Human Research Protection Program: Policy

Review of Research Involving Vulnerable Participants

 

Adopted By: All Campus IRB

Adoption Date: November 10, 2005

Revised: July 10, 2008

Revised: January 22, 2009

Purpose:  This document describes how UW-Madison IRBs review proposed research to determine whether it provides adequate safeguards for vulnerable research participants.

Definitions

I.      Vulnerable participants are those research participants who are likely to be vulnerable to coercion or undue influence or lack decision-making capacity, including:

A.  those in designated vulnerable groups, such as children, prisoners, pregnant women, fetuses, neonates, mentally disabled persons, or economically or educationally disadvantaged persons, and

B.  those who may be vulnerable because of physical condition, e.g., severe illness or pain, psychological or emotional condition, status relationship with a member of the research team, cultural or political factors or other circumstances.

Policy

II.     To approve research involving vulnerable participants, UW-Madison IRBs require that the research procedures include adequate additional safeguards to protect the rights and welfare of these participants consistent with ethical principles and applicable federal regulations, state law and institutional policies.  Belmont Report; 45 CFR 46.111(b) and 45 CFR 46, Subparts B, C and D; 21 CFR 56.111(b) and 21 CFR 50, Subpart D; Wisconsin Mental Health Code, WSA 51.61(1)(j), 51.61(4); Wisconsin Protective Services statute, WSA 55.07.  See, also, Applying State Law in Human Subjects Research Policy.

Ÿ         In its Federalwide Assurance (FWA), UW-Madison commits to applying the federal Common Rule (45 CFR Part 46) to all federally funded or supported research.  UW-Madison applies Subparts B through D of 45 CFR 46 only to research funded by the U.S. Department of Health and Human Services (“DHHS research”).  UW-Madison also applies similar or greater protections to human research participants in all non-federally funded research.

III.    Department of Veterans Affairs (VA) policies prohibit the participation of children, prisoners, pregnant women, neonates and fetuses in VA research protocols.

Procedure

IV.   UW-Madison IRBs systematically evaluate research submitted for initial review, continuing review, or review of changes of protocol to determine whether the research involves participants likely to be vulnerable to coercion or undue influence.

V.    If the IRB determines that a protocol involves vulnerable research participants, the IRB considers the following general criteria:

A.  Whether additional safeguards are necessary to protect the welfare, safety, privacy and confidentiality of these participants.

B.  Whether any additional safeguards are described in the protocol.

C.  Whether the additional safeguards described in the protocol are adequate to protect participants.

 

1.  In determining the adequacy of additional protections for vulnerable participants, the IRBs consider:

 

a.  the degree of risk posed by the research

 

b.  whether the research offers the prospect of direct benefit to the participant

D.  For those vulnerable groups for which specific, additional protections are designated by ethical principles, federal regulations, state law and institutional policies, the IRB evaluates whether the protocol complies with those requirements. 

E.  The IRB is particularly cognizant of the special problems of research involving designated vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons when assessing whether the selection of research participants is equitable.

F.  If an IRB regularly reviews research that involves a vulnerable population, such as children, prisoners, pregnant women, or handicapped or mentally disabled persons, consideration shall be given to the inclusion on the IRB of one or more individuals who are knowledgeable about and experienced in working with these subjects.

 

1.  For DHHS research involving prisoners:

 

a.  a majority of IRB members (exclusive of prisoner members) shall have no association with the prison(s) involved, apart from their membership on the Board, and

 

b.  at least one member shall 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.

G. When approving research that involves vulnerable groups, the IRB will document in its meeting minutes the IRB’s justifications and findings regarding the determinations stated in the applicable federal regulations or the IRB’s agreement with the findings and justifications as presented by the investigator.

VI.   IRB Review of Research Involving Children.

A.  UW-Madison IRBs will approve research involving children only if the IRB finds that the research includes any required additional safeguards outlined in ethical principles and applicable federal regulations, state laws and institutional policies. See, Belmont Report; 45 CFR 46, Subpart D; 21 CFR 50, Subpart D; UW-Madison Federalwide Assurance; Applying State Law in Human Subjects Research Policy.

B. The IRB may also apply OHRP Guidance - Research with Children FAQs, authorizing minors to consent to research participation without parental permission or waiver of permission, if the research involves solely treatments or procedures for which minors can give consent outside the research context under state or local laws.  For more information, contact the UW-Madison Office of Administrative Legal Services.

