Philadelphia — Rutgers researchers made a startling discovery as the pandemic reduced routine doctor visits: Going virtual to test cutting-edge therapies to reach more and diverse patients.
Clinical trials test the efficacy and safety of new drugs or instruments. However, the vast majority of these trials do not include participants representing the United States. According to the American Association of Medical Colleges, African-American patients make up, on average, only 5 percent of clinical trial participants nationally.
Rutgers’ remote experiment with COVID-19 treatments broke down logistical barriers by allowing people to check their symptoms and register through online portals. Trials often require participants to visit doctors regularly for blood draws and check-ups. These visits can last for hours in the middle of a workday and be inaccessible to people who cannot take time off work or lack transportation or child care.
The pandemic has shown why the change is necessary: Moderna reformulated its vaccine trials after the survey of the initial group of participants lacked African Americans and Latinos. The Philadelphia research centers are leading the way in creating more equitable clinical trials to address deep racial disparities in the American health care system. Rutgers, the University of Pennsylvania, and the Fox Chase Cancer Center are among the institutions that are addressing other entrenched challenges, such as racism, mistrust of medicine, and inappropriate community connections.
“The landscape of research and clinical trial participation is radically different than it was before Covid,” said Reynold Panettieri, director of the Rutgers Institute for Translational Science and Medicine.
Research has found that social determinants of health, such as racism, stress, food insecurity, and neighborhood safety, are the top reasons people of color experience more serious illness compared to whites. Genetics can also affect a person’s response to certain cancer treatments.
“You can’t say you have a new drug and it works all over the world,” said Carmen Guerra, associate director of diversity and outreach at the University of Pennsylvania Abramson Cancer Center. “This leaves primary care physicians and oncologists in a difficult position when trying to treat a cancer patient who is African American or Latino.”
For example, a drug used to treat leukemia can be toxic to patients who have a specific genetic mutation because it slows metabolism and allows dangerous ingredients to remain in the body. The mutation turns out to be more common among African-American patients, she said. The only way to know if patients also respond differently to new therapies is to include a wide range of patients in the studies.
The stakes are personal for Anita Conner and her daughter, Kerri Conner Matchett, both certified public accountants who were diagnosed with breast cancer a decade apart.
When Conner found out she had advanced breast cancer in 1998, it would never have occurred to her to ask about a clinical trial.
Conner, now 65 and living in Jenkintown, said she didn’t know much about breast cancer and didn’t know anyone who had it. She is grateful that her doctor suggested a clinical trial.
“We don’t talk about it in our community,” said Conner, who is black.
Early in the pandemic, the US Food and Drug Administration gave the green light to ongoing trials to allow remote participation when possible, a protocol change that often requires extensive review.
Rutgers went a step further by making its new COVID-19 clinical trials fully remote. This approach attracted a more diverse patient population—30 percent of participants were people of color—and allowed researchers to reach out to a broader geographic area and fill seats more quickly, because it was much easier to participate, Panettieri said.
“In a way, it’s always been done at the convenience of the researcher, rather than the patient,” he said of trials.
Decentralized trials that developed out of necessity during the pandemic could lead to a new norm for hybrid trials that include in-person and remote participation, Esther Krofah, executive director of the Milken Institute Center for Public Health, wrote last summer in Health Affairs.
“This year has been the time to reflect on the changes made to the clinical trial business in response to the COVID-19 pandemic and to consider more purposefully how the system should be redesigned,” Krofah wrote in a co-authored article. other former executives from the pharmaceutical sector.
Clinical trials usually require participants who do not have other health problems that could influence the effectiveness of the treatment, or whose disease has not progressed to an advanced stage. This may exclude people of color, who are more likely to have multiple chronic conditions.
In addition, doctors are less likely to recommend clinical trials to African-American and Latino patients, who they assume won’t be eligible, Guerra found in research to be published in June in the Journal of Clinical Oncology.
“These unconscious biases really underestimate the fact that individuals would want to participate if it was offered to them,” he said.
He offered a solution: rules for when in the treatment process doctors should talk to patients about participating in trials.
There are other ways to make clinical trials easier for patients, especially people of color, said Elizabeth Plimack, deputy director of the Fox Chase Cancer Center.
For example, cancer trials tend to overuse placebo, that is, with some participants receiving the new treatment and others receiving the current standard of care, he said. This uncertainty can put off those who are already wary of being part of a medical experiment, she said.
In many cases, the placebo is not needed to prove the effectiveness of cancer treatments. And when it is, the study protocol could then tell patients which group they were in.
“There’s a 50 percent chance that you’ll get there and get an IV of saline,” Plimack said of studies using placebo. “I think we can make trials better for patients.”
Another entrenched obstacle to clinical trial diversity is mistrust in medicine, rooted in a history of medical experimentation in marginalized communities and racism in health care. People repeatedly tell Guerra that they don’t want to be “guinea pigs” and “test subjects.”
“There is a spectrum of trust and you have to earn it,” he said.
That starts by validating the fear and mistrust that people may have about clinical trials.
When Guerra speaks to communities about clinical trials, his presentation includes slides about Pennsylvania dermatologist Albert Kligman’s experiments with inmates at Philadelphia’s Holmesburg Prison between 1951 and 1974. He shows photos of the men with patches of skin missing in the back. He then discusses how medical research policies have changed to ensure that unethical experiments never occur again.
Guerra runs an “ambassador” program that trains former patients, study participants, and family members to connect with underrepresented patient communities.
Conner and her daughter participate in a similar ambassador program at the Fox Chase Cancer Center.
They go to churches and share their personal stories through the nonprofit they created, Praise Is the Cure, to help people feel comfortable asking questions they might not want to ask doctors.
Matchett, now 47, underwent a double mastectomy in 2008 to treat her aggressive type of cancer. At that time, she was 33 years old and had a two-year-old daughter. Nearly a decade later, the cancer recurred in her lungs, and in 2020, she spread to her spine.
Matchett’s first reaction was tears, then gratitude to her mother, whose participation in a clinical trial helped doctors learn more about how to treat the next generation of breast cancer patients.
“There was no way I could go through all the treatment procedures my mother did,” Matchett recalls. “And the doctor told me, ‘You won’t have to do any of that because of all the advances.’
Matchett now has three children, ages 16, 11 and 10, who she says have never known a mother without cancer.
Matchett and her doctors are exploring clinical trial options in addition to chemotherapy, because she wants her children to see her resilience and her determination to help herself and others, like her mother did.