While clinical studies and personalized medicine are clearly the future of cancer treatment, barriers to patient participation come from several directions, including patients, physicians, and the insurance industry. A US Oncology— sponsored survey of oncologists and clinical research professionals found them to be highly optimistic about the future of clinical trials in advancing personalized medicine, despite concerns about the various hurdles. The national survey of 299 oncology and clinical research professionals determined that 58% of respondents were optimistic about trials, while only 25% were ambivalent or unsure (

The study used a blinded survey, with interviews collected between June 29, 2009, and July 6, 2009. The majority of responses (67%) came from a mix of oncologists in medical, radiation, surgical, and hematology specialties; and the remaining 33% were clinical research professionals, such as trial coordinators, study managers, and physicians/investigators (

Matthew Galsky, MD, a medical oncologist with Comprehensive Cancer Centers of Nevada, which is affiliated with the US Oncology network, said he shares respondents’ optimism about the future of clinical trials and the importance of personalized medicine. His practice has approximately 50 trials open at any time, of which approximately 5% have a personalized medicine component.

“We’ve known for as long as chemotherapy has been around that a subset of patients benefit tremendously, and a large proportion don’t benefit at all,” Galsky said. “Yet, we still expose everyone to the same treatment.” He explained the benefit of being able to identify which patients are more or less likely to respond before starting them on therapy. “If we can identify and only treat that subset, and perhaps target the other patients with a newer treatment that might make them more likely to respond overall, we’ll increase the number of patients who benefit and decrease the number of patients suffering side effects.”

More than half (53.2%) of the oncologists and clinical research professionals who responded to the US Oncology survey agreed that recruiting patients for clinical trials designed to evaluate targeted therapies would be less difficult than getting them to enroll in largescale randomized trials of more traditional cytotoxic therapies. At the same time, some patients are reluctant to try investigational drugs.

Galsky employs a philosophy of open and proactive communication that breaks down what he sees as one of the primary barriers to patient participation in trials—patients’ misperception that they will be used as guinea pigs. “I talk to patients about the fact that any current standard treatment options are only standard treatment options because they were the subject of clinical trials several years ago. Hopefully, what we’re studying now will be the next standard of care; it’s an opportunity that will favorably alter the natural history of their cancer sooner.”

The majority of oncologists surveyed (85%) said another benefit of patient participation is when the trial provides treating physicians with genetic test/biomarker information that they can use to manage their patient’s disease. More than three-quarters (77%) said the opportunity to obtain results of a genetic test or biomarker information would influence them to present a trial to a patient. Approximately one-third (33%) of the oncologists said their patients worried, however, that results from these tests might be used against them when seeking insurance coverage. The Genetic Information Nondiscrimination Act (GINA), which took effect in November 2009, prohibits health insurers and employers from discriminating against individuals based on their genetic information, and communicating this to patients might alleviate some of their concerns.

Respondents reported cost and reimbursement as clear barriers to trial participation. More than half of survey respondents said mandated health plan coverage was the most important factor in encouraging patient participation. In addition, more than three-quarters (85%) of respondents indicated that cost/reimbursement alignment affects their ability to treat patients with a personalized medicine approach at least some of the time.

Galsky agrees that insurance is a growing issue that has the potential to dampen accrual, but he expressed surprise that respondents considered it the biggest obstacle, noting that it affects less than 10% of patients significantly. He sees reimbursement as just one of many obstacles, which include lack of time, lack of available studies, and lack of interest. With less than 10% of adults in the United States enrolled in a clinical trial, Galsky said, “We certainly need to look at many other factors that can increase the pool of eligible patients. It has to do with availability of a trial, patient and physician barriers, and the fact that most clinical trials are designed to enroll a patient population…on the healthier side.”

Nicholas Vogelzang, MD, a medical oncologist also with Comprehensive Cancer Centers of Nevada, agrees that reimbursement is a barrier, but he attributes this primarily to the professional time that goes uncompensated. “The clinical trial effort is greater than has been generally emphasized,” said Vogelzang. “That effort is not only in the office in direct discussions with the patient, it [encompasses] follow-up with the family because there are many questions… the consenting process raises additional questions.” He also cited the time involved handling the administrative pieces, “including signing off on every single piece of paper.” As an example, he estimated that on the day he was interviewed for this article, he reviewed and signed at least 20 clinical trial documents within the first 5 hours of the workday.

