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THE COMMITTEE ON HUMAN RESEARCH

UCSF GUIDANCE ON RESEARCH TOPICS AND ISSUES

Vulnerable Subject Populations - Pregnant Women, Fetuses, Neonates or in Vitro Fertilization (Revised February 2005)

 • Brief Overview
 • Inclusion of Pregnant Women or Women of Childbearing Potential in Research
 • Pregnant women are not the target study population
 • Pregnancy is an exclusion criterion
 • Pregnant women as the target study population
 • Contraception and the Risk of Reproductive Harm: Protocol and Consent Issues
 • Terms and Definitions
 • CHR Requirements for Research Involving:
 • Pregnant Women or Fetuses Prior to Delivery
 • Neonates
 • Placenta, the Dead Fetus or Fetal Material
 • Research Not Otherwise Approvable
 • In Vitro Fertilization

Brief Overview

The University supports a policy of providing pregnant women the same opportunities as non-pregnant women to participate in research unless the individual meets legitimate exclusionary criteria or the study poses more than minimal risk to the fetus. Research inclusive of pregnant women increases the likelihood that the knowledge gained can be extended judiciously to this population in society.

Because pregnant women, fetuses and neonates are vulnerable populations, additional protections are described in the regulations (45 CFR 46 Subpart B) enforced by the Office for Human Research Protections (OHRP). These regulations also cover research using human in vitro fertilization as well as human fetal tissue, placenta or post delivery fetal material.

As required by OHRP the Committee on Human Research (CHR) reviews and determines the risk category for all studies involving pregnant women, fetuses, or neonates, as well as research using human fetal materials.

Inclusion of Pregnant Women or Women of Childbearing Potential in Research

During the course of a clinical study, pregnant women or women of childbearing potential may be encountered coincidentally as potential participants. Alternatively, pregnant women and fetuses may be the target study population(s).

Some of the common types of research involving pregnant women are listed below; specific regulatory requirements are also provided.

• Pregnant women are not the target study population: If research targeting a wide population includes women of childbearing potential, there is the possibility of pregnancy.
  • The research protocol should define any conditions for inclusion or exclusion of pregnant women or women of childbearing potential who may be encountered during study enrollment.
  
  
  
  • The consent form for treatment and intervention studies should describe any known risks to the participant (or to the embryo or fetus if the participant is or becomes pregnant). If the risks are not known because there is little experience in pregnant women, the consent form should clearly say so.
  
  
  
  • See the detailed CHR Requirements (internal link to section) for additional conditions imposed by the regulations.



• Pregnancy is an exclusion criterion: If pregnant women are excluded, the application should describe the risks that require exclusion or, if applicable, state that pregnancy is exclusionary due to a lack of knowledge of the risks.
  
  • For research that poses an unacceptable risk to the pregnant women or fetus, non-pregnant participants of childbearing potential should be:
    
    • Instructed on methods to avoid pregnancy during and after the study.
    
    
    
    • Advised about pregnancy testing that may be required before and during the study.
  
  
  
  • The consent form should clearly describe information about avoiding pregnancy and about pregnancy testing that may be required.



• Pregnant women as the target study population: For a complete explanation of the regulatory requirements, see the CHR Requirements section of this guidance.
  
  The following is a brief description of the conditions that contribute to the research risk assessment made by the CHR and a few key points regarding informed consent:
  
  • Research risk assessment:
    
    • If the research holds the promise of directly benefiting the woman or fetus, a greater than minimal risk to the fetus is acceptable.
    
    
    
    • If the research does not hold the prospect of directly benefiting the woman or fetus, the research is allowed if the risk to the fetus is not greater than minimal.
  
  
  
  • Informed consent:
    
    • The pregnant woman’s consent is sufficient if:
      
      • There is the prospect of direct benefit to the woman, the woman and the fetus, or
      
      
      
      • There is no prospect of direct benefit for the woman or the fetus, but the risk to the fetus is not greater than minimal
    
    
    
    • The pregnant woman and the father’s consent is required if:
      
      • There is the prospect of direct benefit solely to the fetus.
      
      
      
      • The father’s consent is not required under specific conditions (see CHR Requirements).

Contraception and the Risk of Reproductive Harm: Protocol and Consent Issues

Prospective study participants should be warned about possible reproductive or lactation risks from study treatments. These risks and the steps to be taken to minimize them should be discussed in both the consent form and in the application. The general discussion that follows is adapted from a more specific discussion in the NIH Guidance on Informed Consent for Gene Transfer Research: Reproductive Considerations.

