By Deborah Borfitz

February 15, 2022 | Inclusive clinical research matters to patients, shapes good science, and is imperative to business success, according to Meghan McKenzie, principal inclusion, internal partnering, in Genetech’s Chief Diversity Office. How to go about increasing diversity in clinical trials was the focus of her keynote presentation at last week’s Summit for Clinical Op Executives (SCOPE) in Orlando, Florida.

“I went into the office thinking I knew a little bit about inclusive research and learned that I need to learn a lot about unconscious bias and being sure we have inclusion in the room,” says McKenzie, referencing the need for diversity in the workforce and in choice of vendor partners as well as in clinical trial participation. Advancing inclusive research has been an enterprise-wide effort of Genentech and its parent company Roche over the past four years and is an organizational necessity due to the changing face of the population.

By 2045, the U.S. is predicted to be a majority-minority nation that is about 45% Caucasian, she says. “If we continue to enroll only people of European ancestry, we won’t have many patients to enroll.”

As it is, new medications are only reaching about 8% of patients worldwide, McKenzie continues. About 90% of the genetic material clinical researchers are using come from patients of European ancestry, highlighting the need to increase the heterogeneity of biosamples in registries.

COVID-19 has underscored the reality of health disparities, with Black and Brown communities seeing two to three times the fatality rate of their White counterparts, says McKenzie. The differences can be seen “everywhere we have data.” Registries of the Centers for Disease Control and Prevention now capture ZIP code at birth (so-called ZNA) and other social determinants of health that can have a potentially huge impact on health and even people’s DNA—and need to be captured in clinical trials.

Consider a Black woman who is diagnosed with breast cancer, she says. “She is 41% more likely to die of that breast cancer in the U.S. than a White woman… and Black women represent only 6% of women in our clinical trials.” How to better reach these patients has therefore become an industry-wide aspiration.

By 2040, a little over half of patients in the U.S. living with Alzheimer’s disease will be Black or Hispanic, says McKenzie. Cancer cases are also rising in lower income countries, and breast cancer rates are increasing among Blacks, Hispanics, and Pacific Islanders everywhere, rousing interest in reaching underrepresented patients in clinical trials both inside and outside the country.

Work To Do

The clinical importance of inclusive research is exemplified by early clinical research on the non-small cell lung cancer drug Tarceva, McKenzie shares. One East Asian woman had 10 times the response as other trial participants and, had she not been included, “we may not have found this new allele that became a target for Tarceva.”

The lung cancer biomarker KRAS is more common in patients of European ancestry, while EGFR mutations are more often seen in people of East Asian ancestry, she continues. The epilepsy drug carbamazepine also more often causes a severe rash in patients of Asian ancestry, she adds.

In patients of African ancestry with asthma, beta agonists are of variable efficacy, says McKenzie. A study of Latino women with breast cancer also led to the discovery of a novel variant with a protective effect.

Health equity can be improved by working with top sites that provide extra patient monitoring vigilance during studies, she says, and is the reason the National Comprehensive Cancer Network recommends clinical trials to patients diagnosed with cancer. Genetech has embraced a collaborative approach to overcoming the barriers to enrollment, but snapshots of drug trials published by the U.S. Food and Drug Administration (FDA) show the industry still has work to do to ensure all races are adequately represented.

Global pivotal trials are still mainly enrolling White patients, says McKenzie. While progress is being made in better representing Asian populations in studies, better outreach is needed to make a dent with other demographic subgroups.

Her advice is to form a council of key advisors focused on bringing diversity to the table. Genetech now has an external group of diversity and inclusion experts—including researchers, physicians, patient advocates, and educators—to help the company frame a strategy and make headway, she says. The council helped Genentech build a three-pronged approach that thinks through the target patient profile, capture of heterogenous real-world data, and partnering opportunities for improving clinical outcomes.

Genentech additionally has partnerships with an Advancing Inclusive Research Site Alliance, launched last year, which is comprised of sites that are particularly good at reaching communities of color, she adds.

