The COVID-19 pandemic provides a narrow but critical window of time for researchers. As investigators try to understand the disease and safe and effective treatments, they must ensure study coordination, interoperable study questions, and most of all clear communication about the trials to potential participants.
The Brigham’s Multi-Regional Clinical Trials (MRCT) Center’s response to these problems has been to develop informative materials for the public to help them understand what it means to participate in this research and to promote global collaboration among COVID-19 clinical trial sites.
The MRCT Center strives to identify challenges and provide ethical, practical, and actionable solutions for global clinical trials while increasing transparency and safety for participants. The MRCT Center developed a series of COVID-19 research flyers to provide foundational knowledge to patients considering participating in research. The information provided, written with clear health literacy principles, describes the complex world of clinical trials. Further, in collaboration with Johns Hopkins University, the MRCT Center developed the COVID-19 Collaboration Platform to encourage investigators around the world to share protocols and aggregate data to increase the speed and reliability of high-quality evidence for the benefit of patients.
A Ray of Hope
Coming to terms with a diagnosis of COVID-19 while stuck in an isolation room away from loved ones is a stressful situation. No matter their background or level of understanding of the disease, patients may have questions about their health while also struggling with fear and loneliness. Even more questions arise if they are asked to participate in clinical trials. That’s why the MRCT Center focused on developing health literate materials to help patients figure out the right questions to ask regarding participation in COVID-19 research.
“It’s important for individuals to know what to ask about before agreeing to be a clinical trial participant,” said Barbara Bierer, MD, faculty director of the MRCT Center. “ ‘Can I withdraw? What happens if I get injured? What happens to my data? What are the alternatives?’ If you’ve never been exposed to research and suddenly you’re sick and asked to participate, you may feel like you don’t have a choice. We wanted to provide an understandable resource to help individuals ask their questions and know that they have a voice.”
MRCT Center research flyers are informational handouts written for patients, friends and family members, health proxies, parents and guardians, and children. They were developed with input from the Patient and Family Advisory Committee at the Brigham to serve as a friendly guide into the world of research as potential participants and their loved ones struggle with the complex decisions surrounding clinical trials.
“Research opportunities can present a ray of hope to someone who is very sick,” said Sylvia Baedorf Kassis, MPH, CYT, a program manager at the MRCT Center. “We can harness that hope in the relationship we build with the patients and create a positive research experience, which is our ultimate goal.”
An independent Institutional Review Board and multiple academic IRBs deemed that the MRCT Center COVID-19 clinical research (“Should I join…?”) flyers, developed with Harvard Catalyst, are general informational brochures for participants that do not need additional IRB review. The flyers have been distributed to a wide range of organizations that the Center works with and have received interest from pharmaceutical companies, academic centers, investigators, and research communities who wish to adapt the flyers for their own use. The Center is responsive to any feedback on the flyers and is open to improving them based on suggestions.
The flyers have been translated into Spanish with the goal of translating them into other languages to increase accessibility for non-English speakers. The translation work is being pursued in collaboration with the COVID-19 Health Literacy Project, which focuses on providing fact sheets to help educate patients from under-resourced and underserved communities. Through this project and with the original COVID-19 research flyers, the MRCT Center continues to provide understandable materials and education for patients.
Collaboration is Key
In addition to the research flyers, Bierer and her colleagues at the MRCT Center are collaborating with Johns Hopkins University on the COVID-19 Collaboration Platform, a platform that emphasizes the importance of sharing protocols for and data from clinical trials. As the pandemic continues, more trials are being initiated each day, and many of them ask similar questions. Instead, collaborating on protocols, combining data and aggregating evidence would increase efficiency and reliability of the results, providing critical information to improve treatment and prevention.
“The pandemic struck quickly; we weren’t prepared for a coordinated response to a pandemic in the United States,” said Bierer. “We saw a proliferation of trials initiated in the U.S.; often many of those were small and single site studies, underpowered due to limited numbers of patients. Further, just as in China and Italy and other places, the infection—thankfully—waned before the requisite number of patients could be enrolled. It would be so much better and effective if we could coordinate multi-site trials.”
The COVID-19 Collaboration Platform team aims to build enthusiasm for posting and sharing protocols that are open for collaboration. One of the challenges is streamlining data standards, definitions, and collection. If different clinical trials use different measures to track symptoms or outcomes of an intervention, it can be difficult to combine the data for analysis. The COVID-19 Collaboration platform is designed to permit downloadable protocols to create multisite trials and support collaboration, to gather as much data as possible using similar data standards, and to assist with analyzing data across studies of similar interventions.
The COVID-19 Collaboration Platform provides necessary infrastructure for clinical trials and encourages scientific communication on a global scale. It aligns with the goals of the MRCT Center to create long-term solutions with real-world practicality and to promote collaboration among multi-regional trials.
Harmonization Across Regions
In addition to its COVID-19 response, the MRCT Center continues to work on several projects that align with its mission of providing ethical solutions to global problems in research. The Center collaborates with multi-stakeholder groups that include pharmaceutical and biotech companies, government organizations, academia, nonprofits, and patient advocates, involving them in the process of identifying issues, understanding the problem, and designing a solution.
One of the projects examines the ethical, regulatory, and practical barriers to conducting global pediatric clinical trials. For many diseases, including COVID-19, there has been less of a focus on research in pediatrics.
“Clinical trials in pediatrics are important because children respond differently to treatments than adults. If pediatric research is not done, clinicians are forced to extrapolate results from adult trials for children,” said Sarah White, MPH, Executive Director of the MRCT Center. “We want to work with representatives across different countries and regions, including those areas that don’t have any pediatric regulations, to reach a harmonized approach to promote research in children.
The MRCT Center promotes global regulatory engagement, working with different groups to solve research problems around the world. The Center involves stakeholder groups, listening to their goals and collaborating with them to make the necessary changes from within. In this way, the MRCT Center plays an invisible role, partnering with stakeholders to help them achieve change and improvement in clinical research.
While the MRCT provided a quick response to COVID-19 with the Collaboration Platform and the research flyers, the Center’s leadership is considering what the pandemic might mean for clinical research in general.
“Across the world, research was shut down due to COVID-19,” said White. “In the case of global clinical trials, each country might have approached the pandemic differently, which could have consequences for the overall study data integrity. Now, as research studies start back up, the MRCT Center is addressing how the clinical research will reopen. “We’re thinking about how to improve global harmonization and how to maintain flexibilities that benefit study participants.”