ASCO 2009: Development Time of Cancer Clinical Trials Linked to Accrual Goals

Roxanne Nelson

June 04, 2009

June 4, 2009 (Orlando, Florida) The longer it takes to develop a clinical trial in oncology, the less likely it is that the trial will be able to achieve its patient accrual goal. A large percentage of trials, unfortunately, do not meet their minimum projected goals, researchers report.

Dr. Steven K. Cheng (Photo courtesy of ASCO)

Results of a new study presented here at the American Society of Clinical Oncology (ASCO) 45th Annual Meeting show that 40% of oncology trials failed to achieve minimum accrual goals. "This roughly translates to 17% of all patients in our sample," said lead author Steven K. Cheng, PhD, a postdoctoral fellow at the Center for Management Research in Healthcare in the Knight Cancer Institute at the Oregon Health and Science University in Portland.

The researchers considered 221 studies, all of which had been approved by the National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP).

Looking specifically at phase 3 trials, more than 3 out of 5 did not meet their minimum project patient accruals.

"Looking specifically at phase 3 trials, more than 3 out of 5 did not meet their minimum project patient accruals," said Dr. Cheng, who discussed the findings at a press briefing. "This is really important because phase 3 trials are the most time consuming and expensive to conduct."

Even though these data don't answer many of the questions regarding patient accrual and length of time to trial activation, it is "hypothesis generating," according to Julie Gralow, MD, who served as moderator at the press briefing. Dr. Gralow is assistant professor of oncology at the University of Washington School of Medicine in Seattle.

"For some trials that didn't meet accrual, it might have been for good reasons, such as seeing toxicity early on, or that another trial answered the question," said Dr. Gralow. "But for many of them it wasn't for a good reason."

Drawing from her own experience in clinical trials, Dr. Gralow pointed out that in some cases, the "standard of care had moved on without phase 3 trial data, so we could no longer randomize patients."

It's frankly a waste of resources.

"But the standard of care didn't move on because of solid data," she said. "It's a tragedy when that happens. It's frankly a waste of resources — what we're seeing is a waste of time, money, and patient effort. We need to speed up the clinical-trial approval process, so that we can get the answers sooner, get drugs approved, get new regimens into patients, and cure more cancer."

Lengthy and Laborious Process

Observations from past research have shown that the development of oncology trials is a lengthy and laborious process. "Specifically, an investigation of phase 3 cooperative-group trials were found to consume, on median, 2.4 years, and to include in excess of 307 steps internally to develop a clinical trial," he said.

Previous studies have also shown that accrual is poor in oncology clinical trials. More than one third (34.4%) of trials conducted at a comprehensive cancer center resulted in 0 accruals, and 59.4% of trials accrued fewer than 5 patients.

"This research bridges 2 past studies and uncovers the finding that development time of clinical trials is related to patient accrual," said Dr. Cheng.

Longer Development Time Equated With Lower Patient Accrual

Although postactivation barriers to oncology clinical-trial accruals are well documented, potential barriers before the trial opens are not. In the current study, Dr. Cheng and colleagues investigated trial-development time and how it affected patient accrual. They reviewed all therapeutic nonpediatric clinical trials developed between 2000 and 2007 that were sponsored by NCI-CTEP. These trials account for approximately half of all oncology-related clinical trials in the United States.

Their sample included 553 phase 1, 1/2, 2, and 3 trials that together enrolled more than 50,000 patients. Development time was defined as the time from initial CTEP submission of the concept to the time the trial began enrolling patients. "In our study, the median time to develop a clinical trial in oncology was found to be 15 months," Dr. Cheng pointed out.

They found that 40% of the trials included in their sample failed to achieve minimum accrual goals, and nearly half (49.2%) of phase 3 trials did not achieve at least 25% of accrual goals. Overall, a total of 8723 patients (17.0% of accruals) were accrued to studies that were unable to achieve the projected minimum accrual goal.

It is critically and ethically imperative to best allocate our patient participants to studies that are most likely to succeed.

"In an era when patient participation in clinical trials is low, it is critically and ethically imperative to best allocate our patient participants to studies that are most likely to succeed," Dr. Cheng said. "We found that studies that developed relatively quickly, between 9 and 12 months, were significantly more likely to achieve the minimum projected accrual [than trials that had a] median development time of 15 months."

Conversely, studies that took the longest time (more than 27 months) were statistically significantly less likely to meet the projected accrual.

Of the phase 3 trials evaluated that had a development time of more than 27 months, only 7% were successful in achieving accrual goals.

Dr. Cheng noted that there were several limitations to their study, 1 being that it only investigated a single end point in achieving clinical-trial success. "Trials may satisfy intended objectives and not meet accrual goals [for] many reasons," he said. "The study also only included NCI-CTEP trials."

Development time is only 1 indicator predicting poor accrual; research into identifying factors behind long development and poor accruals must be conducted, he added.

In addition, there is a lack of detail available regarding the decision for closure. "Research is currently underway at the Center to identify ways to dramatically shorten cancer clinical-trial development times, coupled with evaluations of whether those changes improve accrual," Dr. Cheng concluded.

Dr. Cheng has disclosed no relevant financial relationships. Dr. Gralow reports receiving honoraria from Genentech, Novartis, and Roche; and research funding from Amgen, Bayer, Bristol-Myers Squibb, Genentech, Novartis, Roche, and Sanofi-Aventis.

American Society of Clinical Oncology (ASCO) 45th Annual Meeting: Abstract CRA6509. Presented May 31, 2009.

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