Delivering mail is a delicate process that fails if any step in the process fails. The delivery person must hand deliver the message. If the address is wrong, it won’t reach the right person. If the mailbox is broken, it can’t be delivered. If the recipient lost the key to their locked box, then they can’t receive the message.
Delivering scientific messages is no different. Careful planning and preparation on the part of researchers and communicators goes into getting the message efficiently delivered to an individual. But not every individual is the same, so like a delivery address, scientists often design messages with the recipient in mind. Clinical researchers in particular are increasingly working to improve how they disseminate information about clinical trials and the science supporting them.
Many researchers, clinicians, and communicators are concerned that information about clinical trials and their importance is not being delivered to everyone equally. For example, according to the CDC, American Indian, Black or African American, and Hispanic or Latinx persons are approximately three times as likely to be hospitalized from COVID-19 infections than non-Hispanic white persons. But these groups were underrepresented in vaccine trials (1).
COVID-19 clinical trials aren’t the first to lack proper representation. According to the 2018 U.S. Census Bureau, 60.7% of Americans are non-Hispanic white. However, in the same year, non-Hispanic white Americans made up nearly 90% of the populations participating in clinical trials (2).
“Even when we talk about the most educated people, like doctors or lawyers, or even people with terminal degrees, they don't always understand the importance and the value of clinical trials,” said Ijeoma Opara, a social and behavioral scientist at the Yale School of Public Health.
Researchers are working to develop more effective message “delivery” strategies to make sure that everyone understands the importance of clinical trials and why their participation is needed for testing drugs. People of different races, ethnicities, and sexes can respond differently to the same drug, leading to differences in effectiveness, side effect severity, and dosing (3).
Researchers, clinicians, and scientific communicators are fine-tuning every stage of the messaging process. They want to know who should deliver the messages, how they should be delivered, and how to make that delivery sustainable. Economists and clinicians are teaming up to understand how to effectively communicate scientific information to minorities. And scientists, communicators, and artists are working together to develop illustrated science courses designed with diverse individuals in mind to deliver the information they need to make an informed decision about participating in clinical trials. Pharmaceutical companies such as Sanofi are engaging with communities outside of the clinic through ambassador programs.
“The issue of appropriate inclusion in clinical trials is a long-standing issue, and we have done poorly over time in recruiting appropriate, representative populations of the disease, or those who are intended to use the product or the intervention,” said Barbara Bierer, director of the Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard University who is leading efforts to educate clinicians on inclusive practices. “There’s been a real recognition and a call for change.”
Planning a delivery route
This issue caught Bierer’s attention in 2016 when the FDA published its first drug trial snapshot (4). Every year, the FDA analyzes the available data on participants in clinical trials for newly approved drugs and presents that data to clinicians and patients in a summary report that analyzes participation across trials as well as reports focused on trials related to a single drug.
The first snapshot showed a lower percentage of participation in minority demographics, including women and Black or African American individuals. For example, only 5.4% of all reported participants in clinical trials of FDA approved drugs from 2016-2017 were Black, a stark contrast from the 13.4% of Black individuals in the general population.
This lack of representation was more apparent when these numbers were broken down into fields of research. For example, the CDC reported in 2018 that Black Americans were 30% more likely to die from heart diseases than non-Hispanic white Americans (5). But only 2.5% of participants in clinical trials for cardiovascular disease from 2016-2017 were Black or African American. A recent study published in JAMA Network Open corroborated these results, stating that only 3% of participants in clinical trials that led to the approval of 24 cardiovascular drugs over the past 15 years were Black or African American, while 83% were white (6).
“The vast majority of cardiovascular disease trials historically enrolled white men,” said Stephen Juraschek, a clinician investigator at Beth Israel Deaconess Medical Center. “As a primary care physician, it’s really problematic when I’m sitting with patients and saying, ‘you should take this therapy because it’s shown to improve whatever your health condition is.’ I feel a little disingenuous if I say it’s proving that, but only in white men.”
“It’s a real matter of health equity that people can receive care that’s informed by populations like them,” he added.
Juraschek recently analyzed the recruitment strategies used by researchers leading cardiovascular clinical trials posted on ClinicalTrials.gov from 2000 to 2019 (7). Although the NIH recommends that clinical trials include strategies for recruiting underrepresented groups, it isn’t required. According to Juraschek’s study published in the Journal of the American Heart Association, only 62 of 100 clinical trials had published protocols detailing their recruitment strategies. 21% of the 62 trials had a plan for recruiting underrepresented populations, and only one reached the enrollment goal.