C.  For an IRB to approve DHHS research involving children or FDA research involving children, the IRB must find and document that the research meets the requirements of one of the following categories of research:

 

1.  The research involves no greater than minimal risk and that adequate provisions are made for soliciting the assent of the children and the permission of their parents or guardians, as set forth in 45 CFR 46.408 or 21 CFR 50.55. [45 CFR 46.404; 21 CFR 50.51]

 

2.  That more than minimal risk to children is presented by an intervention or procedure that holds out the prospect of direct benefit for the individual subject or by a monitoring procedure that is likely to contribute to the subject's well-being and all of the following:

 

a.  The risk is justified by the anticipated benefit to the subjects

 

b.  The relation of the anticipated benefit to the risk is at least as favorable to the subjects as that presented by available alternative approaches, and

 

c.  Adequate provisions are made for soliciting the assent of the children and permission of their parents or guardians, as set forth in 45 CFR 46.408 or 21 CFR 50.55. [45 CFR 46.405; 21 CFR 50.52]

 

3.  That more than minimal risk to children is presented by an intervention or procedure that does not hold out the prospect of direct benefit for the individual subject or by a monitoring procedure which is not likely to contribute to the well-being of the subject and all of the following:

 

a.  The risk represents a minor increase over minimal risk

 

b.  The intervention or procedure presents experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations

 

c.  The intervention or procedure is likely to yield generalizable knowledge about the subjects' disorder or condition which is of vital importance for the understanding or amelioration of the subjects' disorder or condition, and

 

d.  Adequate provisions are made for soliciting assent of the children and permission of their parents or guardians, as set forth in 45 CFR 46.408 or 21 CFR 50.55. [45 CFR 46.406; 21 CFR 50.53]

 

4.  For DHHS research, that the research does not meet the requirements of 45 CFR 46.404, 46.405, or 46.406 and all of the following:

 

a.  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 children, and

 

b.  The Secretary, after consultation with a panel of experts in pertinent disciplines (for example: science, medicine, education, ethics, law) and following opportunity for public review and comment, has determined either:

 

i.         That the research in fact satisfies the conditions of 45 CFR 46.404, 46.405, or 46.406, as applicable, or

 

ii.       All of the following:

Ÿ         The research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children

Ÿ         The research will be conducted in accordance with sound ethical principles

Ÿ         Adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians, as set forth in 45 CFR 46.408. [45 CFR 46.407]

 

5.  For FDA regulated research, that the research does not meet the requirements of 21 CFR 50.51, 21 CFR 50.52, or 21 CFR 50.53 and that:

 

a.  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 children, and

 

b.  The Commissioner of Food and Drugs, after consultation with a panel of experts in pertinent disciplines (for example: science, medicine, education, ethics, law) and following opportunity for public review and comment, has determined that either of the following is true:

 

i.         The research in fact satisfies the conditions of 21 CFR 50.51, 21 CFR 50.52, 21 CFR 50.53 above, or

 

ii.       All of the following are true:

Ÿ         The research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children

Ÿ         The research will be conducted in accordance with sound ethical principles

Ÿ         Adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians

 

6.  For each protocol approved under 45 CFR 46.406, 45 CFR 46.407, 21 CFR 50.53 or 21 CFR 50.54, the IRB must also find one of the following:

 

a.  The research does NOT involve wards of the state or any other agency, institution, or entity, or

 

b.  The research meets the criteria for involvement of wards of the State or any other agency, institution, or entity (see, Section III.C.7, below).

D.  Definitions [45 CFR 46.102, 46.402 and 21 CFR 50.3]

 

1.  The terms research and clinical investigation are deemed to be synonymous for purposes of this policy.

 

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

 

a.  In Wisconsin, “children” are generally those persons under the age of 18 years.  For more information, see, Applying State Law in Human Subjects Research Policy.

 

b.  In Wisconsin, emancipated minors are not subject to Subpart D of 45 CFR 46 and are consented as adults.  Emancipated minors include individuals under 18 years of age who are or have been married, who have given birth or who have been freed from the care, custody and control of their parents with little likelihood of returning to the care, custody and control prior to marriage or prior to reaching the age of majority. [WSA 48.375(2)(e), 765.02(2), 880.04(1), 895.037(1)(c)]

 

c.  In Wisconsin, non-emancipated minors may consent to certain treatment or procedures without parental permission.  For more information, see OHRP Guidance - Research with Children FAQs and Applying State Law in Human Subjects Research Policy.  Also, consult with the UW-Madison Office of Administrative Legal Services.

 

3.  Ward means a child who is placed in the legal custody of the State or other agency, institution, or entity, consistent with applicable Federal, State, or local law.

