This story is part of a series on Diversity in Clinical Trials, which will explore the impacts of drug development using data that does not reflect the diverse U.S. population.
To read more in this series, please visit the "Diversity in Clinical Trials" Issue in Focus page here.
The U.S. Food and Drug Administration approved 17 cancer drugs in 2018, and only one of those therapies held a clinical trial with at least 10% participation by black patients.
This statistic underscores what experts say could prove to be a risk to public health safety as the pharmaceutical industry dives deeper into precision medicine and targeted therapies.
Oncology medicines are evolving into therapies that attack specific tumor mutations by targeting certain patient groups' genetic makeup; however, the biological underpinnings and genetics of disease are not studied well enough in minorities to concretely determine reasons for onset.
Cancers like prostate and triple-negative breast cancer disproportionately affect black and Latino patients; triple-negative breast cancer is more common among Latina and black women with an estimated 25% occurrence. Women of these ethnic and racial backgrounds also develop the disease at a younger age and experience a higher rate of death than white women, according to Deborah Vollmer Dahlke, project director for the Texas Life Science Foundation, a nonprofit biosciences research and education organization.
Pharmaceutical companies can be rewarded for exploring the genetic differences in patients and evidence that suggests a drug may work better in one group of people over another. AstraZeneca PLC's lung cancer medicine Tagrisso, for instance, targets the T790M mutation in the epidermal growth factor receptor gene, which is most prevalent in Asian patients.
The U.K.-based pharmaceutical giant therefore included 60% Asian patients and 36% white patients in its global clinical trials, per Tagrisso's U.S. Food and Drug Administration Drug Trials Snapshot. The drug, known as a targeted therapy under the umbrella of precision medicine as defined by the National Cancer Institute, has since been approved in Japan and China, becoming AstraZeneca's bestselling global medicine with sales of $2.3 billion in the third quarter of 2019.
And yet, few companies strive to conduct diverse clinical trials in the cancer space. Minorities collectively made up less than 10% of participants in all cancer drug trials from 1995 to 1999, according to a 2001 FDA review. The numbers have not improved much in recent decades.
In the 2018 class of drugs, Kyowa Kirin Co. Ltd.'s Poteligeo had the greatest number of non-white participants, with 10% African American participants compared to 70% white. Pfizer Inc.'s Daurismo did not record Hispanic participation numbers at all and had 98% white participants, according to the FDA snapshot summary report. A Pfizer representative attributed this to the trial being smaller than usual to speed development. The company did, however, have 37% Asian participants compared to 49% white patients in a lung cancer trial for Lorbrena. That trial included sites in Hong Kong, Japan, Singapore, Korea and Taiwan.
Loxo Oncology Inc.'s gene-specific treatment Vitrakvi, another targeted therapy for multiple cancer types, recruited 72% white patients in clinical trials.
"Ideally, the trial population would accurately reflect the affected populations, but right now it doesn't," Andrea Miyahira, director of research at the Prostate Cancer Foundation, said. "It's around 4% to 12% — obviously to account for the affected population it'd have to be higher than that."
Access to care
Targeted therapies often require an additional molecular test, like a diagnostic, to determine whether a patient has the relevant cancer mutation. This step adds to the complexity and cost of treatment, which already disproportionately affects minorities in the U.S.
"Access to care, insurance, equality care — disparities will only increase as medicine becomes more complex, harder to understand, harder to access," said Miyahira. "Precision medicine is not easy to access for an average person."
Adaptive Biotechnologies Corp. President Julie Rubinstein said the ultimate goal of precision medicine is to identify a cancer patient's unique set of mutations, find the patient's own T cell receptors specific to the mutations, and then use the T cells to beat the cancer — like a personal chimeric antigen receptor T cell therapy.
CAR-T cell therapies are a complex and expensive form of cancer treatment that takes a patient's own immune cells and modifies them to fight the cancer when infused back into the body. Two CAR-T products have been FDA-approved for specific cancers: Novartis AG's Kymriah and Gilead Sciences Inc.'s Yescarta, which both cost upward of $300,000.
Meanwhile, experts worry that the focus on genetics in precision medicine could exacerbate racial disparities.
A global study of 23andMe Inc.'s direct-to-consumer genomic screening for certain BRCA1/BRCA2 and MUTYH gene variants, which are associated with hereditary breast, ovarian and colorectal cancer risk, found that one FDA-cleared test actually delivered false-negatives to patients of color. According to study sponsor Invitae Corp., the test was based on Ashkenazi Jew variants and therefore would present false results to individuals of non-Northern European descent nearly 100% of the time.
A 2004 JAMA article warned that a focus on genetics, or "genetic optimism," could overshadow the array of socioeconomic and environmental factors that also play an important role in disease burden. Perhaps more concerning is the article's finding that zeroing in too closely on genetics and underlying biology could contribute to racial labeling and stereotyping.
"Racial stereotyping enters medical practice when conditions are linked to populations and then to the unexamined assumptions that practitioners might have," wrote the authors, a group of bioethics professors at various medical institutions.
Researchers found that an algorithm generated by UnitedHealth Group Inc.'s Optum was biased toward treating white patients even when black patients were equally sick. The algorithm used healthcare cost to determine treatment, resulting in disparate treatment decisions between white and black patients and further demonstrating physician biases that ultimately allocate less money for treatment of black individuals.
The algorithm was widely used across 50 organizations. New York's insurance regulator has opened an investigation into UnitedHealth Group following the researchers' October publication in the journal Science.
Experts have also flagged industrywide disparities in research and medical leadership, which the U.S. medical research center the National Institutes of Health has sought to amend.
The NIH has limited its laboratory and branch chiefs to 12-year terms in an attempt to encourage racial and gender diversity in leadership turnover, and in turn, what research gets done, and who gets to participate.
Neither the FDA nor NIH have set goals for minority inclusion in clinical trials.
"[We] talk about barriers as if it's always the patient's problem," Dahlke said. "But [we] have to realize that barriers are often institutional and clinical … in reality, many of the barriers are the trial design or the way the institution handles the trials that keeps patients out, whether they're minorities or not."
With a lack of action from government regulatory and research agencies, academics and cancer organizations have had to step in.
Miyahira said two Duke University investigator-led clinical trials are specifically recruiting African American men for prostate cancer treatment, one of which is in collaboration with Johnson & Johnson's Janssen Scientific Affairs.
The Prostate Cancer Foundation is working on partnering with the U.S. Department of Veterans Affairs to open up trials to African American patients, as the VA has a large African American population.
"I hope that the pharma companies are starting to recognize that minorities need to be recruited in clinical trials," Miyahira said.