Contraception Requirements for Clinical Trials

The UC Davis IRB requirements are based on evidence-based risk levels with contraceptive method use and with consideration of reproductive justice. The goals of these requirements are to ensure participants are fully informed and not unnecessarily burdened or restricted as it relates to their reproductive health when participating in a clinical trial. Acceptable contraceptive methods for participation in clinical trials should be based on a combination of factors, including a person’s reproductive potential, lifestyle, health, contraindications, and the risks associated with the research procedures. People unable to become pregnant from sex should not be required to use contraception to prevent pregnancy.

In This Section

Who is Considered Unable to Become Pregnant?

The following persons are considered unable to become pregnant from sex. These criteria apply to a study participant or the sexual partner of a participant.

  • Someone without a uterus or any ovaries.
  • Someone who has had surgery to remove or block their fallopian tubes.
  • Someone who no longer has their period because of menopause.
  • Someone who only has sex with partners who do not produce sperm.

For participants whose sexual activities may result in pregnancy, study teams should:

  • Inform participants of acceptable contraceptive options and confirm that the participant’s selected contraceptive method is appropriate and safe, especially for estrogen-containing contraceptives. Investigators are encouraged to use the U.S. CDC Medical Eligibility Criteria or, if more information is needed, consult with a Complex Family Planning Specialist in the Department of Obstetrics and Gynecology.
  • Provide participants with Contraception Information Sheet(s) during the informed consent process.
  • Counsel study participants to provide the information sheet to their partner(s) so that their partners are aware of the contraceptive requirements of the research and the related risks.

Contraceptive Methods and Efficacy

Per the WHO and CDC, contraceptive methods are divided into 3 categories based on efficacy:

  1. Highly effective (generally a first-year typical use pregnancy risk of 1% or less)
    • Contraceptive implant
    • Intrauterine device
    • Permanent contraceptive procedures:
      • Vasectomy
      • Bilateral salpingectomy
      • Bilateral tubal occlusion or partial salpingectomy

Note: Using a barrier method in addition to a highly effective method will not increase the likelihood of preventing pregnancy.

  1. Moderately effective (generally a first-year typical use pregnancy rate between 1% and 10%)
    • Oral contraceptives
    • Vaginal ring
    • Transdermal patch
    • Injectables

Note: Using a barrier method in addition to a moderately effective method will slightly increase overall effectiveness but will not create a highly effective method.

  1. Less effective (generally a first-year typical use pregnancy rate of greater than 10%)
    • Male and female condoms
    • Diaphragm
    • Cervical cap
    • Vaginal gel
    • Fertility-awareness methods (i.e., natural family planning)*
    • Withdrawal*

* These methods are considered significantly less effective (generally a first-year typical use pregnancy rate of greater than 20%)

Note: “Double-barrier” methods do not create a moderately effective method.

Perfect use failure rates are calculated rates from secondary analyses within clinical trials that do not reflect the “real-life” effectiveness of a contraceptive.  Thus, the definition of effectiveness is based on real-life (typical) use.

Requirements Related to Contraceptives

Protocols may require any of the following related to contraceptive use, even if the requirement is not related to preventing pregnancy:

  • Contraceptive use by participants able to become pregnant
  • Contraceptive use by participants able to get someone pregnant
  • Contraceptive use by participants’ partners, if the partner is able to become pregnant
  • Condom use by participants who make semen, if a risk is possible or exists for drug exposure through semen that could be harmful to a sexual partner (note that this requirement relates to using condoms but NOT for a contraceptive purpose)

Each of these should be addressed independently.

For example, if a study requires partners of participants to use a highly effective method and there is a concern that semen exposure could harm the partner, then condom use is also required to prevent semen exposure (not for contraception).

Contraception Determination for a Clinical Trial:

  1. Review the protocol to make sure the requirements are consistent with reasonable medical practice and do not place an unnecessary burden on a participant or the participant’s sexual partner.
  2. Clarify any distinctions between contraception use to minimize pregnancy risk and contraception (condom) use to minimize semen exposure related to a concern for study drug contact.
  3. Discuss any potential conflicts with a Study Sponsor, if applicable, prior to IRB submission.

Contraception Information Sheet Instructions

The purpose of the Contraception Information Sheet is to provide sexual partners of research participants with information about contraceptive requirements and related risks that may impact them directly. It must be used for all studies in which the protocol or IRB requires sexual partners of participants to use contraception and/or exposure to semen may put the sexual partner of a study participant at risk.

  • Research teams should use the check boxes to indicate the acceptable contraceptive methods based on the requirements of the study protocol before providing the Contraception Information Sheet to subjects.
  • The Contraception Information Sheet does not need to be submitted to the IRB for review, unless edits are made beyond checking boxes.
  • A sufficient number of copies of the Information Sheets should be provided to subjects to share with their sexual partners.