Feature Article

If the Subject Can't Consent, Then What?

By Mary Banks, RN, BS, BSN
Director of the IRB, Boston University Medical Center.
Author has nothing to disclose with regards to commercial support.

Educational Objectives:

• Describe the types of research studies where a waiver of informed consent can be granted.
• State the criteria, as outlined in the federal research regulations, that must be met in order for the IRB to waive the requirement for informed consent.
• Identify when the use of a legally authorized representative for consenting purposes in research is appropriate.
• List the sequence of kinship that the IRB might consider when assessing consent for research by legally authorized representative (LAR).

PRINT

• Consent Requirements
• Waiver of Informed Consent
• When Consent Cannot be Waived
• Legally Authorized Representative
• Dissent
• Decision Tree
• Quiz
  

Informed Consent is a fundamental pillar of human subjects protection. The Belmont Principle of "Respect for Persons" centers on persons being autonomous in their decisions as to whether to participate in research. IRB regulations from the Department of Health and Human Services (DHHS) 45 CFR 46.116 and the Food and Drug Administration 21 CFR 50.20 specifically address the requirement that informed consent be obtained from subjects prior to their participation in research.

So what happens when an investigator wishes to conduct research but consent CANNOT be obtained from subjects? Perhaps subjects are unavailable (a retrospective chart review of records from 1999), unconscious (a study involving comatose ICU patients) or decisionally impaired (elderly patients in an Alzheimer's study), and thus, cannot consent to be part of the research. Does this mean that the research cannot be done?

The good news is that the federal regulations make allowances for such situations. The IRB MAY approve research studies involving subjects who are unable to provide informed consent - but this decision can only be made after careful review and specific determinations are made.

Consent Requirements

The DHHS and FDA regulations require that, unless research is Exempt, informed consent (containing all of the elements of consent) be obtained from each subject or his/her legally authorized representative (LAR). Both sets of federal regulations have similar requirements for elements of consent. A listing of all the required elements of consent can be found by going to DHHS’s Office of Human Research Protection OHRP informed consent checklist. To ensure that the consent forms created by BUMC investigators contain the elements of consent, INSPIR forces the researcher to enter information in text boxes representing some of the required elements; other elements that can be “boilerplate” language are hard-coded into the INSPIR consent templates. This boilerplate language in INSPIR-generated consent forms can only be removed or modified by the IRB office.

Waiver of Informed Consent

Federal regulations allow for waiver of one or more (or all) of the elements of consent if approved by the IRB. If the research is subject to FDA regulations, however, the IRB cannot approve a waiver of consent, except in emergency situations (1 CFR 50.24).

For non-FDA regulated studies the DHHS regulations 45.CFR 46.116(d) allow the IRB to waive the requirement for informed consent when the IRB determines that the research meets four criteria. These criteria, found in Section J4 of INSPIR, are:

1.) the study involves no more than minimal risk to 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.

In order for the IRB to approve a waiver of informed consent investigators must explain how ALL FOUR CRITERIA in Section J4 of INSPIR are met. The important point here is to explain HOW this study specifically meets these four criteria, and not just to reiterate the criteria. It is the researcher’s task to convince the IRB that it is appropriate to waive the requirement for informed consent in this particular study.

For studies that represent greater than minimal risk the IRB cannot approve a waiver of informed consent, except when the very strict FDA or DHHS Exception From Consent for Emergency Research requirements are met.

When Consent Cannot be Waived

Some research studies represent greater than minimal risk to subjects, are subject to FDA regulations or don't qualify under the emergency research waiver regulations. In these instances, when consent cannot be waived, how can investigators conduct the research and still stay in compliance with the consent regulations?

Under certain circumstances, the IRB may approve obtaining consent from a legally authorized representative (LAR). The IRB can only do this after careful review of the research project. The following are some of the considerations that are part of the IRB's deliberations:

Can the study question be answered using a different subject population?
The IRB will want to determine whether the research can take place WITHOUT participation of subjects who cannot consent for themselves. The IRB will consider whether the study question can only be answered using this cohort of subjects or whether the study can be redesigned using subjects who can consent for themselves. If the study can be designed using a different subject population then in most instances the IRB will ask that the enrollment criteria be modified to exclude subjects who cannot consent for themselves.

