Medical ethics - are drug studies reliable? / Charles Zaif

In the early 70s, when Robert Lindsay decided to turn to medical research, he didn't do it for the money. His area of ​​specialization, the effect of hormones on the body's bones, was not a sought-after research area. It was a perfect opportunity for a young researcher to make his mark and help, he hoped, millions of people who suffered from bone loss (osteoporosis). Sometimes when the body ages, the bones lose the ability to regenerate at the same rate at which they wear out normally, and the skeleton weakens. No one, including Lindsay, fully understood the reasons for the depletion, but there was evidence that hormones played a role. Some women develop osteoporosis shortly after menopause, when their hormone levels drop sharply, and it is possible that this drop destroys the balance between bone formation and breakdown. If so, Lindsay assumed, giving hormone pills might stop the progression of the disease and even cure it. From a small, low-budget clinic in Glasgow, Scotland, he launched one of the first clinical studies testing hormonal estrogen therapy to prevent bone loss in menopausal women. Lindsay's star is gone.

His next project had tremendous commercial effects, and he captured the attention of the pharmaceutical industry. In 1984, after moving to the Helen Hayes Hospital, a rehabilitation center north of New York City, he published a study that determined the minimum effective dose of Premarin, an estrogen-based bone thinning drug. The research findings implied that in order to fight bone loss, millions of women should be encouraged to use the drug, and Lindsay therefore became an important personality in the eyes of the drug manufacturer, Wyeth-Ayerst Laboratories. Indeed, the company chose him to make an informational video called "Bone loss: a preventable tragedy".

In the mid-90s, when Wyeth-Ayerst Laboratories was struggling to patent Premarin, Lindsay was already an enthusiastic supporter of the company. He opposed the approval of a generic version of the drug, which could have cut Veith's sales, even though such a generic version would have made treatment easier for patients. His argument was that a generic version might be slightly different from the original drug. This argument may be true for certain drugs, but his position also coincided with the company's position. "All we're asking is that we don't approve something now and regret it," he later told the Associated Press (AP) in 1995. The close relationship between Lindsay and Wyeth and other pharmaceutical companies lasted for decades, sometimes in covert ways. He allowed Wyeth to write drafts of articles for him and received tens of thousands of dollars from pharmaceutical stakeholders who might profit from his research.

The crux of the scandal is not Lindsay's actions but the fact that he is not unusual. Over the past few years, the pharmaceutical industry has found many ways to funnel large sums of money, sometimes enough to finance a son or daughter's university tuition, into the pockets of independent medical researchers whose work is directly or indirectly related to the drugs these companies manufacture and market. The problem lies not only in the pharmaceutical companies and researchers but in the entire system: the institutions that provide research budgets, the research laboratories, the scientific journals, the professional associations and so on. There is no body that provides systems of balance and brakes that are essential to prevent conflict of interests. Instead, the organizations place the responsibility on each other and allow researchers and pharmaceutical companies to very easily discover loopholes in enforcement and then wrap their actions in a shroud of secrecy.

"There is not a single sector of academic medicine, academic research or medical education where connections with industry are not common," says sociologist Eric Campbell, a professor of medicine at Harvard Medical School. But not all of these connections are negative. After all, without the help of the pharmaceutical industry, medical researchers would not be able to translate their ideas into new drugs. But at the same time, Campbell claims, some connections exploit the scientists to sell drugs instead of generating new knowledge.

The connections between researchers and pharmaceutical companies take many forms. For example, lecture promotion offices: a pharmaceutical manufacturer pays a researcher to travel to lectures across the country, often in first class, and the researcher occasionally delivers a speech written by the company and presents slides he has prepared. There are shadow writers: the drug manufacturer takes care of writing the article and pays the scientist (the "guest" authors) so that their name appears in the article and for them to submit the article to a scientific journal. And there is also consulting: a company hires researchers to advise it. The researchers "think companies are interested in their thinking skills, but they're really interested in the brand," says Marsha Angel, former editor-in-chief of the New England Journal of Medicine. "Buying a senior and respected academic researcher, the kind of person who gives talks at conferences, writes textbooks and writes scientific articles is equivalent to 100,000 salespeople."

