Study design

Study designs must be selected that are best able to generate high-quality evidence on the safety and efficacy of medicines. Study design selection should also consider the emotional, practical, and physical realities faced by pregnant and lactating women, ensuring that participation is safe, respectful, and feasible. Where possible, integrating different study designs together for enhanced efficiency should be prioritized.

Randomized controlled trials are the gold standard for assessing the safety and efficacy of a medicine. They collect data in a controlled environment to reduce bias and control confounding, which is critical in generating substantiative conclusions. However, they are often logistically complex and expensive, and it may be difficult to recruit sufficient participants to achieve the sample size necessary to prove efficacy and safety.

Alternative approaches include:

• Adaptive designs, for example, ensuring dosing/regimen adjustment throughout the trial in response to emerging data.
• Observational studies, including case reports, may be used in smaller numbers to gather safety and efficacy data, including on rarer adverse pregnancy outcomes, and assist in the identification of trends of association. A conclusion of causation, however, cannot be attributed.
• Complementary designs, where observational studies are conducted in pregnant and lactating women in parallel to a randomized controlled trial in the broader population, may be considered. Whilst not preferred, these approaches may be utilized for any existing trials to ensure some data on pregnant and lactating women are captured.
• International collaborations are useful to enable pooling of data from similar studies to offset small sample sizes. The challenge lies in ensuring the alignment of protocols across the individual studies to ensure comparability of results.

Alternative approaches may be used for safety recording

Real-world evidence collected from health records, registries and biobanks. These are increasingly used to support long-term safety monitoring and support integration and data linkage internationally across trials and countries. Several models already exist, such as the European Union ConcePTION data collection project and biobank, the SAIL (Secure Anonymised Information Linkage) and the CPRD (Clinical Practice Research Datalink) databases in the United Kingdom of Great Britain and Northern Ireland.