Building the ACTIV Virtual Biorepository: Reflections from the Researchers

Responding to the challenge of COVID-19

During the COVID-19 pandemic, the world experienced an unparalleled health challenge that required an accelerated and innovative research response. Investigators from across the globe began addressing the public health emergency, initiating groundbreaking research to find effective strategies to diagnose, prevent, and treat the dangerous and highly transmissible viral infection.

To better organize the initial collective research response, the National Institutes of Health (NIH) established the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership in the spring of 2020. This partnership designed and operationalized multiple adaptive master protocol driven clinical trials to test potential therapeutic agents for use against COVID-19. These trials were implemented at more than 620 trial sites across the U.S. and internationally.

Although there were promising results from many of the trials conducted, we lacked a streamlined process to centrally manage access to biospecimens collected from each individual trial to promote future research beyond the peak of the pandemic.  To address this concern, RTI played a significant role in the development and implementation of the ACTIV virtual biorepository. This exciting opportunity allowed us to leverage our internal expertise—including insight from researchers, systems architects, and software engineers—to deliver a platform that can have a tremendous impact as we continue to study COVID-19.

The ACTIV virtual biorepository is a key resource for investigators

As a part of the ACTIV public-private partnership, our team at RTI—in coordination with NIH—directed the design and development of a web system that provides an inventory of available biospecimens collected from the ACTIV clinical trials. During these trials, biospecimens were collected for testing; however, many of them were never used and are currently being stored in multiple physical repositories, leaving an excess of untouched specimens. The system—built by our experts—is a critical benchmark in the study of the SARS-CoV-2 virus.  It provides future researchers access to these biospecimens to explore the underlying mechanisms of COVID-19 as well as how the researched therapies work. Such work is critical for preparing for future outbreaks and developing better diagnostic and treatment strategies. 

To facilitate further investigations, researchers can now access the ACTIV Virtual Biorepository to explore and request available specimens to use in their own studies, jumpstarting future trials, and, hopefully, breakthroughs that assist clinical providers in delivering optimal care to patients impacted by COVID-19. We built this with the investigator in mind, ensuring that within the same system, they can easily search what is available and submit a research proposal requesting biospecimen access. Our emphasis is to guarantee that the samples are available for those who are interested. Through the system, investigators can link to instructions and information on how to apply to use the biospecimens. 

Available specimens from ACTIV therapeutic clinical trials     

The web-based virtual biorepository portal provides an easily searchable inventory the ACTIV therapeutic clinical trials that had remaining biospecimens available after trial completion. The inventory is categorized by therapeutic candidate, such as immune modulators, monoclonal antibodies (both in-patient and out-patient variety), antithrombotics, and other therapies. 

• ACTIV-1: Immune Modulators: Investigated immune modulators compounds built to minimize the adverse effects of an overactive immune response to COVID-19 infection.
• ACTIV-2: Outpatient Monoclonal Antibodies and Other Therapies: Investigated interventions that reduce the length of time a person has COVID-19 symptoms and increase the number of participants with undetectable virus.
• ACTIV-4: Antithrombotics and Other Therapies: Investigated interventions to reduce recovery time and improve recovery, including preventing clotting events.
• ACTIV-5: Big Effect Trial: Investigated interventions to improve outcomes in hospitalized adults.

Researchers studying the virus, its effects, and potential therapeutics will have access to biospecimens to accelerate their investigations and encourage discovery. The first biospecimens were made available in July 2023, with additional biospecimens being added as they become available.   

Building the ACTIV virtual biorepository web system from the ground up

Prior to the launch of the system, we worked with investigators and research collaborators from NIH as well as across the ACTIV trials to define system requirements that would allow for an effective, user-friendly research tool.  This included: (1) defining the data required to best characterize the available specimens and the trial participants from which they were collected, (2) discovery and reporting features to aid system users to understand and find available specimens, and (3) easy access to content required to inform research proposals. We also worked with the ACTIV investigators to understand the availability of residual biospecimens for inclusion in the virtual biorepository and gain access to clinical data repositories, and physical biorepository managers to establish linkages to their laboratory inventory management systems. 

The system launched with biospecimens from the ACTIV-4 trials. Incorporation of biospecimens from ACTIV-1 and ACTIV-2 trials is currently underway. As more specimens become available, our hope is that the suite can be widely disseminated, enhancing collaboration efforts to enable scientific progress. 

We have had many inquiries and look forward to more investigators requesting access to the system. Our team urges those interested to contact us to see what is available—maybe it can help spark ideas for future projects. With access to the portal, you can build your own biospecimen query based on biospecimen, trial, and participant-level characteristics and make corresponding biospecimen access requests. For example, you can indicate a specific type of blood from a specific type of participant and see what biospecimens are available that match your needs.  Such queries will allow you to determine if there are sufficient biospecimens available to answer your research question of interest.

A lot of time, effort, and energy was put into this project, and there is still so much on the horizon. We are thrilled to have been a part of this initiative to enhance collaboration and bring the biorepository to others to utilize. What’s next for this system and others? The sky is the limit. The framework can be modeled for other studies, and although it takes coordination, this project shows that it is achievable.  

To learn more about the virtual biorepository or to request access for your own research efforts, visit the https://activ-biorep.org/ or email our team at activ-biorep@rti.org. 

Biorepository supports open science initiative

The ACTIV virtual biorepository promotes a critical component when conducting public health research—collaboration. Making science more equitable and accessible can foster growth and discovery, which is vital when addressing serious public health challenges such as COVID-19. It also is one of the main goals of Open Science, which the White House Office of Science Technology Policy (OSTP) identified as a key research priority moving forward. 

Given the COVID-19 research that RTI has done with funding from the NIH—including the Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies (CONNECTS) project, an initiative led by the National Heart, Lung, and Blood Institute (NHLBI)—we were called upon for our expertise to serve the ACTIV Virtual Biorepository.