A New Look for Clinical Trials

IF YOU WANTED to create a playlist of music that would appeal to many different types of people, you probably wouldn’t ask only middle-aged white men in Los Angeles to tell you their favorite songs. More likely, you’d include people of many racial and ethnic backgrounds from all parts of the country: some who grew up with jazz or salsa music, others who were raised on rock ’n’ roll, and still others who know their Bach from their Beethoven.

Cancer treatments are kind of like a playlist: Not everyone responds to them in the same way. To get clinical trial results that will be applicable to the broadest range of people, researchers need to enroll women and men of different ages and rac​ial and ethnic backgrounds in their studies. Yet, when you look at a room of clinical trial participants, you typically see a ​preponderance of higher-income, middle-aged white men, most of whom don’t have health problems besides their cancer. But what about African-American women with cancer and diabetes? Or elderly Latinos with kidney problems in addition to cancer? Will the treatment be safe or effective for them? If they’re not included in the clinical trial, there is no way to know.

“If you think trials are important, then you have to believe having adequate representation of all populations is important, because that is how we will make sure trial findings are representative and generalizable,” says Susan Eggly, a communication researcher at Wayne State University School of Medicine and Karmanos Cancer Institute in Detroit. It’s also an issue of equal access to health care. “Given that clinical trials are considered the highest-quality care available, it is important to make sure everyone—minorities, women, older people and rural populations—has equal access, and we know right now they don’t,” says Eggly.

Efforts are underway to achieve that goal by increasing the total number of people who enroll in trials, improving outreach to racial and ethnic minorities, and bringing trials to rural communities. Organizations such as the American Society of Clinical Oncology (ASCO) and the Intercultural Cancer Council (ICC) are encouraging researchers to broaden and modify clinical trial eligibility criteria so that a wider range of participants will be eligible for their studies. If these efforts are successful, the result will be clinical trials—and findings—that are more representative of and applicable to all cancer patients who may one day need them.

Increasing Participation

Getting cancer patients to enroll in clinical trials is not a new problem. In 1990, when he was president-elect of the American Cancer Society, Walter Lawrence Jr. wrote an editorial for CA: A Cancer Journal for Clinicians about the need to increase patient participation in clinical trials. “We were trying to rev up physicians’ interest in getting involved with trials,” recalls the now 92-year-old surgical oncologist emeritus at Virginia Commonwealth University Massey Cancer Center in Richmond. “We also knew most of the public thought being in a clinical trial was like being a guinea pig.”

Nearly three decades ago, “when we were raising hell,” says Lawrence, “fewer than 3 percent of patients were enrolled in clinical trials.” Now, the number hovers around 5 percent. Lawrence says the 2 percentage points demonstrate the progress that has been made. They also point to how much remains to be done.

“We need to get going here,” says Edward S. Kim, a medical oncologist at Carolinas HealthCare System’s Levine Cancer Institute in Charlotte, North Carolina. “The field is moving fast, and we need to move the needle on clinical trial enrollment” so that 25 to 30 percent of cancer patients are enrolled in trials. “We used to think that there were not enough trials,” he says. “That’s not the problem. The problem is that we are excluding people unnecessarily.”

Beyond Big Centers

Exclusion can take many forms. Expanding access to clinical trials beyond large urban areas to smaller cities and rural areas has the potential to both increase enrollment and widen access by overcoming one of the most common barriers—transportation. “It’s not uncommon,” says Eggly, “for someone to not take part in a trial because they can’t get there, they can’t afford parking, or because a friend or family member would need to take time off of work to get them there.”

Hematologist-oncologist Suresh Nair, physician-in-chief of the Lehigh Valley Health Network (LVHN) Cancer Institute in Allentown, Pennsylvania, has been on the front lines of efforts to expand clinical trials beyond major cancer centers. In 2010, LVHN became one of 21 National Cancer Institute (NCI)-selected community cancer centers to offer clinical trials. This helped Nair bring the latest immunotherapy trials to the Lehigh Valley. Nair also worked with pharmaceutical companies to make LVHN one of their immunotherapy trial sites. Trial offerings have continued to grow since August 2015, when LVHN became the second member of the Memorial Sloan Kettering Cancer Center (MSKCC) Alliance, which aims to bring new treatments to cancer patients outside New York City. “With 80 percent of cancer care occurring in the community,” says Nair, “that is where trials need to be.”

LVHN currently has about 200 active clinical trials; about 70 are enrolling new patients. Nair says patients are more likely to say yes to a trial close to home than to one at a large cancer center in Philadelphia or New York City, which can take two hours to get to by car or four hours by bus. “I’ve had patients who I tried to refer to trials turn me down, saying unless they know they’ll be cured, they don’t want to travel that far.”

