By NAOMI FREUNDLICH

Last week Francis Collins, the director of the National Institutes of Health proposed important new rule changes for federally-funded investigators that are designed to increase transparency and remove many of the conflicts of interest that abound in biomedical research.

The proposed NIH rules, which are open for comment and expected to go into effect before the end of the year, represent the first time financial reporting requirements have been overhauled since 1995. The rules require investigators to disclose to their institutions all payments they receive from industry above $5,000, as well as any equity position they hold in a company. Research funding, speaking fees, paid authorship and travel expenses all must be part of this accounting. The previous limit was $10,000. The new regulations, which are aimed at reducing or removing industry bias from academic research, also require the academic medical centers to come up with a plan to manage investigator’s conflicts of interest—for example, university officials might insist that an investigator sell stock he owns in a company that helps pay for his research. Institutions will also be required to post all relevant payments (along with names of individual investigators) on a public website.

This action by the NIH is just the latest in the government’s crusade to bring more transparency to biomedical research and medicine. The proposed rules complement the recently-enacted Physician Payments Sunshine Act which by 2012 will require drug and device companies to start recording any payments they make to physicians worth more than $10, and to report them on March 31, 2013. These physician payments include stock options, research grants, consulting fees and travel expenses to medical conferences as well as the various knickknacks (pens, paper weights, scales, etc.) left in doctor offices by sales reps. The Sunshine Act requires that details be posted on-line in a database that can be accessed by the public starting Sept. 30, 2013. Finally, on a related front, Maggie recently wrote about new transparency rules proposed by the FDA’s Joshua Sharfstein that would require drug and device makers to fully disclose all details—positive and negative—about clinical trials.

By devising these new rules, the NIH is clearly acknowledging the complex and growing influence pharmaceutical, biotech and medical device companies have over biomedical research. Ever since the Bayh-Dole Act was passed in 1980, universities and academic investigators have been encouraged to foster relationships with industry, to patent discoveries and to aggressively commercialize the fruits of government-funded research. In 2007, industry accounted for 58% of the $101 billion total in funding for biomedical research while the federal government provided 33%. (Private foundations and public-sector organizations made up the rest.) Many beneficial (and highly profitable) new drugs and devices have resulted from these arrangements and universities and individual researchers have benefited financially in return.

But as industry involvement in academic research has grown, so have concerns about conflict of interest. In the last few years, reports have emerged about academic investigators accepting significant payments from industry and then withholding negative findings about a particular drug or device; choosing to highlight only positive research in their published scientific papers, when speaking at medical conferences or at continuing medical educational seminars. There is also evidence that industry-funded investigators are more likely to promote off-label—and sometimes inappropriate—uses of new drugs to their patients and colleagues.

Investigations conducted by Senator Charles Grassley’s office (one of the sponsors of the Sunshine Act, Grassley has long demanded that drug, biotech and device companies disclose payments they make to researchers and physicians) and also by the media have unearthed other questionable and often unethical practices—including researchers and academic institutions lending their names to scientific articles that are “ghost-written” by industry-paid individuals. Media reports detail prominent physicians and researchers (mostly psychiatrists and orthopedic surgeons) at places like Harvard, Stanford and Emory who received—and failed to fully report to their institutions—hundreds of thousands, if not millions, of dollars in research support, consulting and speaking fees and gifts from pharmaceutical and medical device companies.

In one widely-publicized case, child psychiatrist Dr. Joseph Biederman and two colleagues at Harvard Medical School neglected to report more than $4 million in payments they received from drug companies like Johnson & Johnson who make antidepressants and other psychoactive agents—often prescribed for off-label indications in children. Meanwhile, Biederman’s work “helped to fuel a controversial 40-fold increase from 1994 to 2003 in the diagnosis of pediatric bipolar disorder, which is characterized by severe mood swings, and a rapid rise in the use of antipsychotic medicines in children,” according to the New York Times.

Clearly, the time is ripe for more transparency in biomedical research. The Public Health Service (which includes NIH), issued the first (and only) conflict of interest regulation for government-funded academic investigators back in 1995. According to an article in Science, the current law “requires grantees to report to their institution financial conflicts ‘related to the research’ that are ‘significant’—defined as more than $10,000 per year from a given company, or 5% equity in a company. These cutoff points, says Susan Ehringhaus, an attorney at the Association of American Medical Colleges (AAMC), were arbitrary. Institutions must review the information, reduce or manage any conflicts, and tell NIH if a grant involves a significant conflict.”

