions IRB, the central IRB, clinical 
investigator(s)).  
 
50.  How should an IRB document its review of an emergency research study? 
 
IRB meeting minutes must be in sufficient detail to show attendance at the meetings, actions taken by 
the IRB, the vote on these actions, the basis for requiring changes in or disapproving research, and a 
written summary of the discussion of controverted issues and their resolution (21 CFR 56.115(a)(2)).  
FDA anticipates that a study in which informed consent is not obtained for all subjects is by its very 
nature controversial.  Therefore IRBs must summarize their discussions and decisions regarding the 
required elements for these studies (21 CFR 50.24(a)) in the IRBs written meeting minutes.  For 
example, the IRB would document its discussion of issues raised during community consultation 
activities, particularly discussions of community opposition to, or concern about, the emergency 
research study.  If the IRB approves the study despite the objection of some part(s) of the community, 
the IRB should also document this, and provide its reason(s) for doing so. 
 
51.  What is meant by licensed physician concurrence? 
 
The IRB must have the concurrence of a licensed physician, both initially and at the time of continuing 
review, that the criteria of 21 CFR 50.24 are met (21 CFR 50.24(a)).  The licensed physician must be a 
member of or consultant to the IRB and . . . not otherwise participating in the clinical investigation (21 
CFR 50.24(a)).  Where the licensed physician member(s) cannot participate in the deliberation and 
                                                 
36 In the preamble to the proposed rule, FDA said that the agency anticipates that research involving an exception from 
informed consent will usually be performed at an institution with an IRB.  However, any duly constituted IRB can ensure that 
the rights and welfare of research subjects are protected by fulfilling the requirements of part 56 (21 CFR part 56) and  
50.24, including  50.24(a)(7) requiring public disclosure to and consultation with the communities from which the subjects 
will be drawn.  FDA recognizes that independent IRBs can also review such studies, or institutions can enter into agreements 
to use a centralized IRB review process.  Any agreement delegating review responsibilities to an independent IRB or using a 
centralized IRB Review process should be documented in writing.  See 61 Fed. Reg. 51504  (Comment #18).  
  20  Contains Nonbinding Recommendations 
voting for any reason, participation in the convened meeting by a licensed physician consultant would be 
necessary.  Because the concurrence of the licensed physician member or licensed physician consultant 
is required for the IRB to allow these studies to proceed, IRBs should ensure that meeting minutes 
record the licensed physician members affirmative vote or the licensed physician consultants 
concurrence (21 CFR 50.24(a) and 56.115(a)(2)). 
 
VI.  SPONSORS RESPONSIBILITIES 
 
52.  What are the sponsors responsibilities under 21 CFR 50.24? 
 
In addition to sponsor responsibilities required for the conduct of all clinical trials set out in 21 CFR 
Parts 312 and 812, 21 CFR 50.24 creates additional responsibilities for emergency research conducted 
under this exception from informed consent requirements.  Below is a list of the sponsors 
responsibilities under 21 CFR 50.24 and one possible order in which they might occur.37  (A sample 
flow chart is provided in Appendix C.) 
 
  As part of the investigational plan for the study, the sponsor is responsible for defining the length 
of the potential therapeutic window,38 based on scientific evidence, during which the 
investigational product is to be administered to the subjects (21 CFR 50.24(a)(5)). 
 
  The sponsor is responsible for using an independent data monitoring committee to exercise 
oversight of the clinical investigation (21 CFR 50.24(a)(7)(iv)).39 
 
  The sponsor submits the protocol to FDA in a separate IND or IDE, the cover sheet of which 
prominently identifies the study as involving an exception from informed consent under 21 CFR 
50.24 (21 CFR 50.24(d), 21 CFR 312.23(f), 21 CFR 812.20(a)(4), 21 CFR 812.35(a)). 
 
  The sponsor must obtain FDAs written authorization before the study may proceed (21 CFR 
312.20(c); 21 CFR 812.20(a)(4)(i)). 
 
  The sponsor assists the clinical investigator in developing and providing to the IRB: 
o  information to document that the criteria for the exception from informed consent 
provided in 21 CFR 50.24(a)(1) through (4) are met;  
o  the proposed investigational plan, including informed consent procedures and an 
informed consent document, procedures and information to be used when providing an 
opportunity for family members to object to a subjects enrollment and/or continued 
participation in the study (21 CFR 50.24(a)(6) and (7)(v), and 50.24(b)); 
o  the clinical investigators commitment to attempt to contact the subjects legally 
authorized representative (LAR) to obtain consent, or provide the subjects family 
                                                 
37 Some of the activities under this rule are unique to emergency research studies; the order in which these activities occur is 
not specified in the regulations and may vary. 
38 For more information, see Section IV. Therapeutic Window. 
39 For more information on data monitoring committees, refer to FDAs Guidance on Establishment and Operations of 
Clinical Trial Data Monitoring Committees; 
www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126578.pdf. 
  21  Contains Nonbinding Recommendations 
member an opportunity to object, prior to administering the test article during the time 
allotted for this within the therapeutic window (21 CFR 50.24(a)(5) and (a)(7)(v));   
o  procedures and information to be used in the event of a subjects death to inform a 
subjects LAR or family members about the subjects participation in the investigation 
(21 CFR 50.24(b)); 
o  plans for community consultation and public disclosure prior to the start of the study; and  
o  information about opt-out mechanisms, if any are proposed by the sponsor.  (See also 
Question 68.) 
 
  The sponsor and clinical investigator (or, where appropriate, the IRB, when the IRB has decided 
at its discretion to carry out community consultation activities) conduct the community 
consultation activities.  FDA recommends that one or more IRB members attend the community 
consultation activities in person (see also Question 44), but if an IRB member is not able to do 
so, information gleaned from the community consultation activities should be provided to the 
IRB.  The IRB should determine how information from community consultation activities is to 
be provided to the IRB (e.g., oral report at IRB meeting, written report by the investigator).     
 
  The sponsor must monitor the progress of all investigations involving an exception from 
informed consent under 21 CFR 50.24 (21 CFR 312.54(a), 21 CFR 812.47). 
 
  The sponsor must promptly submit to the IND or IDE file (and to Docket Number 95S-0158 in 
the Division of Dockets Management (HFA-305), identified by the IND or IDE number), copies 
of the information that was publicly disclosed prior to initiation of the clinical investigation (e.g., 
plans for the investigation and its risks and expected benefits); see 21 CFR 50.24(a)(7)(ii), 
312.54(a), 812.47(a)). (See also Question 84.) 
 
  The sponsor must promptly provide in writing to FDA, information related to an IRBs 
determination that it cannot approve a research study under 21 CFR 50.24.  The sponsor must 
also provide this information to investigators who are participating or asked to participate in the 
same or a substantially equivalent investigation, and to other IRBs that have reviewed or are 
asked to review this or a substantially equivalent investigation (21 CFR 50.24(e), 21 CFR 
312.54(b), 21 CFR 812.47(b)). 
 
  If the IRB requires modifications in the plans for community consultation, the sponsor and the 
clinical investigator are responsible for revising the community consultation plans and 
resubmitting them for IRB review (21 CFR 56.109(a)).   
 
  If the IRB requires modifications in the plans for public disclosure, the sponsor and the clinical 
investigator are responsible for revising the public disclosure plans and resubmitting them for 
IRB review (21 CFR 56.109(a)). 
 
  Following completion of the study, the sponsor prepares information to apprise researchers and 
the community(ies) about the study, including demographic characteristics of the research 
population, and the studys results (21 CFR 50.24(a)(7)(iii)). 
  
  22  Contains Nonbinding Recommendations 
  The sponsor must promptly submit to the IND or IDE file copies of the information that was 
publicly disclosed.  The sponsor must also submit the information to Docket Number 95S-0158 
in the Division of Dockets Management (HFA-305), identified by the IND or IDE number (21 
CFR 312.54(a) and 21 CFR 812.47(a)). (See also Questions 84 and 94.)  
 
VII.  CLINICAL INVESTIGATORS RESPONSIBILITIES 
 
53.  What are the clinical investigators responsibilities under 21 CFR 50.24? 
 
In addition to the clinical investigator responsibilities set forth in 21 CFR 312 and 812, 21 CFR 50.24 
creates additional responsibilities for emergency research conducted with an exception from informed 
consent requirements.  Below is a list of the clinical investigators responsibilities under 21 CFR 50.24 
and one possible order in which they might occur.33  (A sample flow chart is provided in Appendix C.) 
 
  The clinical investigator, assisted by the sponsor, provides to the IRB: 
o  materials documenting that the criteria for the exception from informed consent given in 
21 CFR 50.24(a)(1) through (4) are met;  
o  the proposed investigational plan, including informed consent procedures and an 
informed consent document, procedures and information to be used when providing an 
opportunity for family members to object to a subject's enrollment and/or continued 
participation in the study (21 CFR 50.24(a)(6) and (7)(v), and 50.24(b)); 
o  the clinical investigator's commitment to attempt to contact the subject's legally 
authorized representative to obtain consent, or provide the subject's family member an 
opportunity to object, prior to administering the test article during the time allotted for 
this within the therapeutic window (21 CFR 50.24(a)(5) and (a)7(v)); 
o  procedures and information to be used to inform a subject's legally authorized 
representative or family members about the subject's participation in the investigation in 
the event of a subject's death (21 CFR 50.24(b)); and 
o  plans for additional protections of the rights and welfare of subjects, including, at least, 
plans for community consultation and public disclosure prior to the start of the study. 
 
  The investigator and sponsor (or the IRB, when the IRB has decided at its discretion to carry out 
community consultation activities itself) conduct the community consultation activities. IRB 
members should attend the community consultation activities in person, but if that is not 
possible, information gleaned from the community consultation activities should be provided to 
the IRB. 
 
  If the IRB requires modifications in the plans for community consultation, the clinical 
investigator and sponsor would need to revise the community consultation plans and resubmit 
them to the IRB for review and approval. 
 
  If the IRB requires modifications in the plans for public disclosure, the clinical investigator and 
sponsor would need to revise the public disclosure plans and resubmit them to the IRB for 
review and approval. 
 
  23  Contains Nonbinding Recommendations 
  Prior to beginning the study, the clinical investigator should ensure that all individuals, including 
first responders, who will carry out study-related tasks, are informed of their obligations and 
associated regulatory requirements for conducting these studies.  This may necessitate 
conducting specific training programs for first responders and site staff (for example, use of the 
investigational product, timing of and appropriate communication with legally authorized 
representatives (LARs) or family members). 
 
