妊娠期药物安全：方法和挑战

Drug Safety in Pregnancy:Methods and Challenges A review of evaluating maternal exposures and infanthealth outcomes JOYDEEP SARKAR, PhDKARIN DE HAART, MScANNE BROE, PhD MDIAN BONZANI, PhDEMILY BRATTON, PhD Table of contents Executive summary1Introduction2Regulatory trends andchallenges2Methodologies3Drug utilization studies4Prospective pregnancy registry studydesign4Single-arm safety — pregnancysurveillance5Pregnancy outcomes intensive monitoring5Database studies8Future directions9Conclusion9References10 Executive summary This article reviews the current landscape, challenges, and advancements inevaluating drug safety during pregnancy. Particularly for individuals managingchronic illnesses that require ongoing pharmacological treatment, and bothmaternal and infant health might benefit from continued drug exposureduring pregnancy. However, with a lack of data upon drug approval,health care providers lack an evidence base tobalans maternal health needs with fetal safetyremains a critical concern. Regulators provideguidance on pregnancy exposure study design,implementation, and drug labeling. Ongoingrevisions to these guidelines are fostering greaterinternational collaboration and an emphasison harmonizing methodologies. Despite theseadvancements, persistent challenges include ethicalconsiderations, data privacy issues, and the need forstandardizedprotocols. Traditional clinical trials often exclude pregnantindividuals due to ethical concerns, resulting in areliance on real-world data and observational studiesto generate evidence on medication safety. Recenttechnological advances, including mobile datacollection and expanded real-world data sources, haveopened new opportunities to address these evidencegaps and respond to evolving regulatory demands. Overall, the review highlights the importance ofleveraging real-world data, innovative methodologies,and global regulatory collaboration to enhancethe evidence base, thereby supporting safer andmore effective drug therapy decisions for pregnantindividuals and their infants. This review explores the regulatory guidance,methodologies employed for data collection, andexamines innovations and trends. We highlight therole of real-world data and innovative technologies inadvancing research. Introduction Drug exposure during pregnancy is an area of criticalconcern, particularly for individuals managing chronicillnesses that necessitate ongoing treatment. It isestimated that approximately 10% of pregnanciesinvolve individuals with chronic conditions such asasthma, diabetes, or hypertension.1,2These conditionsoften require pharmacological intervention, whichposes unique challenges in balancing maternal healthneeds with fetal safety. For instance, asthma treatment during pregnancyoffers a compelling example of the complexitiesinvolved. Since the 1960s numerous epidemiologicalstudies have demonstrated that asthmatic femalesare at increased risk of complications such as pretermbirth, low birth weight, or even maternal respiratorydistress. Effective treatment plans, including the useof inhaled corticosteroids and bronchodilators, arecritical to maintaining stable respiratory function andensuring positive pregnancy outcomes.3 These therapeutic approaches highlight the importanceof an evidence base for individualized care and thecareful evaluation of drug safety for pregnant individuals. Regulatory trendsandchallenges Since the Thalidomide tragedy,4there has beenheightened scrutiny regarding the effects of drugexposure during pregnancy, emphasizing the necessityof balancing maternal treatment benefits with potentialrisks to the developing fetus. The exclusion of pregnantindividuals from most clinical trials due to ethicalconsiderations complicates the landscape of evidencegeneration. This gap necessitates reliance on real-worlddata studies to identify the safest and most effectivetherapeutic options. Based on US Food and DrugAdministration (FDA) Postmarketing Requirements andCommitments Database (PMR/PMC database), we cansee that especially in the last 15 years an increasingnumber of requests for pregnancy outcome studies.5 Both the European and United States regulatoryguidance play a pivotal role in shaping the conductof pregnancy exposure studies. Current regulatoryguidance provides detailed instructions on numerousaspects, including the implementation of findings indrug labeling, the design and execution of exposureregistries, and methodologies for conducting thesecritical studies. Furthermore, revisions to these guidelines areongoing, fostering broader collaboration amongregulatory agencies to harmonize approaches.Agencies worldwide emphasize the importance ofreal-world evidence and innovative methodologiesto improve understanding of drug safety. However,challenges remain, including ethical considerations,data privacy concerns, and the need forstandardizedprotocols. Advances and expansion in the availability of real-world data and mobile data collection te