Addressing disparities in clinical research starts with trust
There is no health without health equity
Yale School of Medicine and Yale New Haven Hospital are part of the Phase 3 Pfizer COVID-19 vaccine trial, one of the groundbreaking studies undertaken in the hopes of finding the most scientifically validated vaccine in the shortest amount of time. However the trial almost didn’t happen at Yale New Haven Hospital. At the time the trial sites were being chosen, Connecticut did not have a high number of COVID-19 infections, a factor in deciding where these vaccine trials take place. However, New Haven is home to The Cultural Ambassadors, a program 11 years in the making that would land the hospital a coveted spot in the trial and drive its recruitment success.
The Cultural Ambassadors Program is a partnership between Yale Center for Clinical Investigation (YCCI) and respected community leaders to seek greater health outcomes through clinical research, advocacy, and education. The ambassadors advocate for studies that affect their communities and have increased minority participation in clinical research from 3% to 30% between 2010 and 2019.
The program breaks down barriers by addressing how clinical research has historically been approached and shifting that paradigm.
“If we don’t know how well a drug, device or vaccine works in various populations or if certain people are deprived access to treatments because they aren’t involved in trials it is a disservice to science and it’s also simply unfair,” said John Krystal, MD, co-director, YCCI and chief of Psychiatry at Yale New Haven Hospital. “Diversity in clinical trials is a public health and social justice issue.”
A broken system has no pipeline
“The two most well-known examples that haunt the relationship between the medical establishment and minority populations are the Tuskegee experiment and Henrietta Lacks’ legacy,” said Dr. Krystal.
In the Tuskegee Syphilis Study around 600 black men were recruited into a 40 year study by the promise of free medical care. During the “study” participants were subjected to invasive procedures and barred from learning their diagnosis and receiving treatment.
In 1951 Henrietta Lacks’ doctors used cells from a biopsy of her cancer to create and distribute the first human cell line able to reproduce indefinitely, a major advance in studying cancer biology. This was done without asking or telling Ms. Lacks or her family.
In part because of the trust that was broken through these and other such events and in part due to clinical research designs that do not value different community needs and access pathways, new treatments are being developed and tested in the United States predominately on European-American populations. Genetic and environmental differences cause people to respond to drugs and other treatments differently, making broad racial and ethnic representation in trials essential for effective and equitable treatment development.
However, the Cultural Ambassadors Program was not created “top-down” by researchers looking to recruit minorities – and that might be the key to its success.
Sparking dialogue and redefining research
When Tesheia Johnson, chief operating officer, YCCI, and associate director for clinical research for the Yale School of Medicine, was tasked with increasing broadly representative participation for clinical trials, she started by listening. Her focus groups included over 700 people ranging in education from high school to double PhDs from all segments of the greater New Haven community. The resulting data was surprising.
“The idea was for participants to reflect our health system’s catchment area,” said Ms. Johnson. “We began to hear from minorities that they would never participate in clinical trials. One of the questions was if you had cancer, and a doctor told you a clinical trial could save your life, would you participate. The answer was no, across the board.”
“We also asked how we can change minds about participation and the response was – ‘you will never change our minds.’ The only way to open doors was to get trusted community members to work with us. We heard that the church and an organization called Junta would be good partners and that getting them on board might start a dialogue around clinical research.”
Tesheia called her uncle, who was the presiding elder of the local African Methodist Episcopal Zion Church who, after initial concern, relented to setting up one meeting. She stood in front of a room full of people not interested in the cookies she laid out, let alone hearing about clinical trials.
Tesheia shared the focus group insights. She highlighted several examples where the FDA relabeled medications after they went to market because minorities were not involved in the trial and only later did the agency capture certain side effects or efficacy discrepancies across populations. The result was an agreement to keep meeting.
Eventually the group hammered out what an ambassador program would look like. Education and training was the first principle. Today, many of the ambassadors, who are chosen by the community, have 200+ hours of training in clinical research and design.
Meeting the ambassadors
“I never wanted to get involved in this program – never thought about clinical research,” said Reverend Elvin Clayton who has partnered with YCCI for the last 11 years. His most recent work is messaging around the Pfizer trial and COVID-19 testing. “I went to a meeting at the request of our presiding elder,” said Revered Clayton. “Based on what I learned there, I was hooked.” Revered Clayton educates his community about clinical research through social media and a local radio show.
“Research has always been close to my heart,” said Sandra Trevino, LCSW and former executive director of Junta for Progressive Action.
“I joined the program when it started – when there was a lot of distrust. Now people ask how to participate and show up at fairs wanting to learn more because they know someone who has participated. People are more willing to have a conversation. Ten years ago if you mentioned research people would walk away.”
When describing her approach to discussing clinical research, Ms. Trevino says, “allowing individuals to ask questions without judgement, sharing what takes place during a research program and the participant’s rights in terms of changing their mind has been invaluable in building trust.”
Additionally, ensuring materials are available in Spanish is something Sandra says is grossly overlooked and makes a huge impact.
Cultivating the community during COVID-19
When COVID-19 hit, the ambassadors asked YCCI for a virtual meeting to answer questions directly from their communities.
“The meeting had about 400 attendees,” said Brian Smith, MD, co-director, YCCI and chief of Laboratory Medicine at Yale New Haven Hospital. “People asked us: if a poor person needs to go on a ventilator, do they get the same chance of survival as a wealthier person? If a Black person comes to the hospital will they be treated the same as a white person? It was important to share that, in order to minimize unconscious bias based on caretaker’s perceptions, Yale New Haven Health System and Yale Medicine had established written protocols to guide treatment of patients with COVID-19. It was important to present the data that we had on discrepant results by race, gender, and ethnicity in our patients. It is critical for us to work as a partnership between patients and their families and the healthcare team, whether it is in a research trial or standard care. We need to work to have effective mechanisms to hear the issues we have in our relationship with our community.”
Impact and a way forward
At its best the collaboration takes on a life of its own.
“I had the opportunity to speak with the ambassadors about a trial for a new kind of antidepressant that would work faster,” said Dr. Krystal. “During the discussion, concerns emerged about access to mental health and substance abuse services. In a follow-up meeting, we shifted gears to brainstorm how the ambassadors could advocate for people who need treatment.”
The ambassadors also ensure studies are designed for successful enrollment.
In one NIH study, the principal investigator engaged the ambassadors during the application process on a study assessing the stress of parents on infants/toddlers, with a primary assessment being the sleep patterns of the infant.
As originally proposed, the study had multiple survey points and in-person visits. The ambassadors gave critical feedback which modified the trial design to be more reasonable for working parents, recommended significant modifications to the messaging and recruitment strategies, and helped launch the study at multiple clinical sites with the help of church members and health care practitioners. The result was a streamlined study with over 80 percent participants from underrepresented minorities.
“My goal is to keep educating people about the importance of clinical research,” said Reverend Clayton. “I hope every population can consider clinical research so things can be far better for our community and our world.”
“The mentality in research was ‘you should come to us’ and that’s shifted towards meeting people where they are,” said Ms. Trevino. “More than anything we are increasing access through information that is in the right place at the right time.”
As for her hopes for the coming year Ms. Trevino says, “as long as people are healing that is all that matters.” She explained in her clinical practice she is seeing more patients than ever, people who previously would not have entertained therapy. “Now is the year people are sitting down with what has been suppressed, and that is a sign of progress.”