  During the study, the clinical investigator examines, as time permits, easily accessible sources of 
information, such as the medical identification bracelet, for evidence that may indicate the 
individual's willingness or unwillingness to participate in research, and attempts to contact the 
subject's LAR to obtain consent prior to administering the test article during the time allotted for 
this within the therapeutic window and, if feasible, asks the LAR for consent within that window 
rather than proceeding without consent (21 CFR 50.24(a)(5)).  If the LAR is not available, the 
investigator attempts to contact the subjects family member during the time allotted for this 
within the therapeutic window, to ask whether he or she objects to the subjects enrollment in the 
study (21 CFR 50.24(a)(7)(v)). 
 
  During the study, at the earliest feasible opportunity, the clinical investigator informs the subject, 
the subject's LAR, or family member (1) of the subjects inclusion in the study, the details of the 
investigation and other information contained in the informed consent document, and (2) that he 
or she may discontinue the subjects participation at any time without penalty or loss of benefits 
to which the subject is otherwise entitled (21 CFR 50.24(b)).  
 
  If the subject improves, the subject is also to be informed as soon as feasible (21 CFR 50.24(b)). 
 
  If the subject dies before a LAR or family member can be contacted, information about the 
clinical investigation is to be provided to the subjects LAR or family member, if feasible (21 
CFR 50.24(b)). 
 
  The clinical investigator summarizes the efforts made within the therapeutic window to contact 
each LAR or provide each subjects family member with the opportunity to object to the 
subject's participation.  The clinical investigator must make the summaries available to the IRB 
at the time of continuing review (21 CFR 50.24(a)(6)).40 
 
  Following completion of the study, the investigator may assist the sponsor with, or contribute to, 
preparation of information to apprise the communities and other researchers about the study, 
including demographic characteristics of the research population and the studys results (21 CFR 
50.24(a)(7)(iii)). 
 
 
VIII.  COMMUNITY CONSULTATION  
 
Under 21 CFR 50.24, the IRB must find and document that additional protections of the rights and 
welfare of the subjects will be provided, including, at least, consultation (including, where appropriate, 
                                                 
40 61 Fed. Reg. 51510 
  24  Contains Nonbinding Recommendations 
consultation carried out by the IRB) with representatives of the communities in which the clinical 
investigation will be conducted and from which the subjects will be drawn (community consultation; 
21 CFR 50.24(a)(7)(i) and 21 CFR 56.115(a)); and public disclosure for each emergency research 
protocol in which an exception from informed consent is requested (21 CFR 50.24(a)(7)(i-iii)).  For a 
multisite trial, FDA expects the sponsor and investigator to hold community consultation activities for 
communities at all sites.  
 
54.  What is meant by community consultation and what are its goals? 
 
Community consultation means providing the opportunity for discussions with, and soliciting opinions 
from, the community in which the study will take place and the community from which the study 
subjects will be drawn.  These communities may not always be the same; when they are not the same, 
both communities should be consulted.   
 
The goals of community consultation are to:  
  show respect for persons by informing the community about the study in advance;  
  inform community members about the trial in advance and provide a means for affected 
communities to provide meaningful input to the IRB before its decision to approve, 
require modifications to, or disapprove the study;  
  show respect for the community by allowing representatives of the community to identify 
potential community-level concerns and effects of the research; and 
  show respect for subjects autonomy.  Respect may be shown by including in community 
consultation activities individuals who may have, or be at risk for, the condition under 
study (and thereby obtain input from a group that is expected to be similar to the eventual 
study subjects). 
  
55.  What is meant by the community in which the research will be conducted? 
 
FDA interprets the phrase, the community in which the research will be conducted to mean the 
geographic area, e.g., hospital or other facility, or city or region, where the hospital or clinical 
investigator study site is located.  Persons from multiple states served by a regional trauma center, 
emergency room staff or other health care providers affiliated with the hospital or trauma center, and 
regional emergency medical technicians, paramedics and first responders may also be considered part of 
the community in which the research will be conducted.  (See also Questions 56, 65, and 73.) 
 
56.  What is meant by the community from which subjects will be drawn? 
 
FDA interprets the phrase, the community from which subjects will be drawn (i.e., the community at 
risk) to mean the group of patients who share a particular medical or other characteristic that increases 
the likelihood that they (or a family member) may be enrolled in the study.  (See also Questions 55, 65, 
and 73.)  
 
57.  Is community consultation the same as community consent for the study?  Is community 
consent a substitute for individual informed consent? 
 
  25  Contains Nonbinding Recommendations 
No.  Community consultation is not the same as community consent.  Community consent is the idea 
that a communitys leaders can consent to the communitys participation in a study, and thereby 
eliminate the need for researchers to obtain informed consent from individual subjects. Community 
consent is not a substitute for individual informed consent required under the IND/IDE regulations, nor 
can the community consent on behalf of individual members to permit their participation in a study.  The 
usual way of respecting a persons autonomy--by directly obtaining the individuals consentmay be 
impossible for emergency research.  Similarly, community consultation cannot substitute for individual 
consent, although community consultation does represent an opportunity for people situated similarly to 
potential study subjects to hear about the study and express views about it. 
 
58.  What should happen during community consultation? 
 
During community consultation, the sponsor and clinical investigator(s) should   
 
(1) inform the communities that it is proposed that informed consent will not be obtained for 
most (or all) research subjects, including an explanation as to why consent is not feasible (i.e., 
why the research is being conducted using the exception provided under 21 CFR 50.24); 
(2) inform the communities about all relevant aspects of the proposed study, including its risks 
and expected benefits; 
(3) hear and respond to the perspective of the communities on the proposed research;  
and  
(4) provide information about ways, if any, in which individuals wishing to be excluded may 
indicate this preference.  
 
59.  What information should be included in community consultation? 
 
The content and extent of community consultation activities (see below) may vary depending on what is 
known about the product and what is known about the risks posed by the study.  When community 
consultation plans are being developed, the following factors should be considered: 
 
o  protocol design (e.g., whether the investigational product is substituted for or added to 
standard of care); 
o  what is known about the test article (e.g., FDA approved, available safety or toxicity 
information, product history including extent of use, approval in another population or for 
another indication, scientific evidence from other countries); 
o  what is known about the medical condition; 
o  what is known about the safety and efficacy of standard of care (i.e., why existing, 
available treatments are considered unproven or unsatisfactory); 
o  study population (e.g., adults vs. pediatric population);  
o  characteristics of the setting in which the test article will be administered (e.g., will the 
product first be administered in the ambulance by EMTs or in the ER, will the product be 
continued in the ER, what is the availability of resources, what training will be provided 
to personnel who will be involved with the research) 
o  timing of administration of the test article; 
o  invasiveness of procedures necessary to administer the product; 
o  perceived availability or acceptability of alternative treatments.              
  26  Contains Nonbinding Recommendations 
 
At a minimum, the content of community consultation should include: 
 
  A summary of the research protocol, study design, and a description of the procedures to be 
followed, including the identification of any procedures which are experimental; 
  A summary of other available treatment options and what is known about their risks and 
benefits; 
  An estimate of how long the study will last and expected duration of the subjects 
participation;  
  How potential study subjects will be identified; 
  Information about the test articles use, including a balanced description of the risks and 
expected benefits and any relevant information that is known about adverse events;  
  A clear statement that informed consent will not be obtained for most research subjects; 
  The rationale as to why the study must be conducted using an exception from informed 
consent; 
  A copy of the informed consent document; 
  Relevant information that would be part of the informed consent process (21  CFR 50.25(a) 
and (b), as applicable), e.g., available treatments for the condition under study; risks/potential 
benefits of participating in the research; possibility that FDA might inspect the subjects 
records; 
  A description of the therapeutic window, during which the test article must administered, and 
the portion of that window that will be used to contact the subject's LAR;  
  A description of the attempts that will be made to contact the subject's LAR to obtain 
consent, or, if no LAR is available, a family member to provide an opportunity to object to 
the subjects enrollment in the study, both before and after the test article is administered 
(See Questions 38-43); 
  A description of the way(s) in which an individual may express his/her desire not to 
participate and avoid involvement as a subject in the research (e.g., opt-out mechanisms), if 
any will be made available (See Questions 37 and 68); 
  Reasons why community input is important;  
  Known community perceptions/concerns associated with the study, product, and/or standard 
of care; and 
  Identification of individuals to contact for more information about the study. 
 
 (See Question 81 for the contents of appropriate public disclosure.) 
 
60.  Why is community consultation important? 
 
Community consultation helps to ensure that the community(ies) most affected by the research have an 
opportunity for input into the IRBs decision-making process.  Community consultation provides an 
opportunity for the community(ies) to understand the proposed clinical investigation and its risks and 
expected benefits, and to discuss the investigation.   
 
Community consultation also helps to ensure that IRBs, independent, commercial IRBs as well as those 
affiliated with an institution, have the means to acquire (1) knowledge of community attitudes related to 
the proposed research involving an exception from informed consent and (2) information on conditions 
  27  Contains Nonbinding Recommendations 
surrounding the conduct of the research.  Such consultation may also strengthen community confidence 
in the role of the IRB and its decision-making capacity, particularly since the community discussion will 
be considered by the IRB when reviewing the investigational plans for the study.  
 
61.  What is meant by the phrase, representatives of the community (21 CFR 50.24(a)(7)(i)?  Must 
a representative of the community be an elected official? 
 
FDA interprets the terms "representatives of the community" to include not only elected officials, but 
also clergy, local community activists, leaders of advocacy organizations, tribal leaders, school officials, 
and other interested individuals.  Although sites may wish to notify elected officials about the plans for 
the research, simply informing elected officials would not be sufficient to fulfill community consultation 
requirements of the regulations. The types and number of representatives who participate in community 
consultation activities may vary by study or even across sites within the same study. 
 
It is critical that community consultation include the people who are more likely to be affected by the 
research and that they be appropriately consulted during community consultation so that they understand 
the nature of the research.  Information gleaned from broad consultation with the affected communities 
may help the IRB in its review and deliberations related to the study.  
 
62.  How does community consultation differ from public disclosure? 
 
FDA interprets the term community consultation to include discussion(s) with and by a wide group of 
community members and representatives, and includes the IRBs consideration of such discussions 
before the IRB has made a decision as to whether the research should go forward (i.e., two-way 
communication).  FDA interprets the term public disclosure, on the other hand, to be the process of 
providing information to the community(ies), i.e., a one way transfer of information.  (See Section IX. 
Public Disclosure, Question 78, for more details about public disclosure.) 
 
