  Recognizing the importance of real-world data (RWD) for regulatory purposes,
the United States (US) Congress passed the 21st Century Cures Act1 mandating
the development of Food and Drug Administration (FDA) guidance on regulatory
use of real-world evidence. The Forum on the Integration of Observational and
Randomized Data (FIORD) conducted a meeting bringing together various
stakeholder groups to build consensus around best practices for the use of RWD
to support regulatory science. Our companion paper describes in detail the
context and discussion carried out in the meeting, which includes a
recommendation to use a causal roadmap for complete pre-specification of study
designs using RWD. This article discusses one step of the roadmap: the
specification of a procedure for sensitivity analysis, defined as a procedure
for testing the robustness of substantive conclusions to violations of
assumptions made in the causal roadmap. We include a worked-out example of a
sensitivity analysis from a RWD study on the effectiveness of Nifurtimox in
treating Chagas disease, as well as an overview of various methods available
for sensitivity analysis in causal inference, emphasizing practical
considerations on their use for regulatory purposes.
