Research

Human Research Protection Program Policy and Procedure Manual - Section 6

6 Vulnerable Participants in Research

6.1 Purpose

6.2 Definitions

6.3 Involvement of Vulnerable Populations

6.4 Responsibilities

6.5 Procedures

6.6 Research Involving Pregnant Women, Human Fetuses and Neonates

6.6.1 Research Involving Pregnant Women or Fetuses

6.6.1.1 Research Not Funded by DHHS

6.6.1.2 Research Funded by DHHS

6.6.2 Research Involving neonates

6.6.3 Research Involving, After Delivery, the Placenta, the Dead Fetus or Fetal Material

6.6.4 Research Not Otherwise Approvable

6.7 Research Involving Prisoners

6.7.1 Applicability

6.7.2 Minimal Risk

6.7.3 Composition of the IRB

6.7.4 Additional Duties of the IRB

6.7.5 Waiver for Epidemiology Research

6.8 Research Involving Children

6.8.1 Allowable Categories

6.8.2 Parental Permission and Assent

6.8.2.1 Parental Permission

6.8.2.2 Assent from Children

6.8.2.3 Children Who are Wards

6.9 Persons with Impaired Decision Making Capacity

6.9.1 Determination of Decision-Making Capacity

6.9.1.1 Determining Capacity to Consent

6.9.2 Informed Consent and Assent

6.9.3 Surrogate Consent

 

6 Vulnerable Participants in Research
6.1 Purpose

The following procedures describe the requirements for involving vulnerable participants in research under the auspices of Brown University.

 

6.2 Definitions 

Children are persons who have not attained the legal age for consent to research, under the applicable law of the jurisdiction in which the research will be conducted.

 

Delivery means complete separation of the fetus from the woman by expulsion, extraction, or any other means.

 

Fetus is the product of conception from the time of implantation until delivery.

 

Viable fetus is now termed a “viable neonate.”

 

Non-viable fetus is a fetus ex utero that, although living, is not able to survive to the point of independently maintaining heart and respiration. Note: In 45 CFR 46 Subpart B, this definition is used as the definition of a non-viable neonate.

 

Dead fetus is a fetus which exhibits neither heartbeat, spontaneous respiratory activity, spontaneous movement of voluntary muscles, nor pulsation of the umbilical cord if still attached.

 

In vitro fertilization is any fertilization of human ova, which occurs outside the body of a female, either through a mixture of donor human sperm and ova or by any other means.


Neonate means newborn.

 

Viable neonate means being able, after delivery, to survive to the point of being independently maintaining heart and respiration (given the benefit of available medical therapy).

 

Non-viable neonate means the same as a non-viable fetus.

 

Pregnancy is the period of time from confirmation of implantation (through any of the presumptive signs of pregnancy, such as missed menses, or by a medically acceptable pregnancy test), until expulsion or extraction of the fetus.

 

Prisoner is any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures that provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing.

 

Surrogate Consent is consent obtained from a legally authorized representative on behalf of a participant determined to lack decision-making capacity.

 

6.3 Involvement of Vulnerable Populations

When some or all of the participants in a protocol are likely to be vulnerable to coercion or undue influence, the IRB should include additional safeguards to protect the rights and welfare of these participants.  Some of the vulnerable populations that might be involved in research include children, pregnant women, fetuses, neonates, prisoners, or adults who lack the ability to consent, students, employees, or homeless persons.

 

If the IRB reviews research that involves categories of participants vulnerable to coercion or undue influence, best efforts will be made to ensure that the review process will include one or more individuals who are knowledgeable about or experienced in working with these participants. For example, the IRB will include one or more individuals who are knowledgeable about or experienced in working with children, prisoners, or adults with limited decision-making capacity, when reviewing research that involves individuals from these populations.

 

45 CFR 46 has additional subparts designed to provide extra protections for vulnerable populations which also have additional requirements for IRBs.

 

  • Subpart B - Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research
  • Subpart C - Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Participants
  • Subpart D - Additional Protections for Children Involved as Subjects in Research

 

DHHS-funded research that involves any of these populations must comply with the requirements of the relevant subparts.  Research funded by other federal agencies may or may not be covered by the subparts. 