63.  Who should bear the costs associated with community consultation and public disclosure 
activities? 
 
Although FDAs regulations do not state who should bear the costs associated with community 
consultation and public disclosure, the agency anticipates that the sponsor would normally bear the costs 
because community consultation and public disclosure are required to conduct the research.41 
 
64.  May IRBs review the study protocol separately from the community consultation and public 
disclosure plans? 
 
FDA does not recommend reviewing the protocol separately from the other plans.  Because the protocol 
and plans for community consultation and public disclosure can all influence each other, IRBs should 
review the study protocol and community consultation and public disclosure plans as a package.  The 
IRB may review all materials, in order to find and document that the additional protections (community 
consultation and public disclosure) will be conducted.  When community consultation is completed, the 
IRB could then reexamine the protocol, and vote to approve, require modifications to, or disapprove the 
                                                 
41 61 Fed. Reg. 51515 (Comment #66) 
 
  28  Contains Nonbinding Recommendations 
research.  (The IRB may, of course, have questions related to individual items. Because of the 
complexity of these studies, it may take the IRB more than one meeting to review and approve these 
studies.)  
 
Before a clinical study may be initiated, the IRB must find and document that consultation has occurred 
with representatives of the community(ies) in which the research will be conducted and from which 
research subjects may be drawn (21 CFR 50.24(a)(7)(i) and 21 CFR 56.115(a)). 
 
65.  How can clinical investigators identify who belongs to the community from which subjects will be 
drawn? 
 
Clinical investigators may be able to identify or characterize the community at risk for the medical 
condition under study by analyzing the demographics of previous hospital patients. For example, the 
clinical investigator might review the hospital records of the last 50-100 patients admitted to the 
emergency room for the medical condition under study and tabulate characteristics (gender, age, 
ethnicity, etc.).  This will also assist the investigator in identifying the target population(s) that should be 
included in community consultation activities.  (See also Questions 55, 56, and 73.)  
 
66.  What is the IRBs role in the community consultation process? 
 
In order to approve the research, the IRB must find and document that community consultation will be 
provided (including, where appropriate, consultation carried out by the IRB; 21 CFR 50.24(a)(7)(i)).  A 
sponsor may provide to an IRB a model plan and information for use in consultation with the 
community, but it is the responsibility of the IRB to ensure the adequacy of the community consultation 
(21 CFR 50.24(a)(7)(i)).  Sponsors may work with clinical investigators and consult with the IRB in 
developing strategies and plans for consultation with the community(ies).  Sponsors may also wish to 
involve community representatives, including any relevant community leaders and groups, in 
developing community consultation plans for the geographic area in which the research will take place, 
to ensure that the study is in compliance with State or local laws and regulations.   
 
The IRB has discretion to determine the circumstances in which it would be appropriate for the IRB to 
carry out community consultation.  If community consultation is carried out by the sponsor or clinical 
investigator, FDA encourages IRB members to attend community consultation activities in order to hear 
the perspectives and concerns of the communities, and to allow the IRB to consider these concerns and 
objections during the IRBs deliberations about the research.  
 
(See also Question 74.) 
 
67.  Where should the sponsor and clinical investigator obtain information about the study for 
inclusion during community consultation? 
 
Relevant information can be found in the study protocol, investigator's brochure, and the informed 
consent document. 
 
Note that the information to be included in community consultation about investigations conducted 
under 21 CFR 50.24 is also subject to the regulations regarding the promotion of investigational drugs 
  29  Contains Nonbinding Recommendations 
and devices.  A sponsor or investigator shall not represent in a promotional context that an 
investigational new drug or device is safe or effective for the purposes for which it is under 
investigation, or otherwise promote the drug or device (21 CFR 312.7(a) and 812.7(a)). 
 
68.  Must opt-out mechanisms be provided? 
 
No.  Opt-out mechanisms (i.e., ways for an individual to indicate a desire to not participate in research 
involving an exception from informed consent) are not required under 21 CFR 50.24.42    However, 
individuals in the community may ask about them.  Opt-out mechanisms may include, for example, 
providing individuals with a wallet card or medical bracelet that contains a statement that the individual 
does not want to participate in research.  
 
The decision to use opt-out mechanisms is left to the discretion of the IRB, since opt-out mechanisms 
are not required by FDA's regulations.  The IRB should determine whether it is feasible to provide 
individuals in the community with an opt-out mechanism. The IRB may decide in advance to discuss 
ways to opt-out of the study, or such information may be added in response to community consultation 
activities.  FDA recognizes that in a multi-site trial, different IRBs may come to different conclusions 
about the feasibility of using opt-out mechanisms.  Nevertheless, FDA encourages IRBs, investigators, 
and sponsors to work together to maximize the ability of individuals to prevent their inclusion in 
research to which they would object. 
 
Community consultation activities should make the communities aware of any opt-out mechanisms that 
are to be used, and ensure that the community understands that efforts to inform the community may 
nevertheless not reach all community members.  Information about available opt-out mechanisms should 
be part of the public disclosure materials.   
 
For a multisite trial or a study that is reviewed using a centralized IRB process, FDA recommends that, 
if information about opt-out mechanisms is to be offered at any site, consideration should be given to 
providing the opt-out mechanism at all sites.  If the IRB determines that an opt-out mechanism is 
feasible, emergency room (ER) staff, first responders, and emergency medical technicians (EMTs) 
should be trained on the opt-out mechanisms used in the study.  If opt-out mechanisms are required by 
the study protocol, study procedures should include having ER or other staff check potential subjects for 
such mechanisms prior to administering the test article.  Such staff should also be trained to examine, as 
time permits, easily accessible sources of information, such as the medical identification bracelet, for 
evidence that may indicate the individual's willingness or unwillingness to participate in research.  See 
also Questions 37 and 69. 
 
69.  What is the difference between opting-out and providing a family member with an 
opportunity to object to a subjects participation in the study? 
 
An opt-out mechanism is a way that an individual can indicate for him/herself that he/she does not 
want to participate in a study involving an exception from informed consent (e.g., medical jewelry, 
wallet card, annotation on drivers license).  (See also Questions 37 and 68.) 
 
                                                 
42 61 Fed. Reg. 51500 (Comment #2) 
  30  Contains Nonbinding Recommendations 
An opportunity to object is exercised by a family member on the subjects behalf.  Prior to 
administering the test article to the subject, if there is no legally authorized representative available, the 
investigator commits to attempting to locate a family member within the therapeutic window to offer the 
family member the opportunity to object to the subjects enrollment in the study.   
 
70.  How much community consultation activity is necessary? 
 
There is no single acceptable way to accomplish or fulfill the community consultation requirements, nor 
will all studies require the same amount, type, or extent of community consultation activities.  It is up to 
the IRB to review community consultation plans and assess their adequacy, in the context of local issues 
that may need to be considered.  Different IRBs may consider more or less community consultation 
necessary, depending on the unique circumstances of a particular study and the community.  For 
example, a study involving a novel treatment that is being compared with placebo may require extensive 
consultation with the community in which the research will be conducted and with the community from 
which subjects will be drawn.  On the other hand, less extensive community consultation may be 
appropriate for a study comparing an available treatment that is considered unsatisfactory for a particular 
patient population or condition with another product about which much is known (e.g., an approved 
product that is not approved for the specific indication that is the subject of the emergency research). 
 
71.  Should sites, sponsors, or IRBs evaluate the effectiveness of community consultation and public 
disclosure activities? 
 
Sites, sponsors, and IRBs are all encouraged, but not required, to explore ways and/or conduct research 
to evaluate the effectiveness of the community consultation and public disclosure processes. 
 
72.  Who is responsible for conducting community consultation activities? What are the respective 
roles of the sponsor, clinical investigator, and IRB in conducting community consultation 
activities? 
 
The sponsor and clinical investigator have primary responsibility for planning and conducting the 
process of community consultation, hearing the concerns, and making appropriate changes in the plans 
for the research.  The IRB that is reviewing the research is responsible for using the concerns expressed 
during the community consultation process to inform their deliberations and review. 
 
Sponsors and clinical investigators who are conducting emergency research, and IRBs who are 
reviewing these studies, may not have had prior experience with community consultation.  For this 
reason, the sponsor, and clinical investigator may find it productive to consult with one another and with 
the IRB to ensure that the community consultation plans are adequate and carried out in such a way that 
the community understands the proposed clinical investigation, including any risks and potential 
benefits, and has the opportunity to express any concerns. 
  
73.  How can the sponsor and clinical investigator identify the communities that should be included 
in community consultation activities? 
 
To identify the communities, the sponsor and clinical investigator will need to consider the 
characteristics of individuals (e.g., sex, ethnicity, age, risk factors for traumatic injury) who are likely to 
  31  Contains Nonbinding Recommendations 
become the subjects in the study (i.e., the community from which subjects will be drawn).  The sponsor 
and clinical investigator should take steps to ensure that the plans for community consultation include 
(but are not necessarily limited to) measures to reach members of affected groups.  (See also Questions 
55, 56, and 65.) 
 
Example 1: Children with neurological impairments may be at greater risk of having seizures. 
Community consultation plans for a study of seizures in children should include methods to reach the 
community from which subjects will be drawn, in particular, the parents of such children (and, if the 
IRB determines that it would be appropriate, the children themselves), advocacy groups for children 
with neurological impairments, etc. 
 
Example 2:  Young male teenagers are at greater risk of having car accidents that may result in 
traumatic, life-threatening injuries.  Community consultation plans for a study involving traumatic 
injuries should include methods to reach the community at risk, e.g., young male adolescents and their 
parents, teen advocacy groups, teen social groups, and high schools. 
 
Example 3:  Cardiac patients in intensive care units (ICUs) may be at higher risk for cardiac arrest.  
Community consultation plans for treatments for cardiac arrest could include methods to reach ICU 
patients, former ICU patients, family members of ICU patients, ICU physicians, nurses or other staff. 
 
Example 4:  If an external defibrillator is going to be placed in specific locations, consider whether the 
community from which subjects will be drawn lives in or frequents these locations, e.g., assisted living 
facilities for seniors, airports, etc. 
 
74.  What should the IRB do with information received during community consultation activities? 
 
The IRB should consider the community's opinions and concerns, assess the adequacy of the 
consultation process, and incorporate the results of community consultation and discussion into its 
decision making.  For this reason, the IRB may wish to directly hear the community discussions and 
concerns expressed in those discussions, and not rely solely on summary documentation by the clinical 
investigator or feedback reported by others.   (See also Question 66.) 
 
75.  How can the IRB accomplish its review of community consultation plans? 
 
Community consultation is an additional protection of the rights and welfare of the subjects.  The IRB 
must find and document that this additional protection will be provided (21 CFR 50.24(a)(7)(i)).  Thus, 
the IRB would be expected to review the plans for community consultation.  Due to the complexity of 
these studies, such reviews may require more than one convened meeting of the IRB. 
 
The IRB should   
 
  Review, request appropriate modifications in, and approve or disapprove the plans for 
community consultation. 
 
