3.9 Contraception Requirements
Last Revised: 11/21/20175/5/2025
1.0 Purpose
The purpose of this policy and procedure is to describe the contraception requirements for subjects participating in research.research involving drugs, devices or biologics.
2.0 Policy
It is the policy of the Organization that subjects must utilize appropriate contraception methods while participating in research with potential for reproductive toxicity.
2.1. Contraception requirements should be based on the FDAinvestigator’s Pregnancydata driven and Lactationgood Labelingfaith Ruleassessment (forof allthe investigationalrisks to a fetus that are or might be associated with use of the drug applicationsor submitteddevice afterduring 6/30/2015).pregnancy.
Drugsapproved- 2.1.1.
priorFor studies utilizing devices, risks to 6/30/2015fetuses contraceptioninclude requirementsthose mayrisks beassociated basedwith onplacement FDAof Use-in-Pregnancythe Categorydevice, untilincluding Pregnancybut andnot Lactationlimited Labellingto hasrisks beenof submitteddrugs andused approvedfor byanesthesia FDA.or of radiographic procedures needed for placement of the device.
2.2. Female study volunteersPersons who are not of reproductive potential (premenarchal, postmenopausal, or surgically or otherwise sterile)unable to become pregnant) are eligible to participate in research without requiring the use of contraception.
2.3. MalePerson researchcapable subjects,of producing seminal fluid, including those who have undergone successful vasectomy with resulting azoospermia or have azoospermia for any other reason, should use barrier contraception, or their partners should use appropriate contraception, unless the agent has been shown not to be present in seminal fluid, or the agent has been shown to have no genotoxic, reproductive, or developmental effects in nonclinical or clinical studies.
2.4. It is the responsibility of the investigator (with or without the Research Subject Advocate,Advocate and/or other qualified persons, as appropriate) to discussassist the potential study participant (as needed) to understand the risks and benefits of each form of contraception withchoices potential study participants to ensureso that subjectsthey arecan makingmake an informed choice.
2.5. The discussion with the subject (or with an LAR or parent/guardian) regarding contraception requirements should be documented in the source/study record.
3.0 Fetal Risk Categories
basedon3.1. For FDA approved drugs which comply with FDA Pregnancy and Lactation Labeling Rule (PLLR)
, categories are determined by the investigator and are based on data in FDA approved “Prescribing Information” (especially sections 8.1 [Pregnancy] and 8.3 [Females and Males of Reproductive Potential]).
3.2. For drugs not approved by the FDA, or approved drugs that do not comply with the PLLR, categories are determined by the investigator and are based on information in the Investigator’s Brochure related to teratogenicity and genotoxicity, and/or on the published medical literature, and/or on the FDA Use in Pregnancy Category.
3.3. Categories
3.3.1. Group 1: No systemic absorption of drug or biologic.
3.3.2. Group 2: Review of clinical trials conducted in pregnant women,persons, pregnancy exposure registries, and other large scale epidemiologic studies show no evidence of adverse developmental outcomes.
- 3.3.2.1. This would include drugs with FDA Use in Pregnancy category A.
3.3.3. Group 3: In the absence of human data, animal studies show no evidence of adverse developmental outcomes.
3.3.3.1. This would include drugs with FDA Use in Pregnancy category B.
3.3.4. Group 4: Animal studies show evidence of adverse developmental outcomes, at dose levels higher than those to be used in this study.
3.5. Group 5:
- 3.3.4.1. This might include some drugs in FDA Use in Pregnancy category C, depending on dose levels.
3.3.5.
