COVID-19, Diversity & Clinical Trials

According to the US National Library of Medicine, there are currently 1358 COVID-19 specific studies and trials being conducted around the world. Of that, 520 are taking place in Europe and 274 in the USA, rising to 330 for the whole of North America.

However, in the second most populous continent on the planet, Africa, there are just 39 studies ongoing, 27 of which are in Egypt. That means just 2.8% of studies into coronavirus are taking place in Africa. That’s seen a sharp rise, too. There were just three at the beginning of April, all of which were in Egypt.

Forget COVID-19-specific studies for a moment, and the figures shoot up. The National Library’s data covers 338,821 studies in total, with just 9938 of those were conducted in Africa. Bizarrely that equates to 2.9% of studies, meaning that that the proportion of African coronavirus studies are within .1% of the global clinical trial landscape.

From a population perspective this is clearly awry, but perhaps not a huge surprise. African countries (aside from Egypt and South Africa) lack the clinical infrastructure of more developed nations needed to conduct trials. But what about where the infrastructure is there?

A First World Problem

Coronavirus has provided us with a very large and extremely recent data set for research, patient populations and how different ethnic minorities are being affected versus the research. And the early indicators are that those from minority backgrounds are being more adversely affected than others.

In the UK, the first 11 doctors to die of coronavirus were all from Black, Asian or Minority Ethnic (BAME) backgrounds. They have also made up over two thirds of the total number of UK health worker deaths.

The statistics remain damning when expanded to the general UK COVID-19 patient population. 

As of April 30^th, one third of the 6574 COVID-19 patients in intensive care were from non-white ethnic groups. That’s despite those groups making up just 13% of the population as a whole.

However, when we compare that to the statistics around all hospitalised patients with the virus (i.e. not just those in intensive care), just 16.2% are from a BAME background – a much more representative figure. So why are those from BAME backgrounds seemingly getting much sicker with the disease?

That’s a question with a complex, multifaceted answer which has economic, political, genetic and communicative elements to it. But one thing that would help us get that information more quickly would be proportional representation of these groups in clinical trials and research studies. However, that representation is globally lacking.

The Consequences of Underrepresentation in Clinical Trials

In the US, the picture is stark. 40% of Americans belong to a racial or ethnic minority, while 90% of clinical trial participants are white. This is not just a theoretical, scientific, problem either. It’s having devastating consequences for some groups of asthma sufferers.

Asthma is the most common chronic childhood disease in the world. The most common treatment for the condition is a drug called Albuterol, which opens up the medium and large airways in the lungs.

However, a recent genomic analysis has revealed numerous genetic variants between how African-American and Puerto Rican children metabolize the drug when compared to European American or Mexican children. The drug is significantly less effective in treating asthma for the former (who incidentally have the highest prevalence of asthma in the USA), and there is a four-to-five-fold higher death rate from asthma among those groups.

The CRO’s View: “The Demographics of Clinical Trials Don’t Represent the Demographics of the World Population”

Why then, are these groups which take up a significant proportion of the population so underrepresented in clinical trials and who is responsible for rectifying the problem? I asked former CEO and President of Vium Wendel Barr, that question. He replied that the responsibility

“falls on the people who are conducting the trials to make them accessible.

One such organisation, dedicating themselves to a solution to this problem is 2M Research, a minority owned CRO and consultancy focused on diversifying clinical trials. I spoke to VP and Chief Scientific Officer Craig Reist, Chief Growth Officer Keith Tode & SVP and Chief Medical Officer Regina James about how to solve the problem.

Craig told me simply that

the demographics of clinical trials don’t represent the demographics of the world population

When I asked how to solve the problem and who was responsible, Regina answered that a solution required a combined effort from clinicians, researchers and community members, and that

sponsors can consider diversity efforts during the trial design phase and re-evaluate exclusion criteria to ensure that study integrity and diverse representation is accomplished.

Clinicians can reconsider who they are referring to clinical studies. Academicians can make the effort to have diverse representation in their research team and build relationships within the communities they conduct their studies.