The IRB may decide that wider community consultation and discussion are needed to help the 
IRB members better understand concerns about the study raised by specific groups within the 
  32  Contains Nonbinding Recommendations 
community.  The IRB might ask one or more IRB staff members to attend community meetings 
to hear concerns, and also to explain (if necessary) the proposed exception from informed 
consent.  The IRB could also decide to invite community representatives to participate in regular 
or special meetings of the IRB at which the emergency research will be discussed.   
 
  Assess the adequacy of the community consultation. 
 
The IRB should assess whether the community consultation plans adequately provide for 
reaching the community from which subjects will be drawn.  Because of their established interest 
in finding effective treatments for a particular condition, this community may provide the most 
meaningful feedback. 
 
In order to find and document that community consultation has occurred, as required in 21 CFR 
50.24(a)(7)(i), the IRB should determine whether meaningful feedback was secured from the 
community(ies).  Low attendance at meetings does not necessarily mean that there is no interest 
in, or no objection to, the research by the community(ies).  Rather, in cases of limited or no input 
from the community(ies), the IRB may determine that additional efforts should be made to reach 
the community(ies).  
 
  Consider the community concerns and incorporate the feedback, as appropriate, into its review of 
the protocol and informed consent document. 
 
Incorporating the results of the community consultation into the IRBs deliberations is a complex 
matter.  There are inevitably questions of how representative community representatives are, 
and how to interpret the views of the various communities involved in the research, particularly 
if they differ, and what constitutes an appropriate response.  Based on these discussions, the IRB 
could recommend limiting the pool of people from which potential subjects may be drawn, for 
example, if particular populations (e.g., a religious sect within a community) voice opposition to 
participation in the investigation.  In such cases, it would be critical to determine how members 
of such groups can be identified.  In some cases, if the community raises strenuous objections 
and concerns, an IRB may decide that the study should not be performed in that community.  
 
  Reflect consideration of community consultation in the IRBs meeting minutes (21 CFR 
56.115(a)(1) and (2)). 
 
76.  What types of activities can sponsors and clinical investigators engage in to carry out community 
consultation?  
 
The clinical investigator and sponsor (and the IRB, where appropriate) share responsibility for efforts to 
reach the community(ies) (21 CFR 50.24(a)(7)(i)).  Sponsors and clinical investigators should provide 
opportunities for broad community discussion, so that representatives of the community(ies) who are 
likely to be interested in or may be affected by the research may discuss the proposed clinical 
investigation and provide specific, immediate feedback, for example, in face-to-face meetings or 
through an interactive website.  In conducting community consultation activities, sponsors and clinical 
investigators should ensure that representatives from the community(ies) involved in the research have 
an opportunity to participate in the consultation process. 
  33  Contains Nonbinding Recommendations 
 
Sponsors and clinical investigators, (or the IRB, when the IRB has decided to carry out consultation 
activities itself) should use the most appropriate ways to provide for effective and broad-based 
community consultation, as appropriate, in a particular community setting.  Using a variety of 
community consultation activities will broaden the opportunity for community involvement.  
Community consultation activities include (but are not limited to) the following: 
 
o  Standing meetings.  Standing meetings, such as local civic public forums, may be better 
attended because such meetings are already on community members' calendars.  
 
o  Public community meetings or other special meetings specifically organized to discuss the 
research.  Such meetings may be valuable in attracting participation from individuals with 
strong interest in the research.  
 
o  Local radio and/or television talk shows.  Such programs allow viewers to "call in" to express 
their views and concerns. 
 
o  Interactive websites, focus groups and surveys. 
 
Multiple methods may be needed in order to provide the information that the IRB needs from the 
community to review the research.  Consultation activities should be widely advertised so that members 
of as many different groups within the community(ies) as possible are included.  (See also Questions 47 
and 48.) 
 
77.  How many community consultation meetings should be held? 
 
The number of meetings held and the number of members of the community(ies) consulted should be 
based on a variety of factors, such as the size of the community(ies), the languages spoken within those 
communities, the targeted research population and its heterogeneity.  FDA recognizes that each 
community consultation process will be unique, based on the community(ies) involved and the specific 
nature of the investigation.   
 
 
IX.  PUBLIC DISCLOSURE 
 
Public disclosure is required (1) before the emergency research may begin and (2) after the research has 
been completed.  The IRB must find and document that public disclosure has occurred (21 CFR 
50.24(a)(7)(ii) and (iii); 21 CFR 56.115(a)). 
 
78.  What is meant by public disclosure and what are its goals? 
 
FDA interprets the term public disclosure to mean dissemination of information (i.e., one-way 
communication) to the community(ies), the public, and researchers about the emergency research.   
 
The goal of public disclosure prior to initiation of the study is to provide sufficient information to allow 
a reasonable assumption that the broader community is aware of the plans for the investigation, its risks 
  34  Contains Nonbinding Recommendations 
and expected benefits (see 21 CFR 50.24(a)(7)(ii)), and the fact that the study will be conducted without 
obtaining informed consent from most study subjects.   
 
The goal of public disclosure after the study is completed is to ensure that the communities, the public, 
and scientific researchers are aware of the studys results.  Disclosure to researchers of the results, both 
positive and negative, of studies conducted under 21 CFR 50.24 is particularly important because such 
disclosure may help FDA and researchers learn from these studies involving vulnerable subjects who are 
unable to consent. 
 
79.  When must public disclosure occur? 
 
Public disclosure must occur both prior to initiation of the clinical investigation (see 21 CFR 
50.24(a)(7)(ii)) and after the study has been completed (see 21 CFR 50.24(a)(7)(iii)).  The IRB may also 
determine that additional disclosure is appropriate, for example, if new information becomes available 
during the study. FDA recommends that all such disclosures occur promptly and that public disclosure 
after a study is completed or terminated occur within 1 year of the completion or termination date.  (See 
also Questions 86 and 87 for discussion of study completion and termination, respectively.) 
 
 
A.  PUBLIC DISCLOSURE BEFORE THE STUDY BEGINS 
 
80.  Who is responsible for public disclosure activities before the study begins? 
 
The IRB must find and document that information about the emergency research will be publicly 
disclosed (21 CFR 50.24(a)(7)(ii) and (iii)). 
 
Clinical investigators and sponsors are responsible for arranging for public disclosure of plans for the 
investigation and the investigations risks and expected benefits.  FDA encourages sponsors to work 
with clinical investigators and IRBs in developing model strategies and information for public disclosure 
as early as possible. 
 
81.  What information must be publicly disclosed? 
 
In order for the community to understand the risks and expected benefits of the study, the clinical 
investigator and sponsor must disclose the plans for the investigation to the public (21 CFR 
50.24(a)(7)(ii)).  Information that should be disclosed may be found in the informed consent document, 
the investigators brochure, and/or the research protocol.  Similar to community consultation, 
appropriate disclosure includes: 
 
  A summary of the research protocol, study design and a description of the procedures to be 
followed, including identification of any procedures which are experimental; 
  A summary of other available treatment options and what is known about their risks and 
benefits; 
  An estimate of how long the study will last and expected duration of the subjects 
participation;  
  How potential study subjects will be identified; 
  35  Contains Nonbinding Recommendations 
  Information about the test articles use, including a balanced description of the risks and 
expected benefits and any relevant information that is known about adverse events;  
  A clear statement that informed consent will not be obtained for most research subjects; 
  The rationale as to why the study must be conducted using an exception from informed 
consent; 
  A copy of the informed consent document; 
  A description of the attempts that will be made to contact the LAR to obtain consent, or, if no 
LAR is available, a family member to provide an opportunity to object to the subjects 
enrollment in the study, both before and after the test article is administered (See also 
Questions 38-43); 
  If the IRB determines that an opt-out mechanism is appropriate and feasible, a description of 
the way(s) in which members of the community may communicate a decision not to 
participate in the study (e.g., use of medical identification bracelets or wallet cards, 
annotation on drivers license) (See also Questions 37 and 68); 
  The sites or institutions that will be participating in the research; 
  Community perceptions/concerns with the study, product, and/or standard of care that were 
raised during community consultation and any associated modifications that were made to 
the research; and 
  Identification of individuals to contact for more information about the study. 
  
(See also Question 59 for the contents of appropriate community consultation.) 
 
Sponsors and clinical investigators should submit public disclosure materials to the IRB for review prior 
to publication and dissemination.  Such review helps to ensure that the material is written in language 
that is understandable to the community(ies) from which research subjects are drawn and in which the 
research will take place, and may assist the IRBs in finding and documenting that public disclosure will 
occur. 
 
Note that the information to be disclosed about investigations conducted under 21 CFR 50.24 is also 
subject to the regulations regarding the promotion of investigational drugs and devices.  A sponsor or 
investigator shall not represent in a promotional context that an investigational new drug or device is 
safe or effective for the purposes for which it is under investigation, or otherwise promote the drug or 
device (21 CFR 312.7(a) and 812.7(a)). 
 
82.  How should public disclosure be carried out? 
 
FDA recommends that multiple forums and media resources be used to widely disseminate information 
about the study, and where additional information may be obtained.  Registering the study on the 
National Library of Medicines clinical trials web listing, http://www.clinicaltrials.gov, is required for 
applicable clinical trials.43  (See Question 19.) Sponsors may also consider including a reference to 21 
CFR 50.24 in the registration so that it is clear to FDA that the investigation involves an exception from 
informed consent. 
 
                                                 
43 P.L. 110-85, The Food and Drug Administration Amendments Act of 2007, Title VIII, Clinical Trial Databases 
(http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_public_laws&docid=f:publ085.110). 
  36  Contains Nonbinding Recommendations 
Other disclosure activities that may be conducted include: 
 
  targeted mailings to households in the communities, with information about how to obtain 
further details; 
  advertisements and articles in the English language, and if appropriate, foreign language, 
newspapers (Public outreach documents should be translated into languages that are common in 
the area served by the facility where the investigation is being conducted and in the communities 
from which subjects will be drawn.); 
  clearly marked links and information on the sponsors and participating hospitals Internet web 
sites; 
  summary materials that are accessible to non-English speaking or homeless populations who 
reside in the community from which research subjects are likely to be drawn;  
  presentation or distribution of information at meetings of community, local government, civic, 
or patient advocacy groups;   
  letters to local and regional community leaders and first responders (e.g., police, paramedics);  
  announcements to local/regional hospital staff(s); 
  public service announcements and interviews or discussions on talk radio or television 
programs;  
  press conferences and briefings; and 
  meetings or activities provided by hospitals and institutions existing community outreach 
programs. 
 
FDA does not believe that the following disclosure activities, by themselves or in combination, satisfy 
the public disclosure requirements intended under 21 CFR 50.24: a legal notice; sending a letter to 
physician specialists about the study; informing staff at the hospital where the study will take place.  
Such activities, while useful, should be combined with other methods to ensure that public disclosure 
requirements are fulfilled. 
 