Success Stories

McKenzie reports on two, time-relevant success stories: the EMPACTA study showing Actemra reduces the likelihood of needing mechanical ventilation in hospitalized patients with COVID-19-associated pneumonia, and the CHIMES study looking at the treatment effects of Ocrevus on self-identified African American and Hispanic or Latin American participants with a diagnosis of relapsing multiple sclerosis (MS).

The EMPACTA study was prompted by a request from researchers in New Jersey and New York at the peak of the pandemic whose patients were dying, she says. Sites had a hand in crafting the eligibility criteria to ensure patients with comorbidities would qualify.

Of necessity, Genentech was in more regular contact with the study sites and created a twice-monthly forum where they could talk to each other about what was and wasn’t working, says McKenzie. It also intentionally chose sites with catchment areas for communities of color and, where it had the data, those that had historically enrolled well in those communities and had best practices to share. Genetech also worked with nontraditional sites, a few of which had never done a clinical trial and required open lines of communication 24/7.

The CHIMES study was written specifically for African American/Black and Latino patients, populations in which MS appears to be more severe. Here, Genentech partnered with patients in those communities and had separate committees review materials to make sure they were culturally competent, she says. Sites again had a forum for talking with one another to knowledge-share. 

Indication-agnostic patient education, cultural competency training for healthcare professionals, and patient navigation were the top needs identified for reaching communities of color by founding members of the Advancing Inclusive Research Site Alliance—City of Hope (Los Angeles), O’Neal Comprehensive Cancer Center at UAB (Birmingham), Mays Cancer Center (San Antonio), and West Cancer Center (Memphis). The first visible initiative of the alliance was creation of a “What Is a Clinical Research Study?” video, now freely available on YouTube.

Sites report televising the video in their waiting rooms, so patients are empowered to start asking questions, says McKenzie. The video covers why research is needed, using animation and a breakdown of key terms, and seeks to represent different races, ancestries, gender identities, and sexual orientations, “so folks see themselves in this work.”

First Steps

Among the multiple challenges in advancing inclusive research are raising awareness of clinical trials at the same time pandemic-related staffing shortages have made healthcare professionals busier than ever, McKenzie says. She recommends getting started on one or two fronts—using the new patient education video, for example, or addressing unconscious bias in partnership with sites.

Relieving the financial burdens of trial participation is another potential avenue. “Even now, we talk to teams that are reluctant to offer compensation for oncology patients who are in clinical trials even though their opportunity cost of participation is high [giving up time and other treatments and trials],” she says.

Patient stories can be particularly impactful to present not just at town halls but also to an audience of protocol writers, McKenzie adds. They’ll start thinking differently about the burdens of participation and how to address core problems.

Among the steps Genentech has taken to make studies more inclusive is to be visible with its commitment in consent protocols and site contract language, she says. “We’re very lucky to be part of a diversity office that reports directly to the CEO; we’re not 10 layers down in an organization.”

In addition to the site alliance and executive external committee, Genentech has a health equity corporate giving strategy seeking to create a more diverse, inclusive, and equitable future of science. The company has also started giving benefits to employees enrolled in clinical trials, including reimbursement for travel, McKenzie says.

Moreover, Genentech created a diversity inclusion board comprised of senior leaders who have volunteered to be champions for patient-centricity and reducing the burden of trial participation, she says. A good starting point for appreciating the importance of patient insights might be listening to a three-minute YouTube video by author Zoe Chance on “Our Gator Brains” to better understand how the decision-making process works.

Four years ago, now-Chief Diversity Officer Quita Beeler Highsmith together with Global Head of Health Equity and Population Science Nicole Richie started the Advancing Inclusive Research Program focused on addressing disparities in clinical research, says McKenzie.

If the Diverse and Equitable Participation in Clinical Trials (DEPICT) Act goes through, “everybody will have to be submitting inclusion plans with their drug applications,” she notes. The FDA and American Association for Cancer Research also recently recommended that trial sponsors be required to complete a diversity study plan that sets targets for enrolling diverse participants in clinical trials for multiple myeloma, a blood cancer that is twice as deadly in African Americans as in Whites.