Scientific journals are littered with studies that demonstrate how pharmaceutical industry money subverts scientific objectivity. A 2009 study published in the journal Cancer showed that, as reported in the scientific papers, subjects who participated in studies whose authors had conflicting interests survived in some way longer than subjects in studies by clean-handed researchers. A study published in 1998 in the New England Journal of Medicine found a "strong correlation" between researchers' conclusions about the safety of drugs from the calcium channel blocker group, which is used to lower blood pressure, and between their financial ties to the companies that manufacture the drugs.

And this is not only an academic problem. Medicines are approved or rejected on the basis of apparently independent research. When a drug does not work as promised and is taken off the shelves or labeled as dangerous, it is usually possible to find traces of biased studies and the flow of money to scientists. For example, more than 2010 years ago, patients began suing Wyeth after another estrogen drug, Prempro (sold in Israel as Premaryl Plus), was linked to an increased risk of breast cancer, stroke and other diseases. In the trial that took place, Wyeth's shadow writing arrangements and guest authors were a major part of the case. Even when it was the turn of Merck's pain reliever Viox (which has been linked to heart attacks and strokes), payouts from the pharmaceutical industry emerged. For example, in a study conducted on Viox, it appears that academic researchers joined the project financed by Mark after the company had already analyzed all the data. According to a study conducted in 87 and published in the British Journal of Medicine, it turned out that XNUMX% of the researchers who expressed "sympathetic views" towards Avandia, a GlaxoSmith-Kline diabetes drug, despite evidence that it may increase the risk of heart attacks, were related Financial ties to the drug manufacturer. And when a committee of the US Food and Drug Administration debated whether to pull Evandia off the shelves because of the link to heart attacks, it turned out that the members of the committee also received money from the drug companies.

The scientific community's answer to the conflict of interest problem is transparency. Journals, grant-giving institutions, and professional organizations urge researchers to declare acceptance of a committee in front of their research subjects, their colleagues, and anyone affected by their work who have connections that might jeopardize their objectivity. In this way, the scientific community decides if the research is ethical, and when the experiment is finished, to what extent the results can be trusted. It is a method based on respect. But many times researchers do not report a conflict of interest, sometimes because they do not understand that there is a problem. (Scientific American also requests that the authors of the articles voluntarily report conflicts of interest.)

Apparently there is a backup system. Several layers of control should ensure that a conflict of interest is revealed even when researchers are unaware of it or intentionally conceal it. When a scientist does not report a conflict of interest, the university or hospital where they work should notice this and report it. And when a university or a hospital does not fulfill its role, the government institution that finances most of the research, i.e. the American Institutes of Health (NIH), is supposed to do so. Unfortunately, the backup system is extremely flawed. "Institutions often look the other way, or they have pretty weak policies," says Adrienne Pugh-Berman, a professor in the Department of Pharmacology and Physiology at Georgetown University. Worse, not only is the NIH failing to enforce the ethics laws that are supposed to stop the creeping influence of drug company money, but they are apparently breaking the laws themselves.

The US Congress is trying to stop rampant corruption in medical research with legislation. In 2010, Congress passed the Physician Payment Transparency Act as part of health care reform. Since 2013, the law requires all pharmaceutical companies and medical device manufacturers to report most of the money they transfer to doctors' pockets. Since most (but not all) medical researchers are physicians, in theory at least, this data would help universities, research hospitals, and the NIH decide whether a researcher might have a conflict of interest. But this information will be worthless if it is not used.

The case of Robert Lindsay highlights the depth of the problem of medical research being in conflict of interest and how difficult it is to correct the distortion.

In the thick of the entanglement

The pharmaceutical companies' efforts to influence the conduct of science focus on the shadow writers. Once a drug manufacturer can steer the way a research paper is written, it can control, to a large extent, the way doctors and researchers understand and use the scientific result.

One of Lindsay's most prestigious papers from 2002 showed that Parampro has positive effects on postmenopausal women. The article was originally written by Design-Rite, a company hired by Wyeth to write articles for publication in scientific journals. In mid-April 2001, a meeting was held with Lindsay to discuss the development of the article, after which Design-Rite wrote an outline and sent it to Lindsay (Walwith). Design-Right sent a draft to Lindsay for comments in early June, reanalyzed some of the data, and wrote the article. In August, the Journal of the American Medical Association (JAMA) accepted the article for publication. Later that year, Design-Rite wrote the article in response to the critics' comments, and it was published in May 2002. At the end of the article, Lindsay and the other three authors thanked Karen Mittleman for her editorial help, without mentioning her employment by Design-Rite or her connection to Wyeth.