83.  What does the IRB do with the information that has been publicly disclosed? 
 
Ordinarily, the clinical investigator would provide the information that has been publicly disclosed (e.g., 
copies of newspaper advertisements, tapes or transcripts of radio and television shows, minutes of 
community meetings) to the IRB so that the IRB is aware that disclosure has occurred.  As required by 
21 CFR 56.109(g), the IRB must promptly provide the sponsor with a copy of the disclosed information.  
The sponsor, in turn, provides copies to FDA (21 CFR 312.54(a) and 812.47(a)).  See Question 84.  
There may also be situations in which flow of information could vary, for example, if the sponsor 
provides the information to the IRB, at the same time that the sponsor submits the information that has 
been disclosed to the FDA docket. 
 
84.  What does the sponsor do, upon receiving from the IRB the information that has been publicly 
disclosed? 
 
Upon receiving copies of the information that has been publicly disclosed from the IRB, the sponsor 
must submit the information to FDA, i.e., to the IND/IDE and to FDAs Dockets Management at the 
following address:  
 
  37  Contains Nonbinding Recommendations 
Docket Number 95S-0158 (IND#/IDE#)  
Dockets Management Branch (HFA-305) 
Food and Drug Administration  
Room 1061  
5630 Fishers Lane 
Rockville, MD 20852 
 
Telephone: (301) 827-6860 
Fax: (301) 827-6870 
 
See 21 CFR 56.109(g), 21 CFR 312.54(a) and 21 CFR 812.47(a). 
 
Members of the public wishing to examine public disclosure information submitted to the docket may 
visit the FDA's Dockets Management Branch in person, view the materials on-line 
(http://www.regulations.gov/search/Regs/home.html#docketDetail?R=FDA-1995-S-0036), or request a 
copy by sending a Freedom of Information Act request to FDA at the address shown below (21 CFR 
312.130(d) and 812.38): 
 
Food and Drug Administration 
Division of Freedom of Information (HFI-35) 
5600 Fishers Lane 
Rockville, MD 20857 
Telephone: (301) 827-6500 
 
B.  PUBLIC DISCLOSURE AFTER THE STUDY IS COMPLETED OR TERMINATED 
 
85.  What must be disclosed following completion of the clinical investigation? 
 
Following completion of the clinical investigation, the IRB must find and document that sufficient 
information, including the demographic characteristics of the research population and the study results, 
will be disclosed to the community(ies) and to other researchers  (21 CFR 50.24(a)(7)(iii)).44  FDA 
recommends that the sponsor provide the information to the IRB(s) for review prior to disclosure. 
 
The information disclosed should provide sufficient detail to allow a clear understanding of the study 
design and its results, both positive and negative, including: 
  information about the primary outcome(s) of the study; 
  the number and nature of adverse events associated with the test article; 
  whether the study was terminated, and the basis for that decision. 
 
Note that the information to be disclosed about the results of investigations conducted under 21 CFR 
50.24 is also subject to the regulations regarding the promotion of investigational drugs and devices.  A 
sponsor or investigator shall not represent in a promotional context that an investigational new drug or 
device is safe or effective for the purposes for which it is under investigation, or otherwise promote the 
drug or device (21 CFR 312.7(a) and 812.7(a)). 
                                                 
44 For more information about reporting results at clinicaltrials.gov, see 
http://chestjournal.chestpubs.org/content/136/1/295.full?sid=5bf6541b-d31a-4bc2-9460-35a4a3172186.  
  38  Contains Nonbinding Recommendations 
 
86.  What is meant by completion of the clinical investigation? 
 
Completion of the clinical investigation means the date that all study subjects have been enrolled and 
follow-up of primary endpoint data on all subjects has been completed in accordance with the clinical 
protocol.  For studies that involve more than one study site, the sponsor may consider completion of the 
study to occur when data from all of the study sites have been submitted to the sponsor.   
 
87.  What is meant by termination of the clinical investigation? 
 
Termination of the clinical investigation refers to a situation in which a study ends or is discontinued 
before its planned completion (e.g., if a data monitoring committee determines that a study ethically 
requires termination following interim analysis of study data).45  
 
88.  Does FDA expect sponsors to publicly disclose information about studies that have been 
terminated/discontinued? 
 
Yes.  FDA expects sponsors to publicly disclose information about studies conducted under 21 CFR 
50.24 that have been terminated or discontinued in the same way that sponsors must disclose 
information about studies that have been completed.  Note that sponsors must report to FDA when a 
study is terminated or discontinued (21 CFR 312.31(a)(2), 812.150(b)(7)), and it is FDAs expectation 
that the public also be informed of terminations/discontinuances. 
 
The agency has previously stated that there must be a scientific need to conduct clinical investigations 
involving subjects who are unable to consent; if previous investigations have already provided a 
scientific answer to a particular question, this information should be shared broadly with the research 
community.  In the interests of limiting the number of studies that involve subjects who are not able to 
provide informed consent, it is FDAs position that ...broadly sharing both positive and negative 
results of research with the scientific community may reduce or eliminate unnecessary duplication of 
research that has been conducted and verified by others.46 
 
89.  Who is responsible for disclosing information about the study after it is completed or terminated? 
 
The sponsor is responsible for analyzing the results of the overall investigation, including the 
demographic characteristics of the research population, and for ensuring that these results are published 
and/or reported.  
 
90.  When should the sponsor disclose the results of the study? 
 
Disclosure of the study results to the community(ies) should occur within a reasonable period of time 
following completion or termination of the investigation.  For a multi-site investigation, this disclosure 
may require waiting until the data from all sites have been analyzed by the sponsor.  FDA recommends 
that such disclosures occur within 1 year after the date the study was completed or terminated.  (See also  
                                                 
45 21 CFR 812.3(q):  Termination means a discontinuance, by sponsor or by withdrawal of IRB or FDA approval, of an 
investigation before completion. 
46  61 Fed. Reg. 51516-51517 (Comments 75-77) 
  39  Contains Nonbinding Recommendations 
Questions 86 and 87 for a discussion of study completion and termination, respectively.)  
 
91.  Would reporting results of the investigation in the ClinicalTrials.gov database be sufficient for 
purposes of meeting the public disclosure requirements under 21 CFR 50.24 after the study is 
completed? 
 
No.  Such reporting, similar to publication of results in a scientific or medical journal, would likely 
satisfy the requirement to apprise...researchers about the study, including demographic characteristics 
of the research population and its results.  However, the information must also be disclosed to the 
community from which subjects are drawn and the community in which the research takes place (i.e., 
lay persons, members of the general public).  The IRB should review plans to disclose information 
following completion of the clinical investigation, to assure that the plans address appropriate ways of 
disclosing the results to both the lay and research communities (21 CFR 50.24(a)(7)(iii)). 
 
92.  How should the information be disclosed to the community in which the clinical investigation 
was conducted and the community from which the subjects were drawn (21 CFR 50.24(a)(7)(iii))? 
 
Sponsors and clinical investigators should use appropriate mechanisms (e.g., news articles, television or 
radio programs, community meetings) to provide information about the results of the research to the 
community(ies) in which the clinical investigation was conducted and from which research subjects 
were drawn.  It is up to the IRB to determine whether the methods described in the public disclosure 
plans are appropriate for the intended audience. 
 
93.  How can information about the results of the study be disclosed to other researchers? 
 
Sufficient information may be contained in a scientific publication of the results of the completed or 
terminated investigation or in submissions to ClinicalTrials.gov; it may also be communicated by other 
means (e.g., symposia, abstracts, posting on websites).  
 
94.  Must information that is disclosed after the study is completed or terminated be submitted to 
FDAs Public Docket? 
 
Yes.  See 21 CFR 56.109(g), 312.54, and 812.47(a).  (See also Question 84 for more information about 
submission of information that has been disclosed.)  
 
 
X.  CONTACT OF LEGALLY AUTHORIZED REPRESENTATIVES OR FAMILY MEMBERS 
 
Contact with a subjects legally authorized representative or family member may occur at various points 
during the study (e.g., prior to administration of the test article, after administration of the test article, 
after a subject dies).  This section discusses the procedures that must be developed for contacting a 
subjects legally authorized representative or family member at each of these points. 
 
A.  PRIOR TO ADMINISTRATION OF THE TEST ARTICLE 
 
  40  Contains Nonbinding Recommendations 
For each subject unable to provide informed consent, the clinical investigator participating in emergency 
research must commit to attempting to seek written informed consent within the therapeutic window, if 
feasible, from the subjects legally authorized representative (LAR; 21 CFR 50.24(a)(5)).  If no LAR is 
available, the clinical investigator must commit to attempting to contact a family member to provide an 
opportunity to object to the participation of an individual, before administering the test article without 
informed consent, if feasible (21 CFR 50.24(a)(7)(v)). 
 
95.  What procedures for contacting a subjects legally authorized representative (LAR) or family 
member prior to administration of the test article are required by 21 CFR 50.24? 
 
IRBs must find and document that procedures are in place for contacting and providing information to a 
subjects LAR or family member within the therapeutic window or at the earliest feasible opportunity 
(21 CFR 50.24(a)(6) and (a)(7)(v)). 
 
FDA anticipates that such procedures and information will likely parallel those approved by the IRB for 
use in obtaining informed consent from subjects or their LARs.  IRBs must review, approve, and 
document that procedures are in place to be used (1) in attempting to obtain informed consent from a 
LAR, and (2) if no LAR is available, in attempting to contact a family member and provide an 
opportunity for the family member to object, as soon as is feasible, ideally, prior to enrolling a subject in 
the study and administering the test article (21 CFR 50.24(a)(6); see also section IV. Therapeutic 
Window).  
 
96.  How can IRBs ensure that investigators make every attempt to contact the subjects legally 
authorized representative (LAR) or family member within the therapeutic window? 
 
The IRB must review the procedures that will be used to attempt to contact the subject's LAR or family 
member within the therapeutic window, if feasible (21 CFR 50.24(a)(6)).  In addition, the investigator is 
required to summarize efforts made to contact LARs and family members, and make this information 
available to the IRB at the time of continuing review (21 CFR 50.24(a)(5) and (7)(v)).  
  
In order to summarize efforts to contact LARs and family members, the investigator may develop 
his/her own procedures or methods to document how this requirement is carried out.  Examples of 
possible methods, include (but are not limited to): 
 
  The investigator/site staff may record in the case history for each subject information about 
efforts that were made to contact the subjects LAR or family member (e.g., date, time, name 
of individual to be contacted, method of contact [phone, in person], success or failure of the 
effort to contact the LAR/family member, staff member who attempted the contact). 
 
  The investigator may develop a checklist that reflects the required steps for contacting the 
LAR or family member.  The checklist could be completed for each subject who is enrolled 
in the study, and included in the subjects case history or retained elsewhere in the study 
records.  
 
