key: cord-0968609-gkrgg9o3 authors: Senefeld, J. W.; Johnson, P. W.; Kunze, K. L.; van Helmond, N.; Klassen, S. A.; Wiggins, C. C.; Bruno, K. A.; Golafshar, M. A.; Petersen, M. M.; Buras, M. R.; Klompas, A. M.; Sexton, M. A.; Diaz Soto, J. C.; Baker, S. E.; Shepherd, J. R. A.; Verdun, N. C.; Marks, P.; van Buskirk, C. M.; Winters, J. L.; Stubbs, J. R.; Rea, R. F.; Herasevich, V.; Whelan, E. R.; Clayburn, A. J.; Larson, K. F.; Ripoll, J. G.; Andersen, K. J.; Vogt, M. N. P.; Dennis, J. J.; Regimbal, R. J.; Bauer, P. R.; Blair, J. E.; Wright, K.; Greenshields, J. T.; Paneth, N. S.; Fairweather, D.; Wright, R. S.; Casadevall, A.; Ca, title: Program and patient characteristics for the United States Expanded Access Program to COVID-19 convalescent plasma date: 2021-04-11 journal: medRxiv : the preprint server for health sciences DOI: 10.1101/2021.04.08.21255115 sha: 19125e9b1e881520f3fcd37bfcf71a446d30f0f7 doc_id: 968609 cord_uid: gkrgg9o3 Background The United States (US) Expanded Access Program (EAP) to COVID-19 convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19). While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents particularly for vulnerable racial and ethnic minority populations who were disproportionately affected by the pandemic. The objective of this study is to report on the demographic, geographic, and chronological access to COVID 19 convalescent plasma in the US via the EAP. Methods and findings Mayo Clinic served as the central IRB for all participating facilities and any US physician could participate as local physician-principal investigator. Registration occurred through the EAP central website. Blood banks rapidly developed logistics to provide convalescent plasma to hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal trends in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate on a state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions as well as assessing enrollment in metropolitan and less populated areas which did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. A majority of patients were older than 60 years of age (57.8%), male (58.4%), and overweight or obese (83.8%). There was substantial inclusion of minorities and underserved populations, including 46.4% of patients with a race other than White, and 37.2% of patients were of Hispanic ethnicity. Severe or life-threatening COVID-19 was present in 61.8% of patients and 18.9% of patients were mechanically ventilated at time of convalescent plasma infusion. Chronologically and geographically, increases in enrollment in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled patients in the EAP, including both in metropolitan and less populated areas. Conclusions The EAP successfully provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The efficient study design of the EAP may serve as an example framework for future efforts when broad access to a treatment is needed in response to a dynamic disease affecting demographic groups and areas historically underrepresented in clinical studies. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-24 threatening COVID-19 were enrolled in the EAP. A majority of patients were older than 25 60 years of age (57.8%), male (58.4%), and overweight or obese (83.8%). There was 26 substantial inclusion of minorities and underserved populations, including 46.4% of 27 patients with a race other than White, and 37.2% of patients were of Hispanic ethnicity. 28 Severe or life-threatening COVID-19 was present in 61.8% of patients and 18.9% of 29 patients were mechanically ventilated at time of convalescent plasma infusion. 30 Chronologically and geographically, increases in enrollment in the EAP closely followed to support the study infrastructure and study-related costs at participating sites was Patients were eligible for enrollment in the EAP if they were: aged 18 years or older, 102 hospitalized with a laboratory confirmed diagnosis of or suspected/probable infection with 103 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and either had or were 104 judged by a healthcare provider to be at high risk of progression to severe or life-105 threatening COVID-19. Severe COVID-19 was defined by one or more of the following: 106 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 11, 2021. ; https://doi.org/10.1101/2021.04.08.21255115 doi: medRxiv preprint dyspnea, respiratory frequency ≥ 30/min, blood oxygen saturation ≤ 93%, partial pressure 107 of arterial oxygen to fraction of inspired oxygen ratio < 300, lung infiltrates > 50% within 108 24 to 48 hours of hospital admission. Life-threatening COVID-19 was defined as one or 109 more of the following: respiratory failure, septic shock, and multiple organ dysfunction or A single consent form, available in eight languages, was used by all participating sites. Informed consent was obtained from the patient or a legally authorized representative 120 prior to enrollment, except for patients in whom an emergency consent was utilized. The database was updated as needed to fulfill the requirements of the EAP IRB and data 139 collection requirements of BARDA. As the original goal of data collection was to determine 140 safety, updates were needed to capture additional data as enrollment expanded and the 141 study progressed. Enrollment