Compliance Issues Discussion: 
Waiver of Consent/ Waiver of Documentation

OFFICE OF RESEARCH OVERSIGHT (ORO) 
NATIONWIDE TELECONFERENCE 
September 10, 2003

TAKE HOME MESSAGE

Inappropriate applications of waivers of consent or of documentation of consent are frequent noncompliance findings by both ORO and OHRP.  Waivers approved under the two “minimal risk” categories [38 CFR 16.116(d) and .117(c)(2)] may be employed to streamline both the IRB’s work and the research process. Getting used to applying them and documenting their use adequately can make it easier to approve and carry out many types of minimal risk research while also maintaining regulatory compliance. 

RELEVANT REGULATIONS

COMMON RULE 

A.  Waiver or Alteration of Elements of Consent

38 CFR 16.116(c)

[Public Benefit Study Conducted by State or Local Government]

(c) An IRB may approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent set forth above, or waive the requirement to obtain informed consent provided the IRB finds and documents that:
(1) 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: 
(i) Public benefit of  service programs; 
(ii) procedures for obtaining benefits or services under those programs;
(iii) possible changes in or alternatives to those programs or procedures; or 
(iv) possible changes in methods or levels of  payment or benefits or services under those programs; and
 (2) The research could not practicably be carried out without the waiver or alteration.

38 CFR 16.116(d)

[Minimal Risk Study]

 (d) An IRB may approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent set forth in this section, or waive the requirements to obtain informed consent provided the IRB finds and documents that:
(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.

B.  Waiver Of Documentation of Consent

(c) An IRB may waive the requirement for the investigator to obtain a signed consent form for some or all subjects if it finds either:

[When the principal risk to the participant is a breach of confidentiality]

(1) That the only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality. Each subject will be asked whether the subject wants documentation linking the subject with the research, and the subject's wishes will govern; or

Note: For research in which identification of subjects may put them at risk, and the risks are such that this waiver cannot be applied, the researcher may consider obtaining a Certificate of Confidentiality from NIH. Information about Certificates of Confidentiality may be found on the OHRP website: http://ohrp.osophs.dhhs.gov/humansubjects/guidance/certconf.htm

[When the research is minimal risk]

(2)That the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context. In cases in which the documentation requirement is waived, the IRB may require the investigator to provide subjects with a written statement regarding the research.

C. Definition of Minimal Risk

38 CFR16.102(i)

(i) Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.

FDA WAIVER OF DOCUMENTATION AND EXCEPTIONS TO THE CONSENT REQUIREMENT

21 CFR 56.109(c)

(c) An IRB shall require documentation of informed consent in accordance with Sec. 50.27 of this chapter, except as follows: 
(1) The IRB may, for some or all subjects, waive the requirement that the subject, or the subject's legally authorized representative, sign a written consent form if it finds that the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside the research context; or 
(2) The IRB may, for some or all subjects, find that the requirements in Sec. 50.24 of this chapter for an exception from informed consent for emergency research are met.

A rule was issued on Oct. 2, 1996, specifying how 21 CFR 50.24 may be implemented with planned emergency research. This rule was adopted by OHRP under 45 CFR 46.101(i). However, it has not been adopted by the VA.

In addition, emergency treatment using investigational articles is permitted without consent under certain circumstances under 21 CFR 50.23:
(a) The obtaining of informed consent shall be deemed feasible unless, before use of the test article (except as provided in paragraph (b) of this section), both the investigator and a physician who is not otherwise participating in the clinical investigation certify in writing all of the following:
(1) The human subject is confronted by a life-threatening situation necessitating the use of the test article.
(2) Informed consent cannot be obtained from the subject because of an inability to communicate with, or obtain legally effective consent from, the subject.
(3) Time is not sufficient to obtain consent from the subject's legal representative.
(4) There is available no alternative method of approved or generally recognized therapy that provides an equal or greater likelihood of saving the life of the subject.
(b) If immediate use of the test article is in the investigator's opinion, required to preserve the life of the subject, and time is not sufficient to obtain the independent determination required in paragraph (a) of this section in advance of using the test article, the determinations of the clinical investigator shall be made and, within 5 working days after the use of the article, be reviewed and evaluated in writing by a physician who is not participating in the clinical investigation.
(c) The documentation required in paragraph (a) or (b) of this section shall be submitted to the IRB within 5 working days after the use of the test article.

