Research with Adults with Diminished Capacity to Provide Consent Susan Loess-Perez, MS, CIP, CCRC Director, Office of Research Protections DePaul University.

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Research with Adults with Diminished Capacity to Provide Consent

Susan Loess-Perez, MS, CIP, CCRCDirector, Office of Research ProtectionsDePaul University

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ObjectivesExplain the current regulatory

requirements and the background for the requirements for conducting research with persons with diminished capacity

Summarize guidance and literature

Discuss best practices for IRBs who review research that involves persons with diminished capacity

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Regulations-Membership45 CFR 46.107 (21 CFR 56.107)-IRB

MembershipIf an IRB regularly reviews research that

involves a vulnerable category of subjects, such as children, prisoners, pregnant women, or handicapped or mentally disabled persons, consideration shall be given to the inclusion of one or more individuals who are knowledgeable about and experienced in working with these subjects.

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Regulations-Approval Criteria45 CFR 46.111(21 CFR 56.111)-

Approval criteria(3) Selection of subjects is equitable. In

making this assessment the IRB should … be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons.

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Regulations: Consent Requirements45 CFR 46.116 (21 CFR 50.20)The information that is given to

the subject or the representative shall be in language understandable to the subject or the representative

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Intent of regulationsCommon Rule:

◦ identifies “mentally disabled” persons as an example of a group of subjects that are likely to be vulnerable (i.e. subject to coercion or undue influence).

◦recognizes that additional safeguards for this population may be necessary, but provides no specific instructions on how to identify this group of subjects nor on what possible additional safeguards may be.

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Origins of Regulations1974- National Research Act

formed the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research.

In1978 the Commission created Recommendations on the Institutionalized and Mentally Infirm

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IRB Guidebook-1993“The predominant ethical concern in

research involving individuals with psychiatric, cognitive, or developmental disorders, or who are substance abusers is that their disorders may compromise their capacity to understand the information presented and their ability to make a reasoned decision about participation.”

Persons who are institutionalized may have impaired ability to make a free choice, for example they may participate to appear rationale or cooperative in order to obtain release.

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IRB Guidebook-Definitions Cognitively Impaired: Having either a psychiatric disorder (e.g., psychosis, neurosis,

personality or behavior disorders), an organic impairment (e.g., dementia) or a developmental disorder (e.g., mental retardation) that affects cognitive or emotional functions to the extent that capacity for judgment and reasoning is significantly diminished. Others, including persons under the influence of or dependent on drugs or alcohol, those suffering from degenerative diseases affecting the brain, terminally ill patients, and persons with severely disabling physical handicaps, may also be compromised in their ability to make decisions in their best interests.

Competence: A legal term, used to denote capacity to act on one's own behalf; the ability to understand information presented, to appreciate the consequences of acting (or not acting) on that information, and to make a choice. ◦ Competence may fluctuate as a function of the natural course of a mental illness, response

to treatment, effects of medication, general physical health, and other factors. Therefore, mental status should be re-evaluated periodically. As a designation of legal status, competence or incompetence pertains to an adjudication in court proceedings that a person's abilities are so diminished that his or her decisions or actions (e.g., writing a will) should have no legal effect. Such adjudications are often determined by inability to manage business or monetary affairs and do not necessarily reflect a person's ability to function in other situations.

Incapacity: Refers to a person's mental status and means inability to understand information presented, to appreciate the consequences of acting (or not acting) on that information, and to make a choice. Often used as a synonym for incompetence.

Incompetence: A legal term meaning inability to manage one's own affairs. Often used as a synonym for incapacity.

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IRB Guidebook-Recommendations Persons who are institutionalized, particularly if disabled, should

not be chosen for studies that bear no relation to their situation just because it would be convenient for the researcher.

Cognitively impaired subjects should be involved in research only where: (1) they comprise the only appropriate subject population; (2) the research question focuses on an issue unique to subjects in this population; and (3) the research involves no more than minimal risk

A minor increase over minimal risk may be permitted in research involving those institutionalized as mentally disabled, but only where the research is designed to evaluate an intervention of foreseeable benefit to their care

Research involving greater than minimal risk may be acceptable where the purpose of the research is therapeutic with respect to individual subjects and where the risk is commensurate with the degree of expected benefit.

.For research that does not involve beneficial interventions and that presents more than minimal risk, the anticipated knowledge sought should be of vital importance for understanding or eventually alleviating the subject's disorder or condition.

