Advisory committee urges tough new rules at The Hutch

The Fred Hutchinson Cancer Research Center will have the nation's toughest rules against conflicts of interests in human-subject research, if its board accepts recommendations by an advisory panel.

The proposed rules would prohibit doctors, nurses and other staff members from holding financial interests in their clinical trials, and would require that patients considering enrolling in experiments be told about holdings of the center itself.

The recommendations were presented to the Hutch's Board of Trustees Thursday by a panel of community leaders, and were explained to the public in a news conference yesterday.

Board Chairman J. Shan Mullin, who was also a member of the advisory panel, predicted most of the changes would be made within a year, though he said the financial prohibitions would be the toughest ones to adopt.

"I'm expecting that we will move forward and that we will strengthen and tighten our present policies," Mullin said.

Recommendations for Hutch The panel recommended that: • Staff in human clinical trials be prohibited from holding any financial interest in companies that may benefit from the trials. • Prospective research subjects be told of any financial interests by doctors, staff or the center itself. • A new Patient Protection Oversight Committee be formed. • More money be provided for internal review boards.

At the same time, Mullin and the Rev. William Sullivan, former president of Seattle University and chairman of the advisory panel, said The Hutch complies with all current laws and regulations and conforms with patient-safety practices at comparable research centers.

"All institutions can be improved," Sullivan added, "with the possible exception of the Mariners," Seattle's first-place baseball team.

The Hutch board yesterday named a new Patient Protection Oversight Committee of eight members, whose first order of business will be to consider the recommendations. The advisory panel, called the Committee on Patient Protection and Research Trials, was disbanded Thursday after reporting to the board on its five months of work.

It was formed in March, a week after publication in The Seattle Times of an investigative series entitled, "Uninformed Consent: What patients at 'The Hutch' weren't told about the experiments in which they died."

The Times reported that more than 20 people had died prematurely in two failed clinical trials in which Hutch researchers and the center itself had financial conflicts of interest, and that doctors had failed to fully inform the patients of risks and alternatives.

The Hutchinson Center is the leading bone-marrow transplant center in the world, performing about 450 transplants a year. It receives about $140 million a year, two-thirds of its budget, from the federal government.

In the recommendations released yesterday, the advisory panel called for "outright prohibition on the part of individuals involved in human-subject trials of any financial interest in for-profit corporations which may benefit from the result of such trials."

A similar policy was written in June for clinical researchers at The Hutch, but exempted holdings under $10,000 or 5 percent of a company, and applied only to principal researchers and people who recruit patients, inform them or evaluate results.

The advisory panel emphasized that "a policy of outright prohibition of such interest is an important element in maintaining and enhancing public trust in future clinical trials at the Hutchinson Center."

Sullivan said no other research center has an outright prohibition on financial conflicts. The Hutch had a policy nearly that strong between 1983 and 1995, but it was not enforced. Sullivan and Mullin said the old policy was not part of their review of current policies.

Sullivan said two judges, a lawyer and an accountant on the panel said their own professions have absolute prohibitions on financial conflicts of interest, so they thought staff who work on human experiments should, too.

"This is pushing out into new territory here," Sullivan said. "The oversight committee and eventually the board will say yes or no to that, and maybe their conclusion will be that machine won't fly."

The Sullivan panel did not call for prohibition of financial conflicts of interest in the Hutchinson Center's institutional holdings. Most research centers accept company money and stock, though Marcia Angell, former editor of the New England Journal of Medicine, says that, too, should be banned.

Angell yesterday praised The Hutch for taking national leadership and challenged other research centers to follow.

"It sounds terrific to me, but the devil is in the details," she said of the advisory panel's recommendations.

Two of the four experts who worked with the Sullivan panel felt information on potential financial conflicts should not be given to patients. Ernest Prentice of the University of Nebraska Medical Center and Gwenn Oki of the City of Hope National Medical Center, wrote, "Sick patients who are contemplating enrollment in clinical research are usually not in a position to weigh the significance of financial disclosure issues relative to their care."

But Sullivan said the panel "strongly disagrees" and voted unanimously for full disclosure to patients of any financial interest by the center or its staff, similar to disclosures to patients in California since a 1990 state Supreme Court decision on informed consent.

Former Washington state Supreme Court Chief Justice Richard Guy, a member of the Sullivan panel, said in an interview that the panel couldn't see any reason The Hutch couldn't have a simple ban on conflicts, avoiding the complexity of making exemptions and disclosures.

"You don't have to explain anything if you don't have a problem," Guy said.

The other two experts who worked with the panel were James Boyett, of St. Jude's Children's Research Center in Memphis and Margaret Dale of Harvard Medical School.

The panel also made several other recommendations, based on the experts' input. Those include:

• Creating two staff positions to help the center's two Institutional Review Boards, volunteer groups of mostly Hutch employees who review clinical trials for ethics, risks and benefits.

• Hiring a bioethicist to deal with ethical issues in human experiments.

• Establishing better systems to report unexpected injuries or deaths in clinical trials and to decide whether or not experiments meet a "minimal risk" standard for expedited review.

• Asking sharper questions of doctors to report more potential conflicts of interest.

• Disclosing financial conflicts of interest to co-workers in labs and to publications and seminars where results are discussed.

• Guarding against continued influence by researchers who leave experiments because of financial conflicts.

• Setting up a single Data Safety Monitoring Board independent of The Hutch to review select experiments.

• Establishing an Office of Regulatory Affairs.

The Hutch expects to take a leading role in national debates on informed-consent and conflict-of-interest policies, Sullivan said.

Sullivan emphasized the panel was looking at current practices only, not at the past experiments. Those trials are the subject of two federal lawsuits and a federal investigation.

One of the lawyers representing families in the suits, Thomas Dreiling of Seattle, listened to the news conference by phone yesterday, then criticized The Hutch for failing to provide independent advocates for patients and outside review of all new experiments.

"Nothing announced today addresses the harm the Hutch caused the 85 participants of (a leukemia experiment) and their families," Dreiling said in a faxed statement.

Sullivan said The Hutch might be considering the recommended changes even if The Times' stories had never been published, because of national attention on protections for research subjects and conflicts of interest.

The center has a long history of alliances with biotechnology companies. Several researchers are paid regular fees for discoveries licensed by companies. And several serve on boards of scientific advisors, for which they are usually paid or given stock options.

In its series, The Seattle Times reported that during the 1980s, Drs. E. Donnall Thomas, John Hansen and Paul Martin owned stock in Genetic Systems, a company with licensing rights to drugs that The Hutch was testing in clinical trials. The stock made Thomas and Hansen millionaires.

The series also reported that in 1992, Dr. C. Dean Buckner was an adviser to Cell Therapeutics, for which he was given stock options, while he worked at The Hutch testing a drug combination being developed by the company. Other doctors were doing work for private companies while working at the Hutch.

Sullivan said that there has not yet been any study on how many researchers might be affected by a ban on financial conflicts or whether researchers might leave if a stricter policy were adopted.