COVID-19 has changed how many sponsors enrol and retain trial participants. From decentralisation, increased use of wearables and changes in population targeting, the pandemic has seen a shift in both priorities and procedures with regard to enrolment. But is this enough to overcome issues of minority underrepresentation and population disenfranchisement that clinical trials struggled with prior to 2020? We spoke with Ash Rishi, CEO of COUCH Health, about the problems of patient enfranchisement and recruitment, and what can be done to overcome them.

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Tell us about your company’s work, and the causes it supports?

Ash Rishi: I’m the founder of COUCH Health, a patient engagement agency working globally. Over the last few years, one of our core missions has been improving diversity and inclusion within clinical trials.

A lot of our research has centred around determining the best way to do this. Often, this has involved talking to community and spiritual leaders, but I think there’s more we can do. COUCH Health reaches patients through digital marketing, aiming to get them into clinical trials. We’re trying to evolve from a generic advert that’s sent to every population to something more bespoke, e.g. ensuring our language is understandable and relevant to every community. Our challenge is doing that on a global scale. 

To me, this is also a personal challenge. I lost my father in his early fifties to cancer, and I’ve often wondered whether, if he had taken part in a clinical trial, whether my mother and I would have had a few more months with him. Now I run my own company, I hope I can do something to ensure this is a reality for others out there. 

What are the main causes of underrepresentation in clinical trials? To what extent is this a fault of trial sponsors?

AR: It’s a healthcare and health equity issue more than a clinical trial one. You often see what we in the UK call the ‘postcode lottery’. Those in richer boroughs or areas get more innovative treatments, while those of lower socioeconomic standing aren’t getting the treatment they need. 

There’s also the issue that certain communities have a deep mistrust of healthcare, due to political issues such as Brexit or the Windrush scandal in the UK. These have all created an environment of distrust. In the US, there’s the additional issue that healthcare is expensive, and therefore those of lower socioeconomic status have less access. 

Clinical trials have also been designed in a very labour-intensive way. You can’t just have an assessment over the phone; you need to take a day off and go to a site that could be over 100 miles away. If you’re working two jobs, or have to look after several children, this is extremely challenging. Even if you do join a study, it’s doubtful you’ll stay. There absolutely needs to be a revolution in how these trials are run — and hopefully, COVID-19 is bringing about that change.

Is this a case of certain specific therapeutic areas lacking subject diversity, or is it more an overall healthcare / structural problem?

AR: It’s an issue across the board — not any one area in particular. There are some good examples when we talk about female underrepresentation. Cardiovascular disease, which affects men and women equally, has enormous disparity in clinical trials. Even more extreme, Cialis, the ‘female viagra’, would presumably have 100% female trial participants, but 80% of them are men! 

The same can be said for over 65s. Our population is ageing, and this is an important population to target, but they’re not included in trials, either for Alzheimer’s or other conditions. How can we know medications work if we’re not testing them sufficiently? 

Are certain populations more affected by these problems, and to what extent is this reflected in that population’s health? 

AR: The populations most affected differs by country. Obviously, more data has come out of the US than any other country, and so we know that there it’s mainly Black, Hispanic and Native American populations. It’s been reported that Black Americans make up 18% of the US population, and yet represent only 5% of clinical trials. 

We want to reach a place where participants on a specific trial represent the demographic affected by the trial target. Sickle cell disease, for example, affects 60% African Americans, so 60% of the trial demographic should be Black. That’s what we’re trying to encourage sponsors to think about. It’s not just pushing the overall message of recruitment. It’s about engaging specific populations through language and other means. 

What else can organisations do to increase patient-centricity and work with these populations in recruitment?

AR: A few initiatives are working well. We’ve developed cultural safety training. Research sites, which are the element patients interact with most, are trained up on how to be culturally safe, beyond unconscious cultural bias and cultural competency. 

We’ve found that with the reflection exercises on this program, individuals have a lightbulb moment where the get what ‘culture’ means. To put it crudely, many people think white people don’t have a particular culture. But they do, and when people understand their own culture then we can flip it round and apply it to other populations. 

