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Clinical trials to address the COVID-19 public health emergency have broadly excluded pregnant people from participation, illustrating a long-standing trend of clinical trial exclusion that has led to a clear knowledge gap and unmet need in the treatment and prevention of medical conditions experienced during pregnancy and of pregnancy-related conditions. Drugs (includes products such as drugs, biologics, biosimilars and vaccines) approved for a certain medical condition in adults are also approved for use in pregnant adults with the same medical condition, unless contraindicated for use in pregnancy. However, there are limited pregnancy-specific data on risks and benefits of drugs in pregnant people, despite their approval for all adults. The United States Food and Drug Administration-approved medical products are used widely by pregnant people, 90% of whom take at least 1 medication during the course of their pregnancy despite there being sparse data from clinical trials on these products in pregnancy. This overall lack of clinical data precludes informed decision-making, causing clinicians and pregnant patients to have to decide whether to pursue treatment without an adequate understanding of potential effects. Although some United States Food and Drug Administration initiatives and other federal efforts have helped to promote the inclusion of pregnant people in clinical research, broader collaboration and reforms are needed to address challenges related to the design and conduct of trials that enroll pregnant people, and to forge a culture of widespread inclusion of pregnant people in clinical research. This article summarizes the scientific, ethical, and legal considerations governing research conducted during pregnancy, as discussed during a recent subject matter expert convening held by the Duke-Margolis Center for Health Policy and the United States Food and Drug Administration on this topic. This article also recommends strategies for overcoming impediments to inclusion and trial conduct.

Introduction Medical student clerkships are designed to provide students with an opportunity to develop a critical, problem-oriented approach to patient care. Given the time constraints of traditional medical student clerkships, it is not feasible during a short clinical rotation to expose students to all of the pathologic entities within a particular discipline. This is especially true at multiple, often distant clinical sites with varied patient populations. Methods To address this in Pediatrics, we created a series of web-supported case seminars to review a variety of common problems. The teaching cases for the core Pediatric Clerkship are based on the Council on Medical Student Education in Pediatrics Curriculum. Each case is organized to include case objectives, suggested references, a case presentation, and guiding questions. Students prepare for teaching sessions by reviewing the case's objectives, patient presentation, and guiding questions on-line. Seminar sessions use these cases for the review of the clinical approach to patients, organization of data, generation of a differential diagnosis, and management for a variety of pediatric conditions. Sessions are entirely small-group, interactive, and case-based. The curriculum is web-supported and uses multimedia resources to ensure that the cases are standardized and can be delivered efficiently across multiple and distant clinical sites. Results Their quality and presentation have been assessed using anonymous, written evaluations by each student. Responses to this method of teaching have been extremely positive. Students have reported that the teaching is of high caliber and that the topics are high yield. They were also impressed by both the format and the level of interactivity of the sessions. Discussion The cases have now been used as the primary teaching tool in the Pediatric Clerkship for four years. They are continually being refined to incorporate contemporary medical topics and further address LCME mandates.

Background: The Newborn Drug Development Initiative (NDDI) was established to address the lack of substantive data supporting efficacy and safety of drugs in the neonate. Objective: This commentary summarizes some of the ethical issues involved in neonatal drug development. Methods: At the NDDI workshop held March 29 and 30, 2004, in Baltimore, Maryland, members of the Ethics Group were dispersed among the subspecialty groups before convening to discuss common ethical themes. The Ethics Group then met together to identify and discuss those ethical themes that were both important and shared among the groups. These themes are discussed and illustrated with the other NDDI group reports. This workshop was cosponsored by the National Institute of Child Health and Human Development and the US Food and Drug Administration. Results: Neonatal drug research is scientifically and ethically necessary to establish the efficacy and safety of drugs widely used in newborn medicine. However, research involving neonates must be carefully designed to balance potential risks and benefits, with consideration given to the component analysis of risk. The protocols proposed by the NDDI groups would be considered greater than minimal risk and offering prospect for direct benefit, thus adhering to the Department of Health and Human Services' pediatric research regulations (Subpart D). The NDDI groups all proposed randomized controlled clinical trials, with careful attention to scientifically and ethically appropriate control groups. Multiple regulatory bodies have affirmed that in the absence of proven effective treatment or when a proven treatment offers marginal benefits, study designs with placebo controls are ethical. Obtaining parental permission is a complex issue, with a paucity of evidence describing the feasibility of informed and voluntary consent under conditions of duress and a short therapeutic window. The Subpart D regulations offer sufficient protection to critically ill neonates. The application of the revised Subpart B regulations would restrict the use of a waiver of consent for minimal risk research and for emergency research, and would not allow research that offers no direct benefit and no more than a minor increase over minimal risk. Conclusions: Multisite collaboration involving standards of care and institutional review board procedures may be important for establishing scientific and ethical consistency. Ongoing dialogue among researchers, clinicians, parents, and other interested parties is essential to promoting ethically and scientifically sound neonatal clinical research.