 

6.4 Responsibilities

  1. The PI is responsible for identifying the potential for enrolling vulnerable participants in the research proposal. The PI is responsible for identifying participants who are at risk for impaired decisional capacity and who are being asked to participate in a research study with greater than minimal risk. 
  2. The IRB shall include representation, either as members or ad hoc consultants, individual(s) interested in or who have experience with the vulnerable populations involved in a research proposal. 
  3. The IRB reviews the PI’s justifications for including vulnerable populations in the research to assess appropriateness of the research proposal.
  4. The IRB must ensure that additional safeguards have been included in each study to protect the rights and welfare of vulnerable participants as needed at the time of initial review of the research proposal.
  5. The IRB shall continue to review research at intervals appropriate to the degree of risk and determine whether the proposed research continues to fulfill criteria for approval. Information reviewed should include the number of participants considered as members of specific vulnerable populations.
  6. For studies that do not have or are not required to have a Data and Safety Monitoring Board (DSMB) or a Data Monitoring Committee and have entered vulnerable participants, the IRB needs to carefully review a data and safety monitoring plan.
  7. The IRB should be knowledgeable about and experienced in working with populations who are vulnerable to coercion and undue influence. If the IRB requires additional qualification or expertise to review a protocol, it should obtain consultation.

 

6.5 Procedures

  1.  Initial Review of Research Proposal:
    • The PI should identify the potential to enroll vulnerable participants in the proposed research at initial review and provide the justification for their inclusion in the study.
    • The IRB evaluates the proposed plan for consent of the specific vulnerable populations involved. If the research involves adults unable to consent, the IRB evaluates the proposed plan for permission of legally authorized representatives.
    • The IRB evaluates and approves the proposed plan for the assent of participants.
    • The IRB evaluates the research to determine the need for additional protections and consider the use of a data and safety monitoring board or data monitoring committee as appropriate.
    • The PI should provide appropriate safeguards to protect the participant’s rights and welfare, which may include the addition of an independent monitor. The independent monitor is a qualified individual not involved in the research study who will determine the participant’s capacity to provide voluntary informed consent.
      • Examples of studies that may warrant independent monitoring include those involving schizophrenic patients who will be exposed to placebo, drug washout, and/or treatment with agents that are not approved by the Food and Drug Administration (FDA). Populations that may also warrant independent monitoring would include individuals with dementia, schizophrenia, other psychotic disorders or conditions characterized by lack of reality testing (i.e., psychosis). Populations not usually requiring independent monitoring would include those with substance use disorders.
    • The IRB assesses the adequacy of additional protections for vulnerable populations provided by the PI.
  2. Continuing Review and Monitoring.  At continuing review the PI should identify, in the progress report, the number of vulnerable participants enrolled and any that need an independent monitor.

6.6 Research Involving Pregnant Women, Human Fetuses and Neonates
6.6.1 Research Involving Pregnant Women or Fetuses
6.6.1.1 Research Not Funded by DHHS

For research not funded by DHHS, no additional safeguards are required and there are no restrictions on the involvement of pregnant women in research where the risk to the fetus is no more than minimal. 

 

Pregnant women or fetuses may be involved in research not funded by DHHS involving more than minimal risk to fetuses if all of the following conditions are met:

 

  1. Where scientifically appropriate, pre-clinical studies, including studies on pregnant animals, and clinical studies, including studies on non-pregnant women, have been conducted and provide data for assessing potential risks to pregnant women and fetuses;
  2. The risk to the fetus is caused solely by interventions or procedures that hold out the prospect of direct benefit for the woman or the fetus;
  3. Any risk is the least possible for achieving the objectives of the research;
  4. If the research holds out the prospect of direct benefit to the pregnant woman, the prospect of a direct benefit both to the pregnant woman and the fetus, then the consent of the pregnant woman is obtained in accord with the provisions for informed consent;
  5. If the research holds out the prospect of direct benefit solely to the fetus then the consent of the pregnant woman and the father is obtained in accord with the provisions for informed consent, except that the father's consent need not be obtained if he is unable to consent because of unavailability, incompetence, or temporary incapacity or the pregnancy resulted from rape or incest.
  6. Each individual providing consent under paragraph 4 or 5 of this section is fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate;
  7. For children who are pregnant, assent and permission are obtained in accord with the provisions of permission and assent;
  8. No inducements, monetary or otherwise, will be offered to terminate a pregnancy;
  9. Individuals engaged in the research will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy; and
  10. Individuals engaged in the research will have no part in determining the viability of a neonate.