1. Group 5: (1) Review of clinical trials conducted in pregnant
women,persons, pregnancy exposure registries, other large scale epidemiologic studies, or well described case-series show evidence of adverse developmental outcomes; OR
(2) 3.5.2. Animalanimal studies show evidence of adverse developmental outcomes, at dose levels similar to those to be used in this study; OR (3) 3.5.3. Thethe mechanism of action of the drug suggests the possibility of adverse developmental outcomes.outcomes
3.3.5.1. This might include some drugs in FDA Use in Pregnancy categories C (depending on dose levels), D and X
4.0 DefinitionsAllowable Contraception Requirements
4.1. Investigators may or must require contraception in accordance with data driven and good faith estimates of the
FDAlikelihood Use-In-Pregnancyof Categoriesfetal injury due 4.1. Category A: Controlled studies show no risk: Adequate, well-controlled studiesto in pregnantutero women have failed to demonstrate a riskexposure to the fetusdrug inas anyfollows:
trimester of pregnancy.
- 4.1.1.
4.2.Studies CategoryInvolving B:Group No1 and Group 2 Drugs {no evidence of risksystemic in humans Adequate, well-controlled studies in pregnant women have not shown increased riskabsorption of fetaldrug abnormalities(group despite adverse findings in animals nor, in the absence of adequate human studies, animal studies show no fetal risk. The chance of fetal harm is remote, but remains a possibility.
4.3. Category C: Risk cannot be ruled out: Adequate, well-controlled human studies are lacking, and animal studies have shown a risk to the fetus1), or
are lacking as well. There is a chance of fetal harm if the drug is administered during pregnancy; but the potential benefits may outweigh the potential risk.
4.4. Category D: Positiveno evidence of risk:adverse Studiesdevelopmental in humans, or investigational or post-marketing data, have demonstrated fetal risk. Nevertheless, potential benefits from the use of the drug may outweigh the potential risk. For example, the drug may be acceptable if needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective.
4.5. Category X: Contraindicated in pregnancy: Studies in animals or humans, or investigational or post-marketing reports, have demonstrated positive evidence of fetal abnormalities or risk that clearly outweighs any possible benefit to the patient.
5.0 Procedure
5.1. For drugs or biologics for which there is Pregnancy and Lactation Labelling availableoutcomes (
allgroup investigational2)} drug- applicationsThe submitted after 6/30/2015, and all approved drugs for which Pregnancy and Lactation Labelling has been submitted and approved by FDA), the ICFs must include the appropriate standard contraception language based upon the categories in section 3.0 (see Addendum 1 attached at the end of this policy).
5.1.1. Studies Involving Group 1 Drugs
5.1.1.1. Protocolprotocol may not require use of contraception.
4.1.2. Studies involving Group 3 Drugs {No human data but animal studies show no evidence of adverse developmental outcomes} - The protocol may require the use of ONE form of effective contraception; this may include (but may not require) the use of a form of highly effective contraception.
4.1.3. Studies involving Group 4 Drugs {Animal studies show evidence of adverse developmental outcomes, at dose levels higher than those to be used in this study} - The protocol must require the use of ONE highly effective form of contraception, or TWO concurrent forms of effective contraception.
4.1.4. Studies involving Group 5 Drugs {evidence of adverse developmental outcomes; OR mechanism of action of the drug suggests the possibility of adverse developmental outcomes} - The protocol must require the use of TWO forms of concurrent contraception, at least one of which must be highly effective.
4.2. Highly effective forms of contraception (<1 pregnancy per 100 person-years) include long-acting reversible contraception (LARCs), copper or hormonal IUD, or tubal ligation.
4.3. Effective forms of contraception (6-12 pregnancies per 100 person-years) include injectable, oral, transdermal or local (vaginal) hormonal therapy, double barrier methods, diaphragm plus spermicide, or other single barrier methods plus spermicide.
4.4. Persons who practice total abstinence, when this is in line with the preferred and usual lifestyle of the subject may participate in research without requiring the use of contraception. Total abstinence does not include methods of “periodic abstinence” (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal.
4.4.1. Persons not participating in sexual activities that could lead to pregnancy (including but not limited to total abstinence in line with their preferred and usual lifestyle) may be required to utilize barrier or double barrier contraception as above should they deviate from this preferred and usual lifestyle.
4.5. Persons who are not of reproductive potential (premenarchal, postmenopausal, or surgically or otherwise sterile) are eligible to participate in research without requiring the use of contraception.