Lindsay denies that Design-Wright had any significant role in shaping the 2002 article or any article published thereafter. In fact, the company simply "provided a draft according to our guidelines," he says. He and the other authors of the article were responsible for planning and directing the study. If that's true, Lindsay should be credited as one of the authors of the paper, and Mittelman should indeed receive only a brief acknowledgment, according to Phil B. Fontanerosa, editor-in-chief at JAMA. "It is not clear that [Mitelman's] role included planning (of the study), collecting data or analyzing and interpreting the data," he wrote in an email he sent to me.

The use of an external writing company was not a one-off. Kathleen Olth, who worked for Design-Rite, helped Lindsay write an article for the journal Fertility and Infertility in 2009. (After my first interview with Lindsay, he refused to answer any further questions, including who paid Lauth in 2009, and referred me to the media consultants.) Two years later, in an article in the journal Osteoporosis International, Lindsay even thanked Lauth for "supporting scientific writing" and noted that Pfizer (which acquired Veith in 2009) financed the writing. However, he clarified that he was "the only one who conceived the study and the content of the article." The article talked about how a series of hormones from Pfizer's manufacturing house serves as "a new paradigm for the treatment of menopausal women."

Along with getting writing help from Pfizer, Lindsay racked up several payment agreements that had a conflict of interest. According to a database prepared by ProPublica, a group of investigative journalists, in 2009 and 2010 Eli Lilly paid Lindsay more than $124,000, most of it for lectures.

Most scientific journals have rules about reporting financial relationships. The exact details that a scientist must report depend on the research topic and the journal, so it is difficult to decide exactly when a researcher breaks the rules. In several publications Lindsay did report his connections with Eli Lilly, but he did not do so comprehensively. For example, in an article published in the September 2010 issue of the Mayo Clinic Proceedings discussing research on bone thinning (osteoporosis), many of the authors stated that they lectured for Eli Lilly or were connected to the society in other ways, but Lindsay, who was also one of the authors of the article, did not. He later told me that he changed his mind about declaring this type of relationship: "Until recently, I declared relationships with every company whose products were included in my lectures," or articles. "I've changed that philosophy a bit because now, to make sure there's real transparency, I'm going to declare all connections."

Even when the subject of the research was a Lilly product, Lindsay did not always declare his financial ties to the company. In a study published in 2008 in the Journal of Endocrinology and Metabolism and examining whether teriparatide, which is the basis of Lilly's Porteau drug, is affected by other bone loss drugs, there was no mention that Lindsay had served as a consultant and lecturer for Porteau's manufacturer in recent years. "Since everyone in the study was treated with teriparatide, there was no possibility of creating a conflict of interest," says Lindsay. "And of course, [the study] was not supported in any way by Eli Lilly."

The lack of traceability in Lindsay's reporting habits extends beyond research papers. As a prominent researcher, he played an important role in publishing guidelines for the treatment of bone loss, which are used by other doctors. For example, he helped develop and write the American Osteoporosis Foundation's 2008 Osteoporosis Prevention and Treatment Guide. The guide, approved by many physician organizations, discusses the treatment options, and teriparatide in general. ("In general, tripartide is well received by the patients, although some of them suffer from muscle cramps in the legs and dizziness," it says.) In the chapter called "Due Disclosure" the manual states that none of the authors, including Lindsay, have "a relevant financial connection to any entity with a commercial interest. "

Moreover, Lindsay apparently did not mention the potential conflict of interest when he tried to get federal research grants. Although as early as 2004, if not earlier, he was a consultant to Lilly, in 2005 he approached the NIH, the agency responsible for most federally funded American research, to finance research on Porteau. Lindsay wanted to perform a bone biopsy on the patients to see how the drug affected their bone structure. He received the grant. In the years since, Lindsay has received $3.4 million from the NIH to research the drug. In 2010 he applied for another grant to compare two methods of administering the drug. And again, he received the grant, this time in the amount of $364,000 in 2010 and $346,000 in 2011.