 

4.  Parent means a child's biological or adoptive parent.

 

a.  In Wisconsin, a “parent” means either a biological parent, a husband who has consented to the artificial insemination of his wife, or a parent by adoption.  If the child is a non-marital child who is not adopted or whose parents do not subsequently intermarry, "parent" includes a person who has acknowledged paternity by law or been adjudicated to be the biological father.  "Parent" does not include any person whose parental rights have been terminated. WSA 48.02(13)

 

5.  Guardian means an individual who is authorized under applicable state or local law to consent on behalf of a child to general medical care when general medical care includes participation in research.  In FDA regulated research, a guardian also means an individual who is authorized under applicable state or local law to consent on behalf of a child to participate in research.

 

a.  Under Wisconsin law, in addition to a “parent,” as defined, above, a court-appointed “guardian” for an unemancipated child under the age of 18 has the authority to consent to major medical, psychiatric and surgical treatment. [WSA 48.023(1)]  A relative of a minor may be appointed as a minor’s “guardian.” [WSA 48.02, 48.023].  For more information, see, Applying State Law in Human Subjects Research Policy.

 

6.  Assent means a child's affirmative agreement to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent.

 

7.  Permission means the agreement of parent(s) or guardian to the participation of their child or ward in research.  In FDA regulated research, permission must be obtained in compliance with Subpart B of 21 CFR 50 and must include the elements of informed consent described in 21 CFR 50.25.

 

8.  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.

E.  Assent by Children to Research Participation

 

1.  When reviewing research involving children, UW-Madison IRBs will ensure that adequate provisions are made for soliciting the assent of the children when, in the judgment of the IRB, the children are capable of providing assent.  [45 CFR 46.408(a); 21 CFR 50.55]

 

2.  In determining whether children are capable of assenting, the IRB shall take into account the ages, maturity, and psychological state of the children involved. This judgment may be made for all children to be involved in research under a particular protocol, or for each child, as the IRB deems appropriate..

 

3.  Assent by children is not a necessary condition for proceeding with the research if the IRB determines that:

 

a.  the capability of some or all of the children is so limited that they cannot reasonably be consulted, or

 

b.  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,.

 

4.  Even where the IRB determines that the children are capable of assenting, the IRB may still waive the assent requirement if it finds and documents all of the following:

 

a.  The research involves no more than minimal risk to the subjects

 

b.  The waiver will not adversely affect the rights and welfare of the children

 

c.  The clinical investigation could not practicably be carried out without the waiver, and

 

d.  Whenever appropriate, the children will be provided with additional pertinent information after participation. [See, 45 CFR 46.116; 21 CFR 50.55(d)]

 

5.  When the IRB determines that assent is required, it will also determine whether and how assent must be documented. [45 CFR 46.408(a); 21 CFR 50.55]

 

a.  Investigators who plan to enroll children in their protocols should describe in their protocol applications the assent process that will be followed, taking into account the age ranges of the children, as well as the maturity and physical and psychological state of the children.

 

b.  Even if a child is too young to provide assent, investigators should consider and describe in their applications to the IRB how the investigator will identify and respond to situations where the child does not want to participate.

 

c.  Research involving preschool age children must indicate when the research will be conducted (e.g., during the month of October) and the duration of the activities.

 

d.  Respect for a child’s unwillingness to participate is especially critical in research that does not have a therapeutic intent and that exposes the child to some risk.

 

See, Assent by Children Guidance

HS IRBs Policy for Obtaining Assent of Minors

F.  Permission by or Consent of Parent or Guardian

 

1.  When reviewing research involving children, UW-Madison IRBs will assure that adequate provisions are made for soliciting the permission or consent of each child's parents or guardian when required by ethical principles and applicable federal regulations, state laws and institutional policies. (See, Section III.B and III.D.2, above, for a description of when children under the age of 18 may consent to research participation without the permission of parents or guardians.) [45 CFR 46.408(b-d); 21 CFR 50.55] 

 

2.  Where parental permission is to be obtained, the IRB may find that the permission of one parent is sufficient for research to be conducted under 45 CFR 46.404 or 46.405 or 21 CFR 50.51 or 50.52.

 

3.  Where research is covered by 45 CFR 46.406 or 46.407 or 21 CFR 50.53 or 50.54 and permission is to be obtained from parents, both parents must give their permission 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.

