Publish or profit
What's in our best interest?
  In February 2004, the National Institutes of Health (NIH) caught its scientists and physicians off guard with an announcement of new conflict-of-interest (COI) rules restricting NIH employees from holding stock in pharmaceutical companies or medical entities such as health care companies and insurers. The rules marked a sweeping change. Everyone from heads of the national research institutes down to clerical staff was affected.
     It all began with a series of front-page articles in the Los Angeles Times disclosing that senior government scientists were accepting enormous fees—half a million dollars annually in some cases—for outside consulting work, speaking engagements, and other arrangements with private companies. Some were accepting the money while overseeing government funding of research on the companies’ products at the same time.
     The series sparked Congressional hearings and a wave of public interest, and in some circles, new questions about the integrity of medical and pharmaceutical research. After a torrent of complaints that the new rules on COI were too draconian, the NIH found a middle ground. But the proposal and ensuing uncertainty highlighted a thorny issue for research universities.
     “Concerns about conflicts of interest did not start with [the controversy] at the NIH,” says Claudia Adkison, executive associate dean/administration and faculty affairs at Emory School of Medicine (SOM). “This has been a growing issue for quite some time, as the nature of biomedical research and the way it is funded has changed dramatically in recent years. Yes, we do have a responsibility to promote translational research, and, yes, that does mean we must work with the for-profit sector. But we must do so in a way that protects our patients, protects the university, and protects the researchers themselves.”

     In 1980, Congress passed the Bayh-Dole Act, which reversed existing policy and encouraged universities to patent the discoveries of their faculty and try to license them to companies for conversion into for-profit commercial applications. Since that time, some university biomedical research departments around the country have become what one pundit has termed “hotbeds of entrepreneurialism.”
     Universities are eager to patent potentially lucrative technologies and encourage their researchers to work with them in the process. Some researchers with a new discovery are eager to form their own start-up companies, hoping to license the technology from the university to get their new medicine, device, or process to the market as quickly as possible. As a result, through university policies that share the proceeds with the researchers and inventors, researchers and their universities stand to reap millions of dollars from marketable discoveries, although the mega-million successes are relatively rare. This provides a powerful incentive for investigators to explore the cutting edge of science in search of new treatments, proponents say, and at the same time provides more money to be plowed back into future endeavors.
     But critics wonder whether universities’ missions to foster research in the public interest are now inevitably compromised by profit motives. What about research for treatments that affect only a small number of people? Does needed research get abandoned if there’s no market? And can investigators who stand to make millions of dollars really be objective about potential problems with a new drug or technology?
     What are the stakes? The answers aren’t all black and white, says Frank Stout, Emory’s vice president for research administration and a former NIH employee. Yes, there is potential for conflicts to harm research and the university’s mission. But it is up to the research institutions to set policies and standards and foster an appropriate atmosphere that encourages cutting-edge results without compromising scientific integrity. Furthermore, most of the university’s research is funded by NIH without any involvement with industry.
     The university has a guiding principle for ethical conduct in research, a policy on COI in research, an external consulting policy, and a comprehensive program to manage potential conflicts of interest. It demands a high level of integrity from its faculty, he says.
     “The conflict-of-interest policy means you don’t get yourself into a position where your external financial interests conflict with your duties at the university,” he says. “From our viewpoint, academics always comes first. This is what society has entrusted us with, why parents entrust their students to us, why our patients entrust us with their health care, and why the public at large entrusts us with hundreds of millions of dollars for research.”
     If a policy as stringent as the one proposed for NIH employees were expanded to include all scientists receiving government funds, the effect would be dramatic, says Raymond Schinazi, the director of the pediatrics laboratory of biochemical pharmacology in the SOM who served on the first COI committee at Emory. “If dropping all private relationships is one of the conditions of getting NIH funding, then you have to decide whether you want to accept it or seek more money from commercial interests,” he says. “If the researchers can’t find adequate funding, there’s a risk their discoveries will sit on the shelf and benefit no one.”
     Before 1980, the federal government owned and licensed the technology underwritten by its institutions. But a report in the 1970s revealed that 98% of federally financed technology sat idle and never developed into commercial products that might benefit the public. This waste occurred primarily because once a unique idea, discovery, or innovation is published or otherwise enters the public domain, it can no longer be patented by someone or some entity. Without patent protection, companies will not invest perhaps hundreds of millions of dollars in developing a new product if a competitor can then simply copy or use it.
     Then came Bayh-Dole. “The argument behind Bayh-Dole was that there was no incentive to invest big money in the development and marketing of a new product if you couldn’t control it,” says Donald Stein, professor of emergency medicine and neurology at Emory and a co-author of Buying In or Selling Out? The Commercialization of the American Research University (Rutgers Press, 2004). “A lot of great discoveries were not helping anyone because the intellectual property kind of languished in the void.”
     Stout says commercialization of research allows Emory to bring to the marketplace products that benefit patients. “Working with industry promotes economic growth which supports teaching and funds future research,” he says. “When Emory receives a royalty for a product, a percentage goes to the inventor, and the remainder is funneled into continued research and support, both within the researcher’s department and throughout the university.”
     For example, California-based Gilead Sciences and Royalty Pharma paid $525 million to purchase all future marketing rights to Emtriva (FTC Emtricitabine), the HIV and hepatitis B virus drug developed by two faculty members at Emory and partially underwritten by NIH. Based on university policy, Emory will receive 60% of the $525 million, with the remaining $210 million shared by the inventors.
     Bayh-Dole has been very good for Emory. Between 1995 and 1999, Emory’s share of fees and royalties was approximately $29 million. Between 2000 and 2004, it shot up to about $85 million. Even that healthy sum is dwarfed by the recent Emtriva windfall.
Does the potential for researchers to earn such huge sums of money increase the potential that some may be willing to compromise the integrity of their work? Self-described “serial entrepreneur” and Emtriva developer Schinazi says no.
     “If you’re working on something obscure that no one cares about, it might take years to find out,” he says. “But if you’re working on something really important such as a new device for heart surgeries, a brain implant, or novel medicines for hepatitis or HIV infections, if you falsify the numbers you’ll be found out right away because everyone will quickly try to duplicate your findings to confirm the data. Why ruin your career by doing something that stupid?” The truth eventually will prevail.