• Study Specific: Discussions of reproductive harm, and measures taken to minimize harm, should be study-specific. Factors to be considered include:
  
  • Direct teratogenic effects
  
  
  
  • Possible germline effects
  
  
  
  • Effects on a woman’s ability to continue the current pregnancy



• Effects on fertility and future pregnancies
  
  Gender Appropriate: Reproductive harms and steps to be taken to avoid or minimize them may be unique to one gender or may be different for men and women. Consent forms and the protocol should be written to address concerns appropriate to each subject population involved in the study.



• Exclusion and Testing: While some risks legitimately justify exclusion of particular subject groups, in many studies prospective subjects should have the right to make their own choice about the level of risk they will tolerate—after they have been fully informed of the risks and possible benefits of study participation. If exclusion of pregnant women, nursing women, or people who wish to start a pregnancy is justified for a particular study, the application and consent form should explain the reasons for the exclusion and the steps to be taken to avoid problems, such as pregnancy testing prior to treatment and periodically during the study.



• Abstinence and Methods of Contraception: Methods required by the protocol and described in the consent form should be adequate to address the specific risks of the study.
  
  • The time period when steps should be taken—before, during, or after treatment—should be made clear in the application and consent forms.
  
  
  
  • Choices of methods should be as broad as is consistent with subject safety. Subjects should be told the short- and long-term advantages and disadvantages of the allowable methods.
  
  
  
  • Barrier methods should be used where body fluids may transfer infectious agents, vectors, or medications.



• Banking Sperm and Ova: Where appropriate, researchers should address the advisability of banking sperm and ova, including the likely additional costs for participants.



• If Pregnancy Occurs: The application and consent documents should discuss what will happen if a study participant or the partner of a participant becomes pregnant. Typically, the participant should contact the investigator, who can then discuss risks and provide counseling about additional steps to be taken. If the researchers will want to monitor any offspring long term, this should be mentioned in the consent documents. Some studies find it useful to provide special consent forms for participants who become pregnant and wish to continue in the study; the special consent form discusses risks and any special additional precautions or followup.



• Sample Consent Form Wording: The sample consent form wording that follows is adapted from the NIH Gene Transfer guidelines cited above. The NIH guidelines include a number of additional examples that will be useful in many different kinds of studies and for both women and men. The wording in any example will need to be adapted to the particular study and subject population.
  
  

  Example 1: You should not be in this study if you are a pregnant or nursing mother or if you are planning a pregnancy soon. The [study treatments—Name the relevant treatments.] may cause harm to the mother and to unborn or breast-feeding children. You should not become pregnant during the study. If you can give birth or father a child, you must use an adequate form of birth control. If you are able to become pregnant, you must have a negative pregnancy test within [time] before you get the first [treatment], and you will be tested for pregnancy every [interval] during the study. If you become pregnant while in this study, you should tell the study doctor immediately. The study doctor will counsel you about your choices, and, if you decide to stay in the study, will ask you to sign a new consent form.

  Example 2: You should not exchange body fluids with another person after you start the [treatment] and for [time period] after the [treatment] stops. The best way to avoid exchanging fluids is to abstain from sexual activity for the [time period] you are in active treatment. Other, less effective ways to avoid exchanging fluids include barrier contraceptive methods such as [specify].

Terms and Definitions

• Dead fetus: A fetus that does not exhibit a heartbeat, spontaneous respiratory activity, spontaneous movement of voluntary muscles, or pulsation of the umbilical cord.



• Delivery: Complete separation of the fetus from the woman by expulsion or extraction or any other means.



• Fetus: The product of conception from implantation until delivery.



• Minimal risk: 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.



• Neonate: A newborn



• Nonviable neonate: 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 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.



• Secretary: The Secretary of Health and Human Services and any other officer or employee of the Department of Health and Human Services to whom authority has been delegated.



• Viable neonate: A neonate able, after delivery, to survive (given the benefit of available medical therapy) to the point of independently maintaining heartbeat and respiration.

CHR Requirements

CHR requirements are consistent with regulations (45 CFR 46 Subpart B) enforced by the Office of Human Research Protection (OHRP) and are summarized in the table below according to the participant populations defined by OHRP:

• Pregnant women or fetuses



• Neonates



• Human fetal tissue, placenta or post delivery fetal material



• Research not otherwise approvable



• In vitro fertilization