 

6.6.1.2 Research Funded by DHHS

For DHHS-funded research, 45CFR46 Subpart B applies to all research involving pregnant women.  Under 45CFR46 Subpart B, pregnant women or fetuses may be involved in research funded by DHHS if all of the following conditions are met:

 

  1. Where scientifically appropriate, pre-clinical studies, including studies on pregnant animals, and clinical studies, including studies on non-pregnant women, have been conducted and provide data for assessing potential risk to pregnant women and fetuses.
  2. The risk to the fetus is caused solely by interventions or procedures that hold out the prospect of direct benefit for the woman or the fetus or, if there is no such prospect of benefit, the risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge which cannot be obtained by any other means;
  3. Any risk is the least possible for achieving the objectives of the research;
  4. If the research holds out the prospect of direct benefit to the pregnant woman, the prospect of a direct benefit both to the pregnant woman and the fetus, or no prospect of benefit for the woman nor the fetus when risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means, then the consent of the pregnant woman is obtained in accord with the provisions for informed consent.
  5. If the research holds out the prospect of direct benefit solely to the fetus then the consent of the pregnant woman and the father is obtained in accord with the provisions for informed consent, except that the father's consent need not be obtained if he is unable to consent because of unavailability, incompetence, or temporary incapacity or the pregnancy resulted from rape or incest.
  6. Each individual providing consent under paragraph 4. or 5. of this section is fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate;
  7. For children who are pregnant, assent and permission are obtained in accord with the provisions of permission and assent in Section 10.1.3;
  8. No inducements, monetary or otherwise, will be offered to terminate a pregnancy;
  9. Individuals engaged in the research will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy; and
  10. Individuals engaged in the research will have no part in determining the viability of a neonate.

 

6.6.2 Research involving neonates

Neonates of uncertain viability and non-viable neonates may be involved in research if all of the following conditions are met:

 

  1. where scientifically appropriate, preclinical and clinical studies have been conducted and provide data for assessing potential risks to neonates.
  2. each individual providing consent is fully informed regarding the reasonably foreseeable impact of the research on the neonate.
  3. individuals engaged in the research will have no part in determining the viability of a neonate.
  4. the requirements of Neonates of Uncertain Viability or Non-viable Neonates (see below in this section) have been met as applicable.

 

Neonates of Uncertain Viability. Until it has been ascertained whether or not a neonate is viable, a neonate may not be involved in research covered by this subpart unless the following additional conditions have been met:

The IRB determines that:

 

  1. the research holds out the prospect of enhancing the probability of survival of the neonate to the point of viability, and any risk is the least possible for achieving that objective, or
  2. the purpose of the research is the development of important biomedical knowledge which cannot be obtained by other means and there will be no added risk to the neonate resulting from the research; and
  3. the legally effective informed consent of either parent of the neonate or, if neither parent is able to consent because of unavailability, incompetence, or temporary incapacity, the legally effective informed consent of either parent's legally authorized representative is obtained in accord with the provisions of permission and assent, except that the consent of the father or his legally authorized representative need not be obtained if the pregnancy resulted from rape or incest.

 

Non-viable Neonates.  After delivery, non-viable neonates may not be involved in research covered by this subpart unless all of the following additional conditions are met:

 

  1. vital functions of the neonate will not be artificially maintained;
  2. the research will not terminate the heartbeat or respiration of the neonate;
  3. there will be no added risk to the neonate resulting from the research;
  4. the purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means; and
  5. the legally effective informed consent of both parents of the neonate is obtained in accord with the provisions of permission and assent, except that the waiver and alteration of the provisions of permission and assent do not apply.
  6. however, if either parent is unable to consent because of unavailability, incompetence, or temporary incapacity, the informed consent of one parent of a non-viable neonate will suffice to meet the requirements of this paragraph, except that the consent of the father need not be obtained if the pregnancy resulted from rape or incest. The consent of a legally authorized representative of either or both of the parents of a non-viable neonate will not suffice to meet the requirements of this paragraph.

