MEMORANDUM TO: FROM: DATE: RE: Investigators Human Research Affairs November 2004 NOT FOR EXTERNAL DISTRIBUTION

Surrogate Consent to Research for Individuals with Impaired Decision-making Capacity

Research involving individuals with impaired decision-making capacity raises ethical concerns and legal issues. This memorandum outlines the key considerations for you as an investigator and offers a checklist at the end. The IRB may raise additional issues depending on the specific protocol and the group of subjects. The type of research and the risks/benefits of participation by a person who is not competent to give informed consent are critically important to the IRBs consideration of the protocol. You and every member of the research team bear primary responsibility for protecting the rights and welfare of research participants. I. Determining Whether an Individual Is Competent to Give Informed Consent to Research A person generally is legally competent to give informed consent to research when s/he understands the difference between treatment and research, understands the risks and benefits of a specific research protocol and its procedures, appreciates the consequences of acting (or not acting), and is able to make a choice. In research involving a person with impaired decision-making capacity who cannot give informed consent, federal regulations require that you obtain consent from the persons legally authorized representative, as determined by state or local law. A qualified professional first must assess the individuals competency. This should include a formal psychiatric and/or medical assessment that considers what level of understanding is needed for the specific research. General competency measures such as the Clinical Dementia Rating (CDR), the Activities of Daily Living scale, or the Mini Mental Status Exam (MMSE) may be helpful, but generally should not be the sole measure of competency. 1 In a protocol submission to the IRB, you should describe in detail how competency will be assessed, who will perform the assessments, and what that professionals relationship is to the individual and the research team. In order to strengthen the integrity of the enrollment process, in any research involving more than a questionnaire or cognitive test such as a study of a new medication consideration should be given to using an independent professional (who is not part of the research team) to assess a potential subjects competency. Determining Who May Give Surrogate Consent A person with impaired decision-making capacity who cannot give informed consent may participate in research only after you obtain consent from a legally authorized individual on that persons behalf (a surrogate). The determination of who is legally authorized to give consent for a
For example, as a very general guideline, subjects typically would need to have a CDR of (i) 2.0 or better to consent to research involving only questionnaires or cognitive tests (minimal risk); (ii) 1.0 or better to consent to research on a new medication; and (iii) 0.5 or better to consent to research involving a surgical procedure. Also see the appended chart, which provides clinical descriptions and corresponding MMSE scores. CDR websites: http://www.adrc.wustl.edu/adrc/cdrScale.html; http://www.adrc.wustl.edu/adrc/cdrGrid.html; MMSE website: http://www.alzmndak.org/3forprofessionals/diagnosis/mmse.htm.
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specific research protocol will be made by the IRB, in consultation with the Office of the General Counsel (OGC) as appropriate. Persons who might be proposed as appropriate surrogates are described below. These include, in order of general preference: (1) a court-appointed guardian with authority to consent to participation in the research or authority to make health care decisions for a class of diagnostic and therapeutic decisions that are inclusive of the proposed research; (2) a health care proxy or person with durable powers of attorney, whose authority includes making health care decisions inclusive of the proposed research; or (3) a spouse, an adult child, or other close family member. Additional information about guardians and other surrogates is provided below. The IRB has discussed with OGC the legal restrictions underlying the choice of surrogate, and in addition, the IRB and OGC are scheduling educational sessions for investigators to aid you in preparing and carrying out your protocols. In the event that the IRB reviewing your protocol has a question about the appropriateness of the surrogates proposed, it will consult OGC. A. Guardians A guardian must be appointed by the court. A guardian may be either a family member who has agreed to serve in this role or an independent person (typically a lawyer or a social worker). Guardianship authority is specific and may be limited (e.g., to financial decisions). Generally, the authority to consent to research must be specifically requested from the court. Guardians can be temporary or permanent. The process for obtaining a temporary court-appointed guardian (effective for 90 days) can take four to six weeks. Appointing a permanent guardian can take six to eight weeks or more. A guardian will be required in research that is within the jurisdiction of the Massachusetts Department of Mental Retardation. Both that agency and the Department of Mental Health have detailed requirements for agency-related research and may have their own review committees also overseeing the research. If you are considering this type of research and want to know if these requirements apply, information is available at http://www.dmr.state.ma.us/regulations/1003.html or http://mass.gov/Eeohhs2/docs/dmh/regs/reg_104cmr31.pdf or consult OGC. In addition, a guardian typically will be required in research involving greater than minimal risk and no prospect of direct medical benefit. Ethical principles maintain that research with greater than minimal risk and no potential for direct gain requires consideration by fully competent individuals who can meaningfully consider the risks and make informed decisions. The use of decisionally-impaired subjects in this type of research would be considered only in exceptional circumstances; consultation with an IRB chairperson is recommended, and further consultation between the IRB and OGC is likely. Note that if the research has no prospect of direct medical benefit but involves no more than minimal risk, then the IRB should consult with OGC to determine who is the appropriate representative for the subject or whether a waiver of consent is possible. In the above situations or any other protocol in which court-approved guardians are needed, additional information on the guardianship process is available through OGC. Consider incorporating the associated costs into the research budget where appropriate.

