II

V.03

 

 

Exception from Informed Consent Requirements for Emergency Research

 

 

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Objective

This Policy and Procedure describes the allowable exception from informed consent requirements for emergency research.

           

Policy/Procedure

It is the policy of the University of Texas Health Science Center at HoustonÕs (UTHSC-H) Committee for the Protection of Human Subjects (CPHS) to grant a waiver from informed consent for research or an exception from informed consent for qualifying emergency research in agreement with Federal regulations and CPHS policies and procedures.

 

I.    The Secretary of Health and Human Services (HHS) has waived the general requirements for informed consent for research in which 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:

 

A.   That the research activity is subject to regulations codified by the Food and Drug Administration (FDA) at Title 21 CFR part 50 and will be 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 participants who are unable to consent, and

B.    That the requirements for exception from informed consent for emergency research detailed in Title 21 CFR section 50.24 have been met relative to those protocols.

 

II.  The Secretary of Health and Human Services (HHS) has waived the general requirements for informed consent for research in which 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 to the Office of Human Research Protections, Department of Health and Human Services, that all the following conditions have been met relative to the research:

 

A.   The human participants 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 trials, is necessary to determine the safety and effectiveness of particular interventions.

 

1.     The condition does not have to be immediately life-threatening or to immediately result in death.  Rather, the participants must be in a life-threatening situation requiring intervention before consent from a legally authorized representative is feasible. 

2.     Life-threatening includes diseases or conditions where the likelihood of death is high unless the course of the disease or condition is interrupted.

3.     Although the regulation specifically references placebo controlled trials, this was done to indicate that such trials may be conducted when appropriate.  Other controls, e.g., active controls and historical controls, may also be used when they are appropriate and adequate to the task of providing evidence that the drug or device will have the effect claimed.  In virtually all cases, when a placebo is used, standard care, if any, would be given to all participants, with participants randomized to receive, in addition, the test treatment or a placebo.  An exception to this would be the situation in which the test is to determine whether standard treatment is in fact useful.  In that case, there must be a group that does not receive it.

B.    Obtaining informed consent is not feasible because:

1.     The participants will not be able to give their informed consent as a result of their medical condition.  The participants do not have to be comatose, but the medical condition under study must prevent obtaining valid informed consent.

2.     The intervention being studied must be administered before consent from the participantÕs legally authorized representative is feasible; and

3.     There is no reasonable way to identify prospectively the individuals likely to become eligible for participation in the clinical trial.

C.    Participation in the research holds out the prospect of direct benefit to the participants because:

1.     Participants are facing a life-threatening situation that necessitates intervention;

2.     Appropriate animal and other preclinical studies have been conducted, and the information derived from these studies and related evidence support the potential for the intervention to provide a direct benefit to the individual participants; and,

3.     Risks associated with the research are reasonable in relation to what is known about the medical condition of the potential class of participants, the risks and benefits of standard therapy, if any, and what is known about the risks and benefits of the proposed intervention or activity.

D.   The clinical trial could not practicably be carried out without the waiver.

E.    The proposed research 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 participant 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 CPHS at the time of continuing review.

F.    The CPHS has reviewed and approved informed consent procedures and an informed consent document consistent with 21CFR 50.25 and CPHS policies and procedures.  These procedures and the informed consent document are to be used with participants or their legally authorized representatives in situations where use of such procedures and documents is feasible.  CPHS has reviewed and approved procedures and information to be used when providing an opportunity for a family member to object to a participantÕs participation in the clinical investigation consistent with paragraph (a)(7)(v) of this section.

G.   Additional protections of the rights and welfare of participants will be provided, including, at least:

1.     Consultation (including, where appropriate, consultation carried out by the CPHS) with representatives of the communities in which the clinical trial will be conducted and from which the participants will be drawn;

a)     The CPHS shall provide an opportunity for the community from which research participants may be drawn to understand the proposed clinical trial and its risks and benefits and to discuss the trial.

b)    The CPHS shall consider this community discussion in reviewing the research.  Based on this community consultation the CPHS may decide, among other things, that it is appropriate to attempt to exclude certain groups from participation in the trial, or that wider community consultation and discussion is needed.

c)     The CPHS should consider, for example, having a public meeting in the community to discuss the protocol; establishing a separate panel of members of the community from which the participants will be drawn; including consultants to the CPHS from the community from which the participants will be drawn; enhancing the membership of the CPHS by adding members who are not affiliated with the institution and are representative of the community; or developing other mechanisms to ensure community involvement and input into the CPHSÕs decision making process.  It is likely that multiple methods may be needed in order to provide the supplemental information that the CPHS will need from the community to review this research.