Federal regulations regarding potential conflicts of interest in NIH-funded research state that the grantee must report any actual or perceived conflict of interest and the manner in which such conflict of interest was addressed, mitigated, or resolved altogether. Those who do not do so are breaking the law. It seems quite clear, but in reality things are not so clear. Responsibility for law enforcement is passed from one agency to another, and conflicts of interest like Lindsay's often fall through the cracks.

 

track cash flow

Medical researchers receive tens of billions of dollars from the NIH every year. When this much money is involved, there are huge chances of corruption. The NIH staff does not excel at curbing the phenomenon because the institutes do not resolutely look for conflicts of interest in the work of the scientists. When we asked them, for this article, about a possible violation of ethics laws, NIH officials backed each other up.

When we asked Pei Chen, who works at the institutes, about a possible conflict of interest regarding the grants Lindsay received to research the tripartite, she refused to provide copies of documents required by federal law, provided by Helen Hayes Hospital, Lindsay's employer. and are supposed to testify that the conflict of interests was properly handled. Chen insisted that everything was fine. "The NIH is committed to maintaining the public trust by conducting the research it funds impartially and to the highest scientific and ethical standards," she wrote to me in an email. She added, "I can assure you that the institution employing Dr. Lindsay provided the necessary approvals prior to receiving the grant, and he will be required to provide these approvals annually in the year prior to receiving the money." Documents obtained under the Freedom of Information Act contained no mention of any conflict of interest, and nothing in them indicated that Lindsay receives money from the manufacturer of the drug being investigated. NIH officials declined to say whether they were continuing to investigate the matter.

The NIH's approach is not surprising. A few years ago, the Department of Health and Human Services' office of inspector general got its hands on internal NIH correspondence showing that the administration was ordering investigations into conflicts of interest among researchers supported by the institutes. (Full disclosure: My wife works in the Office of the Inspector General but has nothing to do with these studies or this article.) For example, one memo noted, “We should not conduct surveillance and obtain additional details about the nature of the conflict of interest or how it was managed unless there is reason to sufficient to do so.”

Lindsay's case is not unique. Scientists across the US apply for government grants and at the same time take money from pharmaceutical companies, and this often creates a conflict of interest. To get an idea of ​​how much money is flowing from drug companies to NIH grantees, my students and I used a database containing all the institute's grants from 2009 and 2010 and the ProPublica database, which records payments from drug companies, to see which researchers received Payments from drug manufacturers. We were able to identify $1.8 million in payments made by a handful of companies to NIH grantees in New York State alone. The payments were given for lectures, consulting and other services. (Presumably the actual total payments in New York are much higher.) Many of these payments do not appear to create a conflict of interest.

Research grant recipients are not the only ones taking money from drug companies. So do the people who work at the NIH and help decide which of the researchers will receive a grant. Just as we used ProPublica's database to track payments by pharmaceutical companies to NIH-funded researchers, we used this database to track pharmaceutical industry money flowing into the pockets of advisory board members and research committees. In the end, we located almost 70 advisory board members who collectively received more than a million dollars for lectures, consulting and other services to pharmaceutical companies. Some of these payments may violate federal ethics laws, which prohibit members of advisory committees from participating in discussions that may affect organizations that pay them large sums.

The problem therefore runs deeper than a conflict of interest among the recipients of NIH research grants. Money from drug companies seeped into the institutes themselves. If the institutes knew about the possible conflict of interest of their employees and did not properly see that the conflict of interest would not affect the decisions of the committees, then they themselves violated the law. In order to verify this, I submitted a request, based on the Freedom of Information Act, to receive documents that would testify whether the NIH knew about the payments by the pharmaceutical companies to the members of the advisory committee, and if so, whether the institutes allowed the recipients of the payments to fulfill their duties despite the financial ties to the drug manufacturers. The NIH refused to submit the documents. I filed a lawsuit and after nine months of hearings, a federal judge forced the institutes to reveal what they were trying to hide.

Some of the documents obtained as a result of the lawsuit indicate that the resources the NIH directs to monitor conflicts of interest are focused on finding missing forms. Moreover, they testify that several NIH institutions have not taken a single action to enforce conflict-of-interest laws among their employees since 2008. But the most significant documents, the ones the institutes have fought to keep confidential, deal with so-called disclaimers.

