Innovative approaches to COVID-19 medical countermeasure development.

BACKGROUND: The COVID-19 pandemic, while unfortunately notable for immense strain and death throughout the world, has also shown great promise in the development of medical countermeasures. As the global scientific community shifted almost entirely towards vaccines, diagnostics and therapeutics, new trial designs most significantly adaptive platform trials, began to be used with greater speed and broader reach. These designs allowed for deploying and investigating new therapeutics, repurposing currently existing therapeutics and flexibly removing or adding additional medications as data appeared in real-time. Moreover, public-private sector partnering occurred at a level not seen before, contributing greatly to the rapid development and deployment of vaccines. OBJECTIVES: To provide a brief overview of the advances in preventative and therapeutic medical countermeasure development for COVID-19. METHODS: A narrative review of relevant major medical countermeasure trials was conducted using the date range February 2020-December 2022, representing the period of greatest productivity in research to investigate COVID-19. RESULTS: Among the most influential trial designs are the adaptive platform designs, which have been applied to the development of initial COVID-19 antivirals, monoclonal antibodies, repurposing of existing immunomodulatory therapy and assisted in the disproof of ineffective medical therapies. Some of the most prominent examples include the REMAP-CAP, RECOVERY and TOGETHER trials. CONCLUSIONS: Adaptive platform trial designs hold great promise for utility in future pandemics and mass casualty events. Additionally, public-private sectoring is essential for rapid medical countermeasure development and should be further enhanced for future biopreparedness.

Exclusion of pregnant people from emergency vaccine clinical trials: A systematic review of clinical trial protocols and reporting from 2009 to 2019.

BACKGROUND: Existing ethics guidance and regulatory requirements emphasize the need for pregnancy-specific safety and efficacy data during the development of vaccines in health emergencies. Our objective was to conduct a systematic review of vaccine clinical trials during active epidemic periods. METHODS: We searched for Phase II and Phase III vaccine clinical trials initiated during the H1N1 influenza, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Zika, and Ebola virus disease (EVD) outbreaks from 2009 to 2019. Data were extracted from clinical trial protocols identified in the following registries: ClinicalTrials.gov, Pan African Clinical Trial Registry (PACTR), and all primary registries indicated by the World Health Organization's International Clinical Trials Registry Platform (ICTRP). Published studies from registered clinical trials were located through PubMed. Data was extracted on eligibility criteria and pregnancy outcomes. Data from this study is available in the Center for Open Science Data Repository: https://osf.io/nfk2p/?view_only=47deb3b206724af9b46c9c0c0083a267. RESULTS: We identified 96 vaccine clinical trial protocols and included 84 in analysis. 5 records were excluded in screening for irrelevant abstracts, 7 were excluded in full-text assessment (1 for a therapeutic drug trial, 3 for enrolling elderly adults only, 3 for enrolling children/adolescents only). There were no eligible trials for MERS-CoV or Zika virus vaccines. Overall, 8 protocols explicitly included pregnant people; of these, 3 were completed trials with published results. Incidental pregnancies and outcomes of pregnant participants were reported in 2 studies, 10 studies reported serious adverse events related to pregnancy without mentioning total incidental pregnancies. A total of 411 recorded pregnancy outcomes were reported, with 293 from the 3 pregnancy-eligible studies with results. 71 serious adverse events pertaining to pregnancy were reported from all clinical trials with results. CONCLUSION: Pregnant people are underrepresented in vaccine clinical trials conducted during outbreaks, resulting in underreporting of pregnancy-related outcomes and a lack of protection for pregnant people and neonates from infectious diseases.

US Hospital Capacity Managers' Experiences and Concerns Regarding Preparedness for Seasonal Influenza and Influenza-like Illness.

