An inviting beach in Nassau, Bahamas.
Dr. Conville Brown, a cardiologist-researcher in The Bahamas, is at the helm of a fascinating worldwide project: He's leading a movement to help accelerate innovation by providing scientists and patients from around the globe with a legal, cost-effective, and ethically rigorous place to conduct medical research, as well as to offer commercial therapies that are already approved in some jurisdictions, but not others. He recently spoke with Editor-In-Chief Kira Peikoff about The Bahamas' emerging ascendance in the scientific world. This interview has been edited and condensed for brevity.
"You don't want to take shortcuts from the perspective of not giving proper due diligence to the process, but you also don't want it to be overwhelmed with red tape."
Tell me about the work you do in the Bahamas – what is the research focus?
We have a couple research opportunities here. Several years ago, we established the Partners Clinical Research Centre, the idea being that we can partner with different people in different territories in the world, including the United States, and be able to perform ethical research as would be defined and adjudicated by an institutional review board and a properly constituted ethics committee. We do all of this with FDA rigor, but in a non-FDA jurisdiction.
By doing this, we want to look for the science behind the research, and want to know that there is a sound clinical hypothesis that's going to be tested. We also want to know that the safety of the human subjects is assured as much as possible, and of course, assess the efficacy of that which you're testing. We want to do this in the same manner as the FDA, except in a more accelerated and probably less bureaucratic manner. You don't want to take shortcuts from the perspective of not giving proper due diligence to the process, but you also don't want it to be overwhelmed with red tape, so that what could be 3 months takes 3 years. A jet ski turns around a lot faster than the Queen Mary.
Why do you think the clinical research process in other countries like the U.S. has become burdened with red tape?
The litigious nature of society is a contributing factor. If people are negligent, they deserve to be sued. Unfortunately, all too often, some things get taken too far, and sometimes, the pendulum swings too far in the wrong direction and then it's counterproductive, so the whole process then becomes so very heavily regulated and financially burdensome. A lot of American companies have gone outside the country to get their clinical trials and/or device testing done because it's too phenomenally expensive and time-consuming. We seek to make sure the same degree of diligence is exercised but in a lesser time frame, and of course, at a much lower cost.
The other aspect, of course, is that there are certain opportunities where we have major jurisdictions, as in Europe, that have determined that a therapy or device is safe. Those services and devices we can utilize in the Bahamas--not as a clinical research tool, but as a therapy, which of course, the United States is not able to do without FDA approval. That could easily take another five years. So there is an opportunity for us in that window to make available such therapies and devices to the North American community. I like to call this "Advanced Medical Tourism" or "Advanced TransNational Medical Care." Instead of somebody flying nine hours to Europe, they can also now fly to the Bahamas, as little as half an hour away, and as long as we are satisfied that the science is sound and the approvals are in place from a senior jurisdiction, then we can legally serve any patient that is eligible for that particular therapy.
Dr. Conville Brown
(Courtesy)
Are you seeing an influx of patients for that kind of medical tourism?
The numbers are increasing. The stem cell legislation has now been in place for two to three years, so we have a number of entities including some large international companies coming to the shores of the Bahamas to provide some therapies here, and others for research. The vast majority of our clientele are from abroad, particularly the U.S. We fully plan to increase the traffic flow to the Bahamas for medical tourism, or preferably, TransNational Medical Care, Advanced and Conventional.
How do patients find out about available therapies and trials happening there?
Advertising in the international arena for something that is perfectly legal within the confines of Bahamas is par for the course. But the marketing efforts have not been that heavy while all the processes and procedures are being fine-tuned and the various entities are set up to handle more than 100 people at a time.
"We were able to accelerate those programs, and do it a lot less expensively than can be done in continental countries, but just as well."
What kind of research is being done by companies who have come to the Bahamas?
