Carle Foundation Hospital is one of 400 federally designated community research sites comprising a network of 3,400 participating physicians. These sites amass more data about cancer research than at any of the giant cancer centers like Memorial Sloan Kettering. Yet, according to a New York Times report (below), “federal officials have never conducted a systematic review of the community research program.”

A federal investigation of the Carle Cancer Center ( an affiliate of the Carle Foundation) was prompted by complaints to the federal Office of Human Research Protections (OHRP) about the science and safety of patients at the Center. In particular, the trials overseen by the Center’s principle investigator, oncologist, Dr. Kendrith Rowland, who has simultaneously overseen more than 130 clinical trials in more than 20 cancer types.  According to a grant application, the Times reports, Dr. Rowland personally enrolled about one-quarter of the 500 patients that Carle signed up for experimental treatment in a typical year.

The complaint to OHRP was made by the hospital’s vice president for research, Dr. Suzanne Stratton who found that instead of informed patient consent, doctors too often promoted trial treatments as superior to standard approaches, even when there was no supporting evidence.

Researchers who enrolled patients into clinical trials by misleading them about the experimental nature of the trial have embraced a cynical defense strategy invented by a pillar of American psychiatry, Dr. Paul Appelbaum, who coined a concept that shifted the blame for misconstruing experimental treatment with proven therapy, onto patients. Dr. Appelbaum proclaimed that patients suffer from a “therapeutic misconception.” 

However, surveys have shown that not only patients, but referring doctors mistakenly believe that research offers individual patients direct therapeutic benefit–those seeking patients as human subjects have planted false expectations of direct benefit.  

See: Lancet 2001;358:1772-77  and J Clin Ethics 1996;7:60-68
See also, discussion, Clinical trials and the "Therapeutic Misconception" – The War on Cancer, at: http://www.cancerdecisions.com/Townsend/FebMar2002_frm.html
OHRP corroborated Dr. Stratton’s complaints and is continuing its investigation. 

So far, the Times reports, OHRP has issued two letters of criticism — one in June, the second in September — to the nonprofit Carle Foundation Hospital and its affiliated for-profit cancer center.

The investigation has far broader implications for cancer research—beyond Carle. Dr. Stratton stated:
“I have concerns not just about patient safety, but the integrity of the data in the trials. My larger concern is that there may be other community hospitals doing research that, like Carle, evolved in a vacuum.”

The investigation could call into question the scientific evidence that the community research programs generally amass.

Indeed, Dr. Lori Minasian, director of the National Cancer Institute’s community clinical oncology program, said the agency would apply any lessons from Carle’s human research violations “across the entire network” of community hospitals and doctors. “We’ll look at audits, organizational structure and research oversight.”

The Times reports that an outside audit that led to Dr. Statton’s showdown meeting with hospital administrators, found instances of patients having received incorrect doses of drugs, while others were given chemotherapy before, rather than after, the required lab tests. And one patient was enrolled in a study despite having an implanted brain device that, according to the audit, should have disqualified him for safety reasons.

Like most institutional review boards—which are supposed to review research protocols to ensure patient safety and ethical standards—Carle’s IRB was too deferential to the researchers, failing to examine protocols to ensure ethical and safety standards were met.

For her conscientious action, alerting OHRP about gross scientific and safety violations, Dr. Stratton was fired, and ushered out of the hospital later that same day.

posted by Vera Sharav

THE NEW YORK TIMES
October 23, 2009
Research Uproar at a Cancer Clinic
By DUFF WILSON

URBANA, Ill. — Two years after becoming vice president for research at the biggest hospital in this university town, Suzanne Stratton said she had finally seen enough.
She had clashed repeatedly with a doctor who oversaw the local patients enrolled in more than 130 federally sponsored cancer studies — work that the hospital promoted in local television advertisements but that Dr. Stratton, who has a Ph.D. in molecular biology, said was often putting patients and science at risk.

In a meeting with Carle Foundation Hospital administrators late last year, Dr. Stratton demanded that they take action. She cited an outside audit that had found “major deficiencies” in 12 of 29 experiments being overseen by that doctor, potentially endangering patients or skewing the studies’ results. Dr. Stratton says her bosses responding by firing her, ushering her out of the hospital later that same day.

But federal officials, alerted by Dr. Stratton, have corroborated many of the shortcomings she found. They are continuing to investigate — an inquiry with implications for the nation’s cancer research effort that go far beyond the Carle Cancer Center.

In the last quarter century, among the hundreds of thousands of people around the nation who have enrolled in federally financed trials of cancer drugs and treatments, more than one-third have come through the doors of local medical centers like Carle.

Together, these nearly 400 federally designated community research sites and the network of 3,400 participating physicians amass more evidence for cancer science than at any of the giant cancer centers like Memorial Sloan Kettering in Manhattan or M.D. Andersen in Houston, part of the University of Texas.

Because the patients at community centers tend to be older, sicker, less affluent and generally more diverse than those treated at big academic medical centers, they are considered more representative of the national population. So, over the years, the community centers have played important roles in developing new treatments for breast, lung and prostate cancer.
And as far as federal administrators know, many of these clinics have sparkling records.