Unintended consequences
But outright misconduct aside, there is increasing evidence that corporate sponsorship is altering the direction of research and dissemination of research findings.
     A recent study in the New England Journal of Medicine concluded that universities routinely engage in lucrative industry-sponsored research that restricts academic freedom. In the study, Kevin Schulman from Duke University found that “academic institutions rarely ensure that their investigators have full participation in design of trials, unimpeded access to trial data, and the right to publish their findings.” His team surveyed more than 100 medical centers, finding that only 1% involved in multi-center studies had independent access to all trial data.
     Studies published in major British and American medical journals have shown that clinical trials by conflicted investigators (those with financial interest in company sponsors) are more likely to favor the drug or product on trial.
     A recent study by the University of Toronto analyzed 70 clinical trials of a controversial heart drug. The results were telling: 96% of the researchers who were supportive of the drug had ties to companies that manufactured it, and only 37% of those critical of the drug had such ties.
     Investigators truly believe that outside relationships won’t affect their objectivity, but the research indicates that some may be wrong, says Adkison, who developed the SOM’s first conflict-of-interest policy and oversees its compliance program. She also is a founding member of FOCI-Academe (Forum on Conflicts of Interest in Academia), a national organization affiliated with the Association of American Medical Colleges (AAMC) that shares information and strategies on the current state of affairs in this arena.
     The point of COI policies is not to outlaw all conflicts but to manage the conflicts in a way that ensures the integrity of the research as well as protects the patient volunteers who participate in studies, she says. “There is no way we could prohibit researchers from having any potential conflict of interest. We want our program to manage the conflicts effectively.”
     Conflicts in research range from faculty investigators who also serve on speaker’s bureaus and boards to those who accept paid consulting contracts with pharmaceutical and device companies that sponsor their research, to others who have formed private companies to market a drug or technology that they have developed and licensed from the university.
     The management plan required by the medical school’s COI program varies depending on the type of conflict and what role the faculty member plays in a given project. For example, faculty are almost never allowed to serve as principal investigators on clinical trials of a drug or product made by a company with whom they have an outside financial relationship. The compliance reviewers evaluate projects to make sure that patients are fully informed, the patient selection process is unbiased, the data are collected properly, and methods of analysis are appropriate.
     In the School of Medicine, the process starts with a faculty member’s disclosure of external activities to Assistant Dean Brenda Seiton, who works with the SOM’s COI committee, led by pathology chair Tristram Parslow, to review potential conflict of interest. The committee as a whole reviews the case and develops a plan for mediating or eliminating any conflicts that have the potential to compromise research integrity. On behalf of the SOM, Adkison oversees the COI program and insures that the faculty member is informed about whether and how the conflict will be managed.
     “In the future, we need to move toward emphasis on a broader culture of ethics, not just compliance with a policy and set of rules,” says Adkison. “We need to stress ethical standards of research conduct—basically doing the right thing.”

