Owner: Vice President of Academic Affairs
Author: CSS IRB
Contact: irb@css.edu
Policy Number: 35
Effective Date: 10/8/2021

Policy

The CSS IRB does not currently review research involving pregnant women. If this were to change, procedures consistent with the requirements of Subpart B of 45 CFR 46 in addition to those imposed under other CSS IRB policies and procedures, ethical considerations and other applicable federal, state, and local laws for review and approval will be developed.  If a woman becomes pregnant while participating in a study that has not been approved for inclusion of pregnant women, the IRB must be notified immediately so that the IRB can determine whether the subject may continue in the research, whether additional safeguards are needed, and to make the determinations required by the regulations and these policies.

Purpose

This policy describes the requirements and procedures for non-exempt human subjects research involving pregnant women and/or their fetuses. The term “pregnant women” is used in this document to refer to pregnant women and/or their fetuses.  The CSS IRB must consider that research involving women of childbearing potential might involve pregnant women (and viable fetuses), and should evaluate research protocols and risks, inclusion and exclusion criteria, and informed consent procedures, with this in mind.  The CSS IRB may approve research involving pregnant women by following the “Investigator Checklist for Research Involving Pregnant Women” at the end of this policy.

Definitions

Pregnancy. A 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.  (45 CFR §46.202 (f)).

Minimal Risk.  The Regulatory definition of 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 or psychological examinations or tests (45 CFR §46.102(i) and CSS IRB SOP #13 IRB Determination of Minimal Risk).

Allowable Categories 45 CFR 46 Subpart B

Research involving women who are pregnant should receive special attention from the IRB because of women’s additional health concerns during pregnancy and because of the need to avoid unnecessary risk to the fetus. Special attention is justified because of the involvement of the fetus that may be affected but cannot give consent.

When a study involves women of childbearing age, the possibility that some women may be pregnant should always be considered and addressed. The regulations state that research on pregnant women shall not occur unless 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. This condition relies on the review of scientific validity for the study; is there enough background literature and studies to show that the research is potentially safe in pregnant women.
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. The evaluation of risk is paramount for research on pregnant women. For this review the IRB must have at least one member who has expertise on pregnant women and can evaluate the risks in pregnancy. The research may be allowed if there is the prospect of direct benefit to the women or fetus and the benefits outweigh the risks. If there is no prospect of direct benefit, the research can only be approved if it is minimal risk and will lead to important knowledge. Note the term used is “biomedical knowledge” but many people broaden this to “scientific” or “generalizable knowledge.
3. Any risk is the least possible for achieving the objectives of the research. This requirement needs little clarification. The research should not expose the pregnant women or fetus to any unnecessary risks but should use the least risky procedures necessary to achieve the results.
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 45 CFR 46.116 (See, CSS IRB SOP # 16 Informed Consent with Checklist and Templates).
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. Provisions (d) and (e) deal with who must provide consent and sign the consent form. If the research is minimal risk, or prospectively benefits the pregnant women or pregnant women and fetus, the women alone need consent.  If the benefit is solely to the fetus, both the woman and father should consent unless the father is unavailable or it is inappropriate for the father to sign because of the issues listed.
6. 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.  This provision requires that the mother/father providing consent are fully informed in the consent process and consent form about the research, so the person obtaining consent must be very knowledgeable.
7. For children (as defined in Subpart D, § 46.402(a)) who are pregnant, assent and permission are obtained in accord with the provisions of Subpart D and the requirements of state law and the IRB.  (See, CSS IRB SOP # 33 Research Involving Children and Investigator/Reviewer Checklist.)  If the research involves one or more women who are less than 18 years of age, both Subparts B and D (children) must be addressed and satisfied.
8. No inducements, monetary or otherwise, will be offered to terminate a pregnancy.  The research should in no way influence the pregnant women 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. Combined with (h), physicians and nurses involved in the research and also involved with patient care must be careful not to violate these provisions.
10. Individuals engaged in the research have no part in determining the viability of a fetus. If the viability of the fetus is related to the research, the IRB must get an independent and qualified professional to make determinations on viability.

Consent Decision Chart for Pregnant Women and Fetuses

	Direct Benefit to mother only	Direct benefit to mother and fetus	Direct benefit to fetus only	No direct benefit or societal benefits only
Risk is no more than minimal	Mother’s consent	Mother’s consent	Mother and father’s consent	Mother’s consent
Risk is more than minimal	Mother’s consent	Mother’s consent	Mother and father’s consent	NOT approvable by the IRB

(Courtesy of University of Southern Alabama Policy and Procedure (2018): Research Involving Pregnant Women, Fetuses and Neonates)

Obviously, Subpart B is oriented toward biomedical research and indeed drugs, devices and other investigational interventions that may have dangerous effects on the women, fetuses, and pregnancies. But the Subpart also applies to social science research. An example is research on domestic violence, which is often conducted by social scientists.  Abused women may be in greater danger when involved in such research and the abuser finds out. Many parts of Subpart B may not apply to most social science research, but when pregnant women are or may be involved the IRB must consider the risks to pregnant women and decide what parts of Subpart B do apply and must be satisfied.