Is there potential for benefit for individual subjects?
Federal regulations require that IRB review of a study includes a determination that the study meets certain criteria (45 CFR 46.111) . Criteria 45 CFR 46.111(a)(2) states that "risks to subjects are reasonable in relation to the anticipated benefits, if any, to subjects and the importance of knowledge that may reasonably be expected to result". Some research proposals present a prospect of direct benefit to subjects while others present NO prospect of direct benefit to subjects (but offer a benefit to society through increased knowledge).

If subjects are unable to provide consent the IRB may allow for consent by a LAR only when there is prospect of DIRECT benefit to the individual subjects. When there is NO prospect of direct benefit to subjects (even if the study has scientific merit), the IRB is unlikely to approve consent by a LAR.

Legally Authorized Representative (LAR)

Once the IRB approves consent by a LAR, they must then decide who is an appropriate LAR for a particular study. By definition a LAR is:

"an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject's participation in the procedure(s) involved in the research" (45 CFR 46.102(c); 21 CFR 50.3(l)).

The LAR is considered to be providing consent by substituted judgment, which means that "the decision is based on what the ward would have preferred or decided if competent".

The IRB regulations are not specific in stating who may serve as the LAR, so in these instances the IRB turns to the institution's treatment guidelines for guidance.

For clinical care purposes, BMC Patient Consent Policy #3.2 states: "If the patient is deemed to be JUDGMENTALLY IMPAIRED but has not designated a Health Care Proxy or been adjudicated incompetent, he/she may be treated with the assent of their next-of-kin. The sequence of kinship is as follows: spouse, adult child, parent, sibling, etc. Assent of the spouse should be obtained whenever possible. If the spouse is incapable of assenting or cannot be reached within a reasonable period of time, the adult child may assent and so on, down the line of kinship."

The process used to designate the LAR for a subject must be documented in the study record. In order to move forward the investigator must document that there is a LAR available and willing to consent. The LAR must then sign the consent form and indicate his or her relationship to the subject.

It is important to note that there is an important difference between consent for research and consent for treatment. Because research is answering a study question or testing a hypothesis, there is usually uncertainty as to whether the research intervention is better than the standard care. Because of this equipoise the IRB feels, unlike treatment, research is never NECESSARY. Therefore if a subject cannot consent and a LAR cannot be found then the subject cannot be enrolled. In contrast, in a treatment scenario, some treatment may be necessary and may be administered without consent.

Research Proxy
In all instances it is preferable for subjects to consent for themselves. When subjects cannot consent for themselves the next best option is for the investigator to know who (if anyone) the SUBJECT would want to provide consent. For longitudinal research, when subjects might later become decisionally impaired, it is good practice to have subjects appoint a research proxy at the time of initial consent. This must be done while the subject is competent rather than after the subject becomes decisionally impaired.

A legally appointed power of attorney (POA) or "healthcare proxy" is not automatically considered a research proxy. Attorney Patricia Bass from the BUMC General Counsel's office created the following chart that identifies the various types of proxy situations, who can appoint the proxies and the circumstances under which they apply.

LEGALLY AUTHORIZED REPRESENTATIVE FOR RESEARCH

*Substituted Judgment Standard – decision based on what the ward have preferred or decided if competent

Dissent

In all research, whether the subject has consented himself, the IRB has waived consent, the IRB has approved consent by a LAR or the subject has appointed a research proxy dissent is ALWAYS honored. If the subject refuses to participate in portions of or all of the research - even though the subject is decisionally impaired - dissent is honored. Participation in research cannot be forced or coerced.

Temporary Decisional Impairment

If the research calls for enrollment of decisionally impaired subjects (i.e. comatose) who may later become able to consent then arrangements must be made to consent the subjects as soon as they are able. The wishes of the subject always supersede those of the LAR.

Children, neonates, prisoners and mentally retarded subjects

This article deals specifically with enrolling adult subjects. Specific federal regulations exist that address consent and assent pediatric subjects (Subpart D), neonates (Subpart B), and prisoners (Subpart C). Specific state regulations, such as those for enrollment of mentally retarded subjects 115 CMR 10, may apply to some research.

Decision Tree

Investigators may find this algorithm useful when designing a research protocol to ensure that the issues regarding consent are addressed. This same tool will be used by the IRB when reviewing protocols for consent issues.

Summary:

When subjects cannot consent for themselves, there may be other ways in which the research can be conducted. One option is to request that the IRB waive the requirement for informed consent. Another option is to request that the IRB approve the use of an LAR. A third method is through the use of a designated research proxy. For each of these options, the researcher must think through all of the details described above, and include a plan and justification in the IRB application that helps the IRB make the regulatory determinations it must find in order to allow the study to be approved.

Close Window