Learning lessons from the past, MBC Project engages patients to diversify medical research
The Metastatic Breast Cancer (MBC) Project is partnering with and learning from patients and advocates in a shared effort to address disparities in research participation.
One morning last November, researchers and patients involved in the gathered in a conference room at the ӳý of MIT and Harvard. It wasn’t the first time the group had spoken—they’d talked on the phone and online about the project’s mission, which is to bring patients, advocates, and researchers together collaboratively to leverage genomic science in order to benefit those living with the disease. However, it was the group’s first in-person meeting, and they were there to address a particular challenge facing the research team: how to mitigate disparities in research participation.
The guests, all of them African-American patients with metastatic breast cancer and committed patient advocates, had been invited to share their experiences and perspectives, and to help put a persistent problem in context: after a year of recruiting participants via social media and word-of-mouth, the project had enlisted only 60 African-American patients—a mere 2% of the 3,000 individuals who had signed up. The team hoped that, together, they could develop ways to address this recruitment disparity.
The long shadow of medical history
The team felt that the problem couldn’t fully be understood without putting it in historical perspective. To that end, they had invited their colleague Shawn Johnson, a breast cancer researcher at Dana-Farber Cancer Institute (DFCI) with a clinical interest in addressing patient-physician mistrust, to give a presentation on the complicated history of African-Americans and biomedical research.
In his overview, Johnson explained how in America’s early years medical research and the practice of chattel slavery were intricately connected, with physicians routinely purchasing slaves for the purpose of surgical experimentation and anatomical research. He then went on to describe how, as recently as the late 20th century, African-American communities were subjected to unethical experimentation without their knowledge or consent. (In one notorious case known as the Tuskegee Experiment, curative treatment was secretly withheld from Black men with syphilis so that doctors could study the effects of the disease.) Such incidents have raised alarms about consent, compensation, exploitation, and institutional racism in clinical research.
While the medical establishment has worked to address these ethical issues (for instance, establishing Institutional Review Boards (IRBs) that vet research studies to ensure compliance with ethical best practices), this history of exploitation has, nevertheless, left a lasting, damaging legacy. Johnson, who works in the lab of DFCI researcher Geoffrey Shapiro, is among a growing number of researchers and historians who are trying to connect the dots between past abuses and current disparities in health treatment and outcomes.
“I feel there is a tendency for researchers to view these disparities and assume they are strictly due to socioeconomic factors—but that’s overly simplistic,” Johnson argued. “It ignores a culture of mistrust and skepticism that understandably developed following centuries of painful history between African-American patients and the medical research community.”
Johnson and others studying the field of health disparities contend that deep-seated distrust has translated into a reluctance among African-Americans to seek medical care, volunteer for clinical research, or even talk about illness. According to one in 2010, African-American patients were twice as likely as white patients to believe physicians might deceive them, and six times more likely to believe they might be used as “guinea pigs.” Nearly a third said they viewed any invitation to participate in clinical research with suspicion.
It’s a phenomenon that’s : after 1972 (when the horrors of the Tuskegee study became public) there was a sustained decrease in doctor visits by African-Americans as distrust of the medical community spread.
Inherited conditions
While the medical community has made efforts to make amends for these injustices, the stigma attached to clinical research lingers.
The patients who attended the MBC Project meeting said that it was reflected in their own experiences.
“When I first heard about the MBC Project, I knew it was a good thing but, at the same time, I was skeptical,” said Sheila McGlown, a project participant and patient advocate. “I asked myself: Why do they want my saliva? What are they going to do with my medical records?” She did, however, trust her own doctor, who ultimately reassured her about the safety of participating.
Fellow advocate Latonya Wilson had a similar experience. “I asked that same question: after you get this stuff from me—the samples, the records—what’s going to happen to it?”
She said that the researchers explained that her data would have identifying information like names and dates removed, and that it would be added to a public database where other researchers could use it for additional medical studies.
“I was more comfortable once I knew exactly where my information was going to go,” she said.
Johnson thinks that distrust and suspicion continues to fester in part because the medical community would prefer to put that part of its history behind them. Consequently, the issue isn’t openly addressed.