 

4.  For research not regulated by the FDA, if the IRB determines that a research protocol is designed for conditions or for a subject population for which parental or guardian permission is not a reasonable requirement to protect the subjects (for example, neglected or abused children), the IRB may waive informed consent under 45 CFR 46, Subpart A, and the parental or guardian permission requirements of 45 CFR 46.408(b) when authorized by ethical principles and applicable federal regulations, state law and institutional policies. [45 CFR 46.116, 46.408(c)]  

 

To waive requirement of consent or permission of a parent or guardian in these circumstances, the IRB must find that:

 

a.  That an appropriate mechanism for protecting the children who will participate as subjects in the research is substituted taking into account the nature and purpose of the activities described in the protocol, the risk and anticipated benefit to the research subjects, and their age, maturity, status, and condition, and

 

b.  That the waiver is not inconsistent with federal, state, or local law.

 

5.  Consent cannot be waived in FDA-regulated studies except in limited circumstances.  See, Informed Consent Policy, Sec. IV.D.2

 

6.  Permission by parents or guardians shall be documented in accordance with and to the extent required by 45 CFR 46.117 or 21 CFR 50.27.

 

a.  The consent form must indicate that either the child may withdraw or the parent may withdraw the child from the research at any time.

 

7.  Before a person other than the parent or court-appointed guardian of a child can give permission for a child to take part in research, the investigator must consult with UW-Madison legal services office to confirm that the person is authorized under applicable law to consent on behalf of a child to general medical care.

G. Children who are Wards of State

 

1.  When reviewing research involving children who are wards of the state or any other agency, institution, or entity, UW-Madison IRBs will assure that the research includes the special protections in 45 CFR 46, Subpart D and/or 21 CFR 50.56, when applicable.

 

a.  Children who are wards of the State or any other agency, institution, or entity can be included in research approved under 45 CFR 46.406 or 46.407 or 21 CFR 50.53 or 50.54 only if such research is:

 

i.   Related to their status as wards, or

 

ii.   Conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of children involved as subjects are not wards.

 

b.  If the research is approved under paragraph (a) of this section, the IRB shall require appointment of an advocate for each child who is a ward, in addition to any other individual acting on behalf of the child as guardian or in loco parentis. One individual may serve as advocate for more than one child. The advocate shall 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. [45 CFR 46.409; 21 CFR 50.56]

H.  The exemption at 45 CFR 46.101(b)(2), for research involving survey or interview procedures or observation of public behavior, does not apply to research with children, governed by 45 CFR 46, Subpart D, except for research involving observations of public behavior when the investigator(s) do not participate in the activities being observed.

I.   In addition to any ethical principles and applicable federal regulations and state laws governing research with children, UW-Madison IRBs apply the following specific additional protections:

 

1.  SBS IRB and ED IRB:

 

a.  Written assent to participate in research is required of a child who is 11 years old or older 

 

b.  For runaways and homeless children, waiver of parental consent for participation in research is permitted if parents cannot be located, research is not more than minimal risk and research cannot be carried out without the waiver.

 

2.  HS IRB and MR IRB:

 

a.  Minors should be included to the fullest degree possible in decisions about their own health care, including experimental health care.

 

b.  The HS IRB and MR IRB apply different protections depending on whether the research is therapeutic or non-therapeutic and the age of the child.  For more information, see, HS IRBs Policy for Obtaining Assent of Minors.

 

i.         Assent of minors is required in protocols dealing with non-therapeutic research unless the minor otherwise lacks the capacity to consent.

 

ii.       Assent in non-therapeutic protocols shall be obtained from children with normal developmental status aged 7 and older.

 

iii.      Phase I trials should generally be considered therapeutic studies if they hold out the prospect of direct benefit.

 

iv.      For therapeutic research, minors should be included to the degree possible in decisions about their health care, but parental consent is required to be documented.

 

v.        The HS IRB includes more than one member who is a child advocate.  These child advocates are asked to be primary reviewers on research involving children and their expertise is requested on issues relating to involving children in research.

VII.   IRB Review of Research Involving Prisoners

A.  Recognizing that prisoners may be under constraints because of their incarceration which could affect their ability to make a truly voluntary and uncoerced decision whether or not to participate as subjects in research, UW-Madison IRBs will approve research involving prisoners only if the IRB finds that the research includes any required additional safeguards outlined in ethical principles and applicable federal regulations, state laws and institutional policies. Belmont Report; 45 CFR 46, Subpart C; 21 CFR 56.111(b); UW-Madison Federalwide Assurance; Applying State Law in Human Subjects Research Policy.

B. Definitions

 

1.  Prisoner means any individual involuntarily confined or detained in a penal institution, including individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing. This includes situations where a participant becomes a prisoner after the research has commenced.

 

2.  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.