4.6. Exceptions to this policy must be approved by the full IRB after adequate justification by the PI.
5.0 5.1.2.Additional Studies involving Group 2 Drugs (Human data shows no evidence of adverse developmental outcome)Requirements
5.1.2.1. The protocol may require the use of ONE form of contraception, with IRB approval, after justification by the PI.
5.1.3. Studies involving Group 3 Drugs (Animal Data shows no evidence of adverse developmental outcome)
5.1.3.1. The protocol may require the use of ONE form of contraception, with IRB approval, after justification by the PI.
5.1.4. Studies involving Group 4 Drugs (Animal studies show evidence of adverse developmental outcomes, at dose levels higher than those to be used in this study)
5.1.4.1. The protocol must require the use of ONE or TWO form(s) of concurrent contraception.
5.1.5. Studies involving Group 5 Drugs (Animal or Human studies show evidence of adverse developmental outcomes, or drug mechanism of action suggests the possibility of adverse developmental outcomes)
5.1.5.1. The protocol must require the use of TWO forms of concurrent contraception.
5.1.6. For all groups, the ICF must utilize the appropriate standard language.
5.1.7. The duration of contraception must be stated in the IRB Application and in the ICF. If contraception is required for longer than the time the drug is being administered, justification must be provided.
5.2. For drugs or biologics for which Pregnancy and Lactation Labeling is not available, the ICFs must include the appropriate standard contraception language based upon the categories in section 4.0 (see Addendum 1 attached at the end of this policy).
5.2.1. Studies Involving Category A Drugs:
5.2.1.1. Protocol may not require use of contraception. Exceptions to this policy must be approved by the full IRB after adequate justification by the PI.
5.2.2. Studies Involving Category B Drugs:
5.2.2.1. The protocol may require the use of ONE form of contraception, with IRB approval, after justification by the PI.
5.2.3. Studies Involving Category C Drugs:
5.2.3.1. The protocol must require the use of ONE or TWO form(s) or concurrent contraception.
5.2.4. Studies Involving Category D Drugs:
5.2.4.1. The protocol must require the use of TWO forms of concurrent contraception.
5.2.5. Studies Involving Category X Drugs:
5.2.5.1. The protocol must require the use of TWO forms of concurrent contraception.
5.3. For all groups
and categories described above, the ICF must
useinclude the corresponding standard Contraception language in
Addendum 1,1, except:
5.3.2.1. For Group 5 drugs, or category D or X drugs, if the sponsor mandates specific contraception language be included in the ICF this language may be used in lieu of the standard language in Addendum 1,1, provided the IRB determines that the specified language is as protective of the potential fetus, and does not create undue burden on the mother.
subject.
5.4.2.2. If PI wishes to list specific forms of birth control in any of the above categories (rather than the generic “
appropriateeffective method(s) of birth control” found in the IRB-approved template),
and use of an effective form of contraception is allowed per section 4.0, then the list must include at least
(1) condoms (malebarrier or
female)double barrier methods with
or without a spermicidal
agentagent.
and
(2) diaphragm or cervical cap with spermicide, unless the sponsor/PI presents justification that any of these are medically or scientifically inappropriate considering both the nature of the research and the subject population.
5.5.3. The IRB Executive
Chair, on behalf of the IRB Executive Committee,Chair is authorized to negotiate with sponsors and/or PIs to address requests for specific language modifications in the ICF provided the requested modifications are at least as protective as the requirements found in the IRB-approved template.
5.4. In the case of minors and those with impaired decision-making capacity, risks to those who can become pregnant or contribute to a pregnancy, as well as contraception requirements, will be discussed in a developmentally and cognitively appropriate manner.
6.0 Additional Consideration for research involving devices
6.1. Investigators may or must require contraception in accordance with data driven and good faith estimates of the likelihood of fetal injury associated with:
6.1.1. placement of the device, including
6.1.1.1. drugs used for anesthesia, if required to place the device or assure its safe operation; or
6.1.1.2. radiographic procedures, if required to place the device or assure its safe operation; and
6.1.2. use of the device (including, but not limited to, risks related to electrical or electromagnetic safety of the device)
6.2. For risks associated with use of drugs for placement of the device or to assure its safe operation, contraception may be or must be used as described above for research involving drug products.