“It’s tempting for people working in healthcare today to distance themselves and say, ‘I didn’t directly participate in that. It’s not my responsibility.’ But the reality is skepticism of medical research still exists in many patient populations that have historically been vulnerable to abuse. The current medical establishment has inherited these issues, so if you work in the medical field, the problems are still there for you to fix,” Johnson said.
The MBC Project team intuitively gravitated toward the issue. In a way, that responsibility is embodied in the project’s patient-driven mission.
From its inception, the project had relied heavily on existing networks on social media, which they knew might be skewed—by geography, age, race, or other demographics.
“From the start we suspected that the people who signed up for the project might skew white and young because we were relying heavily on existing networks that already leaned in that direction,” explained Corrie Painter, the associate director of operations and scientific outreach for the MBC Project. “The advocates who were part of those networks were amazing and did tremendous work helping us attract patients, but, a year in, our participation numbers confirmed that the same disparities that have been seen in other research studies were reflected in our project as well. ”
The team doubled-down on efforts to reach out to underrepresented populations. They were already working with McGlown, Wilson, and other patient-advocates to improve outreach within the African-American community. These advocates were working to spread the word and recruit patients directly. They had even released a video that attracted media coverage from and the .
The group decided to bring in more advocates to broaden their understanding of the challenges, to gather more perspectives from across the African-American community, and to expand the conversation. November’s all-day visit grew out of that effort.
In addition to Johnson’s presentation, the patient-advocates went on a tour of the ӳý Genomics facilities, met with ӳý leaders, and shared their ideas about how the team might engage the African-American community. In this brainstorming session, transparency was a major theme—particularly in developing educational materials that spoke directly to the safety and value of the project. Representation in those materials was another.
“The more African-American women see other African-American women participate in the project and advocate for it, the more likely it is they’ll feel it’s for them and they will feel comfortable getting involved,” Wilson said.
The patients' conversation with the ӳý is ongoing. On Friday, April 14th, they will return to take part in a symposium on racial disparities in clinical research titled, "." The event aims to be a dialogue with scientists, researchers, cancer patients, and patient-advocates that will examine the historical context of medical and scientific mistrust in African-American communities and the ongoing public health implications of these disparities.
Appreciating human variation, tailoring treatment
There is a pressing reason to recruit more African-American women for the MBC Project: they are disproportionately affected by the disease.
“The MBC statistics for African-American women are worse than average,” explains MBC Project leader Nikhil Wagle, who is also a breast cancer oncologist at Dana-Farber Cancer Institute and an associate member at the ӳý. “They get breast cancer at younger ages, they have a much higher instance of metastatic disease, and they are twice as likely to get triple-negative breast cancer – the most aggressive form of the disease.
“We don’t yet know why there’s this disparity in the statistics. Some of it, such as the higher rate of triple-negative breast cancer among African-American women, likely has to do with biology,” Wagle said. “We need a more complete picture of what’s going on genetically and biologically so that we can better tailor treatments and help to improve breast cancer disparities.”
This goal of matching treatment to the various root causes of disease is at the heart of a movement called “precision medicine,” which is now the centerpiece of a national Precision Medicine Initiative announced by President Obama in 2015.
“We in the cancer field really believe in this,” Wagle said. “We want to be able to individualize treatments for each patient’s particular cancer sub-type. To do that, we need a thorough understanding of the variation that’s out there. We can’t do that without a diverse, representative cross-section of the people who are afflicted with the disease.”
A global perspective
In its need for more diverse patient participation, the MBC Project is no different than other biomedical research studies. Health disparities are a far-reaching and much lamented reality in modern healthcare. In the U.S., as far back as 1985, the medical field recognized that minorities had higher disease, disability, and mortality rates, and the federal Task Force on Black and Minority Health was formed with the goal of investigating and eliminating those disparities. That effort, over time, evolved into the (NIMHD), which is part of the National Institutes of Health (NIH) and which remains committed to that mission today.
