Review of Research Involving Pregnant Women, Fetuses, and Neonates

IV.09

 

 

Review of Research Involving Pregnant Women, Fetuses, and Neonates

 

 

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Objective

This Policy/Procedure describes the process by which the Committee for the Protection of Human Subjects (CPHS) members review protocols involving pregnant women, human fetuses and neonates.  This policy is in effect both for full Committee reviews and expedited reviews.

 

Policy/Procedure

I.     Pregnant women or fetuses may be involved in research if all of the following conditions are met.

A.           Where scientifically appropriate, preclinical studies, including studies on pregnant animals, and clinical studies, including studies on nonpregnant women, have been conducted and provide data for assessing potential risk to pregnant women and fetuses; and

 

B.           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; and

 

C.           Any risk is the least possible for achieving the objectives of the research; and

 

D.           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, her consent is obtained in accord with the informed consent provisions according to regulations; and

 

E.            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 regulations, 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; and

 

F.            Each individual providing consent under paragraph (D) or (E) of this section is fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate; and

 

G.           For children who are pregnant, assent and permission are obtained according to regulations; and

 

H.           No inducements, monetary or otherwise, will be offered to terminate a pregnancy; and

 

I.              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

 

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

 

II.   Research involving neonates

A.     Neonates of uncertain viability and nonviable 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; and

2.      Each individual providing consent is fully informed regarding the reasonably foreseeable impact of the research on the neonate; and

3.      Individuals engaged in the research will have no part in determining the viability of a neonate; and

4.      The requirements of paragraph (B) or (C) of this section have been met as applicable.

 

B.     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 section unless the following additional conditions have been met and the CPHS 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.

 

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

 

D.     Nonviable neonates – After delivery nonviable neonates may not be involved in research unless all of the following additional conditions are met:

1.      Vital functions of the neonate will not be artificially maintained; and

2.      The research will not terminate the heartbeat or respiration of the neonate; and

3.      There will be no added risk to the neonate resulting from the research; and

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 subpart A of 45 CFR §46, except that the waiver and alteration provisions of §46.116(c) and (d) do not apply.

a)            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 45 CFR §46.205(c)(5), except that the consent of the father need not be obtained if the pregnancy resulted from rape or incest.

b)            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 45 CFR §46.205(c)(5).

 

III.         Research involving, after delivery, the placenta, the dead fetus or fetal material.

A.     Research involving, after delivery, the placenta; the dead fetus; macerated fetal material; or cells, tissue, or organs excised from a dead fetus, shall be conducted only in accord with any applicable Federal, State, or local laws and regulations regarding such activities.

 

IV.        The Secretary of the Department of Health and Human Services  (Secretary) will conduct or fund research that the CPHS does not believe meets the requirements of 45 CFR §46.204 or 45 CFR §46.205 only if: [45 CFR §46.207]

A.     The CPHS 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.

 

B.     The Secretary, 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:

1.      That the research in fact satisfies the conditions of §46.204, as applicable; or

2.      The following:

a)            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.

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

c)            Informed consent will be obtained in accord with the informed consent provisions of subpart A and other applicable subparts of this part.

 

V.  Studies in which pregnancy is coincidental to subject selection

A.           Any study in which women of childbearing potential are possible participants may inadvertently include pregnant women. Federal regulations require that, when appropriate, participants be provided a statement that the particular treatment or procedure may involve risks to the participant (or to the embryo or fetus, if the participant is or may become pregnant) which are currently unforeseeable as part of the informed consent process.

1.      The CPHS must judge whether the mother’s participation would pose any risk to the fetus or nursing infant.  In some studies, the CPHS may need to assure that nonpregnant participants are advised to avoid pregnancy or nursing for a time during or following the research. Furthermore, where appropriate, participants should be advised to notify the PI immediately should they become pregnant. In some instances, there may be potential risk sufficient to justify requiring that pregnant women either be specifically excluded from the research or studied separately.

 

VI.        All of the findings and determinations, including protocol specific findings, for research involving the above referenced vulnerable populations, must be 1) stated by the CPHS and included in the minutes or 2) documented in writing for research undergoing expedited review.

 

Definitions:

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

                                   

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

 

Fetus - product of conception from implantation until delivery.

                                               

Neonate - a newborn.

                                   

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

                                               

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

                                               

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 of Health and Human Services, 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 subparts A and D of this part.

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 subparts A and D of 45 CFR §46. [45 CFR §46.205(d)]

 

 

Applicable Regulations and Guidelines

21CFR 50 ( http://www.access.gpo.gov/nara/cfr/waisidx_04/21cfr50_04.html )

21CFR 56 ( http://www.access.gpo.gov/nara/cfr/waisidx_04/21cfr56_04.html )

38CFR 16 ( http://www.access.gpo.gov/nara/cfr/waisidx_04/38cfr16_04.html )

45CFR 46 ( http://www.access.gpo.gov/nara/cfr/waisidx_04/45cfr46_04.html )

ICH E6 ( http://www.ich.org/MediaServer.jser?@_ID=482&@_MODE=GLB )

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