We've been involved in first-in-man procedures for neuromodulation of the cardiovascular system, where we inserted a device into the blood vessels and stimulated the autonomic nervous system with a view to controlling patients' blood pressure and heart rate in conditions such as congestive heart failure. We have also looked at injectable glucose sensors, to continually monitor the blood glucose, and via a chip, can send the blood glucose measurement back to the patient's cell phone. So the patient looks at his phone for his blood sugar. That was phenomenally exciting, the clinical trial was very positive, and the company is now developing a final prototype to commercialize the product. We were able to accelerate those programs, and do it a lot less expensively than can be done in continental countries, but just as well. The Bahamas has also crafted legislation specifically for regenerative medicine and stem cell research, so that becomes an additional major attraction.
Do you ever find that there is skepticism around going to the Caribbean to do science?
When it comes to clinical research and new medical devices, one might be skeptical about the level of medical/scientific expertise that is resident here. We're here to show that we do in fact have that expertise resident within The Partners Clinical Research Centre, within The Partners Stem Cell Centre, and we have formed our partnerships accordingly so that when prudent and necessary, we bring in additional expertise from the very territories that are seeking to accelerate.
Have you seen a trend toward increasing interest from researchers around the world?
Absolutely. One company, for example, is interested not only in the clinical side, but also the preclinical side--where you can have animal lab experiments done in the Bahamas, and being able to bridge that more readily with the clinical side. That presents a major opportunity for parties involved because again, the financial savings are exponential without compromising standards.
"A person who is 75 and frail, he doesn't want to wait to see if he will make it to 80 to benefit from the agent if it's approved in five years. Instead he can come to our center."
Where are some of these researchers from?
The United States, the Czech Republic, Russia, Canada, and South America. I expect significantly more interest once we promote the idea of European products having a welcome niche in the Bahamas, because we accept federal approvals from the U.S., Canada, and the European Union.
What do you think will be the first medical breakthrough to come out of research there?
One of the biggest killers in the world is heart disease, and we have the opportunity to implement a number of cardiac protocols utilizing stem cell therapy, particularly for those with no options. We just completed a state-of-the art medical center that we fashioned after the University of Miami that is getting ready for prime time. The sky will be the limit for the cardiac patient with respect to stem cell medicine.
Second, we are extremely pleased to be involved with a company called Longeveron, which is looking at how one might age better, and age more slowly, particularly with the administration of young blood and mesenchymal stem cells to frail, elderly candidates. Healthy young men have their mesenchymal stem cells harvested, expanded, and then administered to frail, elderly individuals with a view to improving their Frailty Index and functionality (feeling younger). There is a lot of interest in this arena, as one could imagine.
And herein lies the classical scenario for the Bahamas: Longeveron is now recruiting patients for its phase IIB double blind, placebo-controlled clinical trial at multiple sites across the U.S., which will add some two to three years to its data collection. Originally this work was done with NIH support at the University of Miami's Interdisciplinary Stem Cell Institute by Dr. Joshua Hare, and published in the Journal of Gerontology. So now, during the ongoing and expanded clinical trial, with those positive signals, we are able to have a commercially available clinical registry in the Bahamas. This has been approved by the ethics committee here, which is comprised of international luminaries in regenerative medicine. Longeveron will also be conducting an additional randomized clinical trial arm of same at our Centre in The Bahamas, The Partners Stem Cell Centre.
Can you clarify what you mean by "registry"?
In other words, you still have to fit the eligibility criteria to receive the active agent, but the difference is that in a placebo-controlled double-blind clinical trial, the physician/researcher and the patient don't know if they are getting the active agent or placebo. In the registry, there is no placebo, and you know you're getting the active agent, what we call "open label." You're participating because of the previous information on efficacy and safety.
A person who is 75 and frail, he doesn't want to wait to see if he will make it to 80 to benefit from the agent if it's approved in five years. Instead he can come to our center, one of the designated centers, and as long as he meets the inclusion criteria, may participate in said registry. The additional data from our patients can bolster the numbers in the clinical trial, which can contribute to the FDA approval process. One can see how this could accelerate the process of discovery and acceptance, as well as prove if the agent was not as good as it was made out to be. It goes both ways.
"We would love to be known as a place that facilitates the acceleration of ethical science and ethical therapies, and therefore brings global relief to those in need."
Do you think one day the Bahamas will be more well-known for its science than its beaches?
