Evidence-based pregnancy testing in clinical trials: Recommendations from a multi-stakeholder development process.

Most clinical trials exclude pregnant women in order to avoid the possibility of adverse embryonic and/or fetal effects. Currently, there are no evidence-based guidelines regarding appropriate methods for identifying early pregnancy among research subjects. This lack of guidance results in wide variation in pregnancy testing plans, leading to the potential for inadequate protection against embryonic or fetal exposure in some cases and unnecessary burdens on research participants in others, as well as inefficiencies caused by disagreements among sponsors, investigators, and regulators. To address this issue, the Clinical Trials Transformation Initiative convened content experts and stakeholders to develop recommendations for pregnancy testing in clinical research based on currently available evidence. Recommendations included: 1) the study protocol should clearly state the rationale for pregnancy testing and the plan for handling positive and indeterminate tests; 2) protocols should include an assessment of the pregnancy testing plan advantages (reduced risk of embryo/fetal exposure) versus the burdens (participant burden, study team workload, costs); 3) protocols should assess the participant burdens regarding the likelihood of false negative and false positive results; 4) participant administered home pregnancy testing should be avoided in clinical trials; and 5) the consent process should describe the extent of knowledge about the study intervention's potential risk to the embryo/fetus and the limitations and consequences of pregnancy testing. CTTI has also developed an online tool to help implement these recommendations.