For LVHN, Nair says, “the biggest highlight” of the first year of the MSKCC Alliance has been the ability to offer patients access to the TAPUR (Targeted Agent and Profiling Utilization Registry) study, a nonrandomized trial conducted by ASCO. The TAPUR trial tests promising targeted treatments on patients whose tumors have specific genetic mutations. Although the treatments are free for those who participate in the study, patients must have had a comprehensive genomic test performed on a sample of their tumor. MSKCC offers testing to LVHN patients at a reduced cost of $1,600, and LVHN established a fund to provide financial assistance to patients who need it. “We wanted it to be equitable,” says Nair. “We didn’t want to turn anyone away because they couldn’t afford genomic testing.” So far, 10 LVHN patients have been enrolled in the TAPUR study.

Not the “Right” Type

Racial and ethnic minorities have long been underrepresented in cancer clinical trials. In 2005, the ICC launched a four-year project, Eliminating Disparities in Clinical Trials (EDICT), to investigate reasons for this imbalance. They also examined reasons for lack of participation by low-income, elderly and rural residents. Their 2008 report, which included policy recommendations, has been a touchstone for efforts to address the disparities issue.

Armin Weinberg, a health policy researcher at Baylor College of Medicine in Houston and a co-founder of the ICC, led the EDICT initiative. “EDICT became a springboard,” he says. “There were many things that needed to be done. There was nothing one entity or individual could do to correct the problem. But there was something everyone could do.”

Eggly’s research efforts include analyzing audio and video recordings of conversations between cancer patients and their doctors. She hopes her research results encourage health care providers to reconsider assumptions they may have about whether a patient is the type who would take part in a study.

“We have found that communication style and sharing of information differ when doctors talk to black patients and when they talk to white patients,” she says. “We know minorities are as likely to say yes when offered a clinical trial. So, if they are open to it, then you have to ask why they are not doing it. And when you go down that road, it means looking at how the communication process affects their participation.”

As a guiding principle, says Weinberg, the EDICT report encouraged researchers to focus on three Rs: recruitment, retention and return. It’s not enough to just recruit a wider range of people; researchers also need to keep them in the study. Retention can be affected by a range of issues, among them transportation, insurance problems and language differences. “We also found, and this is being addressed better today,” Weinberg says, “that you need to focus on the return, telling people who participated what happened as a result of the trial.”

To reinforce the importance of participant diversity, the National Institutes of Health requires researchers to explain in their grant applications how they intend to recruit people of different racial and ethnic groups into their studies. For its part, the U.S. Food and Drug Administration (FDA) continues to review and update its guidelines that advise researchers on how to collect racial and ethnic data on study participants. In 2015, the FDA launched Drug Trials Snapshots, which presents pie charts of the sex, race and age of participants who took part in studies that led to a drug’s approval. Drug Trials Snapshots also details any differences in benefits or side effects that occurred based on sex, race or age.

Nair’s efforts to bring more clinical trials to the Lehigh Valley also included attempts to increase participation by Spanish-speaking residents. To that end, he hired a bilingual clinical trials coordinator and created an infrastructure that makes additional support and assistance routine for clinical trial participants. This helps ease the burden of the additional tests or scans a trial may require as well as helps to ensure that any treatment side effects are addressed promptly. “By doing those simple things,” he says, “we’ve now increased enrollment of Spanish-speaking patients.”

Modernizing Trial Eligibility

New cancer treatments, like targeted drugs and immunotherapy, work in different ways than chemotherapy and usually have fewer side effects. To ensure trials for these drugs are open to as broad a range of people as possible, ASCO and the nonprofit Friends of Cancer Research tapped Kim, of the Carolinas HealthCare System’s Levine Cancer Institute, to head a committee tasked with reviewing whether commonly used eligibility requirements were unnecessarily excluding patients from trials for new cancer drugs.

“As we start having safer, targeted drugs” with fewer side effects, says Kim, “we can be more liberal in our patient population.” The committee began by looking at why people with brain metastases, organ failure, or diseases like HIV or hepatitis C are routinely excluded from trials.

Stuart Lichtman, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, applauds efforts to broaden access to trials. Lichtman has been working for more than a decade to improve geriatric cancer care and increase participation of elderly patients in clinical trials. Organ dysfunction, like kidney problems, will often make a patient ineligible for a trial, he says, “but who has that problem—older people.”

“No one is saying get rid of eligibility criteria,” he adds, “but the criteria can be modified so we get real-world data that will apply to the older people who will be on these treatments.”

Modifying eligibility criteria to include patients with kidney problems and other illnesses could also help bring more low-income and racial and ethnic minorities into clinical trials. Right now, points out Eggly, “clinical trials tend to exclude patients who have what are essentially diseases related to poverty—diabetes, asthma and obesity. There is a concern that these patients aren’t as likely to do as well on the new drug.”

Kim says modernizing eligibility criteria is an important first step toward “flip[ping] the entire culture of clinical trials and the way we do research. We need to think we have a trial that includes everyone,” he says. “When you go to the grocery store, your expectation is that you will find what you need. That’s how it should be with clinical trials.”

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