into the EAP was stopped after the FDA issued an In order to contextualize whether the patients enrolled in the EAP were reflective of the 149 US population, race and ethnicity data of each state and US territories were retrieved 150 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 11, 2021. ; https://doi.org/10.1101/2021.04.08.21255115 doi: medRxiv preprint patterns, these averages were scaled between 0 (lowest cases/enrollments) and 1 (peak 174 cases/enrollments) and overlaid on a geo-faceted graph. The geo-faceted graph contains Table 1 . A majority of patients 194 were older than 60 years of age (57.8%), male (58.4%), overweight or obese (83.8%), 195 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 11, 2021. ; https://doi.org/10.1101/2021.04.08.21255115 doi: medRxiv preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Patients were enrolled by 12,879 healthcare providers from 2,722 hospitals and acute (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 11, 2021. ; https://doi.org/10.1101/2021.04.08.21255115 doi: medRxiv preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 11, 2021. ; (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 11, 2021. ; https://doi.org/10.1101/2021.04.08.21255115 doi: medRxiv preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 11, 2021. ; https://doi.org/10.1101/2021.04.08.21255115 doi: medRxiv preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Implications for future pandemics 341 The success of the EAP in providing rapid access to convalescent plasma in metropolitan 342 and regional areas of the US that might not otherwise have had access to therapy 343 provides a framework for future efforts when broad access to a treatment is needed in 344 response to an infectious disease outbreak. In this regard it is noteworthy that given that (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. the US, unavailable data due to abridged data collection forms, and missing data due to 370 the nature of a national registry. Additionally, the EAP was designed to provide access to 371 convalescent plasma at hospitals and acute care facilities that were not already part of a 372 clinical trial or did not have the infrastructure to support complex clinical trials. This registry 373 also did not require training of the local investigators or study team members. The design 374 of this national registry provided widespread access to convalescent plasma and easy to 375 complete data collection forms during a worldwide pandemic. This pragmatic approach 376 did not ensure the highest quality of data nor completeness of data. The EAP provided rapid and broad access to convalescent plasma throughout the US 379 and some US territories and was effective at providing therapy for demographic groups 380 that were severely affected by COVID-19. Over time, the EAP provided access to 381 convalescent plasma in response to sudden and exponential changes in SARS-CoV-2 382 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. plasma was generally safe [20, 21] and provided key efficacy data that were an important (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 11, 2021. ; https://doi.org/10.1101/2021.04.08.21255115 doi: medRxiv preprint COVID-19 in the USA: a question of time Prevalence of Asymptomatic SARS-CoV-2 Infection : A 433 Narrative Review 437 et al. Presenting Characteristics, Comorbidities, and Outcomes Among Hospitalized With COVID-19 in the New York City Area Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US Safety Update: COVID-19 Convalescent Plasma in 20,000 Hospitalized Patients PubMed Central PMCID: PMCPMC7368917. 509 21 Early safety indicators of COVID-19 convalescent plasma in 5000 patients US Food and Drug Administration. Code of Federal Regulations Title The REDCap 518 consortium: Building an international community of software platform partners Research 522 electronic data capture (REDCap)--a metadata-driven methodology and workflow 523 process for providing translational research informatics support No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity American Hospital Directory. Hospital Profiles No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity Systems/Downloadable-Public-Use-Files/Provider-of-Services Letter of authorization Silver Spring: US Food & Drug Administration Characteristics and Clinical Outcomes of Adult Patients Hospitalized with COVID-19 PubMed 549 Central PMCID: PMCPMC7737948 Journal Editors form for disclosure of potential 550 conflicts of interest. James M. Blum reports personal fees from Clew Medical, outside the 551 submitted work. No other potential conflicts of interest were disclosed Characteristics of Hospitalized Adults 553 Hospitalization and Mortality 558 among Black Patients and White Patients with Covid-19. The New England journal of 559 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. entities approved 1995-1999 Administration UFaD. CLINICAL MEMORANDUM -COVID-19 Convalescent Rojek AM, Horby PW. Modernising epidemic science: enabling patient-centred 591 research during epidemics Supplemental Table 1. Characteristics of acute care facilities and hospitals that enrolled patients 597 with COVID-19 in the US Expanded Access Program to convalescent plasma All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.