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Goal of Maintaining Public's Trust Brings Research Groups Together on Conflict-of-Interest Guidelines

Renee Twombly

In the wake of the implementation of conflict-of-interest (COI) guidelines at the National Institutes of Health that are among the most stringent of any at federal, private, or public research institutions, a group of universities has made official what was once an informal conflict-of-interest discussion group.

The Conflict of Interest Working Group, which represents about 70 institutions, including 18 of the top 20 NIH grantee institutions, decided in early September that it would affiliate with the American Association of Medical Colleges (AAMC) to become a center for COI issues.

"There is no professional organization solely focused on these issues in universities, and we understand the increasing need for a dedicated forum for professionals who develop these policies and implement them," said Julie Gottlieb, assistant dean for policy coordination at Johns Hopkins University School of Medicine in Baltimore.

Gottlieb was one of two university COI experts who started meeting with other officials in early 2003 to discuss the burgeoning crisis of public confidence in biomedical research and to compare notes about how best to protect their universities against such problems, either perceived or real.

The working group was designed to demonstrate that universities are now working together to make sure that their institutions are paying attention to all aspects of COI, including consulting, stock ownership, intellectual property rights, and COI within institutional review boards.

In short, the group wants to make sure that all of its member universities have taken adequate steps to eliminate or, as Gottlieb says, "credibly manage," COI in each of these areas, measures that will assure the public that research on new medical treatments is based on safety and objectivity.

"Through effective self-governance, we want to show more consistency, greater credibility, and less need for regulation," she said. But Gottlieb also added that, in the final analysis, assuring the public that medical treatments are based completely on merit and not financial interests of scientists "is a very tall order and one that encompasses much more than COI management, such as FDA review, institutional interests, manufacturers' decisions, and so on."

Managing COI

The issue of whether universities have compromised their ethics through close collaboration with industry has been steadily building since the 1980 passage of the Bayh–Dole Act, which encouraged universities to commercialize publicly funded research. Under the act, universities can patent discoveries and share in licensing fees, with a portion distributed to the researcher and to his or her department. In 2001 alone, universities began 494 companies and brought in licensing fees worth more than $1.2 billion.

The arrangement suited many "because it provided synergy and resources that energized and advanced medicine," said Thomas Stossel, M.D., a Harvard Medical School hematologist. The fact that researchers who made discoveries or who were leaders in a field also shared in the bounty served only to grease the wheels of progress, he said. "In the freewheeling days of early biotechnology, amazingly wonderful things happened," Stossel recalled.

Early approaches to COI cases focused on people who abused the system, but that gave way to the notion that the systems in place to stop COI were too lax. Public attention was drawn to the possibility of widespread abuse after the 1999 death of Jesse Gelsinger, who had participated in a gene therapy trial whose leader was a founder of a company that was cosponsoring the research and was hoping to bring this new treatment to the marketplace.

Universities began to require that their researchers disclose corporate sponsorship and that industry–academic collaborations be monitored, but it soon became clear that academic institutions did not agree with each other as to how to manage real or perceived COI.

In 2002, the AAMC issued general, and voluntary, COI guidelines drafted by its task force, saying that financial COI was the single issue that posed the greatest threat to maintaining public trust in biomedical research. A year later, a study in the Journal of the American Medical Association revealed that 34% of articles in major medical journals are written by lead authors with relevant financial interests and that two-thirds of academic institutions hold equity in startup firms founded upon research at those institutions.

Then, in late 2003, the Los Angeles Times published a series of articles on the COI rules for NIH intramural researchers, highlighting how a history of weakening restrictions led to some very profitable collaborations for some scientists after then–NIH Director Harold Varmus, M.D., lifted bans in 1995 that stopped researchers from accepting consulting fees and payment of stock from companies. The series of stories led to a Congressional probe and, eventually, the new, more restrictive rules. (See News, Vol. 97, No. 5, p. 337, "NIH Adopts Strict Conflict-of-Interest Policies for All Employees.")

Cashing In or Advancing Medicine?

NIH director Elias Zerhouni, M.D., has suggested in media reports that there should be a "summit" of government and academic leaders to address COI throughout American medical research. He singled out consulting payments from drug companies as being a "systemic problem" that has the potential to undermine public trust in university medical research. But academic institutions want to avoid blanket rules imposed by Congress or the government, saying that the balance they have to maintain between industry and academic research is delicate—and unique to the university.

