Why aren't cancer patients participating in clinical trials?
Jane Reese-Coulbourne found grape-sized lumps in her breast and underarm when she was 36. Within days, she learned she had stage 3B breast cancer and preoperative chemotherapy was recommended. At the time, Reese-Coulbourne was living in Columbia, Maryland, close enough to the National Institutes of Health to know that some kind of experimental treatment in the form of a clinical trial might lie within driving distance. She didn’t want to wait for a clinical trial as a last resort. She wanted it first.
Clinical trials are research studies that evaluate new treatments, combinations, and doses; better methods for diagnosing or preventing the disease; and new ways to improve quality of life for cancer patients.
For Reese-Coulbourne, she volunteered for a clinical trial using previously untested doses of Adriamycin (doxorubicin) combined with three other drugs. “I wanted to take my best shot right up front,” she says.
She knew the trial was trying to push the limits on how much of the cancer medicine a body could safely withstand, and that she would be getting a lot of toxic drugs—all of which was fine with her. “I was in a ‘more is better’ mode,” she says. Even so, when she pressed the doctors for a prognosis, she was told the drugs might keep her alive, if she was lucky, another two years.
Twenty years later, Reese-Coulbourne is still here to talk about her clinical trial. The treatment melted the tumors, and radiation took care of what remained. She can’t be sure the clinical trial saved her life, but if her cancer ever does reappear, “I would do it again,” she says.
Other patients aren’t so sure about getting their treatment through clinical trials, or are never offered the opportunity to join them. For many reasons—some more important than others—only about 3 percent of adult cancer patients participate in clinical trials, and the number has changed little since the days of Reese-Coulbourne’s diagnosis. Without clinical trials, cancer detection and treatment could not improve. Researchers have worked over the years to improve participation, yet so far nothing has made that figure budge.
But today, the need to get beyond 3 percent has assumed a new urgency. To many longtime cancer researchers, medical science stands at the brink of meaningful change for cancer treatment, driven by an unprecedented understanding of the molecular genetics that enable tumors to develop and spread. Real progress, however, will be slow to reach doctors’ offices without the ability to test which experimental treatments work best, at which doses, in what patients.
“We’re finally beginning to have breakthroughs for what makes cancer tick,” says Joan Schiller, MD, of the University of Texas Southwestern Medical Center at Dallas, who chairs the thoracic oncology committee of the Eastern Cooperative Oncology Group, one of numerous oncology groups that organizes clinical trials. The pace of research today is being slowed, “not because of the lack of ideas or the lack of drugs; it’s the lack of people in clinical trials. It is a major impediment for us making progress in cancer treatment,” she says.
The Institute of Medicine echoed this point when it released a report in April calling for a complete overhaul of the National Cancer Institute’s Clinical Trials Cooperative Group Program, which includes more than 3,100 institutions. “If the clinical trials system does not improve its efficiency and effectiveness, the introduction of new treatments for cancer will be delayed and patient lives will be lost unnecessarily,” states the report. Increasing patient participation in clinical research is among the Institute’s recommendations.
The dilemma is intertwined with history, psychology, and logistics, all of which must operate within an imperfect system of health care. Sometimes doctors aren’t aware of the latest trials or don’t think about bringing them up. Sometimes patients are wary because they don’t know enough to feel comfortable volunteering. Other times patients want to participate, but worry—often justifiably—that insurance won’t cover portions of their care. The list of barriers to clinical trial enrollment fills an entire spreadsheet that encompasses doctors, patients, and the system itself.
“The fact is that none of us are blameless,” says Margo Michaels, executive director of the nonprofit Education Network to Advance Cancer Clinical Trials (www.enacct.org; 240-482-4730), based in Bethesda, Maryland.
Studies have suggested, however, that patients don’t participate largely because their oncologists never mention it. This became apparent to researchers at the University of California at Davis, who in 2004 embarked on a series of experiments to try to increase clinical trial participation. The researchers produced media campaigns to make patients aware of trials and to publicize a California law requiring insurers to cover the costs of routine care associated with clinical trials. In 2008, in the journal Cancer, the researchers reported that the level of awareness and understanding about clinical trials increased markedly. “Unfortunately, better awareness did not translate into willingness to participate,” says Primo Lara, MD, of UC Davis Cancer Center. “So we were wondering, ‘Why is this?’ ”
“In the end, the main barrier we need to overcome is our own culture. We need to change the culture of the treating physician, and make clinical trials part of the standard of care, not just an afterthought.”
Meropol is one of a number of researchers developing ways to change public attitudes about clinical trials. To him, the core theme has gotten lost.
To get that idea across, Meropol has developed an interactive computer program that patients can use in their oncologist’s office or on home computers before their visit. A patient takes a brief survey to identify knowledge gaps and list concerns about clinical trials, and they can then watch brief video clips that address their individual issues. For example, if someone is most concerned about side effects of an investigational treatment, they will view a video that tells them how side effects are monitored and managed. If they worry about the prospect of being a guinea pig, they can watch a clip explaining the amount of research that goes into developing a new treatment, and the safeguards in place for patient safety. “This is not meant to be coercive,” Meropol says. Rather, it addresses the concerns of patients in an individual way.
