Inclusion of Pregnant and Lactating Persons in Clinical Trials Proceedings of a Workshop (2023) / Chapter Skim
Currently Skimming:
6 Promising Innovative Approaches to Evidence Generation
6 Promising Innovative Approaches to Evidence Generation
Pages 65-78
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 65... ...
• In the postmarket setting, pharmacovigilance activities, preg nancy registries, and complementary data sources (e.g., EHR data, claims data) can be used to study pregnancy safety asso ciated with exposure to drug products.
|
From page 66... ...
to enroll in longitudinal prospective cohort studies, or a pregnancy registry, on the basis of … already having had a given exposure or exposures." MotherToBaby is also used to enroll comparison populations of pregnant persons who have not had the exposure that is the subject of study but might have the same underlying conditions with different or no treatment. Chambers described the logistics of conducting studies with participants recruited across the nation, explaining that data on exposures and outcomes are collected via phone interviews with the pregnant participants 1 See https://mothertobaby.org (accessed September 12, 2022)
|
From page 67... ...
.2 Chambers explained that this project brings together real-world data from three parallel study arms: a pregnancy registry, a claims data study, and a case-control study. Another UC San Diego research initiative is Mommy's Milk,3 a human milk research biorepository established in 2014.
|
From page 68... ...
She mentioned the EU ConcePTION project as a model for data collection, analysis, prioritization, and sharing that the United States could follow.4 Engaging Pregnant and Lactating Persons in Real-World Evidence Studies Tolúwalàṣé Ajayi, director of clinical research and diversity initiatives at Scripps Research Translational Institute and assistant professor of pediatrics at UC San Diego and Rady Children's Hospital San Diego, described her personal experience being pregnant during the COVID-19 pandemic and how her obstetrician did not have enough information about the use of the vaccine in pregnant persons to give her any advice about getting it. After discussions with colleagues at American College of Obstetrics and Gynecology (ACOG)
|
From page 69... ...
PHARMACOLOGIC APPROACHES TO EVIDENCE GENERATION There are five key considerations for the use of approved drug products to treat pregnant persons: efficacy in the pregnant person, safety in the pregnant person, safety in the fetus, neonatal safety, and efficacy in the fetus in special circumstances, said Raman Venkataramanan, professor of pharmaceutical sciences and pathology at the University of Pittsburgh.
|
From page 70... ...
Venkataramanan highlighted the need to systematically study drug transport during pregnancy and said studies using a probe medication are valuable. Data can then be used in physiologically-based pharmacokinetic
|
From page 71... ...
. Studies in Lactating Persons Venkataramanan emphasized that lactating persons and pregnant persons are physiologically quite different, and "we need to systematically start doing studies in this patient population, not only from the mother's perspective but also from the baby's perspective." A pharmacologic study in lactating persons would ideally collect all breastmilk pumped over a dosing interval to assess the total amount of drug excreted.
|
From page 72... ...
at FDA.6 She said: The regulation authorizes FDA to require studies at the time of approval to assess a known serious risk or a signal of serious risk, or to identify an unexpected serious risk when available data indicate the potential for a serious risk.7 Further, she said, "Such studies can also be required after approval, if FDA becomes aware of new safety information." In the postmarket setting, pregnancy outcomes associated with exposure to drug products can be assessed using data from p harmacovigilance activities, pregnancy registries, and complementary data sources, and Hua said that "rigorous studies are desired to inform regulatory decisionmaking." Pregnancy registries are prospectively designed and collect detailed patient-level data, but Hua noted that patient recruitment and retention in registries is a barrier. Studies using complementary data sources such as electronic health care data (e.g., EHR data, claims data)
|
From page 73... ...
Ajayi recommended using existing applications that are already popular among pregnant persons, such as WebMD or the Philips pregnancy app, to reach potential clinical trial participants. Chambers and Ajayi said social media and mobile applications are the modern version of the advertising circulars that used to arrive in every mailbox (e.g., Pennysaver)
|
From page 74... ...
requirements. Participants discussed using research platforms to overcome this limitation and provide data continuity across pregnant person, fetus, and infant.
|
From page 75... ...
OPPORTUNITIES TO IMPROVE EVIDENCE GENERATION FOR PREGNANT AND LACTATING PERSONS: BREAKOUT DISCUSSION HIGHLIGHTS To supplement the panel discussions, participants divided into breakout groups to consider opportunities to improve the generation of evidence on the safety and efficacy of drug products that will be used by pregnant or lactating persons.9 A summary of the points made by individual breakout group participants was provided in plenary session by a designated leader for each of the breakout groups.10 Opportunities to Improve the Generation of Clinical Trial Evidence During Pregnancy Three groups considered opportunities to improve evidence generation during pregnancy. Highlights of their discussions were provided by Kavita Shah Arora, associate professor and division director of General Obstetrics and Gynecology at the University of North Carolina at Chapel Hill, Anup Challa, AstraZeneca, and Brittany Bettendorf, University of Iowa.
|
From page 76... ...
The need to develop programs to support sponsors in addressing liability postmarket was also discussed, including the creation of global and no-fault injury compensation funds for harms incurred by pregnant persons during a trial (similar to the National Vaccine Injury Compensation Program)
|
From page 77... ...
Participants discussed the need to build trust in the research enterprise. Ideas proposed included having a trusted health care provider discuss potential trials with their patient and engage in shared decision making, using trusted proxies such as community-based organiza tions to conduct outreach, not rushing through the consent process, having clinical investigators that are representative of the com munity and population being enrolled, committing to share the results of the study with participants and the community where the research is being done, setting expectations about whether or when participants will be told if they were in a control or test arm, and addressing patient fears about legal implications (e.g., undocumented participants, studies involving treatments for ille gal substance use in pregnant persons)
|
From page 78... ...
Lack of knowledge about how to conduct studies with lactating persons was identified as a barrier. Participants discussed the need for comprehensive training programs for clinicians and researchers on the benefits of including lactating persons in clinical trials and on procedures and logistics.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.