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Recommendations –Consent Process All adults, regardless of their diagnosis or condition, should be presumed

competent to consent unless there is evidence of serious mental disability that would impair reasoning or judgment. ◦ Mental disability alone should not disqualify a person from consenting to participate in

research; rather, there should be specific evidence of individuals' incapacity to understand and to make a choice before they are deemed unable to consent.

Persons may have court appointed guardians, who may have conflicting interests:◦ Institutional officials- conflicting interests and loyalties◦ Family members- financial, and emotional, issues, or be ambivalent

IRBs should be cautious about recommending legal proceedings to establish guardianship for the purpose of obtaining consent for research participation.

Consent may be obtained from a legally authorized representative or guardian, but the feelings and expressed wishes of an incompetent person should still be respected. ◦ Consider obtaining assent from the subject.◦ Should incompetent subjects refusal to participate override the consent of the legal

guardian. In some cases, a consent auditor should be appointed by the IRB to

determine whether the subjects actually consent, assent, or object to participation in research, especially if the research involves more than minimal risk and no foreseeable direct benefit.

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National Bioethics Advisory Commission (NBAC)Research Involving Persons with

Mental Disorders That May Affect Decisionmaking Capacity, 1998

Conditions include: Dementia, delirium, Schizophrenia, depression, mental retardation, bipolar disorder, substance abuse disorders

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NBAC Recommendations-IRBs should have at least 2 members familiar

with the disorders or concerns of the populationIRBs should not approve protocols targeting

persons with mental disorders if other types of subjects can be used

IRBs should use heightened scrutiny and investigators should justify the research design

Protocols should include evaluation of risks and benefits and clearly distinguish between direct and other benefits.

No person with capacity to consent should be enrolled without his or her informed consent.

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NBAC Recommendations (cont.)

The potential subject’s objection should be heeded.

If greater than minimal risk research, an independent professional should assess the subject’s capacity to consent.

A person who has been deemed to lack capacity must be told of that determination before the LAR is approached. If the subject objects after LAR permission is obtained, it must be heeded.

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NBAC recommendations (cont.)If Minimal Risk

◦Consent can be waived◦Subject gives consent◦Prospective authorization (advance directive)

of the subject in the event they lose the capacity with LAR permission

◦LAR provides permissionIf Greater than Minimal Risk, but direct

benefit◦Subject gives consent◦Prospective authorization with LAR permission◦LAR permission

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NBAC Recommendations (cont.)

If Greater than Minimal Risk, but no prospect of direct medical benefit◦Subjects gives consent◦Prospective Authorization and LAR

permission◦Protocol approved by federal panel

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NBAC Recommendations- surrogate consentPotential subjects provides Prospective

Authorization to a class of research while they have capacity giving an LAR the ability to enroll them in research after they lose capacity to consent◦ LAR must be available to monitor the subject

during the research

LAR may give permission:◦ The LAR bases decision on best estimate of what

the subject would want◦ LAR available to monitor subject on research◦ LAR chosen by subject or is a relative or friend

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NBAC recommendations-Surrogate consent (cont.)Investigators should accept LAR as per state

law for clinical decisions◦ States should confirm LAR for clinical decisions =

LAR for research◦ Friends may serve as LAR if they are actively

involved in care of the personState law should allow for persons to choose

LAR for researchFor protocols involving subjects whose

capacity may fluctuate, the IRBs should ensure protocols have provisions for ongoing communication (re-consent, consent when the subject regains capacity)

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Literature References Research Consent for Cognitively Impaired Adults:

Recommendations for Institutional Review Boards and Investigators, Alzheimer’s Association, Alzheimer’s Disease & Associated Disorders, Vol. 18, No. 3, July/September 2004, pp 171-175

Research Involving Persons with Cognitive Impairments: Results of a Survey of Alzheimer disease Research Centers in the United States, Cahill, Maura; Wichman, Alison, Alzheimer Disease & Associated Disorders, Vol. 14, January/March 2000, pp 20-27

Protecting Subjects with Decisional Impairment in Research : The Need for a Multi Faceted Approach, Silverman, Henry; Luce, John; and Schwartz, Jack, American Journal of Respiratory Care Medicine, Vol. 169, 2004, pp 10-14

Obtaining Informed Consent for Research : A Model for Use with Participants Who are Mentally Ill, Poythress, Norman, Journal of Law, Medicine & Ethics, 30: 3, Fall 2002 , pp 1-8

Ethical Issues Surrounding the Conduct of Research with Decisionally Impaired Adults, O’Mathuna, Donal, Research Practitioner, Vol. 4, No.2, pp42-50.