As I mentioned, we’re also doing community outreach, where we have materials reviewed by the population we’re trying to reach. This is an important step, because medics and scientists don’t speak in the language of the population. By making the literature more culturally accessible and making the visuals more diverse and representative, we can appeal to populations in a positive, focused way.

Resource-wise, the FDA has brought out guidance recently. In the UK, we’re trying to encourage regulators to make this policy, though we’re probably lagging a little, honestly. But there really are few resources out there. We’re getting case studies soon, however.

In one of your reports, you mention age as a factor in minority reaction to trials and vaccines. Will younger generations see a natural shift in minority representation in trials?

AR: It’s my hope that new generations will see a shift towards representation. Technically, it should improve. Media representation of trials during COVID has been an important step in this. We’re now seeing a better portrayal of trials. But I’m still seeing adverts that miss the point, that are only creating more mistrust. I’m worried we’re making the same mistakes again. Targeting a minority because they’re a minority creates mistrust, because it’s not well understood that there is an issue of diversity in trials!

COVID-19 has dramatically shifted how organisations recruit patients. Have lessons been learnt in terms of diversity and representation? Have there been any negatives to this?

AR: COVID-19 was absolutely an industry eye-opener. People realised that the virus affected populations differently quite early on. Through the trial process, companies like Moderna ensured representation was diverse. 

There were large numbers of trials working to produce a COVID-19 vaccine, and only a few got their products to market. The common denominator for the successful trials was that they generally had stronger data, and this came from more diverse trial populations. There really weren’t many negatives to this pandemic, from a representation perspective.

This proves they can do it! I think the industry has finally woken up a little bit to innovation, new approaches and models, and we will see a boom in this industry, and in the next 2–3 years we’ll see some real and needed innovation. 

To better raise awareness of the diversity and inclusion issue within clinical Trials, Ash has been running Demand Diversity, which is a campaign for change. A mission to raise awareness. And a rallying cry for the industry to do better.

Guided by insight, research and vital collaborations with patients, diverse groups and others in the industry with the same vision, we’re going to drive action and demand that we all take responsibility to do better. You can get exclusive research here.

To discuss these topics further with sector experts, and to ensure you remain up-to-date on the latest in clinical development, sign up for Proventa International’s Clinical Operations Strategy Meeting, set for 15 June 2021.

Joshua Neil, Editor
Proventa International

The post Supporting Diversity in Clinical Trials: An Interview with Ash Rishi, COUCH Health appeared first on Proventa International.

But for its many touted advantages (greater survival rate and quality-of-care for patients; vastly improved drug efficacy; a greater understanding of disease mechanisms), some elements of precision medicine have faced criticism. Perhaps one of the most well-known and troubling concerns of the model is its inherent biases involving ethnicity. While such a fundamental flaw in the underlying data remains, the field cannot advance. We looked at what is being done to change the model, and how effective such initiatives currently are.

The Current Problem

The bias problem has been a known issue for quite a while. In 2018 the Data & Society Research Institute reported that precision medicine could cause harm through discrimination against minority groups. They determined that almost exclusively rich, white men would benefit from the model due to their good insurance and lifestyles. Women, minorities and immigrants would be far less supported.

The major problem of bias lies in historical studies and current datasets: most overwhelmingly consist of white communities. One example is the guidelines for U.S. lung cancer screenings. These are based on a study of 53,000 people, with African Americans making up only 4%. As recently as October 2019 it was found that all minorities are under-represented in U.S. cancer studies, with only 2% of clinical trials focusing on minorities. Earlier in 2019, a study found that 10% of the African genome is missing from the human genome project. 

The issue is not purely in early research and R&D: it is also largely in the clinical trial space. Such trials have long had issues with diversity, caused by several factors. These include a lack of knowledge or awareness of the need for such diversity, a bias against the traditional healthcare system or a lack of insurance and cost problems. Around 20% of drugs are thought to act differently based on race and ethnicity. Pharmacokinetics particularly behave wildly differently between Europeans and East Asians. Other drugs can be more effective in men than women. 