Pregnant Women Who are Not the Target Study Population

When research targets a wide population that will include women of childbearing potential, there is the possibility of pregnancy, coincidental to subject selection.  In the IRB application, the researcher should describe the conditions and requirements (if any) for: (1) inclusion of pregnant women; (2) exclusion of pregnant women; or (3) women of childbearing potential who may become study participants.

The IRB should consider the following issues, for more than minimal, everyday risk:

• Does the IRB application or research protocol define any conditions under which pregnant women or women of childbearing potential who may be encountered during study enrollment can be included or excluded?
• Does the consent form for treatment and intervention studies describe any known risks to the pregnant or lactating woman (or to the fetus or neonate if the woman is or becomes pregnant)? If the risks are not known because there is little experience in pregnant women, does the consent form clearly state this? These risks and the steps to be taken to minimize them should be discussed in the IRB application and in the consent form.
• Should researchers advise participants to avoid pregnancy or nursing for a time during or following the research? Is it appropriate to advise the subjects to notify the researcher immediately should they become pregnant?
• If appropriate, in a section for vulnerable participants include justification for inclusion of vulnerable participants and recruitment strategy. Include safeguards for protecting vulnerable populations. Please refer to OHRP guidelines (below) when choosing the study population. Note that these regulations apply if any participants are members of the designated population, even if it is not the target population (e.g., if a participant becomes a prisoner or pregnant during the study).
• If pregnancy occurs. The IRB application and consent form should describe what will happen if a subject, or the partner of a subject, becomes pregnant. Generally, the subject should contact the researcher, who can then discuss the risks and provide counseling about additional steps to be taken.

FDA Regulations That Govern Research in Pregnant Women

FDA-regulated clinical trials in pregnant women must conform to all applicable FDA regulations, including those related to human subject protections (21 CFR part 56, Institutional Review Boards, and 21 CFR part 50, subpart B, Informed Consent of Human Subjects). In addition, if the trial is supported or conducted by the Department of Health and Human Services (HHS), then 45 CFR part 46 may also apply, which would include subpart B, Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research.  The FDA regulations do not contain a section similar to 45 CFR part 46, subpart B; however, the FDA recommends that these requirements be satisfied for FDA-regulated clinical research. Subpart B requires that trials supported or conducted by HHS meet all of the 10  (45 CFR 46.204 (a) through (j)) conditions.

Resources

Office for Human Research Protection (OHRP) - §46.204 Research involving pregnant women or fetuses. https://www.hhs.gov/ohrp/regulations-and-policy/regulations/regulatory-text/index.html#subpartb

USFDA Guidance Document. Pregnant Women: Scientific and Ethical Considerations for Inclusion in Clinical Trials Guidance for Industry (April 2018);

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/pregnant-women-scientifi c-and-ethical-considerations-inclusion-clinical-trials

NIH Protocol Template for Behavioral and Social Sciences Research – Inclusion/Exclusion Criteria https://www.nccih.nih.gov/grants/toolbox

University of Southern Alabama Research Involving Pregnant Women, Fetuses and Neonates (November

2018)https://www.southalabama.edu/departments/research/compliance/humansubjects/resources/90

2.pregnant.women.pdf

University of Washington Human Subjects Division Pregnant Women or Fetuses https://www.washington.edu/research/policies/sop-pregnant-women-2/ University of South Dakota IRB Pregnant Women, Fetuses and

Neonates.https://www.usd.edu/-/media/files/research/sops/irbmastersoprevisedregs.ashx

Allina Health HRPP/IRB SOPs Research Involving Pregnant Women, Human Fetuses and Neonates

(1/21/19)  https://www.allinahealth.org/-/media/allina-health/files/for-medical-professionals/research/allina-resea rch-administration-home/hrpp-irb-sop-manual.pdf?la=en&hash=50A1A5F7B07CC65A86FB9F9B3471800 3

Duke Health IRB (Reviewer Checklist)

https://irb.duhs.duke.edu/forms/pregnant-women-checklist-research-involving-pregnant-women-or-fetu ses

IRB EasyEd. Subpart B Determinations: Making Decisions about Pregnant Women in Research.  Volume 2 Number 7 © 2017 Apex Ethical

This is a new policy per the 2018 Common Rule Requirements.