  The investigator may appoint an individual to serve as the liaison with the LARs and families 
of study subjects for all research projects.  The goal of having a liaison would be to assure 
  41  Contains Nonbinding Recommendations 
communication with subjects, their LARs, and their families, and thereby better protect the 
subjects rights.  The liaison could document efforts made to contact subjects LARs or 
family members, e.g., keep a log of such contacts. 
 
The IRB should determine how information summarizing efforts to contact LARs and family members 
are to be provided to the IRB (e.g., oral presentation at IRB meeting, written report by the investigator).  
The IRB should review the summaries provided by the investigator at the time of continuing review and, 
if necessary, require modification of the procedures as a condition for continuing approval of the 
research (21 CFR 56.109(a)).  IRBs also have authority to observe or have a third party observe the 
consent process and the research (21 CFR 56.109(f)), and may exercise this authority to directly observe 
the clinical investigators efforts to contact LARs or family members while the research is going on.  
 
97.  These studies involve an exception from informed consent requirements.  Why must an informed 
consent document be prepared? 
 
Although most, and perhaps all subjects will not be able to give consent, an IRB-approved informed 
consent document, consistent with 21 CFR 50.25, must be prepared (21 CFR 50.24(a)(6)).  Informed 
consent is to be obtained from subjects or their legally authorized representatives when feasible.  The 
information in the informed consent document is also to be used when providing an opportunity for a 
family member to object to a subject's participation in the clinical investigation.   
 
98.  What is the purpose of contacting the subjects family member? 
 
The purpose of contacting the subjects family member is to provide an opportunity for a family member 
to object to the subjects participation in the research (21 CFR 50.24(a)(6)).  The informed consent 
document may be used as the source of the information that is explained to the family member; FDA 
recommends that a copy of the informed consent document be given to contacted family member(s). 
 
99.  If a legally authorized representative (LAR) is available, what must the investigator do? 
 
If a LAR is available, the investigator must obtain informed consent from the LAR within the 
therapeutic window, if feasible, before enrolling the subject in the study (21 CFR 50.24(a)(5)).  If the 
LAR refuses to sign the consent form, the subject must not be enrolled in the study (21 CFR 50.20). 
 
100.  If the LAR is not available, but a family member is, what must the investigator or first responder 
do? 
 
The investigator or first responder must ask the family member if the family member objects to the 
subjects participation before enrolling the subject in the study (21 CFR 50.24(a)(7)(v)).  If the family 
member objects or indicates that the subject would not have wanted to participate in a research study, 
the subject must not be enrolled in the study (21 CFR 50.24(a)(6) and (7)(v)). 
 
101.  If the subjects legally authorized representative (LAR) is available, and the LAR agrees to allow 
the subject to participate in the study, must the clinical investigator also contact the subjects 
family member? 
 
  42  Contains Nonbinding Recommendations 
No.  When a LAR is available, the LAR can provide legally effective consent for the subject.  
 
102.  Must a family members objection to the subjects participation in the study be in writing? 
 
No.  A family member may verbally object to an individual's participation in a study.  Such objections 
should be documented, for example, by placing appropriate entries in the individual's case history or 
medical chart.  If more than one family member is present and provided with the opportunity to object to 
the subject's participation in the study, and they disagree, the researcher and family members would 
need to work out the disagreement before the subject may be enrolled in the research.47 
 
B.  AFTER ADMINISTRATION OF THE TEST ARTICLE 
 
103.  How should a subjects family be told about the subjects participation in the study? 
 
Clinical investigators may use various methods to ensure that each subjects family is promptly 
informed about the subjects participation in the study.  FDA recommends that the information be 
communicated through personal contact with the subjects LAR or family if at all possible, and as soon 
as feasible after the enrollment has taken place.  However, FDA recognizes that personal contact is not 
always possible.  To ensure that the information is provided in a timely manner, the information about 
the study should be included in any communications with each subjects family.  When face to face 
contact is not possible, to ensure that the subjects family receives the information, families should be 
notified via methods that allow receipt verification or confirmation (e.g., registered letter, e-mail with 
read receipts).  The investigator could also appoint a liaison, who is responsible for contacting the 
subjects LAR and/or family member.  Sites may consider development and use of a checklist to show 
the steps taken to notify a subjects family about the subjects participation in the investigation. 
 
FDA recommends that sites not simply refer subjects and family members to websites, as these may not 
describe the study sufficiently nor would they allow the family members to obtain prompt, direct 
answers to their questions. 
 
104.  If a subject is enrolled in a study under 21 CFR 50.24, what information must be provided to the 
subject, the subjects legally authorized representative (LAR) or family member? 
 
IRBs must ensure there are procedures in place to provide information at the earliest feasible 
opportunity about the subjects inclusion in the clinical investigation, the details of the investigation and 
other information contained in the informed consent document, to (1) the subject, if the subject's 
condition permits this, (2) the subject's LAR (if the subject remains incapacitated), or (3) if no LAR is 
available, the subject's family member (21 CFR 50.24(b)). The information must include notice that the 
subject, the subjects LAR (if the subject remains incapacitated), or family member (if no LAR is 
available) may discontinue the subjects participation in the study at any time without penalty or loss of 
benefits to which the subject is otherwise entitled (21 CFR 50.24(b)). 
 
105.  What is meant by feasible? 
 
                                                 
47  61 Fed. Reg. 51506 (Comment #25) 
  43  Contains Nonbinding Recommendations 
FDA interprets the term "feasible" to incorporate the idea of "practicability" and recognizes that in some 
instances, for example, it may not be possible to provide information to the subject (e.g., if the 
individual does not survive or is mentally incompetent), or to the subject's legally authorized 
representative or family member (e.g., if the identity of the subject is never determined).48  
 
106.  If a subject regains consciousness, or his legally authorized representative (LAR) is found, must 
consent be obtained from the subject or the subjects LAR in order to continue participation in the 
study? 
 
No, consent is not required for continued participation in the study.  21 CFR 50.24(b) requires the IRB 
to ensure that there are procedures in place to provide information about the emergency research study 
to the subject, the subjects LAR or family member at the earliest feasible opportunity.  However, the 
subject, the subjects LAR, or family member may discontinue the subjects participation at any time. 
 
FDA regulations do not require that written informed consent be obtained from the subject or the 
subjects LAR once the subject is enrolled, in order to continue the subjects participation in the study.  
The IRB may nevertheless decide that developing an informed consent form to be used for continuation 
in the study would be appropriate.  FDA notes, however, that it may not always be possible to develop a 
meaningful informed consent document for continued participation in the research, because the relevant 
information may vary significantly from subject to subject, depending upon when it becomes feasible to 
provide the information to the subject or the subjects LAR.  As FDA noted in the preamble to the Final 
Rule:  
 
  It is up to the IRB to determine whether it is possible or desirable, given the nature of the clinical 
investigation, to have an actual document that could be signed for continued participation in the 
investigation.  The agency notes that such a document, which would be signed after entry into an 
investigation, would not constitute consent for what had already occurred; it could, however, 
serve to document that the subject consented to continued participation in the investigation.49 
 
(See also Question 105, What is meant by feasible?) 
 
107. In the event of a subjects death, must information about the subjects enrollment in the study be 
provided to the subjects legally authorized representative (LAR) or family member? 
 
Yes.  IRBs must ensure that there are procedures in place to provide information about the study to the 
LAR or family member in the event of the subject's death, if feasible (21 CFR 50.24(b)).  Although the 
regulations do not specify when this information should be provided, FDA recommends that the LAR or 
family member be told about the subjects enrollment at the earliest feasible opportunity.  Informing the 
LAR or family member should strike a balance between prompt notice and consideration for the LARs 
or family members emotional state. It may therefore be helpful to consult with a hospital chaplain or 
social worker to determine an appropriate place and time, as soon as possible under the circumstances, 
to provide this information.   
 
                                                 
48 61 Fed. Reg. 51519 (Comment #91) 
49 61 Fed. Reg. 51519 (Comment #94) 
  44  Contains Nonbinding Recommendations 
108.  When must information about the subjects enrollment in the study be provided to the subjects 
legally authorized representative (LAR) or family member? 
 
The regulations require this information to be provided at the earliest feasible opportunity; see 21 CFR 
50.24(b).  In order to assure that the subjects LAR or family member is informed about the subjects 
enrollment in the study, FDA recommends that the investigator inform the LAR and family member in 
person if possible, or if that is not possible, the investigator may do so in writing, using a method to 
confirm delivery, about the subjects participation in the study. 
 
(See also Question 105, What is meant by feasible?) 
 
109.  What records must the clinical investigator maintain with respect to efforts to contact the legally 
authorized representative (LAR) or a subjects family member? 
 
Clinical investigators must summarize efforts made within the therapeutic window to contact each 
subjects LAR for consent, or in the event that a LAR is unavailable, the subject's family member to 
provide an opportunity to object to the subject's participation in the study.  The clinical investigator must 
make the information available to the IRB at the time of continuing review (21 CFR 50.24(a)(5) and 
(a)(7)(v)).  FDA suggests that clinical investigators record this information in the subjects' case histories 
(e.g. study records, subjects' medical records, or other files) so that it may be easily retrieved, analyzed, 
and reported to the IRBs, and so that it is accessible if FDA conducts an inspection.   
 
110.  What access do clinical investigators have to the medical records of research subjects? 
 
Many emergency research studies include both mortality and morbidity endpoints.  Having information 
about both types of endpoints is very important for evaluation of the test article.  Obtaining information 
about morbidity endpoints would generally require examination of the subject or review of the subjects 
medical records.  
 
FDAs regulations require clinical investigators to prepare and maintain adequate and accurate case 
histories (21 CFR 312.62(b) and 812.140(a)).  In general, the investigator should arrange to have access 
to all of the records that are generated and maintained from enrollment until discharge or death, unless 
the subject or the subjects legally authorized representative (LAR) or family member discontinues the 
subjects participation in a study.  (If the subjects participation in the study has been discontinued, see 
also Question 111.)  
 
If the investigator is also the subject's personal physician, then the investigator would continue to have 
access to the subject's medical records, unless the subject or the subject's LAR discontinues the subject's 
participation in the study.  (See also Question 111.) 
 
If the subject has been discharged or transferred to another medical facility (e.g., rehabilitation center, 
nursing home) and the investigator is no longer involved in the subject's daily care, then the investigator 
would have to contact the subject or his LAR to obtain the release of medical records from the subjects 
treating physician and/or the medical facility to the investigator.  
 
  45  Contains Nonbinding Recommendations 
111.  If a subject, legally authorized representative (LAR), or family member discontinues the 
subjects participation in the study, to what records would the researcher still have access? 
 
