Increasing diversity in clinical trials

Diversity at the clinical trial level will help foster more equity in our healthcare system.

Saraswathy (Sara) V. Nochur, Ph.D., is the Chief DE&I Officer at Alnylam Pharmaceuticals, Inc. Previously, she served as the company's Chief Regulatory Officer for 14 years.

The COVID-19 pandemic laid bare our nation's glaring and indisputable health inequities. The number of people infected, hospitalized, or dead from COVID-19 is two to three times higher among the Black and Hispanic populations compared to White, non-Hispanic Americans, according to recent CDC data. Unfortunately, this isn't surprising. Despite significant advances in scientific research, technology and innovation, minority populations in the U.S. continue to be left behind: suffering greater morbidity and mortality—due to hypertension, heart failure, cancer, and many other conditions—often as a result of inadequate care and lack of access to medicines.

The sources of these disparities are complex, often rooted in bias, prejudice, and stereotyping, and involve all of the players in the U.S. healthcare equation: health systems, policymakers, utilization managers and payers, the biopharmaceutical industry, healthcare professionals, and yes, patients themselves. Knowing the system is stacked against them, patients of color often delay doctor visits, postpone treatment and are more skeptical of the safety of FDA-approved medicines.

An important aspect of addressing these inequities, and medicine safety concerns in particular, begins with greater participation of racial minorities in clinical trials for drugs, devices, and vaccines. 

As a biopharmaceutical industry, we have been required to evaluate “special populations” in clinical trials, including the elderly or those with kidney or liver impairment, especially as it relates to dose and safety. Similarly, following the enactment of the Pediatric Research Equity Act in 2007, The Food and Drug Administration (FDA) has required the conduct of relevant clinical studies in children to ensure optimal dosing, efficacy, and safety.  

However, we have neglected to adequately include patients from different racial or ethnic backgrounds in most clinical trials. Bidil, a drug that was approved by FDA in 2005 specifically for “self-identified black patients” for the treatment of heart failure serves to underscore the potential for differences in the benefit/risk profile of drugs based on racial or ethnic background and highlights the need for increasing diversity in clinical trials.  

Fixing this problem can't wait. 

As the latest census data showed, it won't be long before we are a majority-minority nation with non-whites comprising more than half of the U.S. population. It is time for all stakeholders involved to collaborate on a broad, concerted, and sustainable effort to respond to the needs of communities that have long been disenfranchised.  

While there are numerous hurdles to overcome, one that fundamentally needs to be addressed is trust. Although the recent clinical trials for the two mRNA vaccines for COVID included greater racial and ethnic diversity than many previous trials, a Kaiser Family Foundation survey found black adults more likely than white adults to point to concerns about safety and side effects as major reasons for why they probably or definitely would not get vaccinated. Such sentiment is not unreasonable. Starting from the early 1900s and the birth of the American eugenics movement, there is a long and sordid history of conducting trials in African American and Hispanic populations. From the Tuskegee Study to the forced sterilizations of thousands of Black, Hispanic, and Native American women, history has reinforced the notion of scientific exploration as exploitation of racial and ethnic minorities.   

So, what can be done? 

It is encouraging to see that advances are being made in this regard. The FDA has issued guidance on increasing clinical trial diversity. Just this past June, Anna Eshoo, Congresswoman from the 18^th District in California has proposed a draft bill to Congress entitled ‘Diverse and Equitable Participation in Clinical Trials (DEPICT) Act' to enact legislation requiring clinical trial diversity and equity and also proposing grants and funding to enhance community engagement and outreach to underserved communities and to increase the capacity of community health centers to participate in clinical trials.  

As an industry, we must support these initiatives, and simultaneously act on the following:

Engage minority-focused communities directly.

We need to work with non-profit minority community groups and patient advocacy groups to show transparency and build trust. We must actively listen to the concerns of patients and engage in sensitive and culturally appropriate ways of communication. We also have an opportunity to provide education on clinical trial processes and procedures, the need for increasing diversity in clinical trials, and to highlight our commitment to the regulations that are in place to ensure equitable and fair treatment. 

Engage healthcare providers who serve underserved communities. 

This will require investment and engagement for the long term. Well-known academic centers can no longer be the mainstay of sites that conduct clinical trials. We must actively seek out community hospitals and centers that have greater access to patients of diverse backgrounds, train them in good clinical practices and equip them with the resources and infrastructure needed for participation of their patients in trials.  

Restructure trial protocols to maximize participation of under-represented populations.  

We need to fundamentally rethink how we conduct clinical trials to include minorities reflecting their representativeness of the disease condition, and to address the barriers and hesitancy that exists among potential trial participants. Taking into consideration their socio-economic and insurance status, studies should be designed to minimize travel time to trial sites, reduce the frequency and number of assessments, allow for telehealth visits where appropriate, and include innovative ways of gathering and disseminating information.  The use of technological solutions must ensure considerations such as access and equity.  

“Reference ranges” for various laboratory or other parameters that underlie inclusion-exclusion criteria need to be studied further and may need to be adjusted to allow for potential variations based on racial or ethnic differences to ensure inclusion.  

Re-envision clinical trials-related communications and materials to be culturally appropriate and accessible.  

Materials and patient-facing documents need to be tailored to ensure transparency, ease of understanding, and appropriate language to address cultural sensitivities of various ethnic and racial groups. Ease of access to these materials must be taken into consideration.

At Alnylam, we are preparing for future trials by implementing many of these ideas. We also recognize that we don't have all the answers and that is why we have established relationships with national community organizations to understand and help address the challenges and barriers faced by their constituents. We are also actively setting goals for our trials to ensure appropriate representativeness based on disease prevalence and are making concerted efforts to seek sites that can help us meet these goals.  

It is clear that we have bold ideas and the willingness to act. For this to be a sustainable effort, we must work together to transparently communicate to all stakeholders the high risk nature of clinical trials and yet demonstrate the longterm commitment of companies and institutions to the patients and communities they serve. 

With a more diverse workforce demanding equity and inclusion across the board, and with all the relevant parties engaged and collaborating, I am confident that we can make a meaningful difference in diversifying clinical trials resulting in a more equitable society offering quality healthcare to all.