 

Viable Neonates. A neonate, after delivery, that has been determined to be viable may be included in research only to the extent permitted by and in accord with the requirements of IRB review process and research involving children.

 

6.6.3 Research Involving, After Delivery, the Placenta, the Dead Fetus or Fetal Material

  1. Research involving, after delivery, the placenta; the dead fetus; macerated fetal material; or cells, tissue, or organs excised from a dead fetus, must be conducted only in accord with any applicable Federal, State, or local laws and regulations regarding such activities.
  2. If information associated with material described above in this section is recorded for research purposes in a manner that living individuals can be identified, directly or through identifiers linked to those individuals, those individuals are research participants and all pertinent sections of this manual are applicable.

 

6.6.4 Research Not Otherwise Approvable

If the IRB finds that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of pregnant women, fetuses or neonates and the research is not approvable under the above provisions, then the IRB will consult with a panel of experts in pertinent disciplines (for example: science, medicine, ethics, law).  Based on the recommendation of the panel, the IRB may approve the research based on either:

 

  • that the research in fact satisfies the conditions of Section 6.6.1, as applicable; or
  • the following:
    1. the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of pregnant women, fetuses or neonates;
    2. the research will be conducted in accord with sound ethical principles; and
    3. informed consent will be obtained in accord with the provisions for informed consent and other applicable sections of this manual.

 

6.7 Research Involving Prisoners

Prisoners are another of the three classes that are deemed so vulnerable to exploitation in research that there are special rules protecting them. In the past, prisoners were viewed as a convenient research population. 

 

The concern Subpart C, and this document based on Subpart C, attempts to address is whether prisoners have any real choice in participation in research or whether incarceration prohibits free choice.

 

6.7.1 Applicability

This policy applies to all research conducted under the auspices of Brown University involving prisoners as participants. Even though a University IRB may approve a research protocol involving prisoners as participants according to this policy, investigators are still subject to the administrative regulations of the appropriate State Department of Corrections and any other applicable State or local law. [45 CFR 46.301]

 

6.7.2 Minimal Risk

The definition of minimal risk in Subpart C is different than in the rest of the federal regulations. According to 45CFR46.303, minimal risk is the probability and magnitude of physical or psychological harm that is normally encountered in the daily lives, or in the routine medical, dental, or psychological examination of healthy persons.

 

6.7.3 Composition of the IRB

[45 CFR 46.304]

In addition to satisfying the general requirements detailed in the IRB section of this manual, when reviewing research involving prisoners, the IRB must also meet the following requirements:

 

  1. A majority of the IRB (exclusive of prisoner members) must have no association with the prison(s) involved, apart from their membership on the IRB.
  2. At least one member of the IRB must be a prisoner, or a prisoner representative with appropriate background and experience to serve in that capacity, except that where a particular research project is reviewed by more than one IRB, only one IRB need satisfy this requirement.

 

6.7.4 Additional Duties of the IRB

[45 CFR 46.305]

In addition to all other responsibilities, the IRB will review research involving prisoners and approve such research only if it finds that:

 

