For anyone who read about the Carle Cancer Center in the Friday New York Times, you might want to revisit the following story.

On June 18, 2009, The News-Gazette's Debra Pressey was the first to report that the federal government had barred the cancer center from enrolling new patients in its clinical trials.

June 18, 2009

By DEBRA PRESSEY

dpressey@news-gazette.com

URBANA – The Carle Cancer Center has been barred from enrolling new patients in clinical trials, at least temporarily, until several patient protection issues raised in a federal investigation have been resolved.

The order was issued by the grants administration office at the National Cancer Institute, which funds clinical trials at Carle and other medical institutions across the country, according to Dr. Joseph Kelaghan, program director for the Community Oncology and Preventive Trials Group at the NCI's Division of Cancer Prevention.

Kelaghan said Carle won't be permitted to accrue, or enroll, new patients in clinical trials until concerns identified in an investigation by the Office for Human Research Protections have been resolved.

Treatments for those patients already enrolled in studies at Carle may continue, he said.

Both the Office for Human Research Protections – which oversees the rights and well-being of human subjects involved in federally funded medical research – and the National Cancer Institute are arms of the U.S. Department of Health and Human Services.

Kelaghan said the National Cancer Institute acted to restrict Carle's new patient accruals after findings by the Office for Human Research Protections came to light.

"We fund the clinic to accrue patients to clinical trials, and part of that agreement is that they protect human subjects," he said. "Because we're not entirely sure right now, we're not allowing them to accrue any new patients."

Carol Koenecke-Grant, vice president of planning and marketing at Carle Clinic, said patients involved in those ongoing studies can continue to feel confident in their care.

"If there were a concern for patient safety, they would not be allowing us to continue those patients that are currently in trials," she said.

Koenecke-Grant also said the National Cancer Institute asked Carle to temporarily withhold further enrollments to federally funded studies only, but Carle considers the Office for Human Research Protections' inquiries a priority and will withhold new enrollments to all studies while it is in the process of responding.

"Patients currently on studies will continue to be treated and followed as deemed appropriate," she added.

Clinical trials are a major part of cancer treatment across the U.S., offering patients a chance for potentially better outcomes when standard treatments don't work to control or cure their cancer. The National Cancer Institute lists more than 8,000 such trials, and the North Central Cancer Treatment Group – Carle Cancer Center's primary research affiliation – says it enrolls 3,000 new patients a year at research sites across the country.

The Carle Cancer Center, a joint service of Carle Clinic and Carle Foundation Hospital, has been participating in clinical trials for more than 20 years and currently has patients in more than 100 of these studies.

A June 9 letter from the Office for Human Research Protections to Carle Clinic Chief Administrative Officer Michael Bukosky and Carle hospital CEO Dr. James Leonard identified issues connected both to some of those studies conducted by Carle Clinic and the clinical trial oversight and review board based at Carle hospital.

The letter listed 11 separate cancer clinical trials in which issues have been identified and determinations, some of which included:

– The hospital and clinic failed to prepare and maintain adequate documentation of the institutional review board activities for those studies. (Some of the documentation neither the hospital nor the clinic could locate included some approved protocols, review board meeting minutes, sample informed consent forms, continuing reviews/progress reports and/or protocol changes for some of the studies.)

– A research investigator at Carle initiated protocol changes without obtaining the required approval by the institutional review board. (That is permitted only when it's necessary to protect a research subject from a hazard.)

– The Carle review board failed to conduct a review of research under way once a year as required, meaning some studies continued using lapsed protocols.

– Carle Clinic failed to promptly report to the Office for Human Research Protections unanticipated problems involving risks to subjects or others.

Of note, the Office for Human Research Protections wrote, it has documents indicating that as early as November 2008, both the Carle institutional review board and individuals at Carle Clinic were aware of a final audit report revealing unanticipated problems involving risks to subjects or others occurring in multiple studies. (For example, it goes on to state, "12 major deficiencies associated with patient care issues" and "continuing noncompliance, namely systemic problems involving lapses in continuing review of numerous Carle Clinic cancer studies.")

The final audit report referenced was done by the North Central Cancer Treatment Group based at Mayo Clinic in Rochester, Minn. – a national clinical research group sponsored by the National Cancer Institute that designs studies and runs a network of participating research sites, including the one at Carle.

The Office for Human Research Protections included two pages of recommendations to fix the problems, and asked Carle to respond by July 7.

Carle Clinic declined an interview, but Koenecke-Grant responded via e-mail to questions from The News-Gazette. Some of those responses included:

– This past February, Carle Clinic began transferring oversight of all active studies to another institutional review board that has since reviewed and approved 190 clinical trials for the Carle Cancer Center.

– While all clinical trial programs are required to undergo an audit by their research base at least once every three years, the Carle Cancer Center's clinical trials program anticipates audits about every 18 months due to the size of its program. Carle welcomes this feedback "as patient safety is our primary concern."

– Last October, the Carle Cancer Center converted to an electronic tracking system, and during the transition, a small number of studies were noted to have lapsed continuing review and Carle Clinic reported that to the Office for Human Research Protections. Those studies "did not involve patients receiving active treatment, and were follow-up only."

– With respect to the 12 major deficiencies associated with patient care issues found in the audit: Audits and corrective action plans are common in all clinical trial programs.

"Audits are educational in nature and help both the IRB's (institutional review board's) and clinical trial program to continually improve their processes," Koenecke-Grant said.