The vague wording of the 1995 regulation has been its biggest shortcoming. First of all, it gives all of the responsibility for deciding whether or not industry payments represent conflicts of interest to individual researchers, not their institutions. If the investigator does decide that industry payments do represent a conflict, the reporting procedure is so general that the scale of industry influence is hard to judge. According to the Science article, “Many universities ask researchers to check a box if outside payments are above a certain threshold…If that threshold is, say, ‘above $50,000,’ that means a payment of $57,000 or $2 million would look the same. ‘That’s a huge problem,’ because it doesn’t distinguish between minor and major conflicts, says conflicts researcher Lisa Bero of the University of California, San Francisco.”

Because it is so vague, the 1995 regulation has been open to wide interpretation. The net result is a hodge-podge of disclosure policies for investigators that differ from institution to institution. To get an idea of the variety, take a look at the scorecard published by the American Medical Students Association that rates (from A to F) conflict of interest policies at academic medical centers and finds little standardization. In giving out their grades, the group considers a center’s policies for disclosing industry-provided gifts and meals, consulting fees and pharmaceutical samples. The group also looks at how centers handle disclosure of industry funding for continuing medical education programs and whether a medical school has a curriculum that highlights conflict of interest issues. In their 2009 scorecard, a dozen academic medical centers received A’s; meanwhile, some 30 received failing grades for weak policies.

There’s little doubt that the new disclosure rules for NIH-funded investigators will lead to greater transparency at academic medical centers. The university or medical center will now be responsible for deciding if a payment or equity interest represents a conflict, not individual researchers. The institution will be required to take action to reduce an investigator’s financial conflicts of interests and to make them public so that all interested parties—patients, consumers, reporters and legislators—can make informed choices.

Kate Peterson, writing for PostScript, a blog published by the advocacy group Community Catalyst, calls the new rules a “great step toward better transparency that is meaningful to patients and consumers, as it will provide an important crosscheck to the Sunshine database and other disclosure websites for assessing conflicts and compliance.” Alan Coukell, director of the Pew Prescription Project which together with Community Catalyst made similar recommendations on disclosure to the NIH last year, told the Washington Post that there were a few shortcomings: “The rules should require researchers to report any financial interest, even those less than $5,000, he said. The rules also do not require those receiving more than $250,000 to specify the amount any further. ‘From the public’s point of view of trying to assess someone’s financial stake, you’ll have no way of knowing whether they have a $250,000 interest or a $1 million interest,’ Coukell said.”

In the end, the proposed NIH rules, the Physician Payment Sunshine Act and transparency efforts at FDA all point to a concerted effort to rein in improper industry influence in biomedical research. But there’s even more that should be done. Last April the Institute of Medicine published a report entitled, “Conflict of Interest in Medical Research, Education and Practice” that called for even greater transparency in biomedicine—with a greater emphasis on industry reporting of payments. (The report’s recommendations are summarized best in this [NEJM] article.)

“Congress should require pharmaceutical, biotechnology, and device firms to report through a public Web site the payments they make to doctors, researchers, academic health centers, professional societies, patient advocacy groups, and others involved in medicine. A public record like this could serve as a deterrent to inappropriate relationships and undue industry influence. It also would provide medical institutions with a way to verify the accuracy of information that physicians, researchers, and senior officials have disclosed to them.”

Meeting the IOM recommendations would, for example, require pharmaceutical, biotech and device companies to make public their financial support for investigators, as well as seemingly independent patient advocacy groups and disease-specific organizations that are targeted to consumers. It would require professional medical associations (PMAs) like the American Academy of Dermatology or the American College of Cardiology to limit the industry funding they accept for medical conferences and continuing education programs as well as endorsement fees for products like sunscreen and “heart-healthy” foods. It would also require industry to list payments they make to such associations on a public website.

Dr. David Rothman and colleagues at the Center on Medicine as a Profession at Columbia College of Physicians and Surgeons go even further: “PMAs should work toward a complete ban on pharmaceutical and medical device industry funding ($0), except for income from journal advertising and exhibit hall fees.” This would include a range of practices from rejecting industry-funded supplements for journals, industry funding of scientific symposia and conferences, and, most importantly, a requirement that members of committees that draft clinical practice guidelines be free from industry conflicts.

Meeting these goals would be ideal, but likely unrealistic. The connections between industry, professional associations, physicians and biomedical researchers are too complex to be unraveled any time soon. And frankly, the money provided by industry for research is irreplaceable in the current budget climate. But by strengthening the disclosure process, the government is adding a layer of accountability that could help curb at least the most blatant abuses. It’s time to lift the shades on biomedical research and let the sun shine in.

Naomi Freundlich writes for the Century Foundation,
where she works with THCB author Maggie Mahar on the HealthBeat project. Prior
to joining the Century Foundation, she served as Science and Medicine Editor at
Business Week from 1989 – 1997. Her work has appeared in numerous publications,
including the New York Times, Business Week, Real Simple and Parents magazine.