International Comparison Reveals US Shortcomings in Clinical Trial Enrollment

[Hopeful]

Elsevier Global Medical News. 2009 Aug 24, R Finn


SAN FRANCISCO (EGMN) - Virtually every step in the process of taking a clinical trial from submission of documents to patient accrual took significantly longer at a tertiary care medical center in the United States than at a similar institution in Europe, according to a study that compared thoracic oncology trials at Washington University in St. Louis to those at the University of Turin in Italy.
The U.S. trials also lagged in patient enrollment, although this was a problem at both institutions. Investigators reported that nearly two-thirds of the U.S. trials and one-third of the Italian trials enrolled four or fewer patients. Some trials failed to attract any patients.
The median time between submission of documents to university authorities and accrual of the first patient was 153 days at the University of Turin and 221 days at Washington University (P = .012). The median time from submission to opening the trial to enrollment was 113 days at the University of Turin and 163 days at Washington University (P = .048).
Kristina J. Williams, a senior research patient coordinator at Washington University, presented the analysis by Dr. Andrea Wang-Gillam of Washington University and colleagues at the World Conference on Lung Cancer. The meeting was sponsored by the International Association for the Study of Lung Cancer.
The retrospective study involved 83 thoracic oncology protocols approved at Washington University and 54 approved at the University of Turin between 2001 and 2008. At both institutions, most studies were phase II (72% at the University of Washington and 81% at the University of Turin). More studies at the Italian center were sponsored by industry (94%, vs. 53% at the University of Washington).
The steps in the approval process were somewhat different at the two institutions. At the University of Turin, submitted documents went to one committee for budget and contract review and to another for Institutional Review Board (IRB) review. At the University of Washington, documents initially went to three committees: one for budget review, one for contract review, and one for scientific review. Proposals that passed scientific review were sent to the IRB.
The only part of the timeline for which there was no difference between the institutions was the interval between approval of the study and the opening of enrollment. The median was 83 days at Washington University and 90 days at the University of Turin.
The differences between the institutions in the number of patients who enrolled in trials were substantial. Considering only those trials that had closed to enrollment at the time of the analysis (71 at Washington University and 40 at the University of Turin), the investigators found that 15 trials at Washington University (21%) were not able to attract a single patient, another 29 trials (41%) were able to accrue only one to four patients, and only 1 trial (1.4%) accrued more than 20 patients. At the University of Turin, only 2 trials (5%) failed to enroll any patients, 11 (28%) enrolled only one to four patients, and 10 (25%) enrolled more than 20 patients.
The investigators compared Washington University to four other U.S. comprehensive cancer centers, finding similarly disappointing accrual numbers. At those four centers, 21%-34% of trials failed to accrue a single patient, and 7%-15% accrued more than 20.
In commenting on the study, Dr. Richard J. Gralla, chief of hematology and oncology at North Shore University Hospital in Manhasset, N.Y., and Long Island Jewish Medical Center in New Hyde Park, N.Y., identified two areas for improvement in the typical approval process in the United States.
The first is contract preparation. "The hospitals are looking for their own protection. They're looking for indemnification clauses. They're looking for scientific freedom for the authors. These should be boilerplate," Dr. Gralla said. He suggested that the National Cancer Institute or some other organization could provide a sample contract that would not have to be written from scratch each time. (Dr. Gralla was not involved in the Washington University study.)
Secondly, scientific review committees need to be more assertive, according to Dr. Gralla. "I think the scientific review committee is an extremely useful process. But from the data that [Ms.] Williams presented to us, it's not working ... if 20% of the studies enroll nobody," he said. "We need to have scientific committees be tougher. [They should] make sure that we are going to enlist patients. [They should] track who the investigators are who don't enlist patients, and not allow those investigators to put protocols through, because it delays the process for useful protocols."
Ms. Williams said that she had no conflicts of interest to declare. Washington University School of Medicine sponsored the study.

Hopeful