I doubt that. What I would like to say is that the Bahamas would love to always be known for its beautiful beaches, but we would also like to be known for diversity and innovation. Apart from all that beauty, we can still play a welcoming role to the rest of the scientific world. We would love to be known as a place that facilitates the acceleration of ethical science and ethical therapies, and therefore brings global relief to those in need.
The U.S. population is becoming more diverse, but clinical trials don't reflect that, experts say. Some are focusing on recruiting minorities to participate in research.
While racial and ethnic minority groups represent almost half of the U.S. population, the lack of diversity in clinical trials poses serious challenges. Limited awareness and access impede equitable representation, which is necessary to prove the safety and effectiveness of medical interventions across different groups.
A Yale University study on clinical trial diversity published last year in BMJ Medicine found that while 81 percent of trials testing the new cancer drugs approved by the U.S. Food and Drug Administration between 2012 and 2017 included women, only 23 percent included older adults and 5 percent fairly included racial and ethnic minorities. “It’s both a public health and social justice issue,” said Jennifer E. Miller, an associate professor of medicine at Yale School of Medicine. “We need to know how medicines and vaccines work for all clinically distinct groups, not just healthy young White males.” A recent JAMA Oncology editorial stresses out the need for legislation that would require diversity action plans for certain types of trials.
Ensuring meaningful representation of racial and ethnic minorities in clinical trials for regulated medical products is fundamental to public health.--FDA Commissioner Robert M. Califf.
But change is on the horizon. Last April, the FDA issued a new draft guidance encouraging industry to find ways to revamp recruitment into clinical trials. The announcement, which expanded on previous efforts, called for including more participants from underrepresented racial and ethnic segments of the population.
“The U.S. population has become increasingly diverse, and ensuring meaningful representation of racial and ethnic minorities in clinical trials for regulated medical products is fundamental to public health,” FDA commissioner Robert M. Califf, a physician, said in a statement. “Going forward, achieving greater diversity will be a key focus throughout the FDA to facilitate the development of better treatments and better ways to fight diseases that often disproportionately impact diverse communities. This guidance also further demonstrates how we support the Administration’s Cancer Moonshot goal of addressing inequities in cancer care, helping to ensure that every community in America has access to cutting-edge cancer diagnostics, therapeutics and clinical trials.”
Lola Fashoyin-Aje, associate director for Science and Policy to Address Disparities in the Oncology Center of Excellence at the FDA, said that the agency “has long held the view that clinical trial participants should reflect the clinical and demographic characteristics of the patients who will ultimately receive the drug once approved.” However, “numerous studies over many decades” have measured the extent of underrepresentation. One FDA analysis found that the proportion of White patients enrolled in U.S. clinical trials (88 percent) is much higher than their numbers in country's population. Meanwhile, the enrollment of African American and Native Hawaiian/American Indian and Alaskan Native patients is below their national numbers.
The FDA’s guidance is accelerating researchers’ efforts to be more inclusive of diverse groups in clinical trials, said Joyce Sackey, a clinical professor of medicine and associate dean at Stanford School of Medicine. Underrepresentation is “a huge issue,” she noted. Sackey is focusing on this in her role as the inaugural chief equity, diversity and inclusion officer at Stanford Medicine, which encompasses the medical school and two hospitals.
Until the early 1990s, Sackey pointed out, clinical trials were based on research that mainly included men, as investigators were concerned that women could become pregnant, which would affect the results. This has led to some unfortunate consequences, such as indications and dosages for drugs that cause more side effects in women due to biological differences. “We’ve made some progress in including women, but we have a long way to go in including people of different ethnic and racial groups,” she said.
A new mural outside Guadalupe Centers Middle School in Kansas City, Missouri, advocates for increasing diversity in clinical trials. Kim Jones, 51-year-old African American breast cancer survivor, is second on the left.
Artwork by Vania Soto. Photo by Megan Peters.
Among racial and ethnic minorities, distrust of clinical trials is deeply rooted in a history of medical racism. A prime example is the Tuskegee Study, a syphilis research experiment that started in 1932 and spanned 40 years, involving hundreds of Black men with low incomes without their informed consent. They were lured with inducements of free meals, health care and burial stipends to participate in the study undertaken by the U.S. Public Health Service and the Tuskegee Institute in Alabama.