If a subject or the subject's LAR discontinues the subject's participation in the study, the investigator 
would continue to have access to data that have already been collected.   
 
However, the investigator would not have access to the subjects medical records after the date of 
discontinuation (even if the subject has not been discharged from the hospital), unless the subject or the 
subjects LAR specifically consents to such access.   
 
If the subject or subject's LAR has discontinued the subject's participation in the study and the 
subject subsequently dies, access to the individual's medical records from the point of discontinuation 
until the subjects death would have to be obtained from the individual's LAR.  Provisions of the Health 
Information Portability and Accountability Act (HIPAA)50 may apply to the release of medical records 
of individuals who are deceased; there may also be applicable state or local laws.  See also Question 
113. 
 
(See also FDAs guidance, Data Retention When Subjects Withdraw from FDA-Regulated Clinical 
Trials.51) 
 
112.  Why is access to subjects data (e.g., medical and study records) important?  Can a subject 
withdraw use of his or her data that have already been collected, or results in the research 
database?51  
 
A subject may not withdraw use of his or her data that have already been collected.  FDA regulations 
require investigators to prepare and maintain adequate case histories recording all observations and other 
data pertinent to the investigation on each individual treated with the investigational product.  If a 
subject were to be able to dictate whether already collected data are included or excluded, the potential 
for bias would be immense, particularly if the clinical investigation were not blinded.   
 
FDA needs to hear about all important effects of the investigational product, so that the agency can (1) 
ensure that the results of the investigation are not biased, and (2) make a determination as to the 
products safety and effectiveness.  
 
113.  Can information about a subjects death be collected even if the subject has discontinued 
participation in the study? 
 
Yes.  Although a subject may have discontinued participation in a study, data about a subjects death is 
contained in public vital statistics records.  Access to public records is not subject to restriction under 21 
CFR 50.24 or other FDA regulations. 
 
                                                 
50 More information about HIPAA can be obtained from the Office for Civil Rights: http://www.hhs.gov/ocr/privacy/. 
51 www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126489.pdf 
 
  46  Contains Nonbinding Recommendations 
114.  Do FDAs regulations require that informed consent be obtained from a deceased subjects 
family members before public records can be accessed? 
 
No.  Access to public records is not subject to restriction under 21 CFR 50.24 or other FDA regulations.  
The information included in death records may be accessed and collected without triggering FDAs 
informed consent requirements.   
 
Under FDA's regulations, "human subject" means "an individual who is or becomes a participant in 
research, either as a recipient of the test article or as a control.  A subject may be either a healthy human 
or a patient." (See 21 CFR 50.3(g); similar language is found at 21 CFR 312.3 and 812.3(p).)  FDA has 
interpreted its regulations as applicable only to research involving living human subjects.  Since the 
individuals referenced are deceased, such review does not meet FDAs definition of research involving 
human subjects.  FDA has also concluded that a limited look at public death records would, in any 
event, be encompassed by the exception from informed consent for emergency research.52  
 
Public access to autopsy records would be determined by applicable State or local laws and regulations.    
 
115. For emergency research under 21 CFR 50.24, involving an exception from informed consent, 
may an IRB or Privacy Board waive the authorization requirement that would otherwise apply 
under 45 CFR 164.508 of the HIPAA Privacy Rule?  
 
Yes.  Under the Privacy Rule issued to implement the Health Insurance Portability and Accountability 
Act of 1996 (HIPAA), an individual must generally sign a permission, known as an Authorization, 
before a covered entity may use or disclose the individual's protected health information (PHI) for 
research purposes, unless the covered entity receives documentation that an IRB or Privacy Board has 
waived or altered the Authorization requirement. 45 CFR 164.512(i).  In the context of emergency 
research involving an exception from informed consent under 21 CFR 50.24, there may well be 
considerations present, such as the inability of the subjects to provide Authorization as a result of their 
medical condition, that could support an IRB or Privacy Board decision to waive the HIPAA Privacy 
Rule's Authorization requirement.      
 
The Privacy Rule at 45 CFR 164.512(i) contains criteria for waiver or alteration of the Authorization 
requirement by an IRB or Privacy Board.  In particular, the documentation of waiver approval obtained 
by the covered entity must, among other things, include a statement that the IRB or Privacy Board has 
determined that the alteration or waiver, in whole or in part, of Authorization satisfies the following 
criteria:   
 
- The PHI use or disclosure involves no more than minimal risk to the privacy of individuals 
based on at least the presence of (1) an adequate plan to protect PHI identifiers from improper 
use and disclosure; (2) an adequate plan to destroy those identifiers at the earliest opportunity, 
consistent with the research, absent a health or research justification for retaining the identifiers 
or if retention is otherwise required by law; and (3) adequate written assurances that the PHI will 
not be reused or disclosed to any other person or entity except (a) as required by law, (b) for 
authorized oversight of the research study, or (c) for other research for which the use or 
disclosure of the PHI is permitted by the Privacy Rule.  
                                                 
52 See Preamble to the October 2, 1996 Final Rule, Comment #94, 61 Fed. Reg. 51519. 
  47  Contains Nonbinding Recommendations 
 
- The research could not practicably be conducted without the requested waiver or alteration.  
 
- The research could not practicably be conducted without access to and use of the PHI. 
 
Thus, to the extent an IRB or Privacy Board has determined that the circumstances of the emergency 
research subject to an exception from informed consent under 21 CFR 50.24 satisfy the HIPAA Privacy 
Rules waiver criteria, and has documented the waiver approval in accordance with 45 CFR 
164.512(i)(2), a covered entity may use or disclose PHI for the research based on such documentation. 
 
XI.  DATA MONITORING COMMITTEE (DMC) 
 
Before a study may be initiated, the IRB must find and document that an independent DMC has been 
established to exercise oversight of the clinical investigation (21 CFR 50.24(a)(7)(iv)). 
 
 FDA interprets this regulatory provision to permit a sponsor to either establish an independent DMC or 
to secure the services of an already established DMC to exercise oversight of the clinical investigation.  
FDA is making this clarification to provide flexibility to sponsors in meeting the regulatory 
requirements.    
 
For more information on the roles, responsibilities and operating procedures of Data Monitoring 
Committees, please see FDA's Guidance for Clinical Trial Sponsors, Establishment and Operation of 
Clinical Trial Data Monitoring Committees, March 2006.53 The DMC guidance represents FDA's 
current thinking on DMCs and their operations.  
 
XII.  FOR FURTHER INFORMATION 
 
A.  CONTACTS 
 
Sponsors, clinical investigators, and IRBs with questions regarding policy or applications pertaining to 
an exception from informed consent requirements for emergency research under 21 CFR 50.24 may 
contact the appropriate office(s) identified on FDA's website:  
http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/default.htm. 
 
 
B.  FDAs WEBSITES 
 
Good Clinical Practice:  
http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/default.htm 
   Center for Biologics Evaluation and Research (CBER): 
http://www.fda.gov/BiologicsBloodVaccines/default.htm 
   Center for Drug Evaluation and Research (CDER):   
http://www.fda.gov/Drugs/default.htm 
   Center for Devices and Radiological Health (CDRH): http://www.fda.gov/MedicalDevices/default.htm 
                                                 
53 http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126578.pdf 
  48  Contains Nonbinding Recommendations 
 
  
21 CFR 50.24                 APPENDIX A 
   
The text of 21 CFR 50.24 appears below: 
 
Subpart B--Informed Consent of Human Subjects Sec. 50.24, Exception from informed consent 
requirements for emergency research.   
 
(a) The IRB responsible for the review, approval, and continuing review of the clinical investigation 
described in this section may approve that investigation without requiring that informed consent of all 
research subjects be obtained if the IRB (with the concurrence of a licensed physician who is a member 
of or consultant to the IRB and who is not otherwise participating in the clinical investigation) finds and 
documents each of the following: 
 
(1) The human subjects are in a life-threatening situation, available treatments are unproven or 
unsatisfactory, and the collection of valid scientific evidence, which may include evidence 
obtained through randomized placebo-controlled investigations, is necessary to determine the 
safety and effectiveness of particular interventions. 
 
(2) Obtaining informed consent is not feasible because: 
 
(i) The subjects will not be able to give their informed consent as a result of their medical 
condition; 
 
(ii) The intervention under investigation must be administered before consent from the 
subjects' legally authorized representatives is feasible; and 
 
(iii) There is no reasonable way to identify prospectively the individuals likely to become 
eligible for participation in the clinical investigation. 
 
(3) Participation in the research holds out the prospect of direct benefit to the subjects because: 
 
(i) Subjects are facing a life-threatening situation that necessitates intervention; 
 
(ii) Appropriate animal and other preclinical studies have been conducted, and the 
information derived from those studies and related evidence support the potential for the 
intervention to provide a direct benefit to the individual subjects; and 
 
(iii) Risks associated with the investigation are reasonable in relation to what is known 
about the medical condition of the potential class of subjects, the risks and benefits of 
standard therapy, if any, and what is known about the risks and benefits of the proposed 
intervention or activity. 
 
(4) The clinical investigation could not practicably be carried out without the waiver. 
 
  49  Contains Nonbinding Recommendations 
(5) The proposed investigational plan defines the length of the potential therapeutic window 
based on scientific evidence, and the investigator has committed to attempting to contact a 
legally authorized representative for each subject within that window of time and, if feasible, to 
asking the legally authorized representative contacted for consent within that window rather than 
proceeding without consent. The investigator will summarize efforts made to contact legally 
authorized representatives and make this information available to the IRB at the time of 
continuing review. 
 
(6) The IRB has reviewed and approved informed consent procedures and an informed consent 
document consistent with 50.25. These procedures and the informed consent document are to be 
used with subjects or their legally authorized representatives in situations where use of such 
procedures and documents is feasible. The IRB has reviewed and approved procedures and 
information to be used when providing an opportunity for a family member to object to a 
subject's participation in the clinical investigation consistent with paragraph (a)(7)(v) of this 
section. 
 
(7) Additional protections of the rights and welfare of the subjects will be provided, including, at 
least: 
 
(i) Consultation (including, where appropriate, consultation carried out by the IRB) with 
representatives of the communities in which the clinical investigation will be conducted 
and from which the subjects will be drawn; 
 
(ii) Public disclosure to the communities in which the clinical investigation will be 
conducted and from which the subjects will be drawn, prior to initiation of the clinical 
investigation, of plans for the investigation and its risks and expected benefits; 
 
(iii) Public disclosure of sufficient information following completion of the clinical 
investigation to apprise the community and researchers of the study, including the 
demographic characteristics of the research population, and its results; 
 
(iv) Establishment of an independent data monitoring committee to exercise oversight of 
the clinical investigation; and 
 
(v) If obtaining informed consent is not feasible and a legally authorized representative is 
not reasonably available, the investigator has committed, if feasible, to attempting to 
contact within the therapeutic window the subject's family member who is not a legally 
authorized representative, and asking whether he or she objects to the subject's 
participation in the clinical investigation. The investigator will summarize efforts made to 
contact family members and make this information available to the IRB at the time of 
continuing review. 
 