Importance: The 2017-2018 influenza season in the US was marked by a high severity of illness, wide geographic spread, and prolonged duration compared with recent previous seasons, resulting in increased strain throughout acute care hospital systems. Objective: To characterize self-reported experiences and views of hospital capacity managers regarding the 2017-2018 influenza season in the US. Design, Setting, and Participants: In this qualitative study, semistructured telephone interviews were conducted between April 2018 and January 2019 with a random sample of capacity management administrators responsible for throughput and hospital capacity at short-term, acute care hospitals throughout the US. Main Outcomes and Measures: Each participant's self-reported experiences and views regarding high patient volumes during the 2017-2018 influenza season, lessons learned, and the extent of hospitals' preparedness planning for future pandemic events. Interviews were recorded and transcribed and then analyzed using thematic content analysis. Outcomes included themes and subthemes. Results: A total of 53 key hospital capacity personnel at 53 hospitals throughout the US were interviewed; 39 (73.6%) were women, 48 (90.6%) had a nursing background, and 29 (54.7%) had been in the occupational role for more than 4 years. Participants' experiences were categorized into several domains: (1) perception of strain, (2) effects of influenza and influenza-like illness on staff and patient care, (3) immediate staffing and capacity responses to influenza and influenza-like illness, and (4) future staffing and capacity preparedness for influenza and influenza-like illness. Participants reported experiencing perceived strain associated with concerns about preparedness for seasonal influenza and influenza-like illness as well as concerns about staffing, patient care, and capacity, but future pandemic planning within hospitals was not reported as being a high priority. Conclusions and Relevance: The findings of this qualitative study suggest that during the 2017-2018 influenza season, there were systemic vulnerabilities as well as a lack of hospital preparedness planning for future pandemics at US hospitals. These issues should be addressed given the current coronavirus disease 2019 pandemic.

Design for Implementation of a System-Level ICU Pandemic Surge Staffing Plan.

BACKGROUND: The current coronavirus disease 2019 pandemic is causing significant strain on ICUs worldwide. Initial and subsequent regional surges are expected to persist for months and potentially beyond. As a result of this, as well as the fact that ICU provider staffing throughout the United States currently operate at or near capacity, the risk for severe and augmented disruption in delivery of care is very real. Thus, there is a pressing need for proactive planning for ICU staffing augmentation, which can be implemented in response to a local surge in ICU volumes. METHODS: We provide a description of the design, dissemination, and implementation of an ICU surge provider staffing algorithm, focusing on physicians, advanced practice providers, and certified registered nurse anesthetists at a system-wide level. RESULTS: The protocol was designed and implemented by the University of Pittsburgh Medical Center's Integrated ICU Service Center and was rolled out to the entire health system, a 40-hospital system spanning Pennsylvania, New York, and Maryland. Surge staffing models were developed using this framework to assure that local needs were balanced with system resource supply, with rapid enhancement and expansion of tele-ICU capabilities. CONCLUSIONS: The ICU pandemic surge staffing algorithm, using a tiered-provider strategy, was able to be used by hospitals ranging from rural community to tertiary/quaternary academic medical centers and adapted to meet specific needs rapidly. The concepts and general steps described herein may serve as a framework for hospital and other hospital systems to maintain staffing preparedness in the face of any form of acute patient volume surge.

Variation among state-level approaches to addressing alcohol abuse in opioid treatment programs.

In view of their role in licensing opioid treatment programs (OTPs), state opioid treatment authorities (SOTAs) are in a unique position to influence how OTPs address their patients' alcohol abuse. Using data from a telephone survey of SOTAs from the District of Columbia and states that have at least one OTP (n = 46), this study examines the extent to which SOTAs address alcohol abuse in their respective state policies and guidelines for OTPs. Findings indicate that 27 states have overall measures on how to address patients' problematic alcohol use, 23 states require or recommend alcohol education to be provided to all patients, and 17 states have stipulations that address specific actions to be taken if patients present at daily dosing under the influence of alcohol. Although SOTAs generally rate alcohol of at least moderate importance in formulating regulations, many of their policies and guidelines do not deal with various alcohol-related services and issues.