Nevertheless, disparities persist, and in research, they can be quantified. The genomic sample collections currently used for most major research are overwhelmingly from individuals of European descent. Over-reliance on one subpopulation can limit or even skew researchers’ understanding of disease. Disease-associated genetic variants could remain undetected if they circulate largely in underrepresented populations. Or, variants that are rare in individuals of European descent might mistakenly be linked to a disease, when in fact the variant is common (and harmless) when viewed in the broader context of human variation. Moreover, as more disease-associated genetic variants are accounted for in a particular condition, they may collectively point to a biological pathway that may be involved in the development of the disease, opening up another target for treatment.
In addition to the MBC Project, a number of efforts at the ӳý seek to broaden representation in sample collections. In 2013, the ӳý joined several other institutions worldwide to support the , which is working to pool genomic datasets in order to take advantage of their quantity and diversity and accelerate research on human health. Additionally, the ӳý has partnered with the Carlos Slim Foundation to form the Carlos Slim Center for Health Research at the ӳý, which aims to ensure that Latin Americans are represented in—and benefit from—genomic research. Work at the Center has so far included the discovery of genetic risk factors for type 2 diabetes in Latin American populations and previously unobserved drivers of breast cancer. And researchers from the Stanley Center for Psychiatric Research at ӳý have long been part of the multi-national , which has amassed a database of schizophrenia samples that pointed to the first gene to be causally linked to the condition. The center is currently expanding its global samples collection for other psychiatric disorders. And the MBC Project also has plans to partner with patients to bolster outreach within the Latino and Asian-American communities.
Patient gains
Gains in genomic research depend on the generosity of volunteers, who allow scientists to collect and analyze their genomes. That consent is based on a foundation of trust, making it critical for the medical community to build bridges and work with patient-advocates to shape practice and policy.
“We owe everything to the patient community,” said Todd Golub, the ӳý’s chief scientific officer and director of the ӳý Cancer Program. “Donors, advocates, and their families are not only the reason why we do the research, but without their consent and participation, we would be driving in the dark as we look for cures.”
The MBC Project and its younger cousins, the and Prostate Cancer Project, are at the forefront of the patient engagement movement, and the researchers involved say they are learning how to be more effective with every patient they meet.
“From the beginning of this project, we’ve made a point to partner with patients in a very grassroots way,” said Painter. “We teach them about the project so that they can help us reach out into the community. But the only way we’re going to be effective at engaging patients is if we learn as much from them as they learn from us.”
Among the patient-advocates the team hosted, there’s anecdotal evidence that their approach to outreach is being well received. Bridgette Hempstead, an MBC patient and advocate from Seattle, hadn’t yet signed on to the project when she made the cross-country trip to Boston in November. She said that when she was first diagnosed with MBC, she’d been told she had a year to live. She is now NED (no evidence of disease). She said that her experiences have made her aware of the many research efforts out there. She said she’s conscious of her time and resources and, consequently, is particular about which studies she joins. Particularly, she said studies that come to a hard stop when grants run out or papers are published give her pause.
Hempstead signed up for the MBC Project on site, in part because of the commitment of ӳý leadership: Golub, when asked when the project would end, simply said, “Not until we figure this out.”
The advocates said they saw a similar dedication when they visited the facility, where they toured the labs where the samples are sent for sequencing. Seeing the scientists preparing and sequencing the samples, surrounded by notes of encouragement sent by volunteers with their sample kits, left an impression.
“I was totally in awe of the labs. I had no idea there was such a dedicated team of researchers and scientists involved in this work,” said Hempstead. “What I saw was commitment, dedication, and a project that they’re going to stick to until they actually find a treatment for MBC.”
It is a commitment the advocates clearly share. For them, the partnership with the MBC Project represents an opportunity to change history for generations.
“My mom was diagnosed with MBC, and I was diagnosed with MBC,” McGlown said. “Maybe there’s something about my genes that could help my daughter or someone else avoid getting cancer – because it’s not about me anymore. I already have cancer. It’s about who I can help.”
Hempstead shares that sense of obligation. “Most of my community doesn’t survive once they’re diagnosed. I want to make sure they have an even playing field,” she said. “This work we’re doing with groups like the MBC Project, it gives hope to those that are fighting for their lives.”
Learn more about the MBC Project at:
The MBC Project: Reaching Out, Moving Forward