  1. the research falls into one of the following permitted categories [45 CFR 46.306]:
    • study of the possible causes, effects, and processes of incarceration, and of criminal behavior, provided that the study presents no more than minimal risk and no more than inconvenience to the participants;
    • study of prisons as institutional structures or of prisoners as incarcerated persons, provided that the study presents no more than minimal risk and no more than inconvenience to the participants;
    • research on conditions particularly affecting prisoners as a class (for example, research on social and psychological problems such as alcoholism, drug addiction, and sexual assaults);
    • research on practices, both innovative and accepted, which have the intent and reasonable probability of improving the health or well-being of the participant.
  2. any possible advantages accruing to the prisoner through his or her participation in the research, when compared to the general living conditions, medical care, quality of food, amenities and opportunity for earnings in the prison, are not of such a magnitude that his or her ability to weigh the risks of the research against the value of such advantages in the limited choice environment of the prison is impaired;
  3. the risks involved in the research are commensurate with risks that would be accepted by non-prisoner volunteers;
  4. procedures for the selection of participants within the prison are fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners. Unless the principal investigator provides to the IRB justification in writing for following some other procedures, control participants must be selected randomly from the group of available prisoners who meet the characteristics needed for that particular research project;
  5. the information is presented in language which is understandable to the participant population;
  6. adequate assurance exists that parole board will not take into account a prisoner's participation in the research in making decisions regarding parole, and each prisoner is clearly informed in advance that participation in the research will have no effect on his or her parole; and
  7. where the IRB finds there may be a need for follow-up examination or care of participants after the end of their participation, adequate provision has been made for such examination or care, taking into account the varying lengths of individual prisoners' sentences, and for informing participants of this fact.

 

6.7.5 Waiver for Epidemiology Research

The Secretary of DHHS has waived the applicability of 45 CFR 46.305(a)(l) and 46.306(a)(2) for certain research conducted or supported by DHHS that involves epidemiologic studies that meet the following criteria:

 

  1. in which the sole purposes are
    (i) to describe the prevalence or incidence of a disease by identifying all cases, or
    (ii) to study potential risk factor associations for a disease, and
  2. where the IRB has approved the research and fulfilled its duties under 45CFR 46.305(a)(2)–(7) and determined and documented that
    (i) the research presents no more than minimal risk and no more than inconvenience to the prisoner-participants, and
    (ii) prisoners are not a particular focus of the research.

 

The specific type of epidemiological research subject to the waiver involves no more than minimal risk and no more than inconvenience to the participants. The waiver would allow the conduct of minimal risk research that does not now fall within the categories set out in 45CFR46.306(a)(2).

 

The range of studies to which the waiver would apply includes epidemiological research related to chronic diseases, injuries, and environmental health. This type of research uses epidemiologic methods (such as interviews and collection of biologic specimens) that generally entail no more than minimal risk to the participants.

 

In order for a study to be approved under this waiver, the IRB would need to ensure that, among other things, there are adequate provisions to protect the privacy of participants and to maintain the confidentiality of the data.

 

6.8 Research Involving Children
6.8.1 Allowable Categories

Research on children must be reviewed and categorized by the IRB into one of the following groups:

 

  1. Research not involving physical or emotional risk greater than that ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests (i.e., minimal risk). [45 CFR 46.404]
    • The IRB may find that the permission of one parent is sufficient.
    • Assent, as necessary, of a child capable of providing assent based on age and/or cognitive capacity.
  2. Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual participant. [45 CFR 46.405]
    • The risk is justified by the anticipated benefit to the participants;
    • The IRB may find that the permission of one parent is sufficient;
    • Assent, as necessary, of a child capable of providing assent based on age and /or cognitive capacity.
  3. Research involving greater than minimal risk and no reasonable prospect of direct benefit to the individual participant, but likely to yield generalizable knowledge about the participant's disorder or condition. [45 CFR 46.406]
    • The risk represents a minor increase over minimal risk;
    • The intervention or procedure presents experiences to participants that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations;
    • Permission of either both parents, or legal guardian, is required- unless one parent is deceased, unknown, incompetent, or not reasonably available; or only one parent has legal responsibility for the care and custody of the child;
    • Assent, as necessary, of a child capable of providing assent based on age and/or cognitive capacity.
  4. Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate serious problems affecting the health or welfare of children. [45 CFR 46.407]
    • Federally-funded research in this category must be approved by the Secretary of Health and Human Services, and requires consent of either both parents, or legal guardian.
    • For non-federally-funded research, IRB will consult with a panel of experts in pertinent disciplines (for example: science, medicine, ethics, law).  Based on the recommendation of the panel, the IRB may approve the research based on either:
      • That the research in fact satisfies the conditions of the previous categories, as applicable; or
      • The following:
        (i) The research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children;
        (ii) The research will be conducted in accord with sound ethical principles; and
        (iii) Informed consent will be obtained in accord with the provisions for informed consent and other applicable sections of this manual.

