How can we improve blood transfusion practices?

Challenge

Approximately 4.5 million patients a year in the U.S. and Canada receive blood transfusions. But how safe is the blood supply from emerging diseases and can transfusion outcomes be optimized so they can more effectively benefit patients across the lifespan? These are among the questions Westat is answering for the National Heart, Lung, and Blood Institute (NHLBI) as we conduct the 4th iteration of the Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P) program. This program continues to study the links between blood donor, component characteristics, and recipient outcomes, with an increased focus on pediatric populations. It is the first time that pediatric transfusion medicine and the epidemiology of children receiving transfusions have a preeminent focus in the REDS program.

This far-reaching program also includes a transfusion safety research program in Brazil that addresses scientific questions on the safety and adequacy of the blood supply in that country. It extends the Brazilian sickle cell disease cohort that was established in REDS-III to additional pediatric populations and new nested studies. Additionally, the Brazil program will continue monitoring for emerging viral threats to the blood supply, such as Zika, chikungunya, and dengue.

For this work, Westat serves as the Data Coordinating Center (DCC), managing and analyzing data from 4 research hubs and 22 hospitals in 4 dispersed U.S. regions and analyzing data from 6 blood centers in Brazil.

Solution

A project of this size demands extraordinary coordination, cutting-edge “big data” management solutions, expert statistical and analytic methods, and innovative IT support. Westat began work designing and implementing REDS-IV-P study protocols, then developing operations and research protocol manuals, study materials, and advanced data and specimen collection systems.

The complexity of the next task cannot be understated—the collection and harmonization of over 2 billion pieces of data for cumulative, centralized, linked “vein to vein” databases representing donors, donations, blood components, transfusion recipients and non-recipient patients, along with their clinical outcomes.

Our cloud-based Research Data Warehouse (RDW) houses electronic health record (EHR) data of 1.3 million patients from the 22 hospitals, 2.3 million blood donors, and 8 million blood products from the 4 blood centers, and (for some of the multisite studies) omics data on donor and recipient samples using a customized genotype array. Data are sent to Westat through our automated secure data pipeline, then stored on the Amazon Web Services (AWS) cloud and harmonized using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). OMOP allows for comparison across disparate observational data sources and transforms the data into a common data model to aid analysis. This means we can more easily compare data across studies and develop analytic datasets to investigate a variety of research priorities in transfusion medicine.

Then we analyze large data files, processed on a high-performing Linux server, applying advanced “big data” statistical and analytic methods to answer research questions about blood banking, transfusion medicine, and blood safety. Our partners in this effort are the Children’s National Medical Center and the DARTNet Institute. 

Within the REDS program’s infrastructure is a rapid research response capability to address emerging threats to the blood supply during pandemics, such as SARS-CoV-2 or outbreaks of arboviruses, such as Zika, chikungunya, and dengue. When COVID-19 shut down the U.S. in 2020, fears about the safety of the blood supply surfaced. Because of the REDS program’s rapid research response capability, Westat was able to quickly determine that SARS-CoV-2 did not pose a threat to blood recipients.

In addition to data collection, data analysis, and dissemination of findings, Westat also maintains a public-facing and private website, the latter for investigators. Further, we coordinate the collection and shipping of biospecimens that go into a central repository. Westat manages and supports all aspects of program governance and operations to ensure procedures are streamlined, efficient, and effective program-wide. We serve on the Executive Committee, Steering Committees, Publications Committee, and manage over 25 additional committees and working groups to achieve programmatic goals and implement specific research projects and analyses.

Results

The REDS-IV-P program enables large amounts of blood donation and donor epidemiology data to be combined in an effort to understand adverse outcomes, how to eliminate risk factors, and how to safeguard and optimize transfusion therapies across the lifespan.

REDS-IV-P will also continue to evaluate and improve the safety and availability of the nation’s blood supply, and with its rapid response capabilities, quickly address emerging pathogens that could threaten it.

Our construction of “vein to vein” databases will allow outside investigators to rapidly address key research questions regarding transfusion medicine and provide critical knowledge to practitioners to inform blood policy decisions for adult patients as well as for neonates, children, pregnant women, and other understudied patient populations.

Westat is looking at adding novel statistical methods to control for independent variables to determine true causal associations related to health outcomes, and we’re also working to translate and build tables for transfusion data within the OMOP common data model. This will result in a public dataset and other databases that investigators can easily access to obtain vast amounts of valuable data.