The Tsepamo birth outcomes surveillance study has accrued many thousands of women living with HIV from Botswana. The Tsepamo Plus study (Project 1) will continue to collect ARV exposures in pregnancy which are rarely studied with high precision. Because Tsepamo can provide high precision when there is much uncertainty about safety in pregnancy and Botswana typically rolls out new ARVs before other African countries, Tsepamo may be the first to report on novel safety signals. This in turn makes Tsepamo highly influential in the understanding of adverse ARV effects in pregnancy. Moreover, surveillance data alone can and should be used to inform personal, clinical, or societal decision-making, especially when randomized trials are too costly, unethical, or not timely enough. The objectives of this proposal are to evaluate methodologies and provide guidance on methods for making best use of Tsepamo data and similar studies. Specifically, we aim to create guidance on when to publicly report on safety signals based on unplanned analyses; evaluate the statistical properties of various group sequential methods; develop and implement methods to benchmark results from Tsepamo with results from a randomized trial; and develop and improve triangulation strategies within pregnancy-related surveillance data.