Under certain circumstances NIH can grant a waiver, the dismissed government employee who is in a situation of conflict of interest (such as a member of an advisory committee) from the ethics laws. I requested information about waivers granted to several members of the institutes' advisory committees, each of whom, I knew from ProPublica's databases and other sources, had taken thousands of dollars from drug companies. I wanted to find out why the NIH agreed that these people sat on the committees despite the possibility of a conflict of interest and also what the nature of the conflict of interest was.

The vast majority of the payments from the pharmaceutical companies were not mentioned at all in the waivers. For example, Louis Petchek, who at the time sat on the American Board of Neurological Diseases and Stroke, was allowed to attend some meetings even though he held many shares in pharmaceutical companies, but the waiver did not indicate that he received more than $50,000 as a consultant for Pfizer. (Patchek did not respond to our request for comment.) Similarly, the disclaimer of Errol Chinayan, who serves on the American Cancer Institute's scientific advisory board, did not reveal that he received $9,000 from GlaxoSmith-Kline in 2009 and $21,000 in -2010. Chinayan claimed that he reported these payment arrangements to the NIH. Why then did they not appear in the waiver?

At NIH, private cases are not considered. One of the workers at the institutes agreed to talk about the general policy, but only anonymously. In general, consulting fees and lecture arrangements, she said, will not be specified in the waivers but in a separate document that discusses unique issues for which committee members are supposed to disqualify themselves. As this article went to press, Susan Cornell, NIH's Freedom of Information Act supervisor, confirmed that the Institutes had failed to provide certain disqualification documents in response to my request even though they should have.

Due to the lack of traceability of the NIH in disclosing documents and the secrecy that the institutes employ it is impossible to know clearly what is happening there. In the least worst case, the institutes are negligent in detecting and controlling possible conflicts of interest. For example, if the consulting agreements are supposed to be detailed in the waiver documents, why are Lawrence R. Stanbury's consulting agreements with GlaxoSmith-Kline and Starpharma listed in the waiver? (Stanbury, chairman of the pediatrics department at Columbia University's College of Physicians and Surgeons, serves on the scientific advisory board of the American Institute of Allergy and Infectious Diseases.) And why does the disclaimer not include the consulting work he performed for Sanofi Pasteur? "I have no idea why the advice to Sanofi does not appear in the disclaimer," Stanberry wrote to me in an email. The officials in charge of the waivers may have been mistaken.

Eye catching of enforcement

Information obtained through another Freedom of Information Act request, this time to the Office of Government Ethics (OGE), which is supposed to ensure that government agencies such as the NIH comply with ethics laws, indicates that the institutes are not following federal regulations regarding waivers.

From the government's point of view, granting a waiver is a weighty matter that means granting immunity from the law, so it should be done infrequently and with adequate supervision. Federal regulations state that the NIH must obtain approval from the OGE before granting waivers. However, even though the institutes have issued dozens of disclaimers to the members of the advisory committees in recent years, the Ethics Office has only documented three times in which NIH employees consulted with it as required since 2005, and none of the subjects of the consultation was a member of an advisory committee. When I asked NIH officials for comment, they insisted that the institutes fully follow federal regulations regarding waivers, but they did not provide evidence that the institutes consult with the OGE regarding waivers as required by law.

The institutions that provide research funds are supposed to act as an additional brake against conflict of interests, but this is not the case. The NIH has never accepted responsibility for the detection and control of conflicts of interest in the research they fund. In 2007, in response to a complaint from the Office of the Chief Inspector that the NIH manages financial conflicts of interest in an extremely poor manner, Elias Zarhouni, who was then the director of the institutes, claimed that it was not their job to decide which of the researchers followed the ethics laws. "We believe it is essential to maintain objectivity in research," he wrote in a letter to the Office of the Inspector General, "but the responsibility for identifying... a conflict of financial interests must rest with the research institutions." NIH officials say current policy on the issue remains unchanged.

However, research institutions are also known for their failure to address ethical issues related to their researchers. A 2009 Office of Inspector General report examined how institutions receiving NIH research grants identify potential conflicts of interest. He found that 90% of them trusted the researchers to report problems. Even institutions that take a hard public line against conflicts of interest are negligent in enforcing their own policies. In late 2010, ProPublica developed a database of pharmaceutical companies and began monitoring Stanford University's and other universities' strict policies against conflicts of interest. She discovered dozens of employees who received funds from the pharmaceutical industry in violation of the institution's laws.

