Qualitative Analysis of Inquiries Received by FDA Regarding Conduct of Clinical Trials during the Covid-19 Public Health Emergency.

BACKGROUND: This report describes the U.S. Food and Drug Administration (FDA) experience in establishing a dedicated mailbox, and in publishing related guidance, to address concerns among interested parties regarding the conduct of clinical trials during the COVID-19 public health emergency (PHE). METHODS: Six hundred and thirty-four mailbox inquiries were received from March 2020 through February 2022. Qualitative methods were used to provide a structured description of, and identify common themes among, these inquiries. RESULTS: Most inquiries came from U.S.-based interested parties, including sponsors, industry trade associations, academic institutions, hospitals, clinics, research sites, trial participants, and individual persons. Approximately one-fifth of questions were related directly to COVID-19 (e.g., proposals for treatment); other inquiries were related to conduct of routine trial-related activities, and concerns were often focused on maintaining compliance with good clinical practice. In March 2020, FDA published a guidance titled Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency; the document was subsequently revised eight times based in part on issues raised in mailbox inquiries. CONCLUSIONS: The dedicated mailbox enabled expedited communication among invested parties during the COVID-19 PHE; FDA also provided updates of the aforementioned guidance. These efforts supported the continuance of ongoing trials and the initiation of new trials during the PHE in accordance with good clinical practice guidelines, thereby helping to ensure the safety of trial participants while maintaining the quality of trial data. By soliciting and responding to trial-related inquiries and addressing corresponding needs and concerns, FDA improved transparency and communication.

A Comparison of FDA and EMA Pregnancy and Lactation Labeling.

The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have robust collaboration and dialogue around the need for data and the inclusion of pregnant and lactating individuals in clinical trials. Despite this collaboration, the two agencies have their own standards for the format and content of labeling for these populations. To understand these differences, the pregnancy and lactation labeling sections for 31 approved drugs were compared, and trends were assessed for use of language concordance and discordance related to use during pregnancy and lactation between the 2 agencies. Further analysis evaluated the presence of human data included in the labeling. The EMA and the FDA had high discordance between pregnancy and lactation labeling language, in 68% and 71% of labeling, respectively, and only 10% of pregnancy labeling and 16% of lactation labeling include human data. Concordance in labeling language is not the norm but occurs when there is a sizeable body of human data, animal data suggesting a particular safety issue, drug mechanism of action information, or disease-specific considerations. This study highlights the need for more human data to inform prescribing decisions in these populations. The results also suggest that there is an opportunity for alignment in labeling across regions.

Cross-Disciplinary Genomics Approaches to Studying Emerging Fungal Infections.

Emerging fungal pathogens pose a serious, global and growing threat to food supply systems, wild ecosystems, and human health. However, historic chronic underinvestment in their research has resulted in a limited understanding of their epidemiology relative to bacterial and viral pathogens. Therefore, the untargeted nature of genomics and, more widely, -omics approaches is particularly attractive in addressing the threats posed by and illuminating the biology of these pathogens. Typically, research into plant, human and wildlife mycoses have been largely separated, with limited dialogue between disciplines. However, many serious mycoses facing the world today have common traits irrespective of host species, such as plastic genomes; wide host ranges; large population sizes and an ability to persist outside the host. These commonalities mean that -omics approaches that have been productively applied in one sphere and may also provide important insights in others, where these approaches may have historically been underutilised. In this review, we consider the advances made with genomics approaches in the fields of plant pathology, human medicine and wildlife health and the progress made in linking genomes to other -omics datatypes and sets; we identify the current barriers to linking -omics approaches and how these are being underutilised in each field; and we consider how and which -omics methodologies it is most crucial to build capacity for in the near future.