Diversity in Clinical Trials Still Lags

In addition to age, sex, diet, underlying disease, and the concomitant use of other medications, race and genetic factors may play pivotal parts in the variability of subjects' responses to a medication. Regrettably, minority groups are underrepresented in most clinical trials. Often, there are insufficient data to assess the effectiveness or safety of new drugs in members of minority groups, especially Blacks. Concern about this issue led the National Institutes of Health and the Food and Drug Administration to establish guidelines encouraging the inclusion of more women and minority groups in clinical trials. However, it is uncertain whether these guidelines are being implemented and whether the participation of minority groups in clinical trials has increased (King, 2002).

This opening paragraph from a 2002 editorial in the New England Journal of Medicine raised the alarms over the lack of sexual, gender, and racial diversity in clinical trials and the lagging effort being put into correcting the issue over two decades ago. Regrettably, women and minority groups are still vastly underrepresented in most clinical trials in 2023—a scourge that plagues clinical testing and trials across virtually every segment of the medical industry.

A prime example of this lack of diversity exists in the world of HIV prevention:

In 2019, Gilead Sciences announced that they had received approval from the U.S. Food and Drug Administration (FDA) to prescribe Descovy (emtricitabine/tenofovir alafenamide, FTC/TAF) for use as part of a Pre-Exposure Prophylaxis (PrEP) regimen to prevent the transmission of HIV…except for use in people assigned female at birth (Gilead Sciences, 2019).

The primary advantages of using TAF in a PrEP regimen over the previously approved Truvada (tenofovir disoproxil fumarate, TDF) are that TAF is simply a better, safer drug. TAF is absorbed more quickly than TDF and produces higher levels of the active drug in cells, meaning it can be given in smaller doses, leading to lower levels of exposure to the kidneys and less bone density loss—some of the biggest concerns related to the use of TDF as PrEP which led to higher rates of drug discontinuation (Hill, et al., 2018).

And yet, despite the fact that roughly 19% of new HIV diagnoses occurred in women in 2019 (Centers for Disease Control and Prevention, 2022), Gilead Sciences fundamentally failed to successfully include women in their clinical trials to ensure that the drug was effective in “…individuals at risk from receptive vaginal sex” (Gilead Sciences). This resulted in Descovy receiving a black box warning—the strictest labeling requirement that the FDA can mandate for prescription drugs that highlights serious and sometimes life-threatening adverse drug reactions—which essentially precluded over half of the U.S. population from being prescribed the drug.

This lack of diversity isn’t unique to the field of HIV; it extends to every aspect of the medical field, from vaccines to therapeutic drugs to medical devices. This lack of inclusion of essentially anyone other than young and middle-aged men of European descent in testing and trials has created a landscape where commonly used and relied upon vaccines, therapies, and medical devices are administered to patients without any real knowledge of whether or not they are as effective—or even effectively at all—across patient demographic populations.

Another example resides in a widely accepted piece of standard medical equipment: the pulse oximeter. This easy-to-use device measures the saturation of oxygen in the blood by using a cold light source that shines a light through the fingertip, analyzes the light from the light source that passes through the finger, and determines the percentage of oxygen in the red blood cell. Unfortunately, it works poorly on people with non-white skin:

A retrospective cohort study released in the Journal of the American Medical Association Internal Medicine found that compared to white patients, “…Asian, Black, and Hispanic patients had a higher adjusted time-weighted average pulse oximetry reading and were administered significantly less supplemental oxygen for a given hemoglobin oxygen saturation compared with white patients” (Gottlieb, et al., 2022).

To put that in lay terms, non-white patients had higher readings from pulse oximeter devices than white patients because of the way that light penetrates skin tissue, and as a result, received less supplemental oxygen than white patients.

This disparity was particularly important to consider during the height of the Coronavirus 2019 (COVID-19) global pandemic when Black, Hispanic, and American Indian patients were much more likely to contract, experience worse symptoms of, be hospitalized for, and die from COVID than White patients (Tai, et al., 2022). As a respiratory disease, COVID-19 required patients to be placed on respirators in an effort to sustain and save lives, and there were (and still are) serious concerns that relying upon pulse oximetry readings resulted in minority patients receiving inadequate levels of supplement oxygen compared to white patients.

Continuing on the topic of COVID-19, minority patients were overwhelmingly underrepresented in both the Pfizer BioNTech and Moderna mRNA vaccine studies:

Across the three Pfizer trials, over 80% of participants across every age group (12-15 years, 16-25 years, and 18+ years) were white, while Black patients represented only 3-9% of participants, Asians 1-8%, American Indians/Alaska Natives (AI/AN) 0-6%, and Hispanics 3-20%.