B. Surrogates Other Than Guardians As explained earlier, a surrogate other than a court-appointed guardian may have appropriate authority depending on the specific research and any legal restrictions. These other surrogates may include (1) a health care proxy or person with durable powers of attorney, whose authority includes making health care decisions inclusive of the proposed research; or (2) a spouse, an adult child, or other close family member. 2 If you are proposing to use one of these surrogates, you need to inform the IRB of the following issues, and if questions remain for the IRB about whether the proposed surrogates are authorized in a given protocol or for a given subject, it will consult OGC. Key factors that will be considered, along with the specific type of protocol and type of surrogate proposed: the research offers the reasonable potential for direct personal health benefit; the risks are commensurate with other accepted treatments that might be considered, or there are no other accepted, standard treatments and the condition is serious; and the surrogates know the subjects well and have been involved in their care. If the research study meets these factors and involves use of a drug, device, and/or intervention that is within the strict federal definition of minimal risk, 3 then reliance on one of the two types of surrogates noted above likely will be approved. In the event of questions, the IRB will consult with OGC. If, on the other hand, the research study meets the factors above and involves use of a drug, device, and/or intervention that exceeds the strict federal definition of minimal risk, then the IRB will consider several other issues. These include: the nature of the condition under study, and whether the condition responsible for incompetence is the focus of the study; the possible alternative treatments and current standards of care for the condition; the risks and potential benefits of participation; the presence or absence of a placebo arm, and whether risks undertaken by placebo recipients are otherwise commensurate with routine medical risks; and the consent process, including among other details, who is proposed as an acceptable surrogate to give informed consent.

In the event of questions, the IRB will consult with OGC.

According to informal guidance from an OHRP official, if research involves medical treatment and procedures for which a designated health care proxy or next-of-kin ordinarily might consent in a clinical context, then such a person may be an appropriate surrogate to consent to these procedures performed as part of the research. 3 See 45 CFR 46.102(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).

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Understanding How a Surrogate Makes Decisions If you will rely on surrogate consent, you should ensure that the surrogate understands that his or her decisions should be based on substituted judgment. This standard means that the decision reflects a potential subjects own views when s/he had the capacity to express them (such as any prior oral or written expressions by him or her of objection to the types of procedures involved in the research). If a potential subject did not previously express a view on the matter, the surrogate should make the decision based on the potential subjects best interests. In addition, and importantly, even after obtaining a surrogates consent, you still must seek the potential subjects assent, and if s/he objects, should heed the objection. The IRB is aware that there may be situations where the subject cannot provide assent because of his or her medical condition (e.g., when a subject is in shock, is delirious, is intubated, or is heavily sedated). In the event of questions concerning assent or objections, contact the IRB. In addition, contact the IRB and OGC in the event that there is disagreement among potential surrogates about whether to consent to the research. In general, the IRB recommends that when there is disagreement among potential surrogates (usually adult children or spouse of an aged parent), the person not be enrolled in the research.

IV.

