HOW TO PRINT To print this page, use your browser's print button. To print the entire document, download the PDF or click here and use your browser's print button. SAMPLE LANGUAGE Sample 1 - Men and Women Sample 2 - Men and Women Sample 3 - Men and Women Sample 4 - Men and Women Sample 5 - Men Only Sample 6 - Men Only Sample 7 - Women Only TOOLS & BACKGROUND MATERIALS FDA Guidance on Participation of Women of Childbearing Potential in Clinical Studies OHRP Guidance on Participation of Women in Research
MAIN POINTS Potential participants should be informed of the risk of germline alteration and ways to minimize this risk.

NIH GUIDELINES: "To avoid the possibility that any of the reagents employed in the gene transfer research could cause harm to a fetus/child, subjects should be given information concerning possible risks and the need for contraception by males and females during the active phase of the study. The period of time for the use of contraception should be specified. The inclusion of pregnant or lactating women should be addressed."

DISCUSSION
Some vectors used in gene transfer experiments have the capacity to integrate and alter the germ line. When data are inadequate to rule out the possibility of inadvertent germline alteration, non-sterile participants should be informed that the biological consequences of this procedure are not known and, therefore, unborn children, children who are breast-feeding, and mothers could be harmed.

Discussion of the risk of reproductive harm should always be study-specific. Study-specific factors include, but are not limited to, frequency of pregnancy testing and the possibility of inadvertent germline effects, which could be teratogenic.

Reproductive considerations may be unique to one gender or may need to be discussed differently for men and women. It may be worthwhile to have separate sections in the consent form for issues especially pertinent to men or to women.

Avoiding Risk of Reproductive Harm: To avoid the possibility of causing harm or abnormalities to an unborn child, participants and their sexual partners should be encouraged to practice abstinence for an appropriate length of time or, at minimum, to use certain methods of contraception. The short- and long-term advantages and disadvantages of each method should be explained. In some studies, it may be advisable for investigators to discuss sperm and ova banking, which may involve an additional cost to the participant.

The risk of horizontal transmission of the vector-transgene combination to sexual partners should be addressed separately in the consent form. Here, too, the advantages and disadvantages of typical contraceptive methods should be discussed.

Under some circumstances, pregnant or nursing women may not be eligible to participate in gene transfer trials that pose risks of reproductive harm. When such exclusions are justified, investigators should inform potential participants that they will be tested to rule out pregnancy. In some gene transfer studies, women who are breast-feeding may not be eligible for participation or may be asked to stop breast-feeding during and for a specified period after the study completion.

In addition to discussing possible reproductive harms relevant to both sexes, investigators should also discuss with potential participants what will happen if a study participant or the partner of a participant becomes pregnant. This should include information about reporting pregnancies to the investigators, so that risks of harm may be individually assessed and counseling may be offered. It may also include requests for long-term monitoring of offspring.

SAMPLE LANGUAGE

Sample 1 - Men and Women

Risks of harm from this study include the possibility that the genes in some of your sperm (men) or eggs (women) may be permanently changed. Some of these changes could lead to miscarriage or birth defects in your future children. Other changes may have no apparent effects but could still be passed on to future generations. The likelihood of such outcomes is currently unknown.

Sample 2 - Men and Women

It is not known if DNA injected into your muscles can become part of the DNA of your reproductive cells (eggs or sperm). If this happens, it may cause fetal death or birth defects in future pregnancies of participants and their partners. It is also unknown whether or not the gene transfer vector will be present in body fluids (semen, vaginal secretions) and, if so, whether it will be transmitted to a sexual partner.

Sample 3 - Men and Women

You should not be in this study if you are planning a pregnancy soon. The risk of transmission of the gene transfer vector to a sexual partner or an embryo or fetus is unknown. It is possible that harmful side effects could occur to both the mother and unborn or breast-feeding children. You should not become pregnant during the study. The risks of harm from the gene transfer vector to an unborn or newborn child are unknown. If you become pregnant while in this study, you must tell your investigator at once. 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 dose of the gene transfer. You may not take part in this study if you are pregnant or a nursing mother.

Sample 4 - Men and Women

You should not become pregnant or father a child while taking part in this study. Women who are pregnant or breast- feeding may not be in this study. If you are a female who can have children, you will take a pregnancy test and the results will be given to you. You must confirm that you do not plan to become pregnant while on this study. If you are capable of giving birth or fathering a child, you must use an acceptable form of birth control. For women, contraception should go on for [time period] after the last dose of the [gene transfer agent] to ensure that it has completely cleared from your body. For men, contraception should go on for [time period] after the last dose of the [gene transfer agent] to make sure that all sperm in the body during the trial have been replaced. If you or your partner becomes pregnant, or you suspect that you or your partner is pregnant while in this study, notify the investigator at once.

Sample 5 - Men Only

There is no information on whether the vector and gene can be transferred to sperm cells. Thus, the risk of gene transfer to germline cells (sperm cells) is unknown. Transfer of gene to germline cells could cause serious birth defects or fetal death. It could also lead to unknown health problems (such as cancer) in the child. If you may want to have children in the future, we recommend that you bank sperm before beginning the study, so that you have sperm available that has no DNA from the vector and gene. The investigators will provide you with information on sperm banking at [study site] or at your home institution. In addition to sperm banking, fertile men are encouraged to use barrier birth control devices (i.e., condoms). The investigators will notify you when it is safe to stop barrier methods of birth control.

Sample 6 - Men Only

One risk of this study is that [gene transfer agent] could have harmful effects on an unborn child. We do not know if the gene transfer you will get can become part of normal reproductive cells. If it can, it could cause harm to fetuses conceived after the gene transfer. These harms could include birth defects or death of the fetus, or of the child after birth. If you can father a child you should use precautions to prevent any sexual partner from becoming pregnant during this study.

Also, we do not know if the [gene transfer agent] may be present in body fluids. If it is, it could be transmitted to sexual partners. Condoms are essential for preventing transmission to a sexual partner.

Sample 7 - Randomization to Experimental or Control Arm

One risk of this study is that the [gene transfer agent] could have harmful effects on an unborn child. We do not know if the gene transfer you will get can become part of normal reproductive cells. If it can, it could case harm to fetuses conceived after the gene transfer. These harms could include birth defects or death of the fetus, or of the child after birth. If you are capable getting pregnant, you should use precautions to prevent becoming pregnant during this study.

If you become pregnant during the study or suspect that you may be pregnant, you should tell the investigator immediately. You also should not breastfeed during the study.

Also, we do not know if the [gene transfer agent] may be present in body fluids. If it is, it could be transmitted to sexual partners. Condoms are essential for preventing transmission to a sexual partner.