At the Multi-Regional Clinical Trials Center, Bierer aims to encourage clinician researchers to develop a plan for recruiting underrepresented groups for their studies by presenting them with research-backed, effective strategies for engaging the public in healthcare and clinical trials. According to Bierer, her team put together a 400-page document as a “tool to address every aspect of clinical trial design, conduct, and reporting” to help interested clinicians or researchers find ways to make their trials more inclusive. The center she directs also regularly holds free workshops and webinars where clinicians can learn about proven strategies for clinical trial recruitment. Some of the most effective strategies her team has identified require engaging with the public long before clinical trial recruitment begins.
“[Some programs] are really sort of working to encourage participation through knowledge and education. One of the things that we want to make sure of is that we equip and empower people to make important decisions, not [for them] to feel pushed into something,” said Bierer.
Juraschek’s results echoed this sentiment. Clinical trials that published protocols including a plan to recruit underrepresented populations enrolled more Black participants than those that didn’t publish protocols, although only one study met its targeted enrollment numbers. Most of the studies with improved enrollment cited strategies where they engaged with the community, rather than relying solely on strategies such as provider recommendations.
One well known example of the use of community engagement to increase public engagement in health is a study that sought to treat hypertension in Black men, who are disproportionately affected, in barber shops in Los Angeles (8). Barbers either encouraged the men to make lifestyle changes and go to the doctor, or advised them to meet with pharmacists onsite to receive medication and advice. 64% of men who worked with pharmacists in the barbershops had lower blood pressure after 6 months compared to 11% of the group who was simply encouraged to schedule appointments and seek treatment in a clinical setting. The study was so successful that it is now being replicated in barber shops across Nashville, Tennessee by researchers at Vanderbilt University.
Finding a delivery person
For Fatima Stanford, a clinician researcher and director of diversity at the Nutrition Obesity Research Center at Massachusetts General Hospital, the barber shop study suggests that who delivers information about research affects how much the public will engage. She recently teamed up with a research group composed of physicians and Nobel Prize winning economists to understand the effects of different messengers.
Marcella Alsan, a public policy researcher at Harvard University and co-first author of the study published with Fatima Stanford, previously administered a survey and found that African American and Hispanic respondents were less knowledgeable than white respondents about how COVID-19 spread, its symptoms, and how to protect themselves (9). She noted that few public health messages about COVID-19 were delivered by Black, Hispanic, or Native American community members and wanted to know if this contributed to the apparent gap in knowledge. Alsan teamed up with Stanford to conduct a trial that tested whether a message delivered from someone of the same race resonated better with Black and Latinx individuals (10).
“When we looked at COVID-19 and its disproportional impact on communities of color, we saw higher morbidity and mortality rates [in these communities]. We can talk about structural racism; we can talk about health disparities; we can talk about a number of things; but when we start talking about public health messaging, we have to ask, who delivers this message, and does it matter?” said Stanford.
The group recruited 42 physicians of different races, ages, genders, and ethnicities to record video messages. Each video discussed a unique aspect of COVID-19: general information and symptoms, social distancing protocols, and information about masks.
Each of the 14,000 individuals watched three of these videos and completed a survey about COVID-19 including questions such as how to prevent its spread or if it could be asymptomatically transmitted. The control group watched the videos after completing the survey, and the other group completed the survey after watching the three videos. Some watched videos with messages from physicians of the same race or ethnicity while others did not.
Overall, 72% of respondents answered all survey questions correctly before watching the videos, while 80% of respondents who watched videos recorded by physicians of the same race and ethnicity got a perfect score on the survey. Additionally, Black participants showed increased “information seeking behavior” after watching videos recorded by Black physicians. At the end of the survey, they asked for links to more information on topics such as how to disinfect their houses or exercise in small spaces. This finding did not hold true for Latinx respondents, however.
While Stanford tackles the question of who should deliver the message, others are working to understand if how a message is delivered can also change its influence on the receiver. Scientific communicators are exploring if two messengers are better than one by pairing scientists with artists to deliver illustrated scientific courses to a variety of audiences.
