Alex Philippidis Senior News Editor Genetic Engineering & Biotechnology News
Answers include less red tape, more communication and coordination; study cites need for more accrual data.
Just 2% to 5% of adult patients now enroll in U.S. cancer trials, according to estimates offered over the past 15 years—a distressingly low number that has focused the attention of patient advocates, doctors, and at least one pharma giant on finding reasons, and more importantly, solutions.
The National Patient Advocate Foundation (NPAF) identified low trial enrollment as one of several hurdles to cancer R&D that it blames for the average nine-year timeframe for developing new cancer drugs, from discovery to approval—compared with as little as two years for HIV therapies.
In a “white paper” report issued May 30, NPAF attributed low adult enrollment in cancer trials to:
- Industry cost-cutting as biopharmas now conduct 70% of their clinical studies outside the U.S., despite regulatory concerns about the applicability of results to American patients.
- Fewer physicians participating in trials, since reimbursement is lower than for regular practice.
- Poor communication about trials by sponsors to physicians, and by physicians to their patients.
- Criteria that exclude too many elderly patients despite the nation’s graying population.
- Locations based more on where researchers work than where patients live or get treated—a special burden for poorer patients unable to travel to trial sites.
“We have magnificent physicians. We have magnificent infrastructure to support clinical trials. But we also have a lot of hurdles that physicians and patients have to get through in the clinical trial arena,” Nancy Davenport-Ennis, founder and chairman of NPAF, told GEN.
Search for Solutions
NPAF’s white paper, Securing the Future of Innovation in Cancer Treatment, proposed among solutions the creation of Project Innovation. The coalition of cancer patients, family members, and others will promote cancer R&D by pressing for more funding for cancer research, new policies to speed up trials, and better communication and coordination between providers and patients.
“If we are a nation of innovation, and if we believe that we’re a nation that wants to maintain its position as number one in research, discovery, and innovation, we have to create a system that is more supportive of the patient and the physician to get people enrolling in the clinical trials that are here,” Davenport-Ennis added.
A few politicians appear to be heeding NPAF’s message. Earlier this month, U.S. Reps. Leonard Lance (R-NJ), Anna G. Eshoo (D-CA), Dave Reichert (R-WA), and Henry Waxman (D-CA) launched the Congressional Caucus on the Deadliest Cancers. Their goals include raising awareness and advocating for research and other measures. Asked how the caucus will address raising patient enrollment, a spokesman for Lance, John Byers, told GEN: “The caucus is just getting organized and any and all ideas like that are still being ginned up.”
Davenport-Ennis suggests, correctly, that the U.S. should adopt reforms similar to those implemented in the U.K. in 1999.
Frustrated with a low accrual—less than 3.5% of incident cases—the Department of Health, England, created the National Cancer Research Network (NCRN), which is managed by a consortium of the University of Leeds and the Medical Research Council Clinical Trials Unit, and is now part of the National Institute for Health Research.
NCRN’s goals include increasing the numbers of patients in research and the rate at which they are recruited; increasing the number of National Health Service organizations and healthcare professionals participating in studies; and improving coordination of research.
A study published 2011 in the British Journal of Cancer found the enrollment rate rose to 12% of annual incident cases, or 32,000 cancer patients, recruited each year. The percentage of cancer studies meeting their recruitment target nearly doubled—to 74% from 39%—before NCRN’s creation.
“Learn Some Lessons”
The U.S. has nothing like the NCRN or a second U.K. entity, the National Cancer Research Institute, formed to create partnerships that fund and drive clinical trials.
“We could probably learn some lessons in the United States by looking also at what the United Kingdom has done,” Davenport-Ennis said. “There’s an opportunity for us to look at some of the systems that we have used for decades in this country and ask, is there any way that we can improve in the area of communication and coordination?”
NPAF’s report is among several that have highlighted problems with cancer patient recruitment, and resulting consequences.
A 2010 study found that of 495 Phase II and Phase III trials conducted between 1977 and 2006 by the Eastern Cooperative Oncology Group (ECOG)—now merged with the American College of Radiology Imaging Network—27% never completed their planned accrual of patients, while 32% have never been published. Inadequate accrual accounted for the closing of 35% of Phase III trials held by five cooperative groups between 1993 and 2002.
Also in 2010, the Institute of Medicine (IOM) cited inadequate enrollment among several explanations—including a cumbersome oversight structure and a 20% reduction in funding since 2002—for its finding that Phase III trials held through cooperative groups took between 1.25 and 7 years to start up, with half of all such trials never reaching completion. IOM’s recommendations included more funding to cover research costs, and higher reimbursement of costs associated with standard patient care during trials.
NPAF’s white paper cited a commentary published February 10 in the Journal of Clinical Oncology. David P. Steensma, M.D., of Dana-Farber Cancer Institute and Harvard Medical School joined with Hagop M. Kantarjian, M.D., of the University of Texas MD Anderson Cancer Center concluded that regulatory requirements imposed over the past 25 years often complicate efforts to launch and carry out clinical studies.
They cited a study showing that that the cost of research per patient on a Phase IIIa oncology trial has ballooned from between $3,000 and $5,000 in the early 1990s, to between $75,000 and $125,000 in 2013.
Asked how much of that cost reflects patient recruitment, Dr. Steensma told GEN: “I would say it’s probably a fairly small proportion. My guess would be no more than 10% to 15%.”
The expense of pursuing large and at least 30% American patient populations to withstand FDA scrutiny are also among factors in trial costs, he said, adding: “It’s hard to object to having a population large enough to show whether or not a drug actually has an effect.”
Dr. Steensma said cancer trials should be streamlined as recommended in a 2010 Clinical Cancer Research study. David M. Dilts, Ph.D., director of evaluation for the Oregon Clinical & Translational Research Institute, led researchers who discovered that a Phase III cooperative group trial requires 769 steps, 36 approvals, and a median of about 2.5 years from formal concept review to study opening. Dr. Dilts is among co-developers of the National Cancer Institute’s AccrualNet™, a web-based system launched in 2010 to help researchers recruit participants to NIH trials.
“A consent form doesn’t have to list every possible eventuality for a clinical trial. Just because the lawyers say it’s got to be 30 pages because then everything’s listed and that makes people less likely to sue, that’s not helpful,” Dr. Steensma said.
At the American Society of Clinical Oncology’s recent annual meeting, Genentech highlighted its initiatives to draw patients to trials: Investigators videoconference with patients, collecting from them heart rate and other data through telemonitoring devices, while patients use social media to connect with each other and advocates.
“We hope to bring clinical trials to patients, instead of patients to clinical trials,” the Roche subsidiary declared in “The Trouble with Trials,” a presentation by Corsee Sanders, Ph.D., Genentech’s svp and global head of product development innovation and clinical operations.
A study published March 25 in Trials illustrates a key hurdle that must be surmounted. Of 108 trials between October 2007 and September 2010, 47% of 32 industry-sponsored trials furnished accrual data, vs. 37% of 76 trials by government, academic, or cooperative group (GAC) sponsors. Researchers led by Amy P. Abernethy, M.D., Ph.D., director of the Duke Cancer Care Research Program, gathered data via ClinicalTrials.gov, a publication review, and online surveys. GAC and industry need to step up accrual disclosure so that progress can be tracked in bringing trials to patients.