"All of our institutions are operating in a setting where we have multiple conflicting objectives," said Hopkins' Gottlieb. "All of us put patient safety before anything else, but we have to ensure research integrity, engage with companies, as the NIH itself requires, and we have local development pressures. We have to address all these missions while also giving primacy to maintaining the public trust. It is very hard to paint in black-and-white terms."

But the palette varies widely from institution to institution, Gottlieb acknowledged. And although these differences don't provide a neat and transparent picture as to how the institutions are all equally protected against the risks associated with COI, university representatives say they have no present plans to rewrite their policies to match the NIH intramural policies on consulting agreements and stock ownership. Instead, they hope to work through channels such as the Conflict of Interest Working Group to "benchmark where our institutions are in these policies, assess our effectiveness, and develop some greater refinement and perhaps some consensus," Gottlieb said.

It might be a tough task given how research universities view financial COI, particularly the policies that govern consulting agreements. Policies at Harvard Medical School in Boston have swung back and forth in degree of restrictiveness over the years. As of 2004, faculty members cannot participate in clinical research on a technology owned by or obligated to a company and also receive consulting funds of more than $20,000 a year from that company. But the limit was only $10,000 a year from 1994 to 2004. Other changes have made the policy more restrictive. For example, a 2004 change prohibits full-time faculty members from serving in executive positions in for-profit businesses involved in commercial or research biomedical activities.

Still, as is true for many universities, there is no cap on outside income at Harvard Medical School and no limit on the number of companies a researcher can consult for. Margaret Dale, J.D., the school's dean for faculty and research integrity, pointed out, however, that a "conflict of commitment" clause limits the time faculty can spend on outside activities to 20%.

Researchers at Johns Hopkins also have no cap on total outside earnings, and they have a higher threshold of potential income from each consulting contract than do Harvard scientists. Researchers can earn up to $25,000 a year in consulting from the company or companies with a financial interest in a specific research endeavor, but if they exceed that threshold they cannot conduct related research on patients. Still, Hopkins is one of a few institutions that reviews every outside consulting agreement by its faculty to "capture situations where consulting may create a conflict of interest with the research," said Gottlieb.

COI policies at the Fred Hutchinson Cancer Research Center in Seattle underwent substantial examination 3 years ago. Consulting agreements are now capped at $10,000 a year per company, and each agreement is subject to approval, according to associate general counsel Gerianne Sands.

These restrictions were made after a series of articles in the Seattle Times suggested ethical improprieties had taken place in the center's research, although a follow-up lawsuit ruled in favor of the cancer center. "By then, the train was out of the station and we moved forward to make sure that there was not even a chance in the future that someone here would be accused of conflict of interest," Sands said. The cancer center's Board of Trustees had first debated allowing no financial consulting at all "in an attempt to be as pure as the driven snow," but faculty members said that they needed some monies for travel and other expenses associated with research projects, she said.

The University of Texas M. D. Anderson Cancer Center in Houston, a public institution, has taken a different tack. It limits outside income from all sources to 50% of a person's salary, and 25% from one source. Leonard Zwelling, M.D., vice president for research administration, said that only about one-third of the faculty have disclosed that they have an outside relationship, which could include consulting agreements, equity ownerships, speaking engagements, and service on scientific advisory boards. He disdains the notion that researchers should be allowed multiple consulting agreements. "Don't fool yourself that there is a higher purpose to these pursuits. It is about making money and nothing else," he said.



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Leonard Zwelling

 
Harvard's Stossel has a different viewpoint. In a "Sounding Board" article in the September 8 issue of the New England Journal of Medicine, he maintained that COI rules cure a disease that doesn't exist and are stifling medical progress in the process. "In a transparent atmosphere, misconduct can be detected, challenged, and if necessary, purged and punished," Stossel wrote. "The intense energy currently dedicated to demonizing academic–industrial research relationships should be redirected toward developing better ways to identify and facilitate the type of partnerships that have brought more good, by far, than harm."

However COI guidelines end up being implemented in the country's research institutions, Harvard's Dale concludes that "conflict-of-interest issues in biomedical research are likely to continue to be matter for lively discussion and debate."



             
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