Developing clinical trial protocols that include more diverse populations offers opportunity to product developers, marketers

Two years ago, the National Academies of Science issued a report​ on improving representation in clinical trials, exploring existing policies and procedures and how this could be accelerated. It noted that addressing the underrepresentation of women and racial and ethnic minority groups could not only help to tackle health disparities but confer positive economic benefits.

The National Institutes of Health (NIH) hones in on this issue through the National Institute on Minority Health and Health Disparities, with extensive resources on the topic, including how to improve diversity and inclusion in clinical trials.​ This has been taken further by FDA, which issued a draft guidance on diversity in clinical trials​, focusing on diversity action plans. While it is focused on the pharmaceutical industry, the insights are relevant to the supplement space as well.

Ultimately, the intent is to ensure that researchers consider the multiple dimensions of diversity, including age, ethnicity, sex and race, during clinical study enrollment to ensure study populations are truly representative of those who will use the products. The Association of Clinical Research Professionals issued a response document around the FDA draft guidance​ on diversity stating that such diversity should be a requirement, not just a recommendation.

In fact, research studies in the supplement industry have, in many ways, taken cues from the pharma industry. WCG, a clinical research organization (CRO) in the pharma space, released a 2024 trends and insights report​ and put diversity top of the list. 

It noted: “The scientific case for diversity is largely settled. What’s left is continuing to make the case with key stakeholders in moving DEI initiatives for clinical trials forward in a meaningful way.” 

The firm further reported that among companies doing clinical research, its research found that those who saw diversity as a scientific or ethical imperative believed it was more important than those who viewed it through a regulatory or marketing lens. Within the supplement industry, there is an opportunity to get ahead of the curve.

“Increasingly, regulatory bodies and health authorities are emphasizing the need for diverse representation in clinical trials,” said Karin Hermoni, VP of science and innovation at SuanNutra. “Diversity in clinical trials allows researchers to account for biological variations. As an industry, we need to be more tuned in to the diversity in our target audience and make sure it is going to be safe and effective to the wider audience. Results from homogeneous populations might not be representative and applicable to certain groups or minorities.”

Instead, conducting research in more diverse population cohorts may yield even more interesting findings.

“You have data that is more informed, more applicable to various populations; you learn more about your product,” suggested Susan Hewlings, PhD, SVP of scientific affairs at Radicle Science. “People of different sizes, genders and ages are not the same for many reasons. Some of the differences based on these factors could impact the effectiveness of a product in how it is absorbed or metabolized, or that baseline level of the substance being tested could be impacted by one of those factors, which would, in turn, impact its effects.”

Erin Lewis, PhD, scientific director at KGK Science, concurs that studies should be representative of the target geographic and demographic, using recruitment strategies for a wide net and to consider safety that can be neglected in decentralized virtual trials, an issue raised by FDA in a recent guidance.

“This allows the results of the study to be generalized to the greater population, inclusive of both efficacy and safety assessments,” she said. “However, safety of a given product is of significant importance in any trial, which is why it’s important to study safety markers in diverse populations.”

The focus on diversity must be considered from the very beginning, according to Hewlings: “It has to be considered in every aspect of the study design from recruitment, stratification to the statistical plan, to how the research is communicated via scientific publication to marketing messages.”

However, there are differences between the pharma and supplement space, not least because supplements are not curative.

“The pharma industry is very indication-driven: What is the prevalence of this disease relative to the ethnic or racial background,” noted Josh Baisley, SVP of clinical operations at SGS Nutrasource. “We haven’t explored this fully in the dietary supplement industry. But if you’re looking at indication-driven research or researching nutrient deficiencies, you need to look at who is the target population or those in need, and your recruitment should take that into consideration and set diversity targets similar to where the need is.”

That said, supplements are ‘supplementing the diet’ and not preventing or treating a disease state, which Hermoni noted means generally studies are in a healthy population.

“While it makes sense to exclude people taking certain medications, even with the best intentions, we create a knowledge gap,” she said. “Unless we are proactive about recruiting underrepresented groups, we will end up with the same ‘default’ that reinforces the gap.”

There is also a cost consideration at play. 

“There will likely be recruitment challenges, delays, more planning around how you recruit,” Baisley said. “If we’re looking for diversity, the wording is different, the messaging needs to be different, the imaging has to be different to reach the intended audience. Is it the right medium or platform? Do you need translations? It does take time and money, and it’s not just as simple as saying we’ll recruit from this population.”

When taking the next step in recruitment, there is an interest in finding a representative population while also leveraging appropriate resources.

“Typically, recruitment happens through an existing database of participants, social media and community engagement,” Lewis explained. “Collecting information about ethnicity and background during the screening process is an important consideration to know whether a study has adequate diversity and inclusion.”

However, this comes with challenges as well.

“If you think about it, just the fact that a person has to be in person at a university lab, clinic or research site is a constraint,” Hewlings said. “This potentially eliminates individuals who live in rural locations, individuals who work, and those of different sociodemographic status who may not have transportation.”

Instead, Hermoni suggests exploring options such as offering assistance with transportation and flexible schedules while also remaining mindful of cultural sensitivities related to dietary practices or health beliefs. It is also meaningful to share information during recruitment​ about the desire to ensure a diverse population; in one study, 73% of clinical study participants said it was very or somewhat important to them before they enrolled to know the other participants were representative of diverse communities.

Another opportunity could be the use of decentralized and/or virtual trials. The use of such protocols accelerated during the pandemic, leading FDA to issue a new guidance for the pharma industry​ regarding clinical trials with decentralized elements. The agency noted the importance of recruiting a clinical trial population that is reflective of the intended patient population and suggested expanding recruitment through local health care institutions to increase diversity.

This can be taken even further by utilizing a flexible approach, using home visits or at-home data collection. Findings from recruitment firm Antidote​ suggest these types of approaches may overcome the issues that have traditionally hampered participation. They report that non-white individuals, Hispanic patients and women were all more likely to participate in observational trials, compared with white and male respondents. These types of trials will pose both opportunities and challenges, according to Hewlings.

“They can increase diversity because we can recruit people across the U.S. in their everyday environment, so really everyone can participate, of course as long as they meet basic inclusion criteria,” she said. “Every study design has limitations; it is why it is routine to discuss limitations and acknowledge them when communicating scientific results. There are some study designs that don’t allow for decentralized designs; one such example would be pharmacokinetic studies or studies that require advanced testing equipping like an MRI or a VO2Max. However, as at home biological testing, wearables and other technology evolve, some of these limitations will be addressed.”

Hermoni agrees on the potential of virtual studies to increase diversity, as well as on the constraints in terms of data collection.

“While it is easy to collect consumer reported outcomes, it is much more complex to include clinical parameters in the studies,” she said. “While some parameters can be measured via wearables and at-home kits, we are still very limited with sample collection in this type of studies. Moreover, if relying on wearables, we should remember that access to technology may be a barrier for some underrepresented groups, potentially re-enforcing inequalities if not addressed properly.”

Whether virtual, decentralized or hybrid, the protocol will determine the best approach to recruitment and management while ensuring the population reflects the target population.

“You may be able to capture more diversity when recruiting in a decentralized trial,” Baisley said. “Decentralized trials come with other limitations and challenges compared to traditional trials and may require larger numbers of people to improve data quality, so it’s a balance, and it really comes down to what’s right for the protocol and finding a balance between science and marketing when it comes to identifying the target population.”