C.  DHHS biomedical or behavioral research may include prisoners as subjects only if the IRB finds and documents the following requirements of 45 CFR 46.306.  Except as provided below, biomedical or behavioral research conducted or supported by DHHS shall not involve prisoners as subjects:

 

1.  The institution responsible for the conduct of the research has certified to the Secretary of DHHS that the IRB has approved the research under 45 CFR 46.305, and

 

2.  In the judgment of the Secretary of DHHS, the proposed research involves solely one of the following:

 

a.  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 subjects

 

b.  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 subjects

 

c.  Research on conditions particularly affecting prisoners as a class (for example, vaccine trials and other research on hepatitis which is much more prevalent in prisons than elsewhere; and research on social and psychological problems such as alcoholism, drug addiction, and sexual assaults) provided that the study may proceed only after the Secretary has consulted with appropriate experts including experts in penology, medicine, and ethics, and published notice, in the FEDERAL REGISTER, of his intent to approve such research, or

 

d.  Research on practices, both innovative and accepted, which have the intent and reasonable probability of improving the health or well-being of the subject. In cases in which those studies require the assignment of prisoners in a manner consistent with protocols approved by the IRB to control groups which may not benefit from the research, the study may proceed only after the Secretary has consulted with appropriate experts, including experts in penology, medicine, and ethics, and published notice, in the FEDERAL REGISTER, of the intent to approve such research.

 

e.  The HHS Secretarial waiver for certain epidemiological research conducted or supported by HHS functions as a fifth category of permissible research. The criteria for this category are that the research must have as its sole purpose (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. The institution still must review the research under subpart C and certify to OHRP that an appropriately constituted IRB has reviewed the proposal and made all other required findings under HHS regulations at 45 CFR 46.305(a) and receive OHRP authorization prior to initiating any research involving prisoners. All of the other requirements of subpart C apply to research in this category.

D.  To approve federally funded research involving prisoners, UW-Madison IRBs must find all of the following:

 

1.  The research under review represents one of the categories of research permissible under Section C.2, above [45 CFR 46.306(a)(2)].

 

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 subjects 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 subjects 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 subject population

 

6.  Adequate assurance exists that parole boards 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.

 

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. [45 CFR 46.305(a)]

E.  Federally funded prisoner protocols are reviewed either by the HS IRB or the SBS IRB.  

F.  Research targeting prisoners is generally subject to review by the full IRB with a designated prisoner representative present and a majority of IRB members having no association with the prison involved.  Prisoner protocols are generally not eligible for expedited initial review.  For those prisoner protocols that are eligible for expedited continuing review or change of protocol review, the expedited reviewers will include a prisoner representative.  See, Expedited Review Policy.

In non-federally funded HS IRB and MR IRB protocols, if a prisoner is involved only incidentally in research (e.g., treatment trials for AIDs or cancer or medical records studies), a prisoner representative does not have to be present at the IRB meeting when the protocol is considered and approved.

G. When a previously enrolled research participant becomes a prisoner and the relevant research protocol was not reviewed and approved by the IRB in accordance with the requirements of 45 CFR 46, Subpart C, the following procedures apply:

     For all federally-funded prisoner protocols:

 

1.  The principal investigator should promptly notify the IRB of this event.

 

2.  Upon receipt of notification that a previously enrolled research participant has become a prisoner, if the principal investigator wishes to have the prisoner participant continue to participate in the research, the IRB should promptly re-review the protocol in accordance with the requirements of 45 CFR 46, Subpart C.

 

a.  All research interactions and interventions with, and obtaining identifiable private information about, the now-incarcerated participant must cease until the requirements of 45 CFR 46, Subpart C have been satisfied with respect to the relevant protocol.

 

b.  In special circumstances in which the principal investigator asserts that it is in the best interests of the participant to remain in the research study while incarcerated, the IRB Chair may determine that the participant may continue to participate in the research until the requirements of 45 CFR 46, Subpart C are satisfied.

     For non-federally funded HS IRB and MR IRB protocols:

 

1.  The principal investigator should promptly notify the IRB of this event.

 

2.  Upon receipt of notification that a previously enrolled research participant has become a prisoner, if the principal investigator wishes to have the participant continue to participate in the research, the IRB re-reviews the protocol at the next possible IRB meeting to assure compliance with either 45 CFR 46, Subpart C or another procedure that the IRB determines is similarly or more protective of the incarcerated participant.

VIII.  IRB Review of Research Involving Pregnant Women, Neonates and Fetuses

A.  UW-Madison IRBs will approve research involving pregnant women, fetuses and neonates only if the IRB finds that the research includes any required additional safeguards outlined in ethical principles and applicable federal regulations, state laws and institutional policies. See, Belmont Report; 45 CFR 46, Subparts B and C; 21 CFR 50, Subparts A and D; 21 CFR 56.107 and 56.111; UW-Madison Federalwide Assurance; Applying State Law in Human Subjects Research Policy.

