Pregnancy Testing Considerations for Clinical Trials
The U.S. Food and Drug Administration (FDA) expects clinical trials to include a population reflective of that which will receive the drug once marketed, which may include females of reproductive potential. However, there are no specific guidelines for how pregnancy testing should be conducted to prevent the unintended exposure of an embryo or fetus to a study’s intervention, nor how risks should be clearly communicated to women.
CTTI's recommendations can help research sponsors, investigators, and institutional review boards create and review pregnancy testing plans, in an effort to conduct safer, more efficient clinical trials. To help implement the recommendations, CTTI also created the Pregnancy Testing Outcomes Predictor for Clinical Trials, a web application that provides a quantitative method for assessing estimated likely outcomes of different pregnancy testing plans.
Pregnancy testing is a complex issue, and a high level of variability exists among strategies for pregnancy testing in clinical trials. The recommendations and interactive web application provide a standard way to plan for and make decisions about pregnancy testing in clinical trials, while also improving communication and transparency with trial participants. These resources help assess the balance of benefits and burdens of different pregnancy testing plans based on characteristics of a trial and its expected population.
Freda Lewis-Hall, M.D., Chief Medical Officer of Pfizer
“Speaking from the perspective of an industry trial sponsor, we truly appreciate the work done by CTTI to capture and share best practices in defining and ameliorating potential risks to women of childbearing age who participate or consider participation in clinical trials. The adoption of these recommendations will help facilitate medical research in the interest of better health outcomes for women and children.”
Pregnant women are excluded from many, if not most, clinical trials. Although there are several potential scientific justifications for this exclusion (such as the often unknown effects of the normal physiological changes of pregnancy on drug metabolism), the primary rationale is to minimize the risk of adverse effects on an embryo or fetus from exposure to study-related interventions. Little formal guidance is available from regulators on how to develop pregnancy testing plans for clinical trials.
Designing such plans requires balancing several factors: the performance characteristics of a test, the baseline risk of pregnancy in a given population, the potential risks to the embryo/fetus from study interventions, and practical concerns with implementing the testing plan (e.g., the burden on subjects and/or staff and direct costs). The literature suggests inconsistency among sponsors, investigators, and IRBs in applying or considering these factors in the design and evaluation of pregnancy testing plans, and anecdotal reports also indicate widespread variability in these practices.
Evidence-based recommendations that explicitly considers the level of acceptable risk to suggest appropriate pregnancy testing plans can improve the protection of research subjects and reduce the risk of unintended embryo/fetal exposure while also reducing the workload on sponsors, investigators, IRBs, and other stakeholders.
Pregnancy Testing: “Use of Pregnancy Testing in Clinical Trials” (2012-2017)
Improved pre-trial pregnancy testing planning will result in increased safety and efficiency of clinical trials that include females of reproductive potential.
|Team Member||Lisa Mathis||Amgen|
|Team Leader||Claire Jurkowski||Bristol-Myers Squibb (Retired)|
|Project Manager||Sara Calvert||Clinical Trials Transformation Initiative|
|Team Leader||Evan Myers||Duke University|
|Team Member||Avis Danishefsky||Food and Drug Administration|
|Team Member||Cheryl Grandinetti||Food and Drug Administration|
|Team Member||Jeffrey Roberts||Food and Drug Administration|
|Team Member||Catherine Sewell||Food and Drug Administration|
|Team Leader||Melissa Tassinari||Food and Drug Administration (Retired)|
|Team Member||Stephen Mikita||Individual Patient/Caregiver|
|Team Member||Jessica Morse||NC TraCS, University of North Carolina at Chapel Hill|
|Team Member||Veronica Todaro||Parkinson's Disease Foundation|