Low participation raises concern for cancer clinical trials
January 31, 2016 12:00 AM
Dr. Adam Brufsky
By David Templeton / Pittsburgh Post-Gazette
When Lee Giller’s breast cancer returned in November 2012, he faced a prognosis of 26 months to live.
So the 58-year-old Akron businessman, whose estrogen-receptor-positive and BRCA 1 breast cancer had spread to his bones, liver and lungs, said it “didn’t take much arm-twisting” to convince him to join a clinical trial to test a new treatment.
“At that point I was in dire shape and coughing a lot with shortness of breath,” he said. “Bottom line, I did it for self-preservation and self-interest.”
But Mr. Giller said he might have decided against entering a trial when initially diagnosed in 2005, given the five-year survival rate of 93 percent or higher for those with early stage breast cancer.
“I do understand why people are fearful,” said Mr. Giller, now seeking to re-enter the University of Pittsburgh Cancer Institute clinical trial to get the still-experimental treatment on a compassionate basis. “But if you do your homework and check with several doctors and trust your doctors, then you should go for it.”
Nowadays, most adults with cancer are hesitant to join clinical trials with only 3 to 5 percent of cancer patients volunteering to participate. As a result, one in five cancer studies fail to draw enough participants to determine whether or not the new treatment works, states a Fred Hutchinson Cancer Research Center and the University of Washington study published in December.
Researchers are working to resolve the problem in multiple ways, including publicizing the safety and importance of the research and creating patient committees to help make participation more convenient and less stressful.
There’s more active participation for studies involving the skin cancer melanoma and pancreatic, lung and colon cancers due to lower survival rates and fewer treatment options. Success in those trials provides the best hope for extended survival. The real problem rests with breast and other cancers with higher survival and cure rates, although more trials are underway to focus on treating cancers that have spread.
While adult participation rates in Pittsburgh are higher at 6 to 8 percent, the University of Pittsburgh Cancer Institute says it has a 13-percent participation rate. Even with those higher participation rates, there still aren’t enough patients to fill the rosters for research being done at the institute and the Allegheny Health Network.
Scott Ramsey at the Seattle-based Hutchinson Center said some doctors require patients if they want treatment to participate in trials because they lead to better outcomes. Funding is lost and research is stunted when too few patients join clinical trials, which represent the best scientific method to test and validate new treatments and drugs.
“In adult oncology, less than 5 percent of patients are enrolled in trials,” Dr. Ramsey said. “At this point, 10 percent or 20 percent is beyond my dreams.”
Why trials fail
Big turnoffs for patients include the fear of biopsies, additional rounds of chemotherapy or even regular blood draws.
Others include the hassle factor, reluctance to become a guinea pig, and doubts that the study directly will benefit them. Some patients avoid clinical trials because of worry about whether their health insurance will cover the basic care.
“If you’ve just been diagnosed with cancer, there is a lot to think about,” said Adam M. Brufsky, associate director of clinical investigation at the University of Pittsburgh Cancer Institute. “You have to think about what to tell your family, and you may be losing your hair, and you could be sick from the therapy. You have all this going on, and now they want you to be involved in a clinical trial. People can be overwhelmed.”
A commonly voiced local concern, he said, is “will I have to go through the Fort Pitt Tunnel two or three times a week to participate in the trial?”
The guinea-pig argument represents concern that an unproven treatment could be toxic or have unexpected side effects — that benefits won’t offset risks.
He said trial participants receive the best available care with the added chance of receiving the latest treatment years before it is included in the standard level of care. “You won’t be a guinea pig,” Dr. Brufsky said. “At a minimum you are receiving the absolute best standard of care, and the additional new experimental treatment could benefit you even more. Additionally, it could lead to new treatments and procedures not only for you but for coming generations of patients, as well.”
The chance of receiving the latest, most advanced treatment explains why most parents whose children have cancer enroll them in clinical trials. Historically that’s been the universal appeal for these patients. Low participation nowadays is an adult problem.
Before they are launched, clinical trials must undergo scientific review to assure that benefits most likely will outweigh risks.
“I tell patients that being part of a clinical trial increases the safety factor during treatment,” said Thomas Julian, principal investigator for the National Surgical Adjuvant Breast and Bowel Project and NRG Oncology clinical trials in the Allegheny Health Network. “They not only have their own physicians and nurses but there’s another layer of coordinators watching over them to assure side effects are not being ignored. They are being attended to more thoroughly.”
Clinical trials throughout the decades led to today’s advanced breast-cancer treatments that have extended and saved lives while improving the quality of life for patients.
“None of this would have happened had it not been for courageous, empowered women going through clinical trials,” Dr. Julian said. “We would still be treating patients with overly aggressive surgery, unneeded radiation and too much chemotherapy, and not more personalized cancer care with better outcomes.”
Patients often find that participation not only was beneficial to their health but rewarding. For example, Mr. Giller said his son and daughter each have the BRCA 1 gene mutation, as well, raising the risk that eventually they will develop breast cancer.
“Part of my thinking is,” he said, “if it does anything for the good of science then potentially it could help them.”
The more the better
Blame doesn’t rest solely with patients. Researchers sometimes don’t market or explain their trials properly to patients and conduct trials with a focus on results rather than patient well-being, said Carrie Bennette, a Hutchinson Center researcher who authored the study about low patient participation.
The Hutchinson study found that minority participation is even lower due to the time commitment and costs involved, along with cynicism about the benefits and options available to them.
Patient recruitment, known as accrual, is a subject of studies and editorials, with the issue addressed last weekend during an NGR Oncology conference in Atlanta, Dr. Julian said, who like many other cancer researchers has been involved in trials that closed because too few patients signed up.
“You have to provide good, clear information in a way that’s understandable to the patient and the physician,” he said. It must be clear to patients that, at a minimum, they will receive the current standard level of cancer care, potentially with something new that will “drive the process to the next generation of treatments.”
Clinical trials are done in phases, with early ones involving fewer patients and focused on safety, toxicity and dosage levels. Patients sometimes prefer Phase I trials because everyone receives the new treatment.
Phase III trials can involve hundreds and sometimes thousands of patients in multiple centers. In those trials, participants are randomly divided into two or more groups, with one receiving the standard level of care and the other groups receiving a new treatment or new combinations of treatments. Only then can researchers judge whether the new treatment had a notably improved impact.
That explains one concern for participants, especially those with advanced cancers, who still must undergo all testing procedures with a 50 percent and even 33 percent chance of never receiving the new treatment. Once all phases are completed, the U.S. Food and Drug Administration reviews results before deciding whether to reject it or approve it for limited or universal use as a treatment.
Few clinical trials result in potential cures in one step, with many deemed successful if patients on the experimental trial live without recurrence or progression of their cancer for months or years longer than a baseline group, Dr. Brufsky said. For that reason, cancer research usually advances in steps rather than leaps.
“The more people who enroll in cancer clinical trials, the faster we get answers and eliminate drugs that don’t work and approve the ones that do and the faster this all gets done,” Dr. Brufsky said. ”This is how we make future generations of people with cancer live longer and better.”
David Templeton: firstname.lastname@example.org or 412-263-1578.
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