The Helen Hayes Hospital, where Lindsay works, does not strictly enforce its rules, it seems. There is no doubt that the organization is complicated. This is a state facility, so the New York State Department of Health has an interest in the subject, and all research grants are administered by HRI, a non-profit organization that helps the Department of Health obtain external funding for medical research. HRI distributes research grants totaling half a billion dollars annually. Since these are so many research grants and so much money, it is surprising that HRI does not find dozens of cases of conflict of interest every year. "I have been managing funded programs here for 11 years, and I have been employed by HRI in the field of research grant management for 17 years. I have never encountered a conflict of interest,” HRI's Terry Dehm told me. "Not a single case of conflict of interest in any research grant we applied for...we never encountered it."

When I told her that Lindsay had received a research grant from the NIH, passed on to him by HRI, to study Porteau and that he was receiving funds from the manufacturer of the drug he was investigating with government funds, Dehm said that HRI's then-director, Michael Nazarko, would call that day or the next. He never did, nor did he respond to repeated inquiries. Ultimately, a spokeswoman for the New York State Department of Health responded that Nazarco was refusing to answer questions, as were Val Gray, CEO of Helen Hayes, and Felicia Kussman, director of clinical research at Helen Hayes. Kussman received NIH funds to study Porteau even as Eli Lilly paid her more than $135,000 for lectures and consulting, according to ProPublica. When asked for comment, Helen Hayes and HRI emailed a copy of their conflict of interest policy and a statement that "the procedures outlined in the policy document have been followed" in Lindsay's and Kosman's research grants.

A few days after I called Helen Hayes to inquire about a possible conflict of interest in Lindsay's research, hospital officials requested an ethics review of these studies. Initially, the hospital sought an independent committee to decide whether Lindsay's work was in conflict of interest due to his ties to Eli Lilly. But since no such committee was found, the hospital asked its Institutional Review Board (IRB) to examine the matter. (Lindsay was a member of the committee at the time, but he did not participate in the deliberations.) The committee found that Lindsay received a lot of money from Eli Lilly, but it was not there to create a conflict of interest. I learned about these discussions months later, after using the New York State Freedom of Information Act to obtain documents related to research grants.

Unfortunately, IRBs, whose role it is to approve research protocols in clinical trials and ensure that patients are treated appropriately, do not have the necessary tools to answer questions about financial conflicts of interest. "The composition of the IRB committee was never designed to handle [conflicts of interest] in contemporary reality," notes Arthur Kaplan, a bioethicist at New York University Langone Medical Center (and a member of Scientific American's advisory board). "It's clear to me that this guy in Helen Hayes has a pretty serious conflict of interest," Kaplan says. Carl Elliott, a bioethicist at the University of Minnesota, agrees. "The IRB is not the body that should have an opinion," he wrote to me in an email.

In any case, the Helen Hayes Hospital is not prepared to root out a conflict of interest. Their lawyers adopted the wording of the NIH's guidelines for writing research grants, which require researchers to report, among other things, "anything of monetary value, in cash or equivalent, received from a body that funds research (such as consulting fees, scholarship, travel expenses, meals or entertainment)." (The italics were added for emphasis.) This paragraph narrows the scope of things that require reporting. Since Eli Lilly is not the funder of Lindsay's research, but the NIH, payments from her do not appear to create a conflict of interest. And indeed, under the Helen Hayes rules, it's hard to think of circumstances where NIH grantees would be in a conflict of interest situation. There is no reason to think that Helen Hayes is special in this respect. The institutions that manage the research funds have no real incentive to engage in conflicts of interest. The more money the employees get, the better off the employer is. Why make a fuss?

fix the system

Researchers cannot prevent the influence of drug company money. Hospitals and universities are unwilling to do so. At NIH they refuse. Thus millions of dollars of taxpayers' money fund studies whose objectivity is questionable. And Congress, which holds the checkbook, is seething with rage.

Most of the anger is directed at the NIH. The institutes were called to order for non-compliance with the rules of ethics. "I am well aware, from my years as chairman of this subcommittee, that the attitude that 'the rules don't apply to us' is widespread at the NIH," said Congressman Joe Burton of Texas, who chaired the House Energy and Commerce Committee at a 2004 hearing. Due to ethical issues at NIH. "One can only wonder: if the institutes are so permissive regarding the most basic ethics laws in the federal government, what does this say about their ability to manage taxpayers' money, and more importantly, to ensure that research funded with these funds is translated into drugs?" he added. However, the American Institutes of Health persist in their behavior even after pressure from Congress to mend their ways.