 .
Note: 
In the opinion of OPRR/OHRP, under the Common Rule, data from patients treated under these circumstances may not be used for research purposes.

Before applying this exception, consult the FDA Information Sheets. Drug for this use may have to be obtained from the manufacturer under an emergency IND or another expanded access mechanism.

RELEVANT GUIDANCE

Institutional Review Board (IRB), Written Procedures (OHRP Guidance, 2002)

OHRP Compliance Activities: Common Findings and Guidance (OPRR/OHRP Guidance, 2002)

Informed Consent, Legally Effective and Prospectively Obtained (OPRR/OHRP Guidance, 1993)

Guidance on Certificates of Confidentiality (OHRP Guidance, 2003)

Emergency Medical Care (OPRR/OHRP Guidance, 1991)

OPRR/OHRP Institutional Review Board Guidebook (1993):
Chapter III.B. Informed Consent
Chapter IV. E. Epidemiologic Studies

FDA Information Sheets:
Page 2, Frequently Asked Questions
Page 5, A Guide to Informed Consent
Page 6, Exception from Informed Consent for Studies Conducted in Emergency Settings: Regulatory Language and Excerpts from Preamble
Page 7, Emergency Use of an Investigational Drug or Biologic, Exception From Informed Consent Requirement

FREQUENTLY ASKED QUESTIONS

What’s the difference between waiver of consent and waiver of documentation of consent? 
Consider the experience of the participant: Is the participant aware that he/she is participating in a research study? If not, then consent has been waived. If the participant is given all the relevant information and has been asked for consent, but a written consent document is not used, then documentation has been waived. 

What is the difference between a waiver of consent and an exemption? 
An exemption is “outside the Common Rule door” – the Common Rule doesn’t apply, so there is no requirement for consent. Therefore, there is no need to invoke the consent waiver rules when a study qualifies for an exemption (however, research ethics do still apply). A waiver of consent is used only for research that is “inside the door” -- research for which IRB review and approval are required. If a protocol under review meets all the criteria for a waiver/alteration, and that fact is documented in protocol specific terms, then the IRB may waive the consent or documentation requirement.

What constitutes adequate documentation of IRB approval of one of these waivers?
OHRP recommends that when approving a waiver of consent or of written documentation of consent for research reviewed by the convened IRB, these findings be documented in the minutes of the IRB meeting, including protocol-specific information justifying each IRB finding. NCQA standards also include requirements for documentation of waivers (Standard ICS1, Elements 1A and 2A).  Documentation can be accomplished in a number of ways: As an example, the IRB could ask the PI to provide justification addressing each criterion when applying for a waiver/alteration, and then the IRB can consider each point during its deliberations with the discussion documented in the meeting minutes.

Can waivers of consent or documentation be approved via expedited review?
Yes, all the authorities of the IRB may be exercised using an expedited process with the exception of disapproval.  However, it is still necessary to document the reasons for the waiver in protocol-specific terms when the approval is given using an expedited process. 

Can the two types of waiver be used in combination? 
Yes. A combination of waiver/alteration of consent plus waiver of documentation can be used when all the criteria for each are met. An example may be a minimal risk study of a telephone intervention in which the consent will be obtained over the telephone (waiver of documentation) and some aspect of the research purpose will be withheld because revealing it is likely to bias the results (alteration of consent). If the research meets all the criteria under both .116(d) and .117(c)(2), this consent process is approvable.

Criterion #3 under 38 CFR 16.116(d) is, “The research could not practicably be carried out without the waiver or alteration.” What exactly does this mean?
This question can only be answered in the context of the protocol under consideration. Existing guidance suggests that the bar for meeting this criterion is rather high. Remember that obtaining informed consent is the default position, and whether criterion#3 applies is not primarily a matter of the inconvenience or cost of obtaining consent. The bar should not be set so high, however, that some types of truly important research can’t ever be carried out. As discussed in the OPRR IRB Guidebook, this decision is related to the IRB’s responsibility to the weigh the risks and benefits of research. With a waiver of consent, at the very least, patients’ privacy will be breached without their knowledge. Is the research potentially of such importance that it justifies this breach? Is the barrier to obtaining consent such that this research simply can’t be done if consent must be obtained? An example in which criterion #3 might be met is an epidemiological study using identifiable medical information for tens of thousands of patients, many of whom may not be locatable. If the IRB believes the potential benefits of this research outweigh the invasion of privacy it entails (and that the measures taken to protect the information are adequate), then it may decide that a waiver of consent is appropriate. An example in which criterion #3 probably would not be met would be a study in which investigators will interact personally with participants, but the investigators don’t believe they have the time in their own schedules to carry out a consent procedure. Between these two extremes, it is a matter of the IRB’s considered judgment, made after it has carefully weighed the risks, benefits, and the barriers to obtaining consent.