In broad strokes
Just as managing conflicts of interest has grown increasingly complex in the context of the new era of clinical research so has monitoring informed consent, safety, and scientific validity. This broader job of protecting the rights and welfare of people recruited to participate in clinical trials falls to a university’s institutional review board (IRB). But these days an IRB—usually made up of scientists, clergy, doctors, and lay people—is often overwhelmed by the job. At some large research universities, a single IRB must review more than 1,000 clinical trials at once.
     A 1996 report by the Congressional General Accounting Office found that some IRBs spend only one to two minutes of review per study. Board members can’t possibly be experts in every field. In fact, most are in-house researchers whose own studies are likely to come up for review someday.
     Emory is not immune to these challenges. In the past 10 years, in addition to the growth of unsponsored research, the Woodruff Health Sciences Center’s sponsored research has increased from $133 million in 1996 to $326 million in 2005. That growth in turn has placed stress on the research support infrastructure, including its IRB activities. Recently, the university has made significant enhancements to bring this critical component of the research enterprise in line with the growth in sponsored research. The new budget for the Emory IRB reflects an 80% increase in funding and a doubling of the number of people tasked with analyzing research protocols. Among other enhancements, a new electronic IRB system will allow researchers to submit proposals online and create IRB dashboard reports to help monitor IRB volumes, work loads, service, and performance. Emory also is expanding the number of IRB committees from five to seven and increasing stipends for IRB committee chairs.
     Professor James Keller, chair of the uni-versity’s IRB, says that top-down involvement and transparent scrutiny are essential ingredients for successful IRBs. “All the top people involved with research at Emory know how important it is. If things don’t go right, then the whole research process can be shut down.”
     The COI committee works closely with both the Emory IRB and the Office of Technology Transfer, which matches researchers and their ideas with companies or individuals desiring to develop and market products. By sharing reviews of conflicts of interest and its proposed management plan or prohibition, the committee insures these other groups are aware of any conflicted relationships being managed. Through this sharing, “sometimes you discover things you didn’t know,” says Adkison.
     Transparency is at the bottom of all the precautions. After all, says Todd Sherer, Emory’s associate vice president for research and director of the Office of Technology Transfer, “we want to make sure that what we do within our own walls is done without any bias.” The university’s reputation depends on it.

Us vs. them
Schinazi says research misconduct is possible no matter the origin of funding. More important, he believes that open collaboration with private industry is essential if universities are to bring the practical rewards of discoveries to the people who need them.
     “At Emory, I am probably one of the most conflicted people on campus,” says Schinazi, who has started several companies based on his research. “I have been here 28 years, and I love to educate young people. But I also believe a university should be an engine for discovery and development, especially if you combine your efforts with other faculty. Sometimes universities can become too paranoid about conflicts.”
     Schinazi believes that universities can get so caught up in making sure nothing is amiss, they overlook the big picture and become slow, bureaucratic, policing bodies. “We’ve created jobs and saved lives and elevated the university’s reputation a few notches, so give us the benefit of the doubt that we will do the right thing. The bureaucrats should stop building walls and instead create bridges to efficiently facilitate translational research in accordance with Bayh-Dole. There are enough hurdles outside the university to convert an invention to a life-saving product.”
     But speaking from another perspective, giving someone the benefit of the doubt without disclosure and management when lives and the reputation of the institution are at stake is foolhardy, Adkison says. “It just takes one well-publicized adverse event along with the discovery that a researcher has a previously undisclosed financial interest in a study’s outcome to destroy the university’s and the researcher’s credibility.”
     Rather than doing less, she wants to emphasize more—not so much policy and rules but partnering with faculty to build a broader culture of ethical behavior. “I really want the situation to be the faculty and the institution working together to figure out appropriate ways to collaborate with industry, that the school not be perceived as an obstacle to overcome.”
     At the end of the day, Adkison wants the research to withstand close scrutiny. “If questioned, we should be able to say that we have not overlooked something in order to pursue profit, to know that we have done all we could or should.”

Mike Fillon writes books and magazine articles on medical, technology, and science topics.

Forbidden or allowed? 1: Allowed after disclosure, with safeguards against bias and with continuing oversight. 2: Forbidden COI under current Emory policy. 3: Forbidden. 4: Allowed after disclosure and with continued management. 5: Allowed after disclosure and with continued management.


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