By 1947, scientists had figured out that they could provide penicillin to help patients with syphilis, but leaders of the Tuskegee research failed to offer penicillin to their participants throughout the rest of the study, which lasted until 1972.
Opeyemi Olabisi, an assistant professor of medicine at Duke University Medical Center, aims to increase the participation of African Americans in clinical research. As a nephrologist and researcher, he is the principal investigator of a clinical trial focusing on the high rate of kidney disease fueled by two genetic variants of the apolipoprotein L1 (APOL1) gene in people of recent African ancestry. Individuals of this background are four times more likely to develop kidney failure than European Americans, with these two variants accounting for much of the excess risk, Olabisi noted.
The trial is part of an initiative, CARE and JUSTICE for APOL1-Mediated Kidney Disease, through which Olabisi hopes to diversify study participants. “We seek ways to engage African Americans by meeting folks in the community, providing accessible information and addressing structural hindrances that prevent them from participating in clinical trials,” Olabisi said. The researchers go to churches and community organizations to enroll people who do not visit academic medical centers, which typically lead clinical trials. Since last fall, the initiative has screened more than 250 African Americans in North Carolina for the genetic variants, he said.
Other key efforts are underway. “Breaking down barriers, including addressing access, awareness, discrimination and racism, and workforce diversity, are pivotal to increasing clinical trial participation in racial and ethnic minority groups,” said Joshua J. Joseph, assistant professor of medicine at the Ohio State University Wexner Medical Center. Along with the university’s colleges of medicine and nursing, researchers at the medical center partnered with the African American Male Wellness Agency, Genentech and Pfizer to host webinars soliciting solutions from almost 450 community members, civic representatives, health care providers, government organizations and biotechnology professionals in 25 states and five countries.
Their findings, published in February in the journal PLOS One, suggested that including incentives or compensation as part of the research budget at the institutional level may help resolve some issues that hinder racial and ethnic minorities from participating in clinical trials. Compared to other groups, more Blacks and Hispanics have jobs in service, production and transportation, the authors note. It can be difficult to get paid leave in these sectors, so employees often can’t join clinical trials during regular business hours. If more leaders of trials offer money for participating, that could make a difference.
Obstacles include geographic access, language and other communications issues, limited awareness of research options, cost and lack of trust.
Christopher Corsico, senior vice president of development at GSK, formerly GlaxoSmithKline, said the pharmaceutical company conducted a 17-year retrospective study on U.S. clinical trial diversity. “We are using epidemiology and patients most impacted by a particular disease as the foundation for all our enrollment guidance, including study diversity plans,” Corsico said. “We are also sharing our results and ideas across the pharmaceutical industry.”
Judy Sewards, vice president and head of clinical trial experience at Pfizer’s headquarters in New York, said the company has committed to achieving racially and ethnically diverse participation at or above U.S. census or disease prevalence levels (as appropriate) in all trials. “Today, barriers to clinical trial participation persist,” Sewards said. She noted that these obstacles include geographic access, language and other communications issues, limited awareness of research options, cost and lack of trust. “Addressing these challenges takes a village. All stakeholders must come together and work collaboratively to increase diversity in clinical trials.”
It takes a village indeed. Hope Krebill, executive director of the Masonic Cancer Alliance, the outreach network of the University of Kansas Cancer Center in Kansas City, which commissioned the mural, understood that well. So her team actively worked with their metaphorical “village.” “We partnered with the community to understand their concerns, knowledge and attitudes toward clinical trials and research,” said Krebill. “With that information, we created a clinical trials video and a social media campaign, and finally, the mural to encourage people to consider clinical trials as an option for care.”
Besides its encouraging imagery, the mural will also be informational. It will include a QR code that viewers can scan to find relevant clinical trials in their location, said Vania Soto, a Mexican artist who completed the rendition in late February. “I’m so honored to paint people that are survivors and are living proof that clinical trials worked for them,” she said.
Jones, the cancer survivor depicted in the mural, hopes the image will prompt people to feel more open to partaking in clinical trials. “Hopefully, it will encourage people to inquire about what they can do — how they can participate,” she said.