(b) The IRB is responsible for ensuring that procedures are in place to inform, at the earliest feasible 
opportunity, each subject, or if the subject remains incapacitated, a legally authorized representative of 
the subject, or if such a representative is not reasonably available, a family member, of the subject's 
inclusion in the clinical investigation, the details of the investigation and other information contained in 
  50  Contains Nonbinding Recommendations 
the informed consent document. The IRB shall also ensure that there is a procedure to inform the 
subject, or if the subject remains incapacitated, a legally authorized representative of the subject, or if 
such a representative is not reasonably available, a family member, that he or she may discontinue the 
subject's participation at any time without penalty or loss of benefits to which the subject is otherwise 
entitled. If a legally authorized representative or family member is told about the clinical investigation 
and the subject's condition improves, the subject is also to be informed as soon as feasible. If a subject is 
entered into a clinical investigation with waived consent and the subject dies before a legally authorized 
representative or family member can be contacted, information about the clinical investigation is to be 
provided to the subject's legally authorized representative or family member, if feasible. 
 
(c) The IRB determinations required by paragraph (a) of this section and the documentation required by 
paragraph (e) of this section are to be retained by the IRB for at least 3 years after completion of the 
clinical investigation, and the records shall be accessible for inspection and copying by FDA in 
accordance with 56.115(b) of this chapter. 
 
(d) Protocols involving an exception to the informed consent requirement under this section must be 
performed under a separate investigational new drug application (IND) or investigational device 
exemption (IDE) that clearly identifies such protocols as protocols that may include subjects who are 
unable to consent. The submission of those protocols in a separate IND/IDE is required even if an IND 
for the same drug product or an IDE for the same device already exists. Applications for investigations 
under this section may not be submitted as amendments under 312.30 or 812.35 of this chapter. 
 
(e) If an IRB determines that it cannot approve a clinical investigation because the investigation does not 
meet the criteria in the exception provided under paragraph (a) of this section or because of other 
relevant ethical concerns, the IRB must document its findings and provide these findings promptly in 
writing to the clinical investigator and to the sponsor of the clinical investigation. The sponsor of the 
clinical investigation must promptly disclose this information to FDA and to the sponsor's clinical 
investigators who are participating or are asked to participate in this or a substantially equivalent clinical 
investigation of the sponsor, and to other IRB's that have been, or are, asked to review this or a 
substantially equivalent investigation by that sponsor. 
 
  51  Contains Nonbinding Recommendations 
DEFINITIONS                     APPENDIX B 
 
Clinical investigation. (Note: The terms research, clinical research, biomedical research, clinical study, 
study, clinical trial, trial, and clinical investigation are deemed to be synonymous for purposes of this 
guidance.)  The term means: 
 
For drugs (including biological drugs): Any experiment in which a drug/biologic is administered or 
dispensed to, or used involving, one or more human subjects (21 CFR 312.3(b)). 
 
For devices: Any investigation or research involving one or more subjects to determine the safety or 
effectiveness of a device (21 CFR 812.3(h)). 
 
Clinical Investigator.  An individual who actually conducts a clinical investigation (i.e., under whose 
immediate direction the test article is administered or dispensed to a subject). In the event an 
investigation is conducted by a team of individuals, the investigator is the responsible leader of that team 
(21 CFR 312.3(b), 812.3(i)). 
 
Community. A community means a group or groups of people who live and work in a particular region 
and who may be linked by common interests; an interacting population of different kinds of individuals 
constituting a society or association; or, simply an aggregation of mutually related individuals in a given 
location (Webster's Third New International Dictionary, c. 1971).  A community may also include 
persons who share common experiences or conditions. 
 
Community consultation. Community consultation means providing the opportunity for discussions 
with, and soliciting opinions from, the community or communities in which the study will take place and 
from which the study subjects will be drawn.  
 
Data Monitoring Committee (DMC).  A clinical trial DMC is a group of individuals with pertinent 
expertise that reviews on a regular basis accumulating data from one or more ongoing clinical trials.  
The DMC advises the sponsor regarding the continuing safety of current trial participants and those yet 
to be recruited to the trial, as well as the continuing validity and scientific merit of the trial.  For more 
information on DMCs and their operation, see FDA's Guidance for Clinical Trial Sponsors, 
Establishment and Operation of Clinical Trial Data Monitoring Committees, March 2006.54  
 
Emergency Research.  A planned clinical investigation that requires prior written FDA authorization to 
proceed and involves subject(s) who are in a life-threatening situation for which available treatments or 
in vitro diagnostic tests are unproven or unsatisfactory. 
 
Family member.  Any one of the following legally competent persons: spouse, parents, children 
(including adopted children), brothers, sisters, and spouses of brothers and sisters, and any individual 
related by blood or affinity whose close association with the subject is the equivalent of a family 
relationship (21 CFR 50.3(m)).  Definition of "legally competent" may vary by state but in general 
includes an age of majority and an assessment of mental capacity. 
 
Institutional Review Board (IRB).  Any board, committee, or other group formally designated by an 
                                                 
54 http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126578.pdf 
  52  Contains Nonbinding Recommendations 
institution to review, to approve the initiation of, and to conduct periodic review of, biomedical research 
involving human subjects.  The primary purpose of such a review is to ensure the protection of the rights 
and welfare of the human subjects (21 CFR 56.102(g)). 
 
Legally authorized representative (LAR).  An individual or judicial or other body authorized under 
applicable State or local law to give informed consent on behalf of a prospective subject to the subject's 
participation in the procedure(s) involved in the research (21 CFR 50.3(m)).  IRBs and clinical 
investigators should familiarize themselves with applicable local statutes and regulations pertaining to 
the definition of a legally authorized representative. 
 
Life-threatening.  Diseases or conditions where the likelihood of death is high unless the course of the 
disease or condition is interrupted. 21 CFR 50.24 applies only to life-threatening  emergency situations. 
 
Public disclosure.  For purposes of this guidance, public disclosure means dissemination of information 
about the emergency research sufficient to allow a reasonable assumption that the communities are 
aware of the plans for the investigation, its risks and expected benefits, and the fact that the study will be 
conducted without obtaining informed consent for most or even all subjects.  Public disclosure also 
includes dissemination of information after the investigation is completed so that the communities and 
scientific researchers are aware of the study's results. 
 
Sponsor.  A person who takes responsibility for and initiates a clinical investigation (21 CFR 312.3(b), 
812.3(n)).  A sponsor may be an individual, a company, a governmental agency, an academic institution, 
a private organization, etc. 
 
Sponsor-Investigator.  An individual who both initiates and conducts an investigation, and under 
whose immediate direction the investigational test article is administered or dispensed (21 
CFR 312.3(b), 812.3(o)).  A sponsor-investigator assumes the responsibilities of both sponsors and 
clinical investigators. 
 
Therapeutic window.  (1) The therapeutic window is the time period, based on available scientific 
evidence, during which administration of the test article might reasonably produce a 
demonstrable clinical effect.  (2) For investigations of in vitro diagnostic devices (IVDs) that meet the 
criteria for emergency research, the therapeutic window is the time period, based on available scientific 
evidence, during which diagnosis must occur to allow administration of appropriate therapy.   
  53  Contains Nonbinding Recommendations 
 
 
 
APPENDIX C 
 
SUGGESTED FLOW CHART FOR 50.24 STUDIES 
 
 (This is a graphic representation of one way to fulfill requirements for studies conducted under 21 CFR 
50.24.  Alternative approaches may also be used.)  
 
 
 
 
  Clinical investigator (CI) submits study involving an exception from informed consent to the IRB.  (Submission includes study 
  protocol, informed consent document, procedures for contacting LARs or family members, and plans for community consultation & 
  public disclosure.*) 
 
 
CI/Sponso r revise submission. 
IRB reviews submission according to its SOPs, and in particular, for elements required by 
 
21 CFR 50.24(a) and (b).  Are all elements present? 
 
 
No 
  Yes 
 
 
 
IRB reviews community consultation plans** (21 CFR 50.24(a)(7)(i)). Are plans adequate?  Yes
 
 
 
CI/spon sor revise community 
consulta tion plan.  No  Community consultation activities occur, CI 
provides community feedback to IRB.   
 
 
  IRB determines if study is appropriate for 
Yes, but study and/or IC needs 
  community and documents decision in IRB 
modification. 
  meeting minutes. 
 
 
Sponsor  notifies FDA and other  No 
IRBs an d CIs involved in this or  CI/Sponsor revise study and/or IC 
substant ially similar studies.   accordingly. 
  Yes 
 
 
 
 
 
   
  CONTINUED ON NEXT PAGE 
 
 
 
*The investigation plan for the study, community consultation plans and public disclosure plans  
may be revised one or more times based on feedback received during the IRBs review and the  
community consultation/public disclosure process 
 
 
 
  54  Contains Nonbinding Recommendations 
 
 
 
 
 
 
 
SUGGESTED FLOW CHART FOR 50.24 STUDIES 
(Continued from Previous Page)  
 
 
(This is a graphic representation of one way to fulfill requirements for studies conducted under 21 CFR 
50.24.  Alternative approaches may also be used.)  
 
 
 
 
 
 
  IRB reviews public disclosure plans**   Yes
(21 CFR 50.24(a)(7)(ii)).  Are plans adequate? 
 
 
 
 
CI/Spon sor revise plans for public  No  Public disclosure takes place. CI provides 
disclosu re and resubmit.  disclosure information that was used to IRB. 
 
IRB sends information/documents that were 
 
disclosed to the study sponsor.  Sponsor sends information disclosed to FDA 
 
for inclusion in Public Docket 95S-0158. 
IRB f inds and documents that the 
sponsor has a DMC to exercise 
 
oversight of the study;  
        Approves study               Disapproves study 
CI begins enrolling subjects. Study is  IRB reviews study  Study does not proceed. 
 
completed. 
 
 
IRB reviews post-study public disclosure plans (21 
CI/Sponsor provide plans for public disclosure of study results to IRB.  CFR 50.24(a)(7)(iii).  Are plans adequate?  Y es
 
 
CI/Sponsor revise plans for public disclosure of study results.  No
 
Public disclosure takes place. CI provides disclosure 
  information and documents that were used to the IRB. 
IRB sends information/documents that were 
disclosed to the study sponsor. 
Sponsor sends information 
and documents to FDA for 
  inclusion in Public Docket 
**IRB review of community consultation and public  95S-0158. 
disclosure plans may be concurrent OR sequential. 
 
  55