Going Global: Asia-Pacific Region Not Represented in Large Clinical Trials

In the Asia-Pacific region, home to more than 60% of the world’s population, cardiometabolic risk factors are on the rise and the CVD burden is heavy, but the area remains dramatically underrepresented in major clinical trials.

That needs to change, experts argue in a JAMA viewpoint published recently online.

“The reality is that despite the fact that a lion’s share of the burden of disease is going to be where the population is, we don’t tend to perform trials in this region or enroll as many patients from this region in trials,” said Stephen Nicholls, MBBS, PhD (Victorian Heart Institute, Monash University, Clayton, Australia).

The viewpoint follows a clinical trial summit convened by JAMA last year where much of the discussion occurred within a US context, Nicholls told TCTMD. While there was much to be learned for the global trial community, in particular he raised the concept of “how we start to engage the most populated region in the world, which continues to be underrepresented.”

Nicholls, along with his viewpoint co-authors, participated in an analysis published last year in JACC: Asia showing that among cardiometabolic trials published in top-tier journals between 2011 and 2020, only 8.3% of participants identified as Asian and 7.7% came from the Asia-Pacific region, which also provided only 10.1% of authors on those papers.

“We know that it is becoming increasingly important that we have diversity in our clinical trials,” Nicholls said, noting that there has been a push in the US in particular to boost representation of various groups. But, he added, “I don’t think the need for diversity in clinical trials ends at the shores of the United States. And so we need to be thinking about diseases that have a global burden. How are we going to effectively tackle clinical trials in other parts of the world?”

Why Is the Asia-Pacific Underrepresented?

Duk-Woo Park, MD, PhD (Asan Medical Center, Seoul, Korea), a deputy editor of JACC: Asia, told TCTMD that there are multiple factors playing into the low numbers of participants and investigators from the Asia-Pacific region in large CV trials. For one, “mega” trials typically test new therapeutics, which tend to be developed by companies in the US and Europe. Those trials are designed to fulfill requirements for approval by the US Food and Drug Administration or the European Medicines Agency and enroll most participants from those regions, Park said.

In addition, he said, regulatory bodies in certain countries in the Asia-Pacific—such as China, Japan, or South Korea—can be very strict and require locally performed clinical trials before approving new medications or devices.

And finally, the infrastructure and workforce needed to perform large clinical trials varies across the region, with some countries well equipped to take on the challenge and others unable to do so, Park said.

We’ve all been concerned about the way that cardiovascular disease has transformed from a disease of affluent societies to now a disease that affects every country in the world. Stephen Nicholls

Craig Anderson, MD, PhD (The George Institute for Global Health, University of New South Wales, Sydney, Australia), who has helped conduct trials on stroke management and other aspects of CVD across the Asia-Pacific region, picked up on that last point—the heterogeneity of the individual countries—as well. Certain nations, such as China, Japan, South Korea, and, more recently, India, are doing well in terms of performing clinical trials, “but the rest of Asia is pretty sleepy,” he said.

That has to do, in part, with a lack of capacity among physicians in other countries to perform high-quality trials. “You’ve got a huge population need and you’ve got a huge clinical population that could go into trials, but you don’t have the capacity to run the trials to an international rigorous standard that you would expect to be part of an international playing field,” Anderson said.

What this really comes down to is the extensive diversity of the region, he stressed, pointing to differences in socioeconomic status, culture, language, and governance across countries, with challenges also being presented by the vastness of the area and the dual threats of infectious and chronic diseases.

He said this is a huge issue, pointing to the number of people living in the Asia-Pacific region and the high burden of CVD found there. “I think internationally we have a collective responsibility to help this part of the world,” said Anderson.

Getting the Region More Involved

Anderson underscored that “it’s not easy to come up with a single fix because there’s so many different things going on.”

A key component of how well a country is set up to perform clinical trials is the level of economic development, Anderson said. If government leaders can appreciate that their population’s health is a critical component of these trials, then they’ll be more likely to invest resources into performing them.

International pressure from groups like the World Health Organization can help, too, Anderson said.

Because of the heterogeneity, there won’t be solutions that will work for every country, Nicholls underscored. “So how do we have interventions that are fit for purpose across this region? How do we deliver clinical trials in ways that can deliver really meaningful and impactful information so that it can improve the way that we prevent, diagnose, and treat the disease?”

It starts, he said, with health services and governments providing an environment conducive to performing clinical trials, which he acknowledged will be more difficult in lower- and middle-income countries.

Industry also has a critical role to play in developing or repurposing therapies in an affordable way and then creating the evidence needed to show how they can be delivered in different parts of the world, Nicholls said.

“If all we’re doing with a clinical trial is publishing a paper in the New England Journal of Medicine or JAMA and patting ourselves on the back, that’s not enough. That’s clearly not enough,” he commented. “It’s got to be: how does the clinical trial influence practice and how does that influence health outcomes for patients and people in the community?”

Part of what’s going to help is encouraging local leadership in clinical trials and training the trial workforce of the future by building networks and undertaking capacity-building initiatives across the Asia-Pacific, Nicholls said.

“We’re not suggesting that there are simple solutions,” he said. “We think we could punch well above our weight. We’re certainly punching below our weight at the moment. And we think that this was an opportunity for a call to arms to say, ‘Hey, we have the opportunity to change the trajectory of cardiovascular disease in this part of the world, like we’ve been trying to do in other parts of the world.’”

The big picture message is that “we need to arrest this disease,” Nicholls said. “We’ve all been concerned about the way that cardiovascular disease has transformed from a disease of affluent societies to now a disease that affects every country in the world. A lot of it’s preventable. It’s about: how do we get effective strategies in the hands of people who can make a difference? Clinical trials transform the way that we do that. We just want to make clinical trials more global.”