DHR Health Institute: a case study in grassroots clinical trial diversity

Texas institute is improving the quality of healthcare in one of America’s most disadvantaged communities

Led by President and CEO Sohail Rao, DHR Health Institute has set out to prove that the quality of healthcare delivered in a local community can be improved by increasing participation in clinical trials. The institute’s grassroots approach includes a focus on the community’s most pressing health needs; an understanding of its travel and financial constraints; engagement with its leaders and young people; and local infrastructure projects funded with government money.

DHR Health Institute for Research & Development is based in Edinburg, a city of about 100,000 people located in the far southeast of Texas, less than 30 miles from the U.S.-Mexico border. The local population, predominantly Hispanic, many of whom are undocumented, is among the poorest in the U.S. The local prevalence of diseases such as obesity, diabetes, cardiovascular disease, certain types of cancer, and non-alcoholic steatohepatitis (NASH) are all much higher than the national average.

Rao, who joined the institute in 2019, told BioCentury that his goal was to elevate the standard of care being delivered to the institute’s patients by enrolling them in clinical trials. 

“The focus is obviously the patient. All the rest of it is ancillary,” he said, adding that if you want to “take care of the patient, you [should] bring innovative clinical trials.”

DHR focuses on trials studying interventions to treat diseases that are prevalent in the local community, although it also participates in some larger, national trials for diseases that are less common in the region. The number of trials in which the institute is involved has increased more than 20-fold since Rao arrived. 

“When I came here four years ago,” he said, “we were doing about 11 clinical trials. Given the burden of disease in this community, I felt we weren’t providing the level of innovation required.” The institute is now involved in 290 studies, he said, “with practically every major biopharma.”

The institute’s success has hinged on its ability to raise awareness and motivate people to participate in trials, which it has accomplished through a variety of outreach activities. However, key to making that outreach effective is having a research agenda tailored to the community’s needs. That requires cultivating an awareness that extends beyond understanding which diseases are most prevalent locally to the specific needs that are most underserved, and keeping an eye out for situations where the local population may be responding differently than expected to approved therapies.

Plavix: precision community medicine 

Rao said the institute’s study of Plavix clopidogrel exemplifies the importance of clinical trial diversity and how it can elevate the standard of care in a community. 

A prodrug platelet inhibitor developed by Sanofi Aventis and Bristol Myers Squibb Co. (NYSE:BMY), Plavix was approved by FDA in 1997 to prevent heart attack and stroke based on data obtained in Phase III CAPRIE trial, which enrolled 95% white people. A subsequent study, CHARISMA, enrolled 80% white people; two other studies also cited in the drug’s prescribing information, CURE and COMMIT, did not report the ethnic make-up of the patient population.

“Patients who have received a stent or been diagnosed with coronary artery disease would be prescribed Plavix,” said Rao, “but we noticed a sizable number coming back to the ER either with bleeding or their stent closed. It was almost like a revolving door.”

The institute designed a 300-patient study to understand why. It was funded by Cipherome Inc., a California company developing software “to minimize variability in drug response for patients.” 

“There was anecdotal evidence that the enzyme needed to activate Plavix may be dysfunctional in Hispanics,” Rao said. “We found that in about 25% of patients, the enzyme was truly dysfunctional — either overactive or underactive.”

Based on the finding, DHR revised the clinical protocol that governs how stent patients are managed, improving the standard of care in the community.

“It’s now a clinical protocol that every patient has to go through CYP2 enzyme genetic analysis,” he said. “If the patient has a dysfunctional enzyme, they’re switched to another drug.” 

A grassroots outreach

The institute is taking a grassroots approach to clinical trial enrollment based on a community outreach plan that Rao said is designed to address the reluctance of local people to participate in studies.

It enrolls people regardless of immigration status. “We are oblivious to factors that would otherwise impact their access to healthcare,” said Rao. “Our grants or contracts are mostly fully funded. There is no limitation on patients other than the inclusion and exclusion criteria.”

The institute has found that it is most effective not to attempt to sell patients on the idea of clinical trial participation directly, he said. “One of the things that has really made a sizable difference is our ability to reach out to middle school and high school students.”

He said DHR impresses upon the children the idea that clinical research is helpful and should be embraced rather than ignored, a message they then convey to their parents — many of whom work long hours in low-wage farming jobs and would be hard to reach directly. 

The institute also has a team that attends community health fairs, providing blood pressure and diabetes screenings, and “even FibroScans to see if they have liver disease.” Those “value-added” services help attract people to the booth, he said. They also reinforce the message that DHR aims to improve their health. 

The institute holds events of its own dubbed “lunch and learns,” to which it invites community leaders to discuss a particular disease, its prevalence in the community, and how the institute cares for patients. The leaders with whom the institute engages include those “with deep-rooted social connections and networks” such as pastors. As with the teenagers, DHR counts on these leaders to spread the word. 

On the physician side, the institute is targeting community doctors “to get them involved and excited about referring their patients for research.” It’s also lowering the barrier to physician referral with an app that reduces the referral process to “one click,” and incentivizing continued physician participation with a reimbursement model, published in Academic Medicine, the Journal of the Association of American Medical Colleges, that assesses the time physicians spend in “research relative value units.” 

Taking research to the patient

Rao said the institute is “taking research to the patient rather than bringing the patient to research,”  noting that it is not always easy for people in his community to travel. 

“Hispanic people live as a family unit,” he said. “When a patient goes to MD Anderson, San Antonio or Dallas to get treated, it disrupts the entire structure on which they depend for emotional and physical support.” Additionally, he said, “a sizable number of our population are undocumented, and they cannot cross the checkpoint.”

That commitment to bring the research to patients requires infrastructure, which state and federal governments can play an important role in funding. 

“The most important thing right now is infrastructure,” said Rao. “That includes everything from ensuring that we have the right technical capabilities and a brick-and-mortar facility, to the recruitment of world-class physicians to conduct the studies. This is something that the federal government could make a sizable difference in and move this needle much faster if they were to invest in it.”

Taking research to the patient, he said, “is extremely important in this particular region because 33% of people live below the poverty line — it’s practically impossible for them to take a day off work.” 

He praised Texas for helping the institute construct a stand-alone research satellite in Rio Grande City, about 50 miles west of Edinburg. “They are extremely supportive of anything and everything that we do,” he said. The institute is also building a satellite in Brownsville, 60 miles in the opposite direction. 

Rao said that both the state and federal governments have played roles in supporting DHR. “Some of the studies we’re continuing in COVID are actually entirely funded by the federal government,” he said. “Both are extremely important.”

DHR recently submitted an application to the federal government for an $8 million grant to establish “a state-of-the-art research facility” in Edinburg.

If awarded, it would be the institute’s first federal-level infrastructure grant, and would enable it to expand the scope of its research by adding next-generation sequencing capabilities and the ability to participate in Phase I trials.

“Not to have next-gen sequencing at our backdoor is a grave injustice to our community,” said Rao. “And Phase I trials are where the dynamics of a drug are studied. What’s the half-life of a particular molecule? We need to know that in our Hispanic population. Most of the studies we are doing now are Phase II and Phase III.”