Criterion #4 under 38 CFR 16.116(d) is, “Whenever appropriate, the subjects will be provided with additional pertinent information after participation.” What exactly does this mean?
This is, once again, a matter of IRB judgment. Providing additional pertinent information after participation is considered to be always appropriate if the study entailed significant deception. In that case, a face-to-face debriefing may be required. More generally, respect for the persons who unwittingly provide research data may call for dissemination of the results not only to the scientific community but also to the patient community. This can be accomplished by, for instance, summarizing the results of research in newsletters or other mailings, displaying posters in the facility, or giving presentations to patient advocacy groups. Following through this way has the added bonus of building support for the research enterprise among all potential research participants. 

Can a waiver/alteration of consent or waiver of documentation be approved when a study will involve vulnerable subjects?
There is no regulation barring the use of these waivers when the research will involve vulnerable subjects. As in any other case, all the relevant criteria must be met and appropriately documented. One caution would be to be careful not to let the subjects’ limitations influence the decision about whether the research is practicable if consent will be obtained. If the subjects are unlikely to be able to consent, then the VA policies related to surrogate consent would apply. For any study, if the consent requirement would not be waived when subjects are competent to consent, then the same standards must be applied when they are not.

FDA CAUTIONS

FDA regulations do not recognize a waiver/alteration of consent, so consent may not be waived in FDA regulated studies. Note that a waiver of consent is not the same as the exceptions to consent requirements that are allowed under certain emergency situations [21 CFR 50.23(a) and .50.24.]

The FDA regulations [21 CFR 50.109(c)] do recognize a waiver of documentation similar to that in 38 CFR 16.117(c)(2).  Telephone consent for FDA regulated research that does not meet the criteria for waiver of documentation are not allowed, but documentation via fax is acceptable to the FDA.

HIPAA CAUTION

Any time private health information is to be used for research, an appropriate strategy must be used to address the issue of authorization for its use. Authorization is not the same as consent and must be addressed separately.

Generally, an authorization will be necessary if informed consent will be obtained.  However, authorization may require two steps:  an authorization from the subject to be signed at the time informed consent is sought AND a waiver of authorization for activities PRIOR to the informed consent process, such as when a researcher is screening patient records to find potential subjects.  A waiver of authorization may be appropriate in many cases in which either consent or documentation of consent is waived under the Common Rule. Granting a waiver of authorization requires that each criterion for such a waiver is met, and that the IRB or Privacy Board determinations be documented:

45 CFR 164.512(i)(2)
(2) Documentation of waiver approval. For a use or disclosure to be permitted based on documentation of approval of an alteration or waiver, under paragraph (i)(1)(i) of this section, the documentation must include all of the following: 

(i) Identification and date of action. A statement identifying the IRB or privacy board and the date on which the alteration or waiver of authorization was approved; 

(ii)  Waiver criteria. 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:

(A) The use or disclosure of protected health information involves no more than a minimal risk to the privacy of individuals, based on, at least, the presence of the following elements;

(1)  An adequate plan to protect the identifiers from improper use and disclosure;

(2) An adequate plan to destroy the identifiers at the earliest opportunity consistent with conduct of the research, unless there is a health or research justification for retaining the identifiers or such retention is otherwise required by law; and

(3) Adequate written assurances that the protected health information will not be reused or disclosed to any other person or entity, except as required by law, for authorized oversight of the research study, or for other research for which the use or disclosure of protected health information would be permitted by this subpart;

(B) The research could not practicably be conducted without the waiver or alteration; and

(C) The research could not practicably be conducted without access to and use of the protected health information.

Note that while the criteria for approving a waiver of authorization are similar to those for a waiver of consent, they are not exactly the same. For questions about HIPAA requirements, contact Patricia L. Watts at ORD.