Since 2008, Senator Charles Grassley of Iowa has led a series of investigations into several incidents in which NIH grantees failed to report payments from drug companies and universities did not properly punish these researchers. The most striking example was the case of Charles Nemeroff, who until recently served as the chairman of the psychiatry department at Emory University. Emory documents indicate that as early as 2000 there were questions about the adequacy of Namroff's connections with industry, such as money he received from the pharmaceutical manufacturer Smith-Kline Beecham, which was later called Glaxo-Smith-Kline. (The company also donated money to a chair in Namroff's department.) In 2003, scientists accused Namroff of failing to report his relationships with manufacturers of three drugs included in an article published in the journal Nature Neuroscience.

In response, Emory opened an investigation. In 2004, the university determined that Namroff did "many times violate the policy regarding conflicts of interest and counseling and other procedures." When confronted with the findings, Namroff agreed to limit his consulting relationship with GlaxoSmithKline, because of the effects it might have on a research grant he received from the NIH, and also agreed to reduce his involvement with other companies. After a 2008 congressional investigation revealed numerous payments that Namroff failed to report, he stepped down as Emory's psychiatry department chair, and the university barred him from applying for NIH research grants for two years. Namroof Mamory has since moved to the University of Miami, where he serves as the chair of the department of psychiatry and behavioral sciences and the principal investigator of a study that received $400,000 in funding from the NIH.

After these congressional investigations, NIH adopted new procedures requiring grantees to report to their employing institutions any financial engagement valued at more than $5,000. In addition, the procedures require these institutions to report to the public in general terms any conflicts of interest of employees involved in research funded by the NIH. What these changes mean is that the public will have access to more information about the destinations to which the pharmaceutical industry's funds are directed.

NIH Director Francis Collins praised the new regulations because they serve as "a clear message that the US Institutes of Health are committed to promoting objectivity in the research they fund." But the new regulations do not answer the questions of who is responsible for identifying the conflict of interests and how these ethical problems should be managed. "Since the academic institutions themselves know the contexts in which their employees operate and since these are the employees of the institutions and not the employees of the federal government, the responsibility lies with the institutions," says Sally Rockey, the NIH's deputy director for research conducted outside the institutes. "The institutions are in the best position to manage the financial interests of their employees."

The only hope to solve the problem of conflict of interests in science lies in the researchers themselves. Science culture can change. With the help of the scientific press (whose reputation is tarnished by biased studies) and with the help of learned societies (which set the ethical standards by which science should be conducted) scientists can pressure their colleagues to give up the pharmaceutical industry's money. At the very least, they might convince their fellow scientists that in the long run they should be completely transparent about the payments they receive from drug companies.

The best way to provide ethical guidelines and exert social pressure lies in the professional organizations and the scientific press. Lindsay's field is the American Osteoporosis Foundation and the journal Osteoporosis International. Will these organizations agree and be able to lead the process of weeding out the conflict of interests? The person to direct the question to is the former president of the American Osteoporosis Foundation and current editor-in-chief of Osteoporosis International - Robert Lindsay.

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About the author

Charles Seife is a professor of journalism at New York University and the author of Probability: The Dark Art of Mathematical Fraud (Viking, 2010).

in brief

Many researchers maintain close financial ties with pharmaceutical companies that may profit from their research.

The US Congress passed the Physician Payment Transparency Act, which will require pharmaceutical companies and medical device manufacturers to disclose, beginning in 2013, the majority of the money they funnel into doctors' pockets.

But the test case presented in this article shows that neither the scientific institutions nor the scientists themselves show willingness to monitor conflict of interest in research.

Drug safety

Credit: Jen Christensen

Source: Relationship between industry affinity and position regarding the risk of having a heart attack

Following rosiglitazone: a cross-sectional systematic report, by Amy T. Wong, Christopher P. McCoy, Muhammad Hassan Murad, and Victor M. Monturi. BMJ, Volume 340, Issue 7750, 10 April 2010

And more on the subject

• The Pro-Publica database cited in this article
• The University of California, San Francisco database containing pharmaceutical industry documents
• NIH database on research grants