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)

• To obtain a deeper understanding of current practices:
  • For defining the acceptable risk of pregnancy in a clinical trial population
  • For determining which factors, in addition to fetal risk, are considered when choosing a pregnancy testing plan
• To facilitate an informed discussion of practices and challenges in assessing the acceptable risk of pregnancy and implementing a pregnancy testing plan
• To issue recommendations for future approaches for developing pregnancy testing plans for clinical trials based on project findings.

Improved pre-trial pregnancy testing planning will result in increased safety and efficiency of clinical trials that include females of reproductive potential.

• Stakeholder survey to identify practices
• Expert meeting

• A stakeholder survey was conducted to inform an expert discussion on the challenges and potential solutions to improving pregnancy testing.
  • Half of the respondents reported the maximum acceptable risk of pregnancy is less than 1/10,000, which is realistically unachievable.
  • Testing characteristics deemed to be most important were negative predictive value (the reassurance that a subject is not pregnant) and patient burden.
  • When asked about factors that affect negative predictive value, such as age, contraceptive method, type of test, and the timing of the test, stakeholder responses produced ambiguous results. This reflects the lack of evidence-based guidance in these areas.
• One approach to selecting the best pregnancy testing plan involves a model that can estimate likely outcomes of different pregnancy testing plans. CTTI developed a web application that allows for the comparison of possible pregnancy testing plans based on characteristics of a trial and its expected population.