Clinical trials are an integral process for drug development and have allowed the scientific community to make smart, calculated and groundbreaking improvements for all patient communities. However, representation in clinical trials does not accurately reflect the people we live amongst. Almost 40% of the U.S. population identify as part of a minority group, however, only about 17% of clinical trial participants are from minority groups.1,2 Although this has unfortunately been prevalent in the scientific community for years, COVID-19 brought the opportunity to change the way underserved communities are included in all clinical research, which must continue as we begin to move past the pandemic.
“A healthcare crisis can be devastating, but it’s also an opportunity to advance clinical research and improve how we deliver therapies to all who need them,” said Dr. Shalini Mohan, Head of Health Equity & Inclusive Research, U.S. Medical Affairs at Genentech. This, she said, was a key goal of Genentech’s Phase III study evaluating a treatment in COVID-19 – called EMPACTA – which was designed and developed in just two weeks in April 2020. EMPACTA was the first global Phase III trial at Roche and Genentech to focus on enrolling largely underserved and minority patients.
Dr. Jamie Freedman, Head of U.S. Medical Affairs at Genentech, said he considers the EMPACTA study a pivotal moment in the history of clinical trial research. “Early on in the pandemic, the number of hospitalized COVID-19 cases in New York City were skyrocketing and the hospitals couldn’t keep up with the number of admissions. Simultaneously our Health Outcomes research group generated electronic medical record data in collaboration with IBM, in which there was a strong signal in the first few hundred U.S. participants that Black patients were disproportionately being hospitalized compared to White patients.”
“If there was ever a time for an inclusive clinical trial, this was it, because while a pandemic is essentially an equal opportunity infector, it was very clear in 2020 there was a disproportionate impact on certain populations, and inequitable access to care,” Dr. Mohan said. “COVID-19 clinical trials should have had broad representation. If half of the population isn’t represented in the data, then we don’t know if the therapy will work for them,” she said. “That was the problem statement that informed EMPACTA.”
The concept of “inequitable access” was playing out in the most brutal of terms at hospitals like NYC Health and Hospitals-Elmhurst in Queens, New York, where infectious disease specialist Dr. Carlos Salama has practiced for 25 years.
“Here at Elmhurst, we serve an ethnically diverse, low-income population,” he said. “This is our community, and as a public hospital we are committed to providing all of our patients with quality healthcare.”
“It was the perfect storm,” Dr. Salama said. “We went from 12 people on ventilators to 150 people on ventilators seemingly overnight.”
“These are also people who typically work low-wage jobs, so they had no choice but to go back to work, and if they became ill, they had no choice but to return to their apartments, which they shared with a lot of other people. Subsequently, everyone in that apartment would also get sick. I can only describe it as an almost unstoppable, deadly force on our community.”
Dr. Freedman said, “I remember spending Friday evening on the day I learned about Black patients impacted by COVID-19 from our real world research and reaching out to the Genentech New York Medical Science Liaison (MSL) and Managed Care Liaison (MCL) who were the main contacts at all inner city hospitals managing hospitalized COVID-19 patients. The next morning, on Saturday, I called Dr. Salama and other NYC community-based doctors who confirmed their hospitalized patient populations were generally underserved and underrepresented minorities without access to clinical trials for new COVID-19 medicines. They were all interested in a clinical trial. Then I asked my team, including Dr. Mohan, to organize a U.S.-wide underserved, community-based trial, starting in New York with hospitals in the Bronx and Queens. That was the birth of EMPACTA.”
According to Dr. Salama, “A week later, I got a call back from the Genentech team and they said, ‘Let’s do it.’ Genentech asked me to be the lead investigator and to help work with other Genentech-identified investigators and sites. Genentech requested input on the study design from me and the other New York community hospital investigators and they just ran with it. I really felt I was working with a company that genuinely wanted to do the right thing for a population that was being devastated by this disease.”
The Genentech team, which included nearly two dozen employees located in various locations across the country and representing an array of professional and educational backgrounds, gathered over a weekend and finalized the trial protocol by Sunday night. “We worked with an extreme sense of urgency because of the severity of the pandemic during the first wave of COVID-19 that resulted in a ventilator capacity crisis in some areas of the country like New York,” said Dr. Mohan. The team accomplished this by designing a relatively simple protocol with an objective primary endpoint looking at the rate of progression from hospitalization to mechanical ventilation that differed from more complex endpoints used in other COVID-19 studies. By putting the patient at the center of the study with more flexible eligibility criteria, a protocol was created that could be implemented by community hospitals that had less experience working with pharmaceutical sponsors than the typical large academic medical centers.
Dr. Freedman said, “One reason this trial was so groundbreaking is that clinical trials rarely enroll these kinds of patients. Pharmaceutical companies typically go to large academic institutions to run trials because they are very familiar with them and have used them over and over, but that doesn’t mean community-based hospitals cannot also enroll patients and deliver the same high-quality data. In fact, EMPACTA showed this was true and the end results stood up to peer review by a top-tier medical journal, New England Journal of Medicine. This reinforced that community hospitals could be part of larger trials, and also opened the door to running more inclusive research trials for other medications and indications.”
The EMPACTA trial ultimately recruited nearly 400 patients in the U.S. as well as South America and Africa in less than one month. More than half were Hispanic or Latino, about 15% were Black, and about 13% were American Indian or Alaskan Native. Overall, about 85% of enrolled patients were in a minority racial or ethnic group, and the enrollment was completed in only 10 weeks.3
According to both Dr. Mohan and Dr. Salama, the pandemic provided a once-in-a-lifetime learning opportunity and the chance, as Dr. Mohan said, “To put the concepts of health equity and inclusive research into action when and where it was needed.”
“For example, what do we even mean when we use the words ‘unconscious bias?’” Dr. Mohan said. “Most of us have a sense of what we think it means but sometimes it’s hard to see how it impacts our own actions and reactions to patients. In investigators’ minds, they might be unconsciously evaluating whether a person will be a ‘good’ participant in a trial. They’re asking themselves, ‘Will this person be compliant? Will they let me draw blood?’ That is actually a form of bias. What EMPACTA enabled us to do was have open conversations about many of the obvious and subtle issues that can stand in the way of inclusive research.”
As groundbreaking as EMPACTA was relative to advancing the understanding of a potential COVID-19 treatment and creating a new paradigm for treating patients typically overlooked in clinical research, perhaps the study’s most important impact is how it can inform future clinical trials and opens a window into a future where clinical research is truly inclusive and reflective of the world’s population, thus resulting in more robust data for new treatments. It’s an idea that informs how Dr. Mohan, Dr. Freedman and Dr. Salama now approach their work.