6.3. For risks associated with radiographic procedures required to place the device or assure its safe operation, contraception requirement should reflect best clinical practice related to exposure of persons of childbearing potential to standard diagnostic procedures involving radiation.
6.4. For risks associated with use of the device (including, but not limited to, risks related to electrical or electromagnetic safety of the device), contraception requirements should reflect best clinical practice and/or manufacturer recommendations regarding use in persons of childbearing potential, or in pregnant persons.
6.5. For research involving devices that pose risks to a fetus, the ICF must include the corresponding standard Contraception language in Addendum 1, modified as described in Addendum 2.
ADDENDUM #1
ICF Pregnancy Risk Statements
Category A or
Group 12 drugs:
drugs [no evidence of adverse developmental outcomes]:
PREGNANCY RISKS
ItThere is possibleno evidence that the medicinesdrug(s) used in this studyresearch could injure a fetus [{OR an unborn child]child}, if you, or your partner, become pregnant while taking them.them; however it is possible. You have already been told what is known about this possibility, and you are encouraged to ask further questionsquestions.
Category B or Group 2 or
Group 3 drugs when{No contraceptionhuman isdata NOTbut required:
animal studies show no evidence of adverse developmental outcomes}:
PREGNANCY RISKS
It is possible that the medicines used in this study could injure a fetus [{OR an unborn child]child} if you, or your partner, become pregnant while taking them. You have already been told what is known about this possibility, and you are encouraged to ask further questions.
Category B or Group 2 or Group 3 drugs when contraception IS required:
PREGNANCY RISKS
It is possible that the medicines used in this study could injure a fetus [OR an unborn child] if you, or your partner, become pregnant while taking them. You have already been told what is known about this possibility, and you are encouraged to ask further questions.
You may want to discuss this with others before you agree to take part in this study. If you wish, we will arrange for a doctor, nurse, or counselor who is not part of this study to discuss the potential risks and benefits with you and anyone else you want to have present.
Because of the potential risks, you, or your partner, must not become pregnant while you are participating in this study. WomenPersons who can become pregnant must have a negative pregnancy test before entering the study [{and before each treatment – as appropriate]appropriate}.
If you are sexually active and can get pregnant, or can get your partner pregnant, you must use ONE appropriateeffective methodform of birth control every time you have sex, or you must not have sex.
You can get additional information about methods to avoid pregnancy by calling the UNMC Research Subject Advocate’s Office at (402) 559-6941.
You will need to continue to use birth control to avoid pregnancy for X months after finishing the research.
By signing this and being in the study, you are agreeing to not get pregnant while you are on the study and for X months after. Should you become pregnant while on this study, you should immediately notify the study personnel. The investigator will assist you in finding appropriate medical care. The investigator also may ask to be allowed to continue getting information about your pregnancy. You can refuse to provide this information.
Category C or
Group 4 drugs:
drugs {Animal studies show evidence of adverse developmental outcomes, at dose levels higher than those to be used in this study}:
PREGNANCY RISKS
It is possible that the medicines used in this study could injure a fetus [{OR an unborn child]child} if you, or your partner, become pregnant while taking them. You have already been told what is known about this possibility, and you are encouraged to ask further questions.
You may want to discuss this with others before you agree to take part in this study. If you wish, we will arrange for a doctor, nurse, or counselor who is not part of this study to discuss the potential risks and benefits with you and anyone else you want to have present.
Because of the potential risks, you, or your partner, must not become pregnant while you are participating in this study. WomenPersons who can become pregnant must have a negative pregnancy test before entering the study [{and before each treatment – as appropriate]appropriate}.
If you are sexually active and can get pregnant, or can get your partner pregnant, you must use ONE [or TWO] appropriateeffective method(s) of birth control every time you have sex, or you must not have sex.