Community members can learn more about the benefits and risks of participating in trials to help them make an informed decision about participation.

The Academic View: “A Moral, Scientific and Medical Issue”

A study published in May 2019, Increasing Diversity in Clinical Trials: Overcoming Critical Barriers identified 5 barriers to the participation of ethnically diverse patients in clinical trials. They were:

• Mistrust
• Lack of comfort with the clinical trial process
• Lack of information about clinical trials
• Time and resource constraints
• Lack of awareness about the existence and importance of clinical trials

You can read the full report here but the proposed solution echoed that which I discussed with 2M. To pull together a collaborative effort between all stakeholders, take a patient-centric approach and communicate in a way that is accessible and familiar to the patients.

As these groups have almost certainly never had any experience in these settings, it can present a challenge to get through to them and change attitudes toward participation in trials. Reinforcing the ideas that being involved in a trial doesn’t’ mean you are a ‘guinea pig’ is key and that health and safety are prioritised throughout.

Building a strategy which is built on the pillars of strong messaging, existing relationships and effective communication is key to solving the problem. One of many groups dedicated to this cause is the non-profit Center for Information and Study on Clinical Research Participation (CISCRP), who look to educate patients and raise awareness around clinical trials. They aim to connect patients with local clinical trial programmes, via their Search Clinical Trials service. There’s a huge amount of information available on their website designed to communicate much needed information to potential participants.

A Regulatory Solution?

The most effective way to make the industry change their approach is for regulators like the FDA and EMA to change the rules around clinical trial representation, as Japanese regulators have. Due to the variance in drug efficacy and safety between different ethnic populations, Japanese regulators require sponsors to provide data from Japanese participants in trials before they can move to phase II or III of trials in the country.

This has led CROs like PPD to conduct ‘ethno-bridging’ studies to include Asian populations in trials, even those conducted in the US or Western Europe. This is then helping to speed up the roll-out of latter stage trials in Japan as the conditions have already been met.

If proportional regulations were enforced in studies by the FDA/ EMA and others, the issue could be solved and the joint effort from all the responsible parties could gather pace. After all, regulatory changes have had big impact in recent years for other groups. Since the FDA stopped classifying women as a ‘vulnerable population’ in 1993, there has been a huge spike in female participants for novel drug trials, with more than 70% of patients last year being women (many of the trials were female-specific, but the point remains).

The COVID-19 Effect

Now seems a good time to cast a critical eye over the clinical trial landscape whilst so few are being conducted. COVID-19 has had a huge impact on everyone involved in the clinical trial landscape.

CEO of CRO Clinipace Jason Monteleone wrote in early April that COVID-19 caused more trials to be suspended in March this year than in the whole of 2019. A sentiment echoed by other big players like IQVIA, saying 70% of their global sites are currently inaccessible.

The suspension of trials is having a disproportionate impact on another demographic group: the elderly. Aside from being the most vulnerable group to the virus itself, the elderly are often the group with the most to gain from successful clinical trials being concluded. A large proportion of the suspended trials in March were oncology-focused, meaning that many of those patients may not now be receiving their cancer treatment.

Adam Brown Sr, CEO of CRO consultancy ClinArk, wrote on LinkedIn recently that 80% of clinical trials in the USA fail to meet their enrolment goal, with 50% enrolling one or no patients. He added that 82% of all research sites that have clinical trial experience have conducted just ten studies or less.

With clinical trials being disrupted more now than in any other point in my lifetime, it feels like a watershed moment, and a rare opportunity to take stock and some of these issues. Proper patient representation in trials, funded by major education and communication programmes by CROs large and small could go some way to helping address those inefficiencies.

Because if clinical trial results aren’t representative or generalised for all the communities they are supposed to serve, are they doing their job?  

I’d love to discuss any of the points I’ve raised in my article. If you have a comment, question or criticism then please get in touch! You can reach me on LinkedIn or at matthew.barrows@lifesci-cm.com