Doryan Algarra was the head of design at LifeOmic, a precision health software development company, when he had the idea for Lifeology, a software platform where artists and scientists come together to create illustrated courses to explain scientific concepts to the public. Despite working for a health software company, Algarra was not a scientist, and conversations about topics like epigenetics made his eyes glaze over.
But then he learned that honey changes bees’ DNA to give worker and queen bees their defining characteristics from a chapter in The Epigenetics Revolution by Nessa Carey. He thought that others could also benefit from poignant, real-life, science stories. He developed this idea into a vision for Lifeology and presented it to Paige Jarreau, the vice president of science communications at LifeOmic in the summer of 2019.
Jarreau saw potential for more than a science communication platform. Together, the pair expanded the idea and co-founded Lifeology, a product of LifeOmic. At Lifeology, scientists and artists develop interactive digital flashcard courses to break down scientific topics ranging from autophagy to vaccine mechanisms. Each flashcard has an illustration and a sentence of accompanying text written by scientists and medical experts.
“[Art] is kind of a universal language. Regardless of language, it can help you interpret complicated concepts or text,” said Jarreau. “Visuals are concrete. They can take very abstract ideas and create a visual analogy with them that people can process immediately.”
Many of the Lifeology courses are designed like storybooks. The illustrations provide a real, relatable character who walks the reader through a personal science story.
Lifeology recently partnered with Eli Lilly to develop a course titled, “What are clinical trials?” In this course, the cards present a woman named Ana who lives in an assisted living facility and decides to participate in a COVID-19 clinical trial. On one of the flashcards, Ana sits next to a photo of her family resting on a table while she holds a phone to her ear. The text says that Ana’s family has concerns about the risk and the cost of the trial. As readers flip through the cards, they learn about important topics such as informed consent.
As the Lifeology team created COVID-19 related content during the pandemic, Jarreau realized that Lifeology courses might particularly benefit minority communities. “Official sources weren’t necessarily creating messages specifically thinking about these communities and individuals…They’re being hit hardest by COVID-19, but being left out of communications and educational content about the pandemic,” said Jarreau. “Our courses are bite-sized, but they are a huge opportunity to create content and art that speaks to a very specific audience and helps them engage further with the content.”
Lifeology continues to work with Eli Lilly, most recently publishing a course called “What is Early Breast Cancer?” where patients can learn about treatment options, including clinical trials. They even include a link to information about Eli Lilly’s ongoing breast cancer clinical trials.
Lifeology also works with healthcare institutions to make educational content about clinical trials with several focusing on minority audiences. Jarreau began a recent project collaborating to create a course for Native American audiences by interviewing consultants, social scientists, and researchers in the communities to develop a better understanding of her audience.
“We started by trying to learn as much as we could about people’s experiences related to clinical trials in these communities, and only then did we start to try to write the story about what information would be included in the course,” said Jarreau.
Once they were comfortable writing a draft, the team returned to the community consultants for feedback. After they revised their content, they found Native American artists to illustrate the courses. Every step along the way, they wanted to make sure that their content was culturally sensitive and relevant. They asked for help with small details like characters’ names and what food they would eat at a family dinner.
Jarreau hopes that Lifeology can apply what they learned from developing these clinical trial courses in other institutions to ease volunteers’ concerns about participating.
“For me, it's all about collaboration. Are we working with the right artists and writers? Are we engaging community members and reviewers who are within the community that we're trying to reach from the very beginning? And if we do, it just kind of makes every other piece of the challenge of creating the right content and getting it to the right people all that much easier,” said Jarreau.
Communicating with the recipient
Raolat Abdulai, clinical research director at the pharmaceutical company Sanofi, shares Jarreau’s passion for collaboration.
“We ensure that in our protocols, we have input from people with the disease who can provide us with their insights about what they may or may not like about our study design, or what they think could make it even better,” said Abdulai. “You can’t design a clinical trial in silos.”
Abdulai focuses on developing potential treatment strategies for immune driven diseases such as asthma. She spends most of her time researching diseases, understanding patient demographics, and determining if the treatments in development can really meet those patients’ needs. She wants to know where the science leads, but also what patients with the targeted disease request. Ultimately, she uses this information to help design clinical trials to test drugs developed at Sanofi.