Across the four Moderna trials, over 79% of participants across every age group were white, while Black patients represented 0-10%, Asians 1-5%, AI/AN 0-2%, and Hispanics 0-18% (Khalil, et al., 2022).

Khalil, et al., found that this lack of diversity essentially mirrors similar vaccine trials during the development of the H1N1 vaccine in 2009. After the H1N1 pandemic, much handwringing occurred across the U.S. medical establishment over the low uptake of vaccination among minority populations, particularly Black and Hispanic people. Little attention was paid at the time, though, to the vast disparity in H1N1 vaccine trials, in which 91% of participants were white (Khalil, et al.). The majority of studies published about this lack of diversity were not published until 2021 and 2022…in the wake of the COVID-19 vaccine trials.

So, how do we fix what is clearly a broken system? The answers seem simple:

As referenced in the opening paragraph of this piece, federal guidance has been in place since the 1990s “encouraging” increased recruiting of diverse patient populations, and those guidelines have been updated since that time.

• Enhancing the Diversity of Clinical Trial Populations — Eligibility Criteria, Enrollment Practices, and Trial Designs Guidance for Industry (FDA, 2020)

• Minority Health and Health Disparities Strategic Plan 2021–2025 (National Institutes of Health, 2021).

But time is money in the pharmaceutical and medical device industries, and most companies are simply either unwilling to invest the time, effort, and resources to recruit significantly diverse patient populations when it’s far more profitable and expedient to work with an easily accessible and willing white population that is perceived to be more compliant with the requirements of trials (and this, also, is a biased belief).

The truth is that many companies too often fall back on the beliefs that there are too many cultural barriers to overcome in order to recruit Black, Hispanic, and AI/AN patients for clinical and device trials, that it’s too costly to actively try to overcome those barriers, and that the patients are “difficult to deal with” during the process. These biases persist despite many of the scientists, themselves, involved in these trials being from racially and ethnically diverse backgrounds. Why invest these resources when you can bring a vaccine, drug, or device to market with FDA approval much faster by using the “reliable” population?

The reason they must invest is that the consequences of their failure to diversify result in the loss of human lives. When these companies fail to live up to their duty to fully test their products, minority populations pay the price. If they are not going to willingly do so, then the FDA needs to step in and institute minimum participation requirements in order to receive approval, even if that means the upheaval of existing “norms” around the approvals process.

New Faces Join Efforts to Address Health Disparities

Five amazing, dynamic, and extremely well-intentioned professionals have committed themselves to promoting health equity by joining the PlusInc Board of Directors. By lending their expertise and experience to our leadership, PlusInc has taken a giant step forward in our efforts to address health disparities.

In late 2022, PlusInc seated a trio of fabulous women — Kassy Perry, Laura Friedman, Meg Cooksey — from three very different lines of work. Kassy Perry is a force all her own. A shrewd strategic thinker with uncommon creativity, Kassy is also a smart tactician. She presently serves as the President & CEO of Perry Communications Group, , which she founded in 1996. Laura Friedman is currently a Senior Vice President, Communications and People Strategy Lead for Markets Technology at Citigroup. Prior to joining Citi, she previously served as the Associate Director of Communications at Workforce Opportunity Services (WOS), as well as the Communications and Programs Manager at Hearing Health Foundation (HHF). Mary M. “Meg” Cooksey, RN-BC, currently serves as Nurse Manager for the Division of Infectious Diseases at MedStar Georgetown University. Meg is Board-Certified in Ambulatory Care Nursing and has a special interest in ensuring equity in access to vaccines for underserved populations.

In early 2023, PlusInc seated a dynamic duo: Glen Pietrandoni and Vanessa Lathan. Glen Pietrandoni, R.Ph., AAHIVP is chief advocacy officer at Avita Care Solutions, passionate healthcare advocate, and internationally respected HIV and LGBTQ+ activist. Glen is deeply engaged in Avita's mission to advocate for health equity and the 340B Drug Pricing program. Vanessa Lathan, MPH, BSW is an HBCU-educated, unapologetic Black and communities of color-focused change agent driven to dismantle oppressive and systemic racism policies within sexual and reproductive health. Vanessa is a Senior Program Manager for the Southern HIV Impact Fund program at AIDS United.

These new faces join long-time board members, Andrew Richter and Michelle Anderson, as well as 2021-seated board members, Michael Pickering, and Jonathan J. Pena, MSW, LCSW-A. Check out our phenomenal leadership team here!