B.  UW-Madison IRBs will apply the special protections in 45 CFR, Subpart B to all DHHS research involving pregnant women, human fetuses, neonates of uncertain viability, or nonviable neonates.

C.  The exemptions at 45 CFR 46.101(b)(1) through (6) are applicable to research involving pregnant women, neonates and fetuses under Subpart B.

D.  Definitions [45 CFR 46.202]

 

1.  Dead fetus means a fetus that exhibits neither heartbeat, spontaneous respiratory activity, spontaneous movement of voluntary muscles, nor pulsation of the umbilical cord.

 

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

 

3.  Fetus means the product of conception from implantation until delivery.

 

4.  Neonate means a newborn.

 

5.  Nonviable neonate means a neonate after delivery that, although living, is not viable.

 

6.  Pregnancy encompasses the period of time from implantation until delivery. A woman shall be assumed to be pregnant if she exhibits any of the pertinent presumptive signs of pregnancy, such as missed menses, until the results of a pregnancy test are negative or until delivery.

 

7.  Viable, as it pertains to the neonate, means being able, after delivery, to survive (given the benefit of available medical therapy) to the point of independently maintaining heartbeat and respiration. The Secretary may from time to time, taking into account medical advances, publish in the FEDERAL REGISTER guidelines to assist in determining whether a neonate is viable for purposes of this subpart. If a neonate is viable then it may be included in research only to the extent permitted and in accordance with the requirements of 45 CFR 46, Subparts A and D.

E.  Pregnant women or fetuses may be involved in research if the IRB finds that all of the following conditions are met [45 CFR 46.204]:

 

1.  Scientifically appropriate, preclinical 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.  Either that 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

 

a.  if there is no such prospect of benefit:

 

i.         the risk to the fetus is not greater than minimal, and

 

ii.       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.  No inducements, monetary or otherwise, will be offered to terminate a pregnancy.

 

5.  Individuals engaged in the research will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy.

 

6.  Individuals engaged in the research will have no part in determining the viability of a neonate.

 

7.  Consent requirements

 

a.  The pregnant woman’s consent will be obtained in accord with 45 CFR, Subpart A when:

 

i.         the research holds out:

Ÿ         the prospect of direct benefit to the pregnant woman

Ÿ         the prospect of a direct benefit both to the pregnant woman and   the fetus, or

Ÿ         no prospect of benefit for the woman nor the fetus

 

ii.       risk to the fetus is not greater than minimal, and

 

iii.      the purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means.

 

b.  The consent of the pregnant woman and the father will be obtained in accord with 45 CFR 46, Subpart A when the research holds out the prospect of direct benefit solely to the fetus.

 

i.         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

 

c.  Each individual providing consent under 45 CFR 46.204(d) or (e) is fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate.

 

d.  For children, as defined in 45 CFR 46.402(a), who are pregnant, assent and permission are obtained in accord with 45 CFR 46, Subpart D.

F.  Neonates of uncertain viability and nonviable neonates may be involved in research if the IRB finds that all of the following conditions are met [45 CFR 46.205]:

 

1.  Scientifically appropriate, preclinical and clinical studies have been conducted and provide data for assessing potential risks to neonates.

 

2.  Each individual providing consent under Sections G.2 or H.5, below, 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 Sections G or H, below, have been met if applicable.

G. 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 Subpart B unless the following additional conditions have been met:

 

1.  The IRB determines that:

 

a.  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

 

b.  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

 

2.  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 45 CFR 46, Subpart A, except that the consent of the father or his legally authorized representative need not be obtained if the pregnancy resulted from rape or incest.

H.  Nonviable neonates. After delivery nonviable neonates may not be involved in research covered by Subpart B 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.

 

5.  The legally effective informed consent of both parents of the neonate is obtained in accord with subpart A of this part, except that the waiver and alteration provisions of 45 CFR 46.116(c) and (d) do not apply. However, if either parent is unable to consent because of unavailability, incompetence, or temporary incapacity, the informed consent of one parent of a nonviable 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 nonviable neonate will not suffice to meet the requirements of this paragraph.

I.   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 45 CFR 46, Subparts A and D.  Thus, the exemptions at 46.101(b)(2), for research involving survey or interview procedures or observations of public behavior, would not apply.  See, 45 CFR 46.204(d).