 

6.8.2 Parental Permission and Assent
6.8.2.1 Parental Permission

In accordance with 45CFR46.408(b) the IRB must determine that adequate provisions have been made for soliciting the permission of each child’s parent or guardian.

 

Parents or guardians must be provided with the basic elements of consent as stated in 45CFR46.116(a)(1-8) and any additional elements the IRB deems necessary.

 

The IRB may find that the permission of one parent is sufficient for research to be conducted under 45CFR46.404 or 45CFR46.405.  The IRB’s determination that consent must be obtained from both parents will be documented when a protocol receives expedited review, and in meeting minutes when reviewed by the convened committee.

 

Consent from both parents is required for research to be conducted under 45CFR 46.406 and 45CFR 46.407 unless

  • one parent is deceased, unknown, incompetent, or not reasonably available; or
  • when only one parent has legal responsibility for the care and custody of the child.

 

The IRB may waive the requirement for obtaining consent from a parent or legal guardian if:

  • the research meets the provisions for waiver in 45CFR46.116(d)(1-4) and if the IRB determines that the research protocol is designed for conditions or a participant population for which parental or guardian permission is not a reasonable requirements to protect the participants (for example, neglected or abused children).
  • an appropriate mechanism for protecting the children who will participate as participants in the research is substituted, and that the waiver is not inconsistent with Federal State, or local law.  The choice of an appropriate mechanism would depend upon the nature and purpose of the activities described in the protocol, the risk and anticipated benefit to the research participants, and their age, maturity, status, and condition.

 

Permission from parents or legal guardians must be documented in accordance with and to the extent required by 45CFR46.117.

 

6.8.2.2 Assent from Children

 

Because “assent” means a child’s affirmative agreement to participate in research, (45 CFR46.402(b), the child must actively show his or her willingness to participate in the research, rather than just complying with directions to participate and not resisting in any way. When judging whether children are capable of assent, the IRB is charged with taking into account the ages, maturity, and psychological state of the children involved. The Brown University IRB has the discretion to judge children’s capacity to assent for all of the children to be involved in a proposed research activity, or on an individual basis.

 

The IRB should take into account the nature of the proposed research activity and the ages, maturity, and psychological state of the children involved when reviewing the proposed assent procedure and the form and content of the information conveyed to the prospective participants. For research activities involving adolescents whose capacity to understand resembles that of adults, the assent procedure should likewise include information similar to what would be provided for informed consent by adults or for parental permission. For children whose age and maturity level limits their ability to fully comprehend the nature of the research activity but who are still capable of being consulted about participation in research, it may be appropriate to focus on conveying an accurate picture of what the actual experience of participation in research is likely to be (for example, what the experience will be, how long it will take, whether it might involve any pain or discomfort). The assent procedure should reflect a reasonable effort to enable the child to understand, to the degree they are capable, what their participation in research would involve.

 

The IRB presumes that children ages 7 and older should be given an opportunity to provide assent. Generally, oral assent through the use of a script and/or reading the document with the child, would be obtained from children 7 - 11 years of age. Written assent using a written document for the children to sign may be sought for older children.

 

At times there may be inconsistency between parent permission and child assent. Usually a "no" from the child overrides a "yes" from a parent, but a child typically cannot decide to be in research over the objections of a parent. Obviously, there are individual exceptions to these guidelines, when assent is less obligatory due to study procedures involving treatment for serious health conditions (such as when the use of an experimental treatment for a life threatening disease is being considered). The general idea, however, is that children should not be forced to be research participants, even when their parents consent to it.

 

If the IRB determines that the capability of some or all of the children is so limited that they cannot reasonably be consulted or that the intervention or procedure involved in the research holds out a prospect of direct benefit that is important to the health or well-being of the children and is available only in the context of the research, the assent of the children is not a necessary condition for proceeding with the research.

 

Even when the IRB determines that the participants are capable of assenting, the IRB may still waive the assent requirement under certain circumstances.