Health Disparities Portfolio Expanded to Include More Chronic Health Conditions

In 2022, PlusInc launched its national campaign to raise awareness about health disparities among marginalized communities in the United States. Health Equity can only be achieved by addressing and changing the systemic institutional and societal barriers that result in health disparities. Initially, our health disparities portfolio focused on COVID-19, Escherichia coli Pyomyositis (ExPEC), HIV/AIDS, Mental Health, Respiratory Syncytial Virus (RSV), Substance Use Disorder (opioids, stimulants), and Viral Hepatitis (HBV, HCV). Next year, we will expand our reach into seven additional chronic health conditions to complement the work we’re already doing.

In 2023, PlusInc’s expanded health disparities portfolio will include:

1. Behavioral Health

2. Cancer - Colon

3. Cancer - Melanoma

4. Cardiovascular Disease

5. Maternal Health & Mortality

6. Respiratory - Asthma

7. Respiratory - Chronic Obstructive Pulmonary Disease (COPD)

The additions represent a broad array of the health issues long plaguing marginalized communities in the United States, as well as others emerging as incident rates increase and more data becomes available on them. For example, we have known for quite some time that poor maternal health outcomes disproportionately impact communities of color. According to the U.S. Centers for Disease Control & Prevention (CDC), black mothers are three times more likely than white mothers to die from maternal health complications, and many of them avoidable with better care. Additionally, a federal study on maternal deaths yielded a very troubling statistic: most (like, 90%) maternal deaths among Indigenous mothers were preventable. More troubling is pregnant mothers are now being threatened by a new trend in the United States, namely maternity care ‘deserts’ are on the rise.

But there are other deserts impacting quality healthcare. There are significant care gaps in behavioral health. Fortunately, there is a new behavioral health data mapping tool, which could remedy the problem. Change won’t happen unless such tools are accompanied by heightened awareness, additional resources, and better community outreach. PlusInc exists to help in this effort.

Moving forward into next year, PlusInc will build upon our momentum we started this year by not only taking a deeper dive into the health disparities surrounding these chronic health conditions, but also evaluating how they’re impacting local communities.

Health Disparities in Merced & Stanislaus Counties

PlusInc and Legacy Health Endowment are working to address health disparities in Merced and Stanislaus Counties in California. Like many communities in California, both Merced and Stanislaus Counties have many health conditions afflicting its residents. Our collaborative effort pays particular interest in how COVID-19, Hepatitis B, Hepatitis C, Mental Health Services, Substance Use Disorder and HIV/AIDS are impacting our local communities. Legacy Health Endowment provides funding and technical support to create healthcare solutions and facilitate improved wellness within Stanislaus and Merced Counties.

-> Learn more about health disparities in Merced County

-> Learn more about health disparities in Stanislaus County

Due to the incidence rate being so low for some of these health conditions in Merced and Stanislaus Counties, county data are not broken down into demographic categories in order to protect the identities of patients. Nonetheless, it does provide a glimpse into what is happening in the northern San Joaquin Valley section of the Central Valley, California. To achieve greater health equity, our healthcare infrastructure needs to identify the health disparities that exist in the United States, and how they can vary from one health condition or another.

Patients Have a Stake in Health Equity, too

In recent years, “health equity” terminology has become increasingly used in the national conversation about healthcare in the United States. Health equity is often used interchangeably with another term, health disparities, although each one has its own unique meaning. According to the U.S. Centers for Disease Control & Prevention (CDC), “Health equity is when everyone has the opportunity to be as healthy as possible. Health disparities are differences in health outcomes and their causes among groups of people. Many health disparities are related to social determinants of health, the conditions in which people are born, grow, live, work and age.” (CDC, 2020) To achieve greater health equity, our healthcare infrastructure needs to identify the health disparities that exist in the United States, and how they can vary from one health condition or another.

In 2016, a multimodal survey of mayors and health commissioners was conducted by Jonathan Purtle, et al. and it yielded some interesting findings. First of all, less than half of the mayors and health commissioners contacted took the time to complete the survey — which in and of itself, is a sad indictment on how those officials prioritize public health in their respective jurisdictions. That aside, Purtle reported, “Forty-two percent of mayors and 61.1% of health commissioners strongly agreed that health disparities existed in their cities. Thirty percent of mayors and 8.0% of health commissioners believed that city policies could have little or no impact on disparities.” Not surprisingly in today’s political climate, ideology is strongly associated with opinions about disparities. (Purtle, 2018)

Maybe part of the problem is the terminology, health equity and health disparities, is not defined explicitly. Nearly a decade ago, Paula Braveman, MD, MPH warned, “Ambiguity in the definitions of these terms could lead to misdirection of resources.” Dr. Braveman outlined the why explicit definitions are needed, because “not all health differences are health disparities” (Brakeman, 2014).

Health disparities exist, as defined by Dr. Bravemen through a social justice lense, and they are getting worse. Whereas numerous organizations committed to health equity exist, none approach health disparities specific to health conditions from the patient perspective. This is why PlusInc exists.