Clinical trials are the lifeblood of drug development. No medicine can win approval without being proven safe and effective in volunteers. However, as USA Today reports, during the early months of the COVID-19 pandemic, most clinical research was derailed by shuttered clinics and hospitals that didn’t have time for anything but urgent care. Suddenly, virtual visits and in-home care – which had seemed impossible before – became routine.
Meanwhile, COVID-19 trials received the kind of seemingly unlimited money and public support that may never be seen again. The combination taught clinical trial companies several lessons, some of which seem likely to stick long-term. One was the need for diversity.
“If you want people to show up for treatments, you’d better have tested the drugs or vaccines on people who look like them,” said Arthur Caplan, a medical ethicist at the New York University Grossman School of Medicine.
Before the pandemic, trial organizers said they aimed for diversity. “We talked a good game about it, but we never really did that much,” said Dr. Paul Evans, CEO and president of Velocity, which conducts later-phase trials for drug companies. “It’s no longer lip service.”
Now, trial organizers are going out of their way to reach patients of diverse backgrounds and in areas that used to be overlooked. They are using video chats instead of all in-person visits to make trials more convenient. And they are reconsidering strict criteria that eliminate those with common medical conditions and often disproportionately affect people of color.
Clinical trials remain the most expensive part of drug development, and the push for diversity drives up the cost even more, Evans said. Reaching beyond the usual sources takes time and effort. It takes about 12 years to get a drug to market, largely because of the time for clinical trials, said Natalie Schibell, research director at Forrester Research, which analyzes business, marketing and technology trends.
According to USA Today, in a typical trial, about 30% of patient volunteers drop out. Recruiting each patient costs about $6,500 and replacing one can run $19,500 – as much as $600,000 to $1 million if it’s an early-stage trial with few patients, Schibell said. “All that data, all those resources down the tube.”
But the improvement in medical care is worth the extra effort and cost to keep diversifying trials, Evans said. “It certainly means we have a better scientific basis for approving drugs and allowing them to be widely prescribed.”
Why do Clinical Trials Need Diversity?
Simply put, different ethnicities often affected by diseases differently, and also react differently to medications and vaccines, so when conducting a trial, if you’re going to get a true result, you must include everyone across the spectrum.
The blood cancer multiple myeloma, for instance, appears more often among people who are African American – but they are less likely to be included in clinical trials than people who are white, said Dr. David Gerber, a medical oncologist in the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern in Dallas. Scientists won’t understand the biological differences until more African Americans can participate in trials, he said.
The same is true in Alzheimer’s disease. Inheriting a gene known as APOE4 has been linked to a dramatically increased risk for developing Alzheimer’s. But that higher risk has mostly been seen among people who are white, said Rhoda Au, director of global cohort development at the Davos Alzheimer’s Collaborative, which works to accelerate innovation in diagnostics and drug development.
Something different could be going on among participants who are Black and maybe Hispanic, she said. Even less is known about the gene among people who are Asian-American, because a large study has never been done in those trial patients. To broaden the diversity of its trial participants, the Davos Alzheimer’s Collaborative is conducting clinical research in 16 countries in addition to the U.S.
But the push to include trial participants from across the world also requires researchers to rethink some of their traditional approaches, said Au, a dementia and aging expert at the Boston University School of Medicine. In the U.S., the question considered hardest on a cognitive test asks people to look at a picture of an abacus and name it. But abacuses are commonplace in China. “They’re using the same test” in China and the U.S., Au said, but “it’s not the testing the same thing.”
As USA Today notes, typically, it’s the healthiest, most advantaged patients who participate in clinical trials, the ones who can afford and physically manage to get to the major medical center where trials are usually held. And they are the ones whose doctors know about the trials and encourage their patients to participate.
To encourage more people to participate in trials, the process has to be easy and affordable, experts said. Volunteers are allowed to be reimbursed for the cost of participation – transportation, parking, lunch money – but won’t join if they have to travel too far, said Janelle Sabo, vice president of clinical research capabilities at Eli Lilly, the pharmaceutical giant.
The average American spends at least 80% of their time within 25 miles of their home. “If you can figure out how to deliver a clinical study in that same radius, your likelihood of a patient participating is over 70%,” Sabo said. Beyond that, the figure starts to drop. “By the time you’re 75 miles or more, you’re at single-digit percentages of patients that will say yes.”
Because clinical trials have historically been done at major medical centers, anyone who didn’t live close to one wasn’t likely to participate. And for even those who live close by, “if it costs $10 to get there and they work three jobs, that doesn’t fit very well,” Sabo said.
In 2020, Bristol Myers Squibb decided that at least 25% of its U.S. trial sites should be close to diverse populations. “We’re at 55% right now,” said Kate Owen, the company’s senior vice president of global development operations. At those trial sites, where the company has deliberately hired a diverse staff, people of color make up about 40% of participants, she said. “Having the clinics there is making a difference.”
Lilly took time during the pandemic to reconsider how it conducts studies, exploring ways to decentralize its trials and avoiding the requirement that participants come into a specific building. “We really looked at what is the best way to deliver that clinical study in the patient’s community,” Sabo said.
Sabo helped set up mobile research units – converted recreational vehicles that contained everything needed for a trial, including blood draws, labs to analyze that blood and high-tech equipment like that used to scan eyes for disease. Then, the RV could be driven to a nursing home. “These mobile research units have allowed us to reach a patient population that does reflect the patients we’re intending to treat,” Sabo said.
Digital technology was transformed from a possibility to practice during the pandemic. “Pre-pandemic, people were interested and less enthusiastic,” Au said. “They become more willing to consider technology as a result of the pandemic.” Older people, who had been thought unable to use computers, adapted. “If a worldwide pandemic prevents them from doing what they want to do,” she said, “they’ll find a way.”
Telemedicine also avoids “white coat syndrome,” in which patients get nervous when they have to see a provider in a health care setting, said Forrester’s Schibell. People are more relaxed in their own environment, she said. “You get a lot more data and a more realistic perspective on that patient.”
The expansion of broadband internet into rural areas, which is expected over the next two to five years, should allow companies to conduct more decentralized clinical trials with more diverse populations, Schibell said.
“When you think about the potential benefits of decentralized clinical trials for gaining real-world evidence, helping companies stand out from the competition, helping to earn trust … this is really the best way to go for the future of pharmaceuticals.”
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