 

The Assent Form

Researchers should try to draft a form that is age appropriate and study specific, taking into account the typical child's experience and level of understanding, and composing a document that treats the child respectfully and conveys the essential information about the study. The assent form should:

 

  1. tell why the research is being conducted;
  2. describe what will happen and for how long or how often;
  3. say it's up to the child to participate and that it's okay to say no;
  4. explain if it will hurt and if so for how long and how often;
  5. say what the child's other choices are;
  6. describe any good things that might happen;
  7. say whether there is any compensation for participating; and
  8. ask for questions.

 

For younger children, the document should be limited to one page if possible. Illustrations might be helpful, and larger type makes a form easier for young children to read. Studies involving older children or adolescents should include more information and may use more complex language. 


6.8.2.3 Children Who Are Wards

 

Children who are wards of the State or any other agency, institution, or entity can be included in research involving greater than minimal risk and no prospect of direct benefit to individual participants, but likely to yield generalizable knowledge about the participant's disorder or condition, only if such research is:

 

  1. related to their status as wards; or
  2. conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of children involved as participants are not wards.

 

If the research meets the condition(s) above, an advocate must be appointed for each child who is a ward (one individual may serve as advocate for more than one child), in addition to any other individual acting on behalf of the child as legal guardian or in loco parentis.


The advocate must be an individual who has the background and experience to act in, and agrees to act in, the best interests of the child for the duration of the child's participation in the research and who is not associated in any way (except in the role as advocate or member of the IRB) with the research, the investigator(s), or the guardian organization.

 

6.9 Persons with Impaired Decision Making Capacity

Research involving persons with impaired decision-making capability may only be approved when the following conditions apply:

 

  1. Only incompetent persons or persons with impaired decision making capacity are suitable as research participants. Competent persons are not suitable for the proposed research. The investigator must demonstrate to the IRB that there is a compelling reason to include incompetent individuals or persons with impaired decision-making capacity as participants. Incompetent persons or persons with impaired decision-making capacity must not be participants in research simply because they are readily available.
  2. The proposed research entails no significant risks, tangible or intangible, or if the research presents some probability of harm, there must be at least a greater probability of direct benefit to the participant. Incompetent people or persons with impaired decision-making capacity are not to be participants of research that imposes a risk of injury, unless that research is intended to benefit that participant and the probability of benefit is greater than the probability of harm.
  3. Procedures have been devised to ensure that participant’s representatives are well informed regarding their roles and obligations to protect incompetent participants or persons with impaired decision making capacity. Health care agents (appointed under Durable Power of Attorney for Health Care (DPAHC)) and next-of-kin, or guardians, must be given descriptions of both proposed research studies and the obligations of the person’s representatives. They must be told that their obligation is to try to determine what the participant would do if competent, or if the participant's wishes cannot be determined, what they think is in the incompetent person's best interests.

 

6.9.1 Determination of Decision-Making Capacity

The decision-making capacity of a potential research participant should be evaluated when there are reasons to believe that the participant may not be capable of making voluntary and informed decisions about research participation.

 

The investigator and research staff must have adequate procedures in place for assessing and ensuring participants’ capacity, understanding, and informed consent or assent.  The IRB will evaluate whether the proposed plan to assess capacity to consent is adequate.

 

For research protocols that involve participants with mental disorders that may affect decision-making capacity, the IRB may determine that capacity assessments are necessary, unless the investigator can justify why such assessments would be unnecessary for a particular group.

 

For research that poses greater than minimal risk, the IRB may require investigators to use independent and qualified professionals to assess whether potential participants have the capacity to give voluntary, informed consent. Even in research involving only minimal risk, the IRB may require that the study include a capacity assessment if there are reasons to believe that potential participants’ capacity may be impaired. It is not necessary to require a formal capacity assessment by an independent professional for all potential research participants with mental disorders.

 

For research protocols involving participants who have fluctuating or limited decision making capacity the IRB may ensure that investigators establish and maintain ongoing communication with involved caregivers. Periodic re-consent should be considered in some cases. Third party consent monitors may be used during the recruitment and consenting process, or waiting periods may be required to allow more time for the participant to consider the information that has been presented.