But federal officials have never conducted a systematic review of the community research program. And if Carle’s problems turn out to be any indication, the community centers may not always be adhering to the rigorous protocols of research medicine that the National Cancer Institute expects them to follow. That could call into question the scientific evidence that the community research program amasses.

The investigation is being conducted by the federal Office for Human Research Protections, an arm of the Department of Health and Human Services. So far, the office has issued two letters of criticism — one in June, the second in September — to the nonprofit Carle Foundation Hospital and its affiliated for-profit cancer center.

Meanwhile, the National Cancer Institute has shut down new patient enrollment in the studies at Carle, although it has allowed existing patients to continue experimental treatment there.

Dr. Lori Minasian, director of the National Cancer Institute’s community clinical oncology program, said the agency would apply any lessons from Carle’s human research violations “across the entire network” of community hospitals and doctors. “We’ll look at audits, organizational structure and research oversight,” she said in an interview.

Carle executives declined to comment for this article. But in their official responses to federal authorities — another response is due Tuesday — they say they have made changes, including retraining the principal investigator and other doctors, appointing new oversight managers, and “a top-to-bottom review” of protections for patients in clinical trials.

But they deny trying to cover up problems or that Dr. Stratton was fired for whistle-blowing. She has threatened to sue.
“I was devastated,” Dr. Stratton said recently.

“I have concerns not just about patient safety, but the integrity of the data in the trials,” she said. “My larger concern is that there may be other community hospitals doing research that, like Carle, evolved in a vacuum.”

The National Cancer Institute provides relatively limited financing for the community program. Carle, one of the bigger recipients, received about $1 million last year in federal research support, which does not go far in supporting the many trials under way at any one time. The greater value is the prestige the program bestows on the community clinics, making them regional magnets for doctors and patients alike.

The principal researcher at Carle, Dr. Kendrith M. Rowland Jr., is an oncologist who built a local reputation for offering the latest in cancer care. He once treated the wife of a bank owner who later donated $10 million to the cancer center.

Dr. Rowland, 55, has simultaneously overseen more than 130 clinical trials in more than 20 cancer types, a grant application shows, and he personally enrolled about one-quarter of the 500 patients that Carle signed up for experimental treatment in a typical year.

But Dr. Stratton, whom Carle hired in early 2007 to help oversee the cancer research effort, said Dr. Rowland was headstrong and had resisted her suggestions for improving standards.

Dr. Rowland did not respond to numerous telephone calls and e-mail queries, or to a reporter who visited his office; instead, he sent an aide to say he was too busy to talk. Carle representatives said Dr. Rowland would not comment, nor would the chief executive of the 305-bed hospital, Dr. James C. Leonard, who had fired Dr. Stratton.

Before coming to Carle, Dr. Stratton was well regarded in cancer research circles. She had more than a decade’s experience in clinical trials, including serving as the principal researcher in three national studies of prostate cancer. Dr. Stratton had also led a group that oversaw all drug and device trials for the University of Arizona Medical Center.

When she arrived at Carle, Dr. Stratton says, she was surprised to find a lax approach to a fundamental principle of clinical research — informed patient consent. Instead, she said, doctors too often promoted trial treatments as superior to standard approaches, even when there was no supporting evidence.
And she said that Carle’s institutional review board, which is supposed to monitor patient safety and doctors’ ethics, was too deferential to the researchers and failed to keep its own files.

In the audit that led to her showdown meeting with hospital administrators, there were instances of patients’ having received incorrect doses of drugs, while others were given chemotherapy before, rather than after, the required lab tests. And one patient was enrolled in a study despite having an implanted brain device that, according to the audit, should have disqualified him for safety reasons.

“I can’t stress enough how serious things are over there as far as noncompliance goes,” she wrote in an e-mail message to the hospital chief last November, shortly before she was dismissed.

In a June 9 letter, the federal investigators said they had found evidence of Dr. Rowland’s “interference” with reporting problems to authorities; “continuing noncompliance” with federal research rules set up to protect patients and data; and “systemic problems involving lapses in continuing review of numerous Carle Clinic cancer studies.” The two reports are posted on a federal Web site.

Carle responded in a July 13 letter to a federal official, obtained by The New York Times. Carle argued that the violations were minor, that it was making improvements and that its doctors performed good research. It also said any interference by Dr. Rowland was not intentional.
Whether lapses at Carle were the result of ambitious doctors taking on more work than their local setup could handle, or shortfalls in financing and oversight, may not be known until the federal investigation concludes.

And Carle may prove an exceptional case. After all, most community programs have provided valuable research without running afoul of federal authorities.
But some experts in community medicine say that many of the local programs simply fly under the federal government’s radar. And they contend that some of those clinics lack the support staff, record-keeping systems and institutional oversight of larger centers to assure proper ethics and patient safety in experimental medicine.
“Trouble occurs when institutions dabble,” LaDale K. George, a Chicago lawyer who has advised dozens of community hospitals performing clinical research, said in an interview. “Well-run, organized, clearly designed, this is an activity that has manageable human risk and minimal compliance risk. Disorganized, decentralized — you have significant risk.”

Copyright 2009 The New York Times Company