Safe Expectations: Current State and Future Directions for Medication Safety in Pregnancy Research

Abstract

Medication use in pregnancy is common, but information about the safety of most medications in pregnant women or their infants is limited. In the absence of data from randomized clinical trials to guide decisions made by regulators, clinicians, and patients, we often have to rely on well-designed observational studies to generate valid evidence about the benefits and risks of medications in pregnancy. Spontaneous reporting, primary caseecontrol and cohort studies, pregnancy exposure registries, and electronic health data have been used extensively for studying medication safety in pregnancy. This article discusses these data sources, their strengths and limitations, and possible strategies and approaches to mitigating limitations when planning studies or interpreting findings from the literature. Strategies discussed include combining data sources across institutional or national borders, developing and using more sophisticated study designs, and taking advantage of existing analytic methods for more complex data structures, such as time-varying exposure or unmeasured confounding. Finally, we make recommendations for study designs that aid in better risk-related communication. (Clin Ther. 2019;41:2467e2476)

Pregnant women's perceptions of risks and benefits when considering participation in vaccine trials

“…The high value women place on human pregnancy data when deciding about participation points not only to the importance of designing vaccine trials to specifically address the health interests of pregnant women, but also to conducting robust follow-up on women inadvertently vaccinated in the periconception period during vaccine trials or rollouts, and to making a carefully contextualized analysis of these data available in a timely manner. It is critical to characterize the quality and quantity of evidence available, and make clear the limitations of data from inadvertent exposure [29] . Given the potential for a small or false safety signal to derail further investigation or development of a promising vaccine for protecting pregnant women, all communication should include the best available background rates of pregnancy outcomes [29] .…”

“…It is critical to characterize the quality and quantity of evidence available, and make clear the limitations of data from inadvertent exposure [29] . Given the potential for a small or false safety signal to derail further investigation or development of a promising vaccine for protecting pregnant women, all communication should include the best available background rates of pregnancy outcomes [29] .…”

How Did Research on Medication Safety in Pregnancy Define, Develop and Advance the Field of Pharmacoepidemiology?

“…One of the most important contributions of pharmacoepidemiology has been the development of cutting-edge methods for bias control in observational-data studies. Wood et al 14 introduce these concepts, with a focus on how to address what is known as "confounding by indication," which occurs when we attribute a poor outcome to a drug, when, in fact, the reason for taking the drug causes the outcome. For example, attributing a higher risk for stroke to the use of antihypertensive medications could be spurious due to confounding by indication, because the risk for stroke will be higher among patients who are prescribed antihypertensive therapy.…”

“…How, for instance, should readers of the Journal interpret possible selection biases in pharmacoepidemiology studies of a pregnancy outcome that included only live births to women required to have been continuously enrolled in a health insurance plan? Wood et al 14 and others 15 acknowledge the benefit of augmenting or linking claims data with other sources, such as birth registries, electronic health records, and other primary data-collection sources to address these challenges.…”

“…This trend increases the need for practical guidance 17 on the interpretation of observational research as pharmacoepidemiologists navigate "old-world" epidemiologic problems borne anew in electronic health data and other robust, administrative data sources. The pharmacoepidemiologic studies in this issue 14,16 provide a historical perspective on some of the most important contributions of pharmacoepidemiology, and also provide practical guidance by introducing and exemplifying methodologic approaches to analyzing and interpreting observational data that are translatable to many fields. Finally, as the US Food and Drug Administration has termed its medication safety surveillance database the Sentinel Initiative, the role of pharmacoepidemiologists might be best explained to patients as being sentinels for medication safety, en garde, keeping watch to prevent any future "thalidomide disasters," and providing timely and accurate medication safety information for public health.…”