J.  DHHS research that the IRB finds does not meet the requirements of 45 CFR 46.404, 46.405, or 46.406 may only be approved if the following requirements are met:

 

1.  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

 

2.  The Secretary of DHHS, after consultation with a panel of experts in pertinent disciplines (for example: science, medicine, ethics, law) and following opportunity for public review and comment, including a public meeting announced in the FEDERAL REGISTER, has determined either:

 

a.  That the research in fact satisfies the conditions of 45 CFR 46.204, as applicable, or

 

b.  All of 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 pregnant women, fetuses or neonates.

 

ii.  The research will be conducted in accord with sound ethical principles.

 

iii.  Informed consent will be obtained in accord with the informed consent provisions of subpart A and other applicable subparts of this part. [45 CFR 46.207]

K.  UW-Madison IRBs will assure that all research involving, after delivery, the placenta, the dead fetus, macerated fetal material, or cells, tissue, or organs excised from a dead fetus is conducted in a manner consistent with ethical principles and applicable federal regulations, state law and institutional policies. See, Belmont Report; 45 CFR 46, Subpart B; Applying State Law in Human Subjects Research Policy; Fetal Tissue Policy.

L.  According to Wisconsin law, children under 18 years of age who are or have been married, who have given birth or who have been freed from the care, custody and control of their parents, with little likelihood of returning to the care, custody and control prior to marriage or prior to reaching the age of majority are emancipated and, therefore, are consented as adults.

M. The UW-Madison SBS IRB does not allow the inclusion of pregnant women in research, in which the investigator will have the participants drink alcohol.

N.  Before approving drug studies involving pregnant women or women of child-bearing age, the health sciences IRBs will review the following:

 

1.  Effect of drug on reproductive health, including teratogenic effects

 

2.  Whether protocol includes pregnancy checks in recruitment plan or as requirement of on-going participation

 

3.  Whether protocol requires participants to notify investigator if participant becomes pregnant

 

4.  Whether protocol describes procedures if pregnancy occurs:

 

a.  Participant removed from study

 

b.  Counseling provided about possible outcome due to research participation

IX.    Research Involving Other Vulnerable Groups

A.  Individuals with Impaired Decision-making Capacity

 

1.  UW-Madison IRBs review protocols involving individuals with impaired decision-making capacity who are likely to be vulnerable to coercion or undue influence to assure that additional safeguards are included in research protocols to protect the rights and welfare of these participants, as required by federal regulations as well as applicable ethical principles, state law and institutional policies . Belmont Report; 46 CFR 46.111(b); 21 CFR 56.111(b); WSA 51.61(1)(j), 51.61(4), 54.15, 54.25, 54.46 and 55.07.  See, also, UW-Madison Applying State Law in Human Subjects Research Policy; Research with Adults Lacking Consent Capacity Policy.

 

2.  To approve research involving individuals with impaired decision-making capacity, UW-Madison IRBs must find that the criteria set forth in the UW-Madison’s Research with Adults Lacking Consent Capacity Policy are satisfied.  This policy does not apply if either of the following conditions is true:

 

a.  The research will occur outside the state of Wisconsin.  If the subjects lacking capacity to consent are at performance sites outside of Wisconsin, this policy will not apply to that site.  Instead, the law of the state where the subjects are located will prevail.

 

b.  The research involves patients with a psychiatric diagnosis.  Special considerations, and in some cases special rules, may apply to such research, including additional required protections for subjects.

 

     If either of the above conditions applies to the research being reviewed, please consult with an attorney in the UW-Madison Office of Administrative Legal Services.

 

3.  Definitions.  See, Research with Adults Lacking Consent Capacity Policy.

 

4.  For Veterans Affairs Medical Center (VAMC) research involving adults unable to consent, see, VA Handbook 1200.5, paragraph 11 and Appendix D; see, also, Research with Adults Lacking Consent Capacity Policy.

B.  Individuals Receiving Protective Services or Treatment for Mental Illness, Substance Abuse or Alcohol Dependency in Wisconsin

 

1.  Research involving individuals receiving protective services, voluntarily or involuntarily, because of aging, chronic mental illness, developmental disabilities or like incapacities or receiving inpatient or outpatient treatment for mental illness, development disabilities or substance and alcohol dependency in Wisconsin must comply with the special conditions imposed by Wisconsin law.  Wisconsin Mental Health Code, WSA 51.61(1)(j), 51.61(4); Wisconsin Protective Services statute, WSA 55.07.  For additional information, consult with an attorney in the UW-Madison Office of Administrative Legal Services.  See, also, Applying State Law in Human Subjects Research Policy.

 

2.  When UW-Madison IRBs review research that involves such individuals, the IRBs consider:

 

a.  rationale and justification for involvement in research of individuals receiving such services, including an explanation as to why individuals not receiving such services could not be used.

