Patients in Clinical Trials Are Receptive to Most Testing

Recruiting adults with cancer to take part in clinical trials is an ongoing challenge in the United States, but the growing number of studies for targeted therapeutics and the positive news emerging from these studies might help turn that around. Trials of targeted agents depend heavily on pharmacokinetic and pharmacodynamic testing to assess outcomes, prompting a team of researchers to investigate how willing patients are to undergo various testing procedures in the trial setting.

Raoul Tibes, MD, PhD, associate director of the Acute and Chronic Leukemia Program at the Mayo Clinic in Scottsdale, Arizona, led the collaborative study, which he describes as the first of its kind. "This has never been asked in a prospective and such a systematic way," he said in an interview. Tibes and his colleagues from Scottsdale Healthcare and the Translational Genomics Research Institute believe that the results will be useful in planning future clinical trials, particularly of molecular-targeted therapies. "Looking at data in detail, it may inform what specific tests are easier tolerated by patients and those can be incorporated preferentially in trials over others," explained Tibes.

The researchers analyzed the willingness of 61 patients with advanced cancer to submit to various pharmacodynamic and pharmacokinetic tests, including imaging, while participating in a clinical trial. Perhaps not unexpectedly, the patients were more willing to undergo noninvasive tests, such as urine and blood testing, than they were to submit to invasive procedures like tumor and skin biopsies. When it came to imaging, patients were more receptive to getting ultrasounds, radiographs, echocardiograms, computed tomography (CT) scans, and positron-emission tomography (PET) scans than they were to undergoing magnetic resonance imaging (MRI).

"In general, patients were educated [beforehand] about the procedures," said Tibes. Since all the patients had advanced malignancies, he suggested they were likely not as concerned about the long-term effects of radiation exposure from repeated imaging tests as someone in the general health care setting might be.

Although the study found that some patients were less willing to have a biopsy during a trial than some of the other tests, "Skin biopsies did not pose great burden on patients," Tibes noted. More reluctance was observed when it came to tumor biopsies, but nearly all the patients consented to at least 1 tumor biopsy and several agreed to repeat the procedure. Patients who found an invasive test inconvenient or had negative feelings about the experience were somewhat less willing to repeat the test. Tibes said, "This tells us that researchers can ask for tumor biopsies but need to be mindful of the number to ask for."

The study included 39 men and 22 women, but the data show "gender was not a major determining factor" of a patient's willingness to undergo testing. "Demographics, overall, had little influence," said Tibes. The investigators did find that "college graduates and patients with higher income had a higher positive association with willingness to undergo most tests." Patients with insurance coverage were also more likely to agree to requested procedures.

Tibes said the study "supports clinical trials that have frequent biomarker collection and imaging studies and gives clinical researchers the data on hand to support this." He said this is important in an era where many of the newer drugs are targeted therapies, requiring complex analyses of molecular factors to assess matters like cancer origin, disease progression, and treatment response.

Having information about how a drug is expected to work for a particular patient provides that patient with greater reassurance about participating in a trial for a novel drug. "The more scientifically rational and the more data, including molecular data—even data that is still experimental—the more support it lends to participate in a particular study," said Tibes.

In most trials involving a novel drug, a lot of unknowns remain, but Tibes believes this does not deter most patients. "New agents and drugs can work even without us understanding why and still offer great clinical benefit,” he pointed out. "Patients that have few treatment options left are willing to try these options."

Although the study did not attempt to measure whether explaining a test helped elicit the patient's cooperation, Tibes said his involvement conducting trials indicates, "If tests and procedures are explained to a patient, most patients are willing and agreeable to have these performed." He added that patients in phase 1 trials are generally more willing to undergo procedures than suggested by experts and others who have never been directly involved in early oncology trials beyond talking about how much is reasonable to ask of patients.

"In my experience, patients in a phase 1 setting understand the limitations of clinical research, but it still gives patients and their loved ones hope that something can be done!" said Tibes, who then added, "Hope dies last."

The study by Tibes and associates appears online in the journal Cancer and is scheduled for inclusion in the July 15, 2011, print edition.