Using a Patient Advocate as an Additional Safeguard

In select research, such as that involving greater than minimal risk but offering a potential for direct benefit, additional protections may be prudent. For example, you may propose or the IRB may recommend using a patient advocate (informally or formally designated, as explained below) to help ensure the integrity of the consent process. An informal patient advocate may be an independent person participating in a specific patients care. For example, an emergency room or primary care physician could assist with decision-making and could serve as an advisor to a surrogate when the patient is too ill to provide consent (e.g., when experimental use of a new monoclonal antibody therapy for acute stroke is being contemplated). Such a physician would have additional patient-specific insight into the acute and/or chronic medical condition. This person would have important knowledge of the specific situation and could provide an independent professional opinion, considering only the best interests of the patient. A formal designated patient advocate is typically an independent physician, nurse, or social worker who has agreed to perform this duty routinely, for every subject in a highly challenging protocol (e.g., implantation of an artificial heart, or xenotransplantation). Such a person is highly familiar with the specific protocol and its risks and benefits, and typically has expertise in psychiatry, psychology, or mediation and difficult decision-making, in addition to medical knowledge. The advocates role is to consider the risks and benefits of the proposed research, with the best interests of the subject in mind, and advocate for that individual in communication with you and the surrogate. Informal advocates are frequently recommended by the IRB; formal protocolspecific advocates are only occasionally recommended, for unusual or risky studies.

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Checklist for Investigators If you are submitting a protocol that may involve subjects who have impaired decisionmaking capacity and cannot give informed consent, please review the following issues to be addressed in the protocol submitted for IRB review. The guidance in this memo is based on applicable law and guidance from OHRP, National Bioethics Advisory Commission, and other sources. 1. Thoroughly justify the research study design, including why individuals with decisional impairments are necessary to and appropriate for the research, and what safeguards will be taken to minimize risk. Be sensitive to how a procedure that generally entails little to no physical or psychosocial risks may affect someone who has limited (or no) understanding of the situation. Describe the level of understanding needed to consent to the specific research. (Refer back to footnote 1 on page 1.) Describe in the protocol who will perform individualized competency assessments and how. Inform the IRB as to whether fluctuations in any subjects competency can be expected; if so, the protocol should describe how you will assess subjects competency on an ongoing basis, what opportunity subjects will have to appoint legal representatives either early or later in the study, and what educational efforts are planned. In addition, as OHRP has suggested, consider whether a waiting period during the recruitment and consent processes would better permit an individual to reflect on his or her participation and to consult with family members. The IRB typically will require this waiting period it is one of the reasons why you are asked on the application to indicate how long an individual has to consider participation in the proposed study. Address in the protocol what other safeguards you will use during the recruitment and consent processes to avoid coercion of subjects and surrogates to participate in the research. The safeguards that you provide should be appropriate for the extent of experimental risk and the severity of the subjects decisional impairments. Explain the type of surrogates you propose to rely upon (see list above, in II.), and if applicable, address the factors described in II.B. Address in the protocol how you will seek the assent of subjects who lack the capacity to consent and heed an incompetent subjects objection to enrollment or continued participation. Indicate how you will seek a subjects consent to continue participating, should the person regain the capacity to consent. Address in the protocol how you will ensure that subjects and their families understand the difference between research and treatment during the entire consent process. Clearly distinguish between treatment and research, and between clinician and investigator, in the 5

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consent form. Describe how you will document informed consent. Documentation of informed consent, while always important, is especially critical when a person has been determined to lack capacity to consent to research and someone else is giving informed consent. Relevant support should be included in research records (including, for example, the basis of the determination of the subjects incompetency, and a copy of the guardianship order or health care proxy, or if that is not possible, documentation of the surrogates close relationship with and reasonable knowledge of the subject and other relevant underlying circumstances). Note that the IRB will not waive the requirement that a surrogates consent be in writing, except in exceptional circumstances (consult with the IRB if you are proposing to obtain telephonic or other oral consent the IRB Chair is available by pager in urgent situations. Please contact the Human Research Office for information: http://healthcare.partners.org/phsirb/hrcoffice.htm). As stated above, you and every member of the research team bear primary responsibility for protecting the rights and welfare of research participants. This guidance is intended to help you submit necessary information to the IRB so that it can review this area of research, which has heightened sensitivity because of the populations involved and applicable legal restrictions.