2.     Public disclosure to the communities in which the clinical trial will be conducted and from which the participants will be drawn, prior to initiation of the clinical trial, of plans for the research and its risks and expected benefits.;

a)     The CPHS will determine the information to be disclosed, which could include the information that is found in the informed consent document, the investigatorÕs brochure, and the research protocol.

b)    The CPHS shall consider how best to publicly disclose, prior to the start of the clinical trial, sufficient information to describe the trialÕs risks and benefits.

c)     Initial disclosure of information will occur during the community consultation process, thus allowing the individuals to raise concerns and objections.

 

    1. Public disclosure of sufficient information following completion of the clinical trial to inform the community and researchers of the study, including the demographic characteristics of the research population, and its results.
    2. Establishment of an independent data monitoring committee to exercise oversight of the clinical research; and
    3. 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 participantÕs family member who is not a legally authorized representative, and asking whether he or she objects to the participantÕs participation in the clinical trial.  The investigator will summarize efforts made to contact family members and make this information available to the CPHS at the time of continuing review.

 

III.           CPHS is responsible for ensuring that procedures are in place to inform at the earliest feasible opportunity, each participant, or if the participant remains incapacitated, a legally authorized representative of the participant, or if such a representative is not reasonably available, a family member, of the participantÕs inclusion in the clinical trial, the details of the research, and other information contained in the informed consent document.  Also ensure that there is a procedure to inform the participant, or if the participant remains incapacitated, a legally authorized representative of the participant, or if such a representative is not reasonably available, a family member, that he or she may discontinue the participantÕs participation at any time without penalty or loss of benefits to which the participant is otherwise entitled.  If a legally authorized representative or family member is told about the clinical trial and the participantÕs condition improves, the participant is also to be informed as soon as possible.  If a participant is entered into a clinical trial with waived consent and the participant dies before a legally authorized representative or family member can be contacted, information about the clinical trial is to be provided to the participantÕs legally authorized representative or family member, if feasible.  CPHS determinations required by 21CFR ¤50.24(a) and the documentation required by 21CFR ¤50.24(e) are to be retained by CPHS for at least three 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) and 21 CFR 50. 

 

A.   The CPHS will determine whether it is possible or desirable, given the nature of the clinical trial, to have an actual document that could be signed for continued participation in the trial.

1.     The document that would be signed after entry into a trial would not constitute consent for what had already occurred; but it could serve to document that the participant consented to continued participation in the trial.

2.     The investigator shall document in the study notes that the participant, legally authorized representative, or family member was informed of the participantÕs inclusion in the clinical trial, and other information contained in the informed consent document.

 

IV.          If the investigator is to hold the investigational new drug application (IND)/investigational device exemption (IDE), then protocols involving an exception to the informed consent requirement under 21CFR 50.24 must be performed under a separate IND or IDE that clearly identifies such protocols as protocols that may include participants 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.

 

V. If the CPHS determines it cannot approve a request for exception from informed consent requirements in emergency research be cause the clinical investigation does not meet the criteria according to Federal regulations, CPHS policies and procedures, or other relevant ethical concerns, the CPHS must document its findings and provide these findings promptly in writing to the clinical investigator who will forward same to the sponsor of the clinical trial.  The sponsor of the clinical investigation must promptly disclose this information to FDA and to the sponsorÕs clinical investigators who are participating or are asked to participate in this or a substantially equivalent clinical investigation of the sponsor, and to other IRBs that have been, or are, asked to review this or a substantially equivalent investigation by that sponsor.

 

VI.          Because of special regulatory limitations relating to research involving prisoners, and research involving fetuses, pregnant women, and human in vitro fertilization, this waiver is inapplicable to these categories of research. 

 

 

Definition:  For purposes of this waiver, family member means any one of the following legally competent persons:  spouses; 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 participant is the equivalent of a family relationship.  

 

Applicable Regulations and Guidelines

21CFR 50 ( http://www.access.gpo.gov/nara/cfr/waisidx_04/21cfr50_04.html ) 

45CFR 46 ( http://www.access.gpo.gov/nara/cfr/waisidx_04/45cfr46_04.html )

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Updated 5/2007, Report broken links