Table 1

Summary of requirements for institutional consent/waiver of consent

Declaration of Helsinki—Ethical Principles for Medical Research Involving Human Subjects (2013)

  • A serious threat to the prospective participant requires immediate intervention; and

  • either no standard efficacious care exists or the research offers a real possibility of direct benefit to the participant in comparison with standard care; and

  • either the risk of harm is not greater than that involved in standard efficacious care or it is clearly justified by the direct benefits to the participant; and

  • the prospective participant is unconscious or lacks the capacity to understand risks, methods and purposes of the research; and

  • third party authorisation cannot be secured in sufficient time, despite diligent and documented efforts to do so; and

  • no relevant prior directive by the participant is known to exist.

Informed Consent

  • Research involving subjects who are physically or mentally incapable of giving consent done only if their condition is a necessary characteristic of research group.

  • Must seek informed consent from the legally authorised representative.

  • If no representative available and research cannot be delayed, can proceed without informed consent but state specific reasons for involving these subjects in the study and need approval of research ethics committee.

  • Obtain consent to remain in study as soon as possible

US Department of Health and Human Services (HHS). Office for Human Research Protections (2016)21 Waiver or alteration of the requirements for obtaining informed consent from adult subjects can occur under any of the following three provisions:

  1. Public benefit or service programmes: an REC can waive the requirement to obtain informed consent under the U.S. Department of Health and Human Services (HHS) regulations with the following conditions met:

    1. the research could not practicably be carried out without the waiver or alteration; and

    2. the research or demonstration project is to be conducted by or subject to the approval of state or local government officials and is designed to study, evaluate or otherwise examine:

      1. public benefit or service programmes;

      2. procedures for obtaining benefits or services under those programmes;

      3. possible changes in or alternatives to those programmes or procedures; or

      4. possible changes in methods or levels of payment for benefits or services under those programmes.

  2. Research in general: an REC may waive the requirement of informed consent with the following four conditions met:

    1. the research involves no more than minimal risk to the subjects;

    2. the waiver or alteration will not adversely affect the rights and welfare of the subjects;

    3. the research could not practicably be carried out without the waiver or alteration; and

    4. whenever appropriate, the subjects will be provided with additional pertinent information after participation.

  3. Research in emergency settings: an REC may waive the requirement for obtaining informed consent if the requirements of the HHS Secretarial waiver are met.


For research involving children, an REC may waive the requirements for obtaining parental or guardian permission under any of the following:

  1. The REC makes and documents the required findings as described above.

  2. The REC determines that a research protocol is designed to study conditions in children or a subject population for which parental or guardian permission is not a reasonable requirement to protect the subjects (eg, neglected or abused children), and the following two additional criteria are also met:

    1. an appropriate mechanism is in place to protect the children, and

    2. the waiver is not inconsistent with federal, state or local law. REC may waive the requirement for obtaining parental or guardian permission if the research involves more than minimal risk to the child subjects.

US Food and Drug Administration: 21CFR50.24 (2018)Exception from informed consent requirements for emergency research:

  1. REC (with the concurrence of a licensed physician who is a member of or consultant to the REC 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 randomised placebo-controlled investigations, is necessary to determine the safety and effectiveness of particular interventions.

    2. Obtaining informed consent is not feasible because:

      1. The subjects will not be able to give their informed consent as a result of their medical condition.

      2. The intervention under investigation must be administered before consent from the subjects' legally authorised representatives is feasible.

      3. 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:

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

      2. 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.

      3. 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.

Canada Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans
(2014)22 		Same as Declaration of Helsinki
Alterations to Consent Requirements
The research ethics board (REB) may approve research that involves an alteration to the requirements for consent if the following apply:

  1. the research involves no more than minimal risk to the participants;

  2. the alteration to consent requirements is unlikely to adversely affect the welfare of participants;

  3. it is impossible or impracticable to carry out the research and to address the research question properly, given the research design, if the prior consent of participants is required;

  4. in the case of a proposed alteration, the precise nature and extent of any proposed alteration is defined; and

  5. the plan to provide a debriefing (if any), which may also offer participants the possibility of refusing consent and/or withdrawing data and/or human biological materials.


Consent for Research in Individual Medical Emergencies
Subject to all applicable legal and regulatory requirements, research involving medical emergencies shall be conducted only if it addresses the emergency needs of the individuals involved, and then only in accordance with criteria established in advance of such research by the REB. The REB may allow research that involves medical emergencies to be carried out without the consent of participants or of their authorised third party, if all of the following apply:

  1. a serious threat to the prospective participant requires immediate intervention;

  2. either no standard efficacious care exists or the research offers a realistic possibility of direct benefit to the participant in comparison with standard care;

  3. either the risk is not greater than that involved in standard efficacious care or it is clearly justified by the prospect for direct benefits to the participant;

  4. the prospective participant is unconscious or lacks capacity to understand the risks, methods and purposes of the research project;

  5. third party authorisation cannot be secured in sufficient time, despite diligent and documented efforts to do so; and

  6. no relevant prior directive by the participant is known to exist.


When a previously incapacitated participant regains decision-making capacity, or when an authorised third party is found, consent shall be sought promptly for continuation in the project and for subsequent examinations or tests related to the research project.
Declaration of Helsinki11

  • a serious threat to the prospective participant requires immediate intervention; and

  • either no standard efficacious care exists or the research offers a real possibility of direct benefit to the participant in comparison with standard care; and

  • either the risk of harm is not greater than that involved in standard efficacious care or it is clearly justified by the direct benefits to the participant; and

  • the prospective participant is unconscious or lacks the capacity to understand risks, methods and purposes of the research; and

  • third party authorisation cannot be secured in sufficient time, despite diligent and documented efforts to do so; and

  • no relevant prior directive by the participant is known to exist.

US Department of Health and Human Services (2005)

  • The research involves no more than minimal risk to the subjects.

  • The waiver or alteration will not adversely affect the rights and welfare of the subjects.

  • The research could not practicably be carried out without the waiver or alteration.

  • Whenever appropriate, the subjects will be provided with additional pertinent information after participation.

FDA Final rules (1996)

  • Available treatments are unproven or unsatisfactory.

  • The research cannot practicably be carried out otherwise and is necessary to determine the safety and effectiveness of the intervention.

  • It is not feasible to obtain informed consent from the patient or the patient’s legal representative.

  • The risks and benefits of the experimental procedure are reasonable compared with those associated with the patient’s medical condition and standard therapy.

  • Additional protections such as consultation with the community, public disclosure of the study design and attendant risks prior to its commencement and public disclosure of study results when complete.

  • FDA will also review the protocol design and other information on the proposed therapy before the study is allowed to proceed.

Canada Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans
(2010)		Same as Declaration of Helsinki.

  • REC, research ethics committee.