 

It is often possible for investigators and others to enable persons with some decisional impairments to make voluntary and informed decisions to consent or refuse participation in research. Potential measures include repetitive teaching, group sessions, audiovisual presentations, and oral or written recall tests. Other measures might include follow-up questions to assess participant understanding, videotaping or audio-taping of consent interviews, second opinions, use of independent consent observers, interpreter for hearing-impaired participants, allowing a waiting period before enrollment, or involvement of a trusted family member or friend in the disclosure and decision making process.

 

Both investigators and IRB members must be aware that for some participants, their decision-making capacity may fluctuate. For participants with fluctuating decision making capacity or those with decreasing capacity to give consent, a re-consenting process with surrogate consent may be necessary.

 

Although incompetent to provide informed consent, some persons may resist participating in a research protocol approved by their representatives. Under no circumstances may participants be forced or coerced to participate.

 

In the event research participants become incompetent or impaired in decision making capacity after enrollment, the PI is responsible for notifying the IRB and RPO. The PI is responsible for developing a monitoring plan which follows the guidelines outlined above for incompetent and impaired decision making research participants.   

 

6.9.1.1 Determining Capacity to Consent

Decisional capacity in the research context has been interpreted by the American Psychiatric Association as requiring:

 

  • ability to evidence a choice,
  • ability to understand relevant information,
  • ability to appreciate the situation and its likely consequences, and
  • ability to manipulate information rationally.

 

A range of professionals and methods may be utilized to assess capacity. In general the consent assessor should be a researcher or consultant familiar with dementias, or other impairing conditions, and qualified to assess and monitor capacity and consent in such participants on an ongoing basis. The IRB will consider the qualifications of the proposed individual(s) and whether he or she is sufficiently independent of the research team and/or institution.

 

The majority of studies conducted at Brown University only allow enrolling participants who have the capacity to consent. For studies that have been approved for enrolling vulnerable populations who may lack capacity to consent, there must be someone who is able to assess capacity of each potential participant to consent. The PI may determine after appropriate medical evaluation that the prospective research participant lacks decision-making capacity and is unlikely to regain it within a reasonable period of time.

 

A person who has been determined to lack capacity to consent to participate in a research study must be notified of that determination before permission may be sought from his or her legally authorized representative to enroll that person in the study. If permission is given to enroll such a person in the study, the potential participant must then be notified. Should the person object to participating, this objection should be heeded.

 

6.9.2 Informed Consent and Assent

Whenever the participants have the capacity to give consent (as determined by qualified professionals), informed consent should be obtained and document in accordance with Section 5 above.  When participants lack the capacity to give consent, investigators may obtain consent from the legally authorized representative of a participant (surrogate consent) as described below.

 

A person who is incompetent or has been determined to lack capacity to consent to participate in a research study should be informed about the research to the extent compatible with the participant’s understanding and, if possible, the participant should give their assent to participate, sign and date the written informed consent or a separate assent form. If the person objects to participating, this objection should be heeded.

 

Both investigators and IRB members must be aware that for some participants, their decision-making capacity may fluctuate. For participants with fluctuating decision making capacity or those with decreasing capacity to give consent, a re-consenting process with surrogate consent may be necessary. Although incompetent to provide informed consent, some persons may resist participating in a research protocol approved by their representatives. Under no circumstances may participants be forced or coerced to participate. 

 

6.9.3 Surrogate Consent

The regulations generally require that the investigator obtain informed consent from participants. Under appropriate conditions, investigators also may obtain informed consent from a legally authorized representative of a participant (surrogate consent).

 

Definition: Legally authorized representative means an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective participant to the participant's participation in the procedure(s) involved in the research [45 CFR 46.102(c)].

 

This policy is designed to protect human participants from exploitation and harm and, at the same time, make it possible to conduct essential research on problems that are unique to persons who are incompetent, or who have an impaired decision-making capacity.

 

Surrogate consent may be obtained from a court appointed guardian of the person or a health care agent appointed by the person in a Durable Power of Attorney for Health Care (DPAHC). For example, a participant might have designated an individual to provide consent with regard to health care decisions through a durable power of attorney and have specified that the individual also has the power to make decisions on entry into research.