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Institutional 'Diversity' May Impact Patient Participation in PGx Research, Study Finds


NEW YORK (GenomeWeb) – Race is associated with how willing people are to take part in pharmacogenomics research, but it may not be the lone factor, researchers asserted in a report published in the July issue of the Journal of the National Cancer Institute.

"Our study demonstrates that race alone does not explain participation" in correlative studies, researchers led by Moffitt Cancer Center's Howard McLeod wrote in the paper. "Factors at the institutional level also need to be considered."

In an effort to better understand the factors that influence why a patient may or may not agree to participate in PGx analysis, McLeod and colleagues from several other institutions looked to nearly 8,500 cancer and leukemia patients enrolled in seven Phase III trials from 2002 to 2013. Patients were enrolled into studies for non-Hodgkin's lymphoma, breast, gastric, colorectal, pancreatic, and prostate cancers and recruited through Cancer and Leukemia Group B (CALGB) cooperative group sites, as well as the National Institutes of Health's Clinical Trials Support Unit (CTSU).

There were optional, correlative research opportunities in these studies. For example, researchers could request tumor tissue for genomic analysis and an additional vial of blood for PGx analysis. Since this was the first time an NCI-funded cooperative group trial was asking patients for germline DNA for PGx analysis, McLeod's group was interested in exploring what factors influenced their participation.

Overall, McLeod's group found high levels of participation in the PGx research component, with more than 80 percent of patients across the seven studies agreeing to donate blood samples. However, nonwhites were less willing to participate (71 percent) compare to Caucasians (83 percent). People recruited from CALGB sites were more likely to consent to the PGx portion than those recruited from CTSU sites, but participation among non-whites was statistically significantly lower at both CALGB and CTSU sites compared to Caucasians.

Most patients who agreed to partake in the PGx portion also consented to partake in another optional research component. Still, at the time these large studies were conducted, correlative analysis, like the PGx aspect, was more of an afterthought than it is today.

"It used to be that the correlative sciences were the frivolous portion of the trial," McLeod told GenomeWeb. "In the modern era, these correlative science pieces are often the informative and impactful part of the trial."

The tumor and germline genomic analyses that were part of these early CALGB trials have informed the field about a number of gene-drug associations. For example, these studies provided data on the risk of neutropenia in patients with UGT1A1 variants following treatment with irinotecan, and improved understanding of how lung cancer patients with EGFR-, ROS1- or ALK-positive tumors respond to certain treatments.

"These were important data sets because they were prospectively accrued and audited clinical trial data, as opposed to a tumor bank at someone's home institution," McLeod said. 

As new studies published daily improve the field's understanding of life-threatening diseases, it is ever important to understand the barriers to genomics research participation and ensure studies are conducted in an equitable manner, said McLeod. Looking at the initial data, however, his team was puzzled to find disparities in PGx research participation since these patients had already volunteered for cancer studies. "It's not like they were afraid of going on trials," he said. "Yet, they didn't do the pharmacogenomics piece."

Delving a bit more into why self-reported race and the institutional site might influence PGx study participation, McLeod's group calculated a proxy they refer to as "institutional diversity." Because there were low numbers of patients recruited at some sites, researchers used the percentage of non-white cancer patients a particular center registered for any national cooperative group trial to calculate its level of institutional diversity.

Approximately 80 percent of 800 sites that registered 10 or more patients in these trials received a diversity estimate. The majority of sites had low institutional diversity, while 24 institutions, representing more than 200 patients, fell on the high end. As the score increased, suggesting greater diversity, the likelihood of patients partaking in the PGx component decreased regardless of race, the researchers reported in their JNCI paper.

We always talk about getting the community more involved. Well, there are some really good reasons to do it now.

Although McLeod's group couldn't draw definitive conclusions in this investigation, it appeared that what "institutional diversity" was really pointing at was the economic disparity between institutions. Researchers considered exploring the economics angle more deeply but was restricted by the data available in the context of the CALGB studies. However, they surmised from the information at hand that sites that received high diversity scores would generally serve patients with a variety of incomes.

"Institutions like this typically have fewer resources than the institutions that serve the better-insured population," he reflected. "We didn't have all the information to flat out state this but what we seemed to be exposing is that the institutions that are under-resourced may not have the time or expertise to go get patients to be in all aspects of clinical trials." Instead of expending finite resources to recruit optional biospecimen trials, poorer institutions may choose to focus on getting patients access to the drug being studied, McLeod and colleagues wrote in the JNCI paper.

Other studies have suggested that patients treated at resource-poor heathcare facilities have more limited access to genomic tools. McLeod and colleagues highlighted in the paper a 2013 study involving Genomic Health's Oncotype DX breast cancer recurrence test, which showed that patients treated at municipal hospitals were less likely to receive the gene expression diagnostic compare to patients at tertiary care hospitals.

Similarly, resource disparities may explain the difference in PGx research participation seen between CALGB and CTSU sites. CALGB sites had additional funding for correlative scientific research that they could put toward enrolling patients for optional components such as the PGx analysis. "No one makes money with NIH-funded research," McLeod said. "You're just trying to lose less money than you would otherwise."

But CTSU sites may not have had this extra incentive. "It is our understanding that CALGB institutions were eligible for greater per-patient support for companion studies than non-CALGB sites that registered patients through the CTSU," researchers wrote in the JNCI.

The NCI set up the CTSU so researchers in the community and those at non-CALGB institutions could partake in government-funded studies. While the CTSU mechanism has a positive intent, McLeod said that in practice the process makes the research less personal. "When you're in a cooperative group, it's like your village and you put a lot of energy into making your village the nicest possible," he said. "When you're in a big generic metropolis you maybe don't have the same level of ownership."

Physician-patient interactions may also be holding back PGx research participation, though the present study couldn't explore this specifically. McLeod's group suggested that some patients may fear that data from genetic research may be misused to for a racist agenda, and physicians may not be familiar with PGx testing.

Although some doctors may not be fully comfortable with genomics, at least in the cancer realm, "they are much better off than they used to be," McLeod observed. "It's hard to practice oncology now without knowing something about genomics. That's a big difference from the study that we're talking about to current times."

At Moffitt's educational boot camps, doctors have opportunities for case-based learning that incorporate genomics, but Moffitt doesn't advertise this as genomics education. "It's about how do you solve a patient's problem, not how do you learn genomics," McLeod said. "Most oncologists don't want to become genomics experts, but they're more than happy to use tools to treat their patients better. So, we just stopped calling it genomics and just called it better patient care."

McLeod noted that based on the present research, his team is hoping to partner with payors and clinical trial sites to conduct a more in-depth investigation into why patients may not be receiving genomically guided treatment or the reasons why they may refuse participation in trials. With payors, for example, researchers could track when doctors don't order genetic testing even when supported by guidelines.

"We went in to this thinking [some] patients just say no" to PGx research, McLeod said, noting that institutional factors the study hinted at surprised his team. "We always talk about getting the community more involved. Well, there are some really good reasons to do it now, and we're going to miss out for a substantial population of patients if we don't."