For designing trials that reflect the patient population for each disease, researchers select trial sites carefully. Michael Matthay, a clinician scientist at the University of California, San Francisco, is conducting a clinical trial to test a mesenchymal stem cell-based therapy to treat patients with acute respiratory failure. He selected the Zuckerberg San Francisco General Hospital as one of his study sites since it serves many individuals who are socially and economically disadvantaged.
Matthay received supplemental funding last summer from the California Institute for Regenerative Medicine to add a site at the University of California, Davis, which also serves a diverse population in the Sacramento area.
Investing in the local community is a crucial part of recruiting a diverse set of participants. Abdulai discovered the possibilities science could offer in high school when she was mentored by a woman who worked at the FDA, and she wants to do the same for others. She engages directly with the community in Boston to ensure that they understand the importance of clinical research and how they can contribute.
“It’s important for us not to just fly into communities and do clinical trials, right? It’s important for us to actually develop relationships with communities that are sustainable and lead to long-term engagement,” Abdulai said.
Connecting with patients in the community can even redirect scientific inquiries. Michael Kurilla, the director of the division of clinical innovation at the National Center for Advancing Translational Sciences, has seen this happen many times. He leads the clinical and translational science awards program, which funds institutional programs focused on helping researchers conduct better translational science. Part of that is community engagement.
“A lot of times, a particular scientific question, which is not an irrelevant question, has no relevancy or meaning to the individual suffering from that disease,” said Kurilla. “It’s not that you have to [choose] one or the other, but if you engage with those patients of a particular condition, you can actually think about designing a trial that will not only answer your scientific question, but will address important questions that the patients and healthcare providers for those patients are actually interested in.
Kurilla came across a disconnect between patients and clinicians when studying degenerative joint diseases. Clinicians want to develop drugs to slow the rate of degeneration, which is measured by the rate of joint narrowing. However, slowing the progress of the disease doesn’t relieve much pain. Although a clinician may consider a treatment a success by joint measurements, the patient doesn’t see the benefit.
Abdulai has never entirely redirected a scientific enquiry based on patient feedback, but she has made changes to aspects of the trial protocol. Coming in for assessments once a week may be a burden, so some trials allow for telehealth assessments or at home assessments. Some patients may have limited flexibility in their work schedules, so weekend visits may be most effective. Decreasing barriers to access improves retention.
Researchers are discovering that patient involvement before a clinical trial starts helps design a trial that effectively answers a scientific question and addresses the target patients’ needs. Defining effective communication strategies and implementing lasting engagement in local communities seems to be an effective approach for academic and industry researchers alike.
“As scientists, we have so much to give to these communities, and I think it has to be a sustainable relationship and not just solely based on recruitment for a clinical trial,” she said.
Delivery to your door
Sanskriti Thakur, the chief growth officer of the digital health company Medable, said that she and the Medable team are pursuing a “noble endeavor,” where patients don’t need to go online to learn about clinical trials; they can just walk into their local pharmacies.
Medable’s endeavor began online. The company’s flagship product is an end-to-end decentralized clinical trial platform that limits the number of times a patient needs to travel to a research site or doctor’s office while they participate in a trial. Participants interact with doctors and researchers virtually, receive shipped medications, complete daily surveys on their conditions, and train to use the tools needed to measure outcomes such as daily vitals. Medable even partners with companies to organize home health nurses if there is a procedure that a patient may struggle to conduct themselves, such as a blood draw.
The decentralized platform has yielded positive results. Medable claims that some clinicians who used their platform for fully virtual or hybrid trials saw retention rates of 90% and a 200% increase in patient recruitment. This is dramatic since 30% of people who enroll in a clinical trial drop out, and 80% of US clinical trials never recruit enough patients to start their studies.
“The ultimate outcome is better access, better affordability, and better medications,” said Thakur. “But it’s not enough to have the right technology. You must engage with the community and bring the technology directly to the patients.”
Medable recently teamed up with CVS Pharmacy to meet potential participants where they are. Many patients don’t live near a research site, limiting their access to trials. However, nearly 90% of people live near one of the 26,000 CVS Pharmacies in the US. Thakur believes that increased access will make clinical trials more inclusive, especially for vulnerable populations. In the first year of this collaboration, CVS Pharmacy has helped 300,000 patients join clinical trials.
Time will tell if Medable’s collaboration with CVS Pharmacy will yield improved recruitment of underrepresented populations.
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