sachrp strauss flynn 7-08 subcommittee on the inclusion of individuals with impaired decision-...

SACHRP Strauss Flynn 7-08

Subcommittee on the Inclusion of Individuals with Impaired Decision-

making in Research [SIIIDR] Presentation to SACHRP

July 15, 2008

David H. Strauss, M.D. and

Laurie Flynn and Co-chairs


From the SACHRP Charter

The committee shall advise, consult with, and make recommendations on matters pertaining to…protections for human subjects in research…with special emphasis on special populations, such as…the decisionally impaired.


From the SIIIDR Charge

The Subcommittee will develop recommendations for consideration by SACHRP about whether guidance and/or additional regulations are needed for research involving individuals with impaired decision-making capacity.


Background/Challenges

1. Existing federal regulations and regulatory guidance relevant to individuals with “impaired decision-making” do not adequately address key ethical concerns regarding the rights and welfare of this most vulnerable category of research participants;


Regulatory “References”

§46.111 Approval

(a)(2) Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result.”

(b) When…subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included…

(a)(3) Subject selection is equitable…be particularly cognizant of special problems…(with) vulnerable populations.


Regulatory References (Cont’d)

§46.107 Membership:

If an IRB regularly reviews research that involves …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.


Regulatory “References”

§46.116

“Information… shall be in language understandable to the subject…”


Basis

2. Prior efforts (National Commission, NBAC, NHRPAC, NIH points to consider) to affect federal protections specific to “decisional impairment” have not been successful;

Background/Challenges-2


Basis

3. For those prospective subjects who are “unable to consent” for themselves, the absence of adequate, consistent, or in many cases, any state law creates significant problems for research protections;



LAR and the Regulatory “Dead End”

• The federal regulations require the subject’s “legally effective informed consent”

• They also allow consent by a “legally authorized representative (LAR)” to the “procedures used in the research.”

• But, the federal regulations do not define LAR. This is left to the applicable local (State) law.

• The States, with rare exceptions, have not defined LAR for research, and some do not define it at all.


Basis

4. Solutions must provide appropriate protections and address the need for advancement in clinical therapeutics and knowledge of disease processes and their broader psychological and social context.



Paul Appelbaum, Jeffrey Botkin*, Anne Donahue, Laurie Flynn, David Forster*, Lisa Leiden*, John Luce, John Oldham, Laura Roberts, Gustavo Roman, David Strauss*

*SACHRP Members

Current SIIIDR Membership


SIIIDR meetings since the 3/08 SACHRP meeting

• April 4 teleconference• May 2 teleconference • June 27 teleconference• June 18 and 19 meeting, Rockville, MD• Two day on site meeting scheduled for August

Recommendation Description/Purpose Type Comments Status

I Defines the term “consent capacity” and recommends its use

Guidance Approved by SACHRP

II Describes the nature of impaired “consent capacity” as it pertains to research participation


III Describes safeguards related to the identification of individuals with impaired consent capacity


IV Clarifies the meaning and interpretation of LAR within Subpart A

Guidance Additional safeguards will be provided by interim guidance on approval criteria described in recommendation VIII

For preliminary presentation at the July 2008 SACHRP meeting

V Defines the roles and responsibilities of the surrogate decision-maker/LAR

Guidance Outlined; for review at August SIIIDR meeting

VI Defines the involvement of subjects in choice of surrogate, in consent, and in assent

Guidance Serves to promote the autonomous involvement subjects with impaired capacity in research decision-making processes to the extent possible and consistent with their abilities and desires

As above

VII Defines who may provide consent (the LAR) in the absence of “applicable law”

Component of a new regulatory subpart to 45CFR46

Describes a hierarchy to guide institutions and IRBs on who may consent on behalf of a subject who lacks consent capacity. Will be linked to rules related to approval criteria described in recommendation VIII

For preliminary presentation to SACHRP July, 2008

VIII Approval Criteria Interim Guidance/a component of new regulatory subpart (?)

This will serve as interim guidance (“additional safeguards”) related to review and approval of research under subpart A. It will be also be considered as a component of a new regulatory subpart

Outlined, in progress. Concept for presentation at SACHRP, July 2008; For further development at August SIIIDR meeting

IX Recommendation to HHS Model Legislation/Regulation

This proposal will develop and encourage the promotion of model state legislation/regulation

Outlined


Interdependence of Recommendations

• Provides a balance of “permissiveness” (or latitude for IRBs) and “restrictiveness’ (specifying required additional safeguards);

• Considers the effect of varying timelines for “enactment” of guidance vs. regulations on current practice;

• Carefully considers the “risks and benefits” of regulations vs. guidance.


Approval criteria and what is a

“reasonable”risk-benefit relationship

when consent is provided by an LAR

How do we define (and how do IRBs, Investigators Identify) the populations

requiring additional protection?

How do we decide who may provide consent

for those who are unable to consent for

themselves?