“Pharmaceutical companies spend an enormous amount of money on trials and get back probably less than they would like to get back—sometimes trials close, sometimes they don’t accrue well...If they could say this is a business loss, to me, it would encourage a pharmaceutical company to stay in the field.”

There are a number of proposed initiatives that have the potential to significantly impact and promote personalized medicine. On a scale of 7, survey respondents rated the following initiatives as 6 or 7, indicating their view that these prescriptives would be very effective:

• Government subsidization of clinical trials for personalized medicine (54%)

• Industry collaboration on the development of personalized medicine (53%)

• Tax credits for research and development (R&D) in the biotech/pharmaceutical industry to encourage efforts to develop personalized medicines (50%)

• National patient databases for matching patients with appropriate clinical trials (49%)

Vogelzang sees R&D tax credits as having the greatest likelihood for success, particularly if given to companies studying rare cancers that are at risk for accumulating high, unbudgeted expenses with the potential to drive them from the field. “Pharmaceutical companies spend an enormous amount of money on trials and get back probably less than they would like to get back—sometimes trials close, sometimes they don’t accrue well,” noted Vogelzang. “If they could say this is a business loss, to me, it would encourage a pharmaceutical company to stay in the field.”

Assessing Trials and the Role of Academic Medical Centers

Like most practices participating in clinical trials, Comprehensive Cancer Centers of Nevada has a thorough process to assess trials and determine whether resources are justified. As an affiliate of US Oncology, the practice uses a two-pronged review process.

First, US Oncology conducts a review similar to that used to assess an academic medical center. A committee of disease-specific physicians runs protocols and discusses the merits of the trials from scientific and clinical perspectives. Then, the practice conducts a similar review to determine whether the trial is suitable for its patient population. Survey respondents agreed that a review process is critical, with more than half saying that reviewers must assess whether the resources consumed by the trial are scientifically justified.

For smaller practices, the staff and resources needed not only to assess but also to run the trials are difficult to amass. A practice’s existing infrastructure and culture are also key factors. Vogelzang said physicians who are oriented academically earlier in their career are more likely to be successful in accruing to and participating in clinical trials.

Galsky agreed. “I think networks are the best way to participate, and there are many different networks throughout the United States,” he said. “It’s hard for small practices to do it without the support of some national infrastructure.”

Half of survey respondents reported that they perceive patient recruitment for clinical trials as most successful in academic medical centers. “I think that’s the common perception, but it depends on how you determine success,” Galsky said. “If you look at phase III studies, which are the studies that have led to the approval of drugs to treat cancer, and look at where the majority of those patients were enrolled, you’ll find that it isn’t in academic centers, it’s usually in the community,” he said. “It’s not a matter of the building, but a matter of who is conducting the trials.”

The physicians, the pharmaceutical companies, and the government and professional organizations involved in oncology research agree that increasing adult participation in clinical trials is needed if care is to continue to improve. Yet, the oncologists and clinical research professionals surveyed reported that only 5% of their patients participate in clinical trials each month. Looking only at oncologists, this increased to 15%, but this was still far short of the 38% of patients oncologists said are likely to benefit from clinical trial participation.

The National Cancer Institute (NCI) and American Society of Clinical Oncology are actively looking for ways to increase enrollment in cancer trials. On April 29-30, they are jointly sponsoring the “Cancer Trial Accrual Symposium: Science and Solutions,” in Bethesda, Maryland, which will emphasize strategies for increasing participation overall and target minority and other underrepresented populations. NCI plans to use evidence presented at the meeting to assist in developing AccrualNet, a new online resource that will help physicians and staff at clinical sites with trial recruitment.

Surveys like the one conducted by US Oncology are a good first step because they help identify what oncologists and clinical research professionals perceive as barriers to clinical trial participation. Addressing these concerns is a critical component of any organized effort to remedy the historically low participation of adults with cancer in clinical trials and integral to moving closer to the ultimate goal of providing personalized care for every patient with a cancer diagnosis.

Articles

Participation in clinical trial research is essential to continued improvement in cancer care. Yet, fewer than 10% of U.S. adults enroll in trials. A recent US OncologyÃ¢ï¿½ï¿½sponsored survey found that most
oncologists remain optimistic about the future of clinical trial research. We discuss obstacles to clinical trial enrollment with Nicholas Vogelzang, MD, and Matthew Galsky, MD, of the Comprehensive CancerCenters of Nevada.

By Elizabeth Freid Vocke

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