Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study
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Abstract
The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (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 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. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma.
Methods and findings
Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician–principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had—or were at risk of progression to—severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns 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 at the 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 areas and less populated areas that 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. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects.
Conclusions
These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease.
Trial registration
ClinicalTrials.gov NCT#: NCT04338360 .
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SciScore for 10.1101/2021.04.08.21255115: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The Mayo Clinic Institutional Review Board (IRB), the central IRB for the registry, approved the protocol (IRB #20-0033412, NCT#: NCT04338360), all amendments, and provided regulatory oversight for all sites and investigators.
Consent: A single consent form, available in eight languages, was used by all participating sites.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable To maximize access to COVID-19 convalescent plasma, no exclusion criteria were used, thereby, enabling access to vulnerable adult populations who may not be eligible for clinical trials, including pregnant women and prisoners. Table 2: …
SciScore for 10.1101/2021.04.08.21255115: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The Mayo Clinic Institutional Review Board (IRB), the central IRB for the registry, approved the protocol (IRB #20-0033412, NCT#: NCT04338360), all amendments, and provided regulatory oversight for all sites and investigators.
Consent: A single consent form, available in eight languages, was used by all participating sites.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable To maximize access to COVID-19 convalescent plasma, no exclusion criteria were used, thereby, enabling access to vulnerable adult populations who may not be eligible for clinical trials, including pregnant women and prisoners. Table 2: Resources
Software and Algorithms Sentences Resources Study data: Demographic and clinical characteristics of enrolled patients were collected using the Research Electronic Data Capture system (REDCap, v.9.1.15 – v10.0.33 Vanderbilt University, Nashville, TN) [24, 25]. REDCapsuggested: (REDCap, RRID:SCR_003445)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations: Numerous challenges were encountered during the development and implementation of this national registry. Given the constraints on health care resources during the COVID-19 pandemic [42], this national registry used a modern design with creative solutions to overcome the epidemiological and contextual challenges of the pandemic [43]. These creative solutions included a central academic IRB for oversight, streamlined registration for sites and physicians, simple online data collection forms, robust support center accessible via email or telephone, limited patient exclusion criteria, limited restrictions on concomitant therapies, and no initiation or monitoring site visits. Several important limitations resulted from this design, however, including adjustments in required data collection elements which were inversely related to the number of cases of COVID-19 in the US, unavailable data due to abridged data collection forms, and missing data due to the nature of a national registry. Additionally, the EAP was designed to provide access to convalescent plasma at hospitals and acute care facilities that were not already part of a clinical trial or did not have the infrastructure to support complex clinical trials. This registry also did not require training of the local investigators or study team members. The design of this national registry provided widespread access to convalescent plasma and easy to complete data collection forms during a worldwide pandemic. This ...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04338360 Approved for marketing Expanded Access to Convalescent Plasma for the Treatment of … Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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