 

b.  the method by which the investigator will assess whether the individual is capable of consent and, if not, whether an authorized legal representative is available to consent to participation in research on behalf of the individual.  For additional information, consult with an attorney in the UW-Madison Office of Administrative Legal Services.  See, also, Research with Adults Lacking Consent Capacity Policy.

 

c.  whether state law requirements have been satisfied. Wisconsin Mental Health Code, WSA 51.61(1)(j), 51.61(4); Wisconsin Protective Services statute, WSA 55.07.  For additional information, consult with an attorney in the UW-Madison Office of Administrative Legal Services.  See, also, Applying State Law in Human Subjects Research Policy.

 

i.         written permission has been obtained from the appropriate officials at the institution providing the services to the participant for the conduct of the research at that institution, and

 

ii.       the research may also need to be approved by the Wisconsin Department of Health and Family Services (DHFS). (consult with UW-Madison Legal Services department).  Wisconsin Mental Health Code, WSA 51.61(1)(j), 51.61(4); Wisconsin Protective Services statute, WSA 55.07; Applying State Law in Human Subjects Research Policy.

C. Institutionalized Individuals

 

1.  Institutionalized individuals are those individuals who are voluntarily or involuntarily residing in an institution, such as a nursing home or residential psychiatric institution, because of physical or mental conditions. Characteristics of the institutional setting create circumstances that may compromise the voluntary nature of participation in research.

 

2.  UW-Madison IRBs will approve research involving institutionalized individuals, only if the research includes adequate safeguards to protect the rights and welfare of these participants, as required by ethical principles and applicable federal regulations, state law and institutional policies. See, Belmont Report; 46 CFR 46.111(b); 21 CFR 56.111(b); WSA 51.61(1)(j), 51.61(4) and 55.07; Applying State Law in Human Subjects Research Policy; Research with Adults Lacking Consent Capacity Policy.

 

3.  Ethical principles suggest that 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. Nevertheless, IRBs should not assume that all institutionalized individuals are incapable of competent and voluntary consent.

 

4.  When UW-Madison IRBs review research that involves institutionalized individuals, the IRBs consider:

 

a.  rationale and justification for involvement in research of institutionalized participants, including an explanation as to why non-institutionalized individuals could not be used.

 

b.  the method by which the investigator will assess whether the institutionalized individual is capable of consent and, if not, whether an appropriate legal representative is available to consent to participation in research on behalf of the institutionalized individual.  For additional information, consult with the UW-Madison Office of Administrative Services.

 

c.  if an institutionalized individual is receiving protective services or treatment for mental illness, substance abuse or alcohol dependency in Wisconsin, whether state law requirements have been satisfied.  See, Section IV.B, above.  Wisconsin Mental Health Code, WSA 51.61(1)(j), 51.61(4); Wisconsin Protective Services statute, WSA 55.07; Applying State Law in Human Subjects Research Policy.

D.  International Research Participants

 

1.  When UW-Madison IRBs review research that involves participants residing in other countries, the IRBs consider:

 

a.  whether additional safeguards are necessary to protect the welfare, safety, privacy and confidentiality of these participants in light of legal, cultural and political considerations [See, International Research Guidance]

 

b.  whether any additional safeguards are described in the protocol, and

 

c.  whether the additional safeguards are adequate to protect participants.

 

d.  the most appropriate method of obtaining informed consent, taking into account the literacy level of the subjects and confidentiality concerns.

 

i.   In some cases, oral consent may be more appropriate than written consent because signing a consent form would put the participants at greater risk.

 

ii.   Consent should always be obtained in the native language of the participants. The consent form or oral consent script must be provided to the IRB in the participant’s native language and an English translation must be provided.

E.  Non-English Speaking Participants

 

1.  Consent should always be obtained in the native language of the participants. A consent form or oral consent script in the participant’s native language and an English translation must be provided to the IRB.

 

2.  When UW-Madison IRBs review research that involves non-English speaking participants, the IRBs consider:

 

a.  Whether the enrollment of non-English speaking participants is justified by the research questions

 

b.  Whether recruitment and consent documents are translated into the native language of participants. 

 

c.  Whether the individuals communicating information to the participant or the representative during the consent process will provide that information in language understandable to the participant or the representative.

F.  Illiterate Participants

 

1.  If participants are illiterate, the IRB may require an oral consent process or the use of a subject advocate.

G. Participants with Status Relationships

2.  In most cases, UW-Madison IRBs do not allow direct recruitment of participants by someone in a status relationship with those individuals (e.g., supervisor/employee, faculty member/student).  See, Recruitment of Subjects with Status Relationships (Relatives of Research Staff, Employees, and Students) Guidance.