Groups concerned about cancer are also trying to make it easier for patients to gather information about trials, and find out if they qualify without having to rely on physicians to obtain the information. The Dr. Susan Love Research Foundation has teamed up with Avon Foundation for Women to launch the Love/Avon Army of Women (www.armyofwomen.org; 866-569-0388), which has set out to build a database of one million women (with or without breast cancer) who have indicated they are willing to participate in research studies searching for the causes of breast cancer. In November, lung cancer advocacy organizations and several large pharmaceutical companies launched the Lung Cancer Clinical Trials Call to Action (www.emergingmed.com/networks/LungCancerAlliance; 800-698-0931), a service that will help patients navigate through clinical trial information to see if they qualify for treatment through a research study.
Other solutions will require fundamental changes in the way studies are designed, such as making entry criteria not so rigid that patients are excluded for reasons that have nothing to do with their cancer. (For example, studies often stipulate that volunteers have no other medical issues, such as high blood pressure—a condition that affects more than 73 million Americans.) And reducing the paperwork and time commitment asked of community oncologists won’t happen until cancer researchers, pharmaceutical companies, and regulators reach agreements that will satisfy both the need for research progress and the need to protect patient safety.
“I think what we need is more of the public to speak up and say, ‘This is not acceptable. We’ve got to start making progress more quickly because my family member might be diagnosed with cancer,’ ” says UT Southwestern’s Schiller.
And in the end, every eligible patient will still not participate, simply because each decision arises from a person’s own life experiences, says Reese-Coulbourne. “How people look at clinical trials, I think, has to do with how they deal with risks in their own lives. If you’re somebody who only wants to do just enough—and I don’t mean that in a pejorative way—you’re going to be less inclined.” But for others, clinical trials may offer a chance to be part of their own cure today, and the cure for others tomorrow.
Download CURE’s A Patient’s Guide to Clinical Trials at www.curetoday.com/patient_guides.
After the study appeared, Lara’s research team held a series of focus groups, asking potential patients why they did not volunteer for trials. The main reason: their oncologists’ silence. “I met the enemy, and it was us,” Lara says. Even when patients better appreciate the integration of treatment and science, they abide by their doctors’ guidance. “In the end, the main barrier we need to overcome is our own culture. We need to change the culture of the treating physician, and make clinical trials part of the standard of care, not just an afterthought,” he says.
Pediatric oncologists have done this well—about half of treatment for children occurs through clinical trials, which is one reason why experts believe death rates for children with cancer have improved dramatically, falling by 50 percent since 1975. (Adult cancer mortality has seen only modest improvements, falling 12 percent in women and 21 percent in men since the early 1990s.)
But Lara and others understand why doctors aren’t always eager to jump into clinical trials. “Physicians are being squeezed just like everybody else in medicine,” says Schiller. In a smaller community practice, an oncologist who participates in a trial faces a mountain of paperwork, an often unpaid time commitment, and the possibility of hiring an extra nurse just to take care of the patients on studies. “Many physicians just don’t want to bother with it, frankly,” she says.
Or they must refer their patient to a major cancer center that already has much of the infrastructure in place to run clinical trials, or a colleague who already participates in clinical trials. But for financial and professional reasons, most oncologists would prefer to keep their patients.
There’s also a pocketbook problem. Many patients want to be treated with experimental approaches, but often fear they can’t afford it. While the drugs and basic tests are usually supplied, insurance companies may not reimburse other costs that could be associated with a new drug study, even treatment for common side effects like nausea or neutropenia.
“Unfortunately, a lot of insurance companies have it in their policies to outright deny experimental treatment,” Michaels says. She says about 30 states have passed laws like the one in California, requiring insurance companies to cover standard treatment under clinical trials. (The National Cancer Institute provides a list of states that require clinical trial coverage at www.cancer.gov/clinicaltrials/ctlaws-home.) Nonetheless, rules can vary from state to state, and policy to policy. Even simple charges, like parking fees for extra checkups or travel costs if the trial is being conducted at a hospital in another town, add up. “This is a legitimate fear for a lot of patients,” she says.
In the future, it may not be. The new health care reform law mandates that insurers cover the standard care costs associated with clinical trials. That provision goes into effect in 2014.
Sometimes patients have other, less tangible reasons for not seeking clinical trials. They fear they won’t get treatment if they end up randomly sorted into the wrong group—when, in fact, cancer clinical trials generally use the given standard of care for a comparison, not a placebo.
“Another misconception is that clinical trials are for people on death’s door,” says Neal Meropol, MD, of Case Comprehensive Cancer Center and Case Western Reserve University in Cleveland. “The reality is that patients most likely to benefit from a clinical trial are those patients who are in the best shape. The requirements commonly exclude patients who are very sick.”