Solutions to the Bias

Aware of the problem, many researchers are taking correcting measures. In 2015 the U.S. National Institutes of Health, undertaking an enormous Precision Medicine Initiative study, made significant efforts to address the issue. In the study, minority groups were over-represented relative to the general population, allowing for greater statistical significance when studying them.

Similarly, the Population Architecture using Genomics and Epidemiology study, published in June 2019, conducted a genome-wide association study of 26 phenotypes in almost 50,000 non-European individuals. It found that a mutation rare in Europeans occurs in 1% of Latinos and 6% of African Americans, proving the utility of such research. A CDC study found African American individuals twice as likely as Europeans to die from uncontrolled hypertension. Another found that Native Americans are ethnically most inclined to type 2 diabetes.

These programs, and others such as the All of Us Research Program, are addressing the issue in an extremely slow and long-term way, however. They do not in themselves take steps to correct the issue today, nor do they address fundamental underlying concerns around patient engagement and current pharmacological incompatibility. 

National genomic initiatives and their kind can greatly help target the demographics of each country. However these still avoid the issue that so many pharma companies create drugs with a particular, largely white, population in mind. A lack of efficacy and arguable safety here is often still unaddressed. 

This touches on the issue of clinical trials: with limited trial diversity, the effect of a drug on a given population just cannot be accurately ascertained. Having said that, last year the FDA issued draft guidance on enhancing trial diversity and improve enrolment practices to better represent a population along racial and ethnic lines. 

There are also many wider ways to address the lack of diversity in clinical trials. CROs and universities, which often have a wider reach and better connectedness than many pharmaceutical companies, can use their influence to encourage awareness and understanding. 

Pharma companies seeking to increase diversity can increase their cultural and linguistic competency. This means understanding cultural differences and requirements as well as simply speaking the common language. New technologies which increase comfort and access to medicine, such as wearables or virtual trials, can also have a big impact in trial uptake. 

On a broader front, scientists can ensure that from the outset studies take into account variable cost management policies. This ensures greater individualisation of treatment, dependent on ethnicity and heritage. 

One alternative is the customisation of current medicines for different minority populations. The H3D company is a great example of this, created to tailor medicines for African-American communities. It also fosters the running of clinical trials in Africa, a continent on which only 2% of global studies take place. This is for a number of reasons: lack of predictability, long timelines and the centring of quality trials on only a few centres across the landmass stand among others. The centre attempts to treat malaria, tuberculosis and anti-microbial resistance, particularly optimising those drugs for the treatment of individuals of African descent. 

Several other organisations are doing excellent work in the area, including the Wellcome Trust DELTAS program and the GSK Africa OpenLab.

What Difficulties Remain?

Even with programs like H3D, a number of challenges remain. Alongside the lack of big pharma clinical trials held in the continent, the attracting and retaining of talent in such organisations is difficult. 

Another concern is regulatory pressure. While the African Medicines Agency has moved the regulatory field forward in recent years, much still needs to be done. Collaboration between drug regulators and the pharma industry must increase. Regulators must widen their capacity to review drugs, allowing for simultaneous introduction of products. Drugs take on average five to ten years to reach Africa after U.S. launch, and as such increased speed and efficiency of getting to market are imperative. 

Conclusion

From a cursory glance at the hundreds of statistics on the subject, it is clear there is still a considerable lack of diversity in precision medicine research. Until it is confronted and overcome, precision medicine will be at best biased and at worst unreliable and potentially unsafe. Both immediate and more far-reaching initiatives are certainly in the pipeline. It is clear however that more must be done to rebalance the issue as soon as possible.

Precision medicine is the future. As it stands, it is one of the most promising pathways to greater healthcare and better, safer treatment for all. But until the mentioned methods see greater take-up, the future is a hope more than an inevitability. 

Joshua Neil, Editor
Proventa International

The post Avoiding Bias in Precision Medicine appeared first on Proventa International.