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NIH Guidance Research Involving Individuals with Questionable

Capacity to Consent: Points to Consider (first issued 1999, current version November 2009)◦ Must have a process for evaluating consent capacity

May be multi-step plan

◦ IRBs evaluate what additional safeguards are appropriate on a protocol per protocol basis

◦ Consent ongoing process Disorders with progressive or fluctuating capacity

◦ IRB membership: professionals with appropriate background, knowledge, and

experience; patient advocacy groups; experts in consent capacity; experts in ethical issues with vulnerable populations Ad hoc consultants

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NIH Guidance (cont.)Therapeutic Misconception and the consent

processAdditional safeguards

◦ Independent consent monitor◦ Method of assessing capacity to consent◦ Use of educational techniques to enhance the

consent process multi-media presentations, combination of oral and written Step-wise consent, interactive questioning, additional

education, and repetition Continuous dissemination and communication

Supplemental materials Waiting periods- allow for family conference or

consultation Use of LAR and Advance Directives

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NIH OHSR Information Sheet 7Research Involving Cognitively Impaired

Subjects: A Review of Some Ethical Considerations (11/21/2006)

http://ohsr.od.nih.gov/info/sheet7.html Assent of the cognitively impaired subject is

necessary, but not sufficient. Must do more to verify this is what the subject would do if they were making the decision

Promotes use of advanced directives (Durable Power of Attorney)and appointment of a representative

Presents 8 cases or categories

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OHRP FAQs if an adult lacks capacity to consent, for example, as a

result of trauma, mental retardation, some forms of mental illness, or dementia - whether temporary, progressive, or permanent - only a LAR for that adult can give consent for participation in the research, unless the requirement to obtain informed consent is waived

In longitudinal studies involving progressive disorders or aging populations, enrolled subjects may be competent to consent on their own behalf at the outset, yet may experience effects of progressive or intermittent disorders that lead to decisional impairment during the course of the study. In these situations IRBs and investigators should consider the need to discuss with the prospective subjects whether they should designate someone to serve as a LAR at the outset of the study

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SACHRPSubcommittee on Inclusion of Individuals

with Impaired Decision-Making in Research◦ The Subcommittee will develop either one or both of

the following products, depending on its conclusions: (1) recommendations on the interpretation of specific Subpart A provisions that will enhance protections for this population; and (2) recommendations for a new subpart under 45 CFR part 46 (and FDA's human subject protection regulations) that would provide additional regulatory protections for this population.

◦ http://www.hhs.gov/ohrp/sachrp/20090715lettertohhssecretary.html new guidance and/or additional regulations are necessary to

provide appropriate research protections for individuals who have impaired consent capacity

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SACHRP RecommendationsUnderstanding capacity to consent IRB review and membershipConsent autonomy and LAR roleValue self determination even when capacity is

limited; assent, dissentGuidance should define role of LAR and limitationsGuidance to better define applicable lawCreate new subpart that describes hierarchy for LAREncourage states to create research specific laws

for third party consent

http://www.hhs.gov/ohrp/sachrp/mtgings/mtg03-09/present.html

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Best Practices for IRBsEvaluate your state laws and obtain legal

counsel guidance on interpretation and applicability to research◦ Medical Patient Rights Act (IL410 50/3.1)

No physician may conduct any research program or experimental procedure on a patient without the prior informed consent of the patient or, if the patient is unable to consent, the patient's guardian, spouse, parent, or authorized agent.

◦ Illinois Power of Attorney Act (755 ILCS 45) Rules for appointing a person for property, personal, or healthcare decisions

◦ Illinois Health Care Surrogate Act (IL755 40) Describes who can be a surrogate for healthcare decisions and the order of

priority

◦ Illinois Living Will Act (IL 755 CS 35) Limits some of 755-40

◦ Mental Health Treatment Preference Declaration Act (755 ILCS 43/10) Allows for advanced directives related to mental health treatment

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IRB Best PracticesReview NBAC guidance and SACHRP

recommendations Benchmark other institutionsCreate guidance specific to your

organization◦Utilize the guidance from legal counsel◦Consult expertise in decisionally impaired

populations◦Incorporate levels of review and

anticipate the type of populations at your institution

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Best Practices for IRBsConsider consent templates with surrogate

consent or advanced directive languageMake decisions regarding additional protections

and consent processes on a protocol per protocol basis◦ Consider the population◦ When to require an independent assessment of capacity◦ Consider the use of consent monitors◦ When should advance directives be included◦ Risk level: minimal, minor increase over minimal,

greater than minimal◦ Benefit

Direct or indirect No benefit

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Q & AContact Information:

Susan Loess-Perez, MS, CIP, CCRCDirector, Office of Research ProtectionsDePaul University(312) [email protected]