Because of the possible risk to the fetus [{OR an unborn child]child}, methods of natural family planning are not, by themselves, reliable enough to avoid pregnancy.
You can get additional information about methods to avoid pregnancy by calling the UNMC Research Subject Advocate’s Office at (402) 559-6941.
You will need to continue to use birth control to avoid pregnancy for X months after finishing the research.
By signing this and being in the study, you are agreeing to not get pregnant while you are on the study and for X months after. Should you become pregnant while on this study, you should immediately notify the study personnel. The investigator will assist you in finding appropriate medical care. The investigator also may ask to be allowed to continue getting information about your pregnancy. You can refuse to provide this information.
Category D or
Group 5 Drugs:
Drugs {evidence of adverse developmental outcomes; OR mechanism of action of the drug suggests the possibility of adverse developmental outcomes}:
PREGNANCY RISKS
It is possible that the medicines used in this study could injure a fetus [{OR an unborn child]child} if you, or your partner, become pregnant while taking them. You have already been told what is known about this possibility, and you are encouraged to ask further questions.
You may want to discuss this with others before you agree to take part in this study. If you wish, we will arrange for a doctor, nurse, or counselor who is not part of this study to discuss the potential risks and benefits with you and anyone else you want to have present.
Because of the potential risks, you, or your partner, must not become pregnant while you are participating in this study. WomenPersons who can become pregnant must have a negative pregnancy test before entering the study [{and before each treatment – as appropriate]appropriate}.
If you are sexually active and can get pregnant, or can get your partner pregnant, you must use TWO appropriateeffective methods of birth control every time you have sex, or you must not have sex.
Because of the possible risks to a fetus [{OR an unborn child]child}, methods of natural family planning are not, by themselves, sufficiently reliable to avoid pregnancy.
You can get additional information about methods to avoid pregnancy by calling the UNMC Research Subject Advocate’s Office at (402) 559-6941.
You will need to continue to use birth control to avoid pregnancy for X months after finishing the research.
By signing this and being in the study, you are agreeing to not get pregnant while you are on the study and for X months after. Should you become pregnant while on this study, you should immediately notify the study personnel. The investigator will assist you in finding appropriate medical care. The investigator also may ask to be allowed to continue getting information about your pregnancy. You can refuse to provide this information.
Category
ADDENDUM X#2 Drugs:
(For SinceStudies studiesInvolving Devices)
ICF Pregnancy Risk Statements are as described in Addendum #1, except the first paragraph of the drugPregnancy inRisks humans,statement should be replaced with:
It is possible that the device {or substitute the actual name} or investigational or post-marketing data, have demonstrated fetal risk, contraception is required and the language must be at least as protective as Category D language above. If the sponsor or FDA require inclusion of specific language relatingprocedure to fetal risk, monitoring for pregnancy and prevention of pregnancyput in the ICF,device itif mayappropriate} beused included,in this study could injure a fetus [OR an unborn child] if you are pregnant or become pregnant. You have already been told what is known about this possibility, and redundantyou categoryare Dencouraged languageto deleted.ask further questions.
DOCUMENT HISTORY:
Written: 12/28/2015 (Approved: 12/28/2015) - original author not recorded
Revised: 11/21/2017 - revision not documented
Revised 11/27/2024 - Revised to base contraception requirements on PLLR rather than previous FDA Use-In-Pregnancy category; revised to use gender neutral language; added comment that risks to those who can become pregnant or contribute to a pregnancy, as well as contraception requirements, will be discussed in a developmentally and cognitively appropriate manner (section 5.4); stylistic changes.
Revised 5/5/2025 - Revised purpose to specify policy addresses contraception requirements for subjects participating in research involving drugs, devices or biologics; added additional considerations for research involving devices (sections 2.1.1 and 6.1 thru 6.5); added ADDENDUM #2 (ICF Pregnancy Risk Statements for studies involving devices); minor stylistic changes and correction of typographic errors.