Framework for SIIIDR activities

•Clarifying current definition of LAR

•A federal definition of LAR in the absence of applicable law

•Promoting model state legislation


•Subject Selection

•IRB Membership

•Reasonable risk

•Defining the role of the LAR

•Optimizing the involvement of the subject in decision-making

•Extent of prior specification of wishes by the subject

•Relationship of LAR to subject

•Definition of consent capacity

•The nature of impairment in consent capacity

•Safeguards related to the identification of individuals with impaired consent capacity



Population: Recommendations I, II, III

LAR: RecommendationsIV, VII, IX

RecommendationsV, VI

Approval:Recommendation VIII

Recommendation Description/Purpose Type Comments Status

I Defines the term “consent capacity” and recommends its use


II Describes the nature of impaired “consent capacity” as it pertains to research participation


III Describes safeguards related to the identification of individuals with impaired consent capacity


IV Clarifies the meaning and interpretation of LAR within Subpart A

Guidance Additional safeguards will be provided by interim guidance on approval criteria described in recommendation VIII

For preliminary presentation at the July 2008 SACHRP meeting

V Defines the roles and responsibilities of the surrogate decision-maker/LAR

Guidance Outlined; for review at August SIIIDR meeting

VI Defines the involvement of subjects in choice of surrogate, in consent, and in assent

Guidance Serves to promote the autonomous involvement subjects with impaired capacity in research decision-making processes to the extent possible and consistent with their abilities and desires

As above

VII Defines who may provide consent (the LAR) in the absence of “applicable law”

Component of a new regulatory subpart to 45CFR46

Describes a hierarchy to guide institutions and IRBs on who may consent on behalf of a subject who lacks consent capacity. Will be linked to rules related to approval criteria described in recommendation VIII

For preliminary presentation to SACHRP July, 2008

VIII Approval Criteria Interim Guidance/a component of new regulatory subpart (?)

This will serve as interim guidance (“additional safeguards”) related to review and approval of research under subpart A. It will be also be considered as a component of a new regulatory subpart

Outlined, in progress. Concept for presentation at SACHRP, July 2008; For further development at August SIIIDR meeting

IX Recommendation to HHS Model Legislation/Regulation

This proposal will develop and encourage the promotion of model state legislation/regulation

Outlined


RECOMMENDATION VII [DRAFT]for preliminary consideration


The subcommittee on the Inclusion of Individuals with Impaired Decision-making in Research (SIIIDR) recommends that HHS develop a Subpart to 45CFR46 to include new regulations related to the inclusion of adults who lack consent capacity.

Recommendation VII [Draft]


While this subpart will describe additional safeguards for IRB review and approval of research with adults who lack consent capacity, its primary intent is to define a hierarchy of individuals who may provide consent on behalf of individuals who lack consent capacity when a legally authorized representative (LAR) for research is not defined in state or local law.



SIIIDR makes the following recommendations for inclusion in this subpart:



1. When and IRB approves the conduct of research under Subpart A and determines that it is appropriate for consent to research to be obtained from the legally authorized representatives of adult subjects who lack decisional capacity to consent on their own behalves:



a. Such determination must be made at a convened meeting of the IRB and not by means of expedited review, unless the research qualifies for waiver of consent1;

1An initial determination must be made by the convened IRB. Subsequent review and approval of this research with regard to the inclusion of individuals lacking consent capacity would follow guidance on continuing review.



b. Where applicable law exists to determine who is authorized to serve as an LAR to consent to a subject’s participation in research, consent may only be obtained from an LAR in accordance with this law.



c. In the absence of applicable law determining who is authorized to serve as an LAR to consent to a subject’s participation in research, one of the persons listed below, in the following descending order of priority, shall be considered the subject’s LAR and may consent to participation on behalf of the subject:



i. A person designated by the subject, while retaining the decisional capacity to do so, to make decisions for him/her regarding participation in research;

ii. A person by the subject, while retaining the decisional capacity to do so, to make decisions for him/her regarding non-research health care decisions;

iii. The subject’s legal guardian with authority to make health care decisions for the subject;



iv. The spouse, or if recognized by applicable law, the civil union partner or domestic partner of the subject;

v. An adult son or daughter of the subject;

vi. A parent of the subject;

vii. An adult brother or sister of the subject;

viii. An adult who has exhibited special care and concern for the subject.



d. The LAR shall make a decision regarding consent on behalf of the subject in accord with applicable law. In the absence of applicable law, the decision shall be based on his/her judgment as to the decision that the subject, if he/she retained decisional capacity, would have made. If the LAR is unable to determine the decision that the subject would have made, he/she shall make the decision that appears to be in the subject’s best medical, psychological and other interests2.



2It is not the intent here to exclude without further consideration studies which are not anticipated to offer direct benefit (and therefore are not in the “subjects interests”) but which do not qualify for waiver of consent. Reference here to “medical, psychological, and other” is meant to capture interests beyond those specifically related to healthcare.



Recommendation IV [Draft]For preliminary consideration


A legally authorized representative is defined at 45CFR 46.102 (c) as “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 research.”

Recommendation IV [Draft]


HHS should support the development of guidance to clarify the current HHS interpretation of “applicable law.” This guidance should include the basis for the Department’s interpretation of what constitutes applicable law. Specifically:



1. As the laws defining who may provide consent to research for a subject who lacks consent capacity take many forms and vary widely among the states, guidance should describe the sources upon which an institution or IRB may rely to determine who may serve as a legally authorized representative.



2. Guidance should describe examples of sources of “applicable law” in states with laws or regulations that address consent to treatment but do not specifically consider consent to research. This guidance will serve to clarify the current HHS interpretation that permits institutions and IRBs to allow research consent by individuals authorized under laws that allow consent to the “procedures involved in the research.”



3. Guidance should clarify that individuals defined by community or other standards (e.g. institutional policies, standards of care) in the absence of specific judicial statutory or regulatory authority do not constitute legally authorized representatives.


sachrp strauss flynn 7-08 subcommittee on the inclusion of individuals with impaired decision-...

Documents

sachrp strauss flynn

laurie flynn

subject slide

human subjects

prospective subjects

research siiidr presentation

regulatory references

regulatory dead