Table 4. Specific recommendations for pregnancy testing in clinical trials.

Recommendations for investigators and sponsors in developing a clinical trial protocol:
The protocol should clearly state the specific purposes of pregnancy testing in the research study	Prevent or minimize embryo/fetal exposures to study drug/intervention by: Confirming non-pregnant state at time of enrollment and, if applicable, prior to any subsequent exposures; and Detecting early pregnancies to determine whether to continue participation in the study
The protocol should describe the procedure for handling positive or indeterminate pregnancy tests	Define a positive test as it relates to the specific pregnancy testing plan (actual measured level of hCG that is considered positive) Define an indeterminate test (level of hCG, which will vary by study population age and underlying medical condition, and type of pregnancy test used) Define: Procedures for follow-up testing and evaluation of both positive and indeterminate tests and procedures for continuing, holding, or stopping study interventions and appropriate medical follow-up in the event of positive or indeterminate test results (based in part on the potential embryo/fetal risks of exposure to study interventions and the potential benefit to the participant from continued study participation)
Recommendations for investigators when developing a pregnancy testing plan
Assess the balance of the pregnancy testing plan advantages (reduced risk of embryo/fetal exposure) versus burdens (participant burden, study team workload, costs).	This can be done using formal quantitative or qualitative methods. Formal quantitative methods incorporating parameters including age of study population, type of contraceptive methods used by the study population, type of pregnancy test used and its detectable threshold of hCG, and the proposed timing of testing during the menstrual cycle) to estimate: The negative and positive predictive values of a proposed testing strategy; and The absolute differences in exposures prevented based on variable testing options Alternatively, a semi-quantitative or qualitative assessment of risks and burdens considering the same factors.
Assess participant burdens regarding the likelihood of false negative results and unintentional embryo/fetal exposure, and likelihood of false positive results	Invasiveness of testing (serum versus urine tests) Timing of testing (random versus timed to the menstrual cycle) and study interventions Implications of false positives (repeat testing, delay in receipt of study interventions, study withdrawal, anxiety/worry) for the patient
Avoid participant-administered home pregnancy tests in clinical trials	Although patient-administered tests offer convenience to both participants and study staff, disadvantages include Consistent evidence of observer variability in interpretation of consumer pregnancy test results Potential for emotional distress in event of participant-read false negative result and subsequent embryo/fetal exposure Potential for desire to continue in study affecting interpretation of ambiguous test results
Recommendations for participant education during the consent process*
Clearly articulate extent of knowledge about potential embryonic or fetal risks from exposure to study intervention	In addition, acknowledge in the informed consent process that: Pre-clinical testing on animals may not fully inform assessment of risk in humans; and Even when clinical trial and/or post-market data are available, overall knowledge about potential embryo/fetal risks may be minimal
Clearly explain the limitations and consequences of pregnancy testing to participants during the consent process	Potential for false negatives—No available test will detect 100% of pregnancies Potential for false positives—The possibility of a positive test in non-pregnant participants—this varies based on patient age, other conditions, and type of test The implications of a positive or indeterminate test for study participation: What additional tests/procedures will be performed to confirm a pregnancy? Who decides on whether to continue or terminate study participation? What criteria will be used to make that decision? How will pregnancy outcomes be followed? Who is responsible for ensuring patients will have appropriate medical follow up?

* Acknowledging efforts to simplify the informed consent form, these recommendations apply to the consent process. For example, a separate concise information sheet could be created for females of reproductive potential (FRP) or if desired included in the consent form as a separate page for FRP only.