In 2017, Yale School of Medicine Dean Robert Alpern was the senior author of a study published in the Clinical Journal of the American Society of Nephrology. The study examined the effectiveness of pharmaceutical company Tricida Inc.’s leading product TRC101 — a drug that collects excess acid found in the digestive tract.
Alpern and the other authors of the paper concluded that the drug, which is targeted at patients with ill-functioning kidneys, was not only safe but effective.
In the study, Alpern reported that he consulted for Tricida — a disclosure that he believed at the time was an adequate representation of his ties to the company. But according to a December 2018 joint report by The New York Times and ProPublica, Alpern failed to reveal a crucial detail in his disclosure: He served on Tricida’s board of directors and owned company stock.
As The New York Times and ProPublica continued to release reports detailing the extent to which high-profile doctors have skirted disclosure policies, the News conducted its own investigation into the reporting habits of School of Medicine faculty.
The News used a government database to look into the industry ties of hundreds of medical school physician-scientists — those who hold a doctor of medicine degree. Of those who had received over $10,000 in cumulative industry payments for services such as consulting or for items such as lodging, food and beverages, most did not consistently disclose these relationships in their published research — including two prominent Yale doctors with leadership positions.
Researchers with industry ties, according to School of Medicine Chair Luciano Del Priore, are often the world’s leading experts on drug development. They enter paid roles with consultancies in order to provide valuable information to the pharmaceutical companies charged with manufacturing new drugs. These relationships, Del Priore said, help get new treatments to patients faster.
But to bioethicists, health policy experts and doctors — including Del Priore — issues arise when scientists fail to comprehensively disclose their commercial relationships in published research.
Most of the faculty members contacted by the News maintained that their initial disclosures were accurate or that their industry ties were not relevant to their published research.
But experts do not necessarily agree. Associate Director of Santa Clara University’s Health Care Ethics program Ann Mongoven thinks that it is “almost impossible for modern medicine and research” to be conducted without conflicts of interest. But when it comes to inaccurate disclosures, Mongoven said it comes down to three possibilities: “Sloppiness, deliberate deceit or highly questionable distinction-making.
“I am a believer in full disclosure”
In general, when a research group submits a study for any publication, they will also send a disclosure of its conflicts of interest along with its research manuscript, according to Rajnish Mehrotra, the editor in chief of the Clinical Journal of the American Society of Nephrology. The disclosure is then used to guide peer reviewers as they scrutinize the research, allowing them to vet the work for potentially biased results.
But these policies are not uniform across journals and other entities, causing confusion among authors, according to Del Priore.
For example, while the Journal of the American College of Cardiology requires authors to “disclose any relationship with industry … within the past 2 years that might pose a conflict of interest,” the journal Cancer Discovery requires authors to “disclose upfront any relationships that they believe could be construed as resulting in an actual, potential, or perceived conflict of interest.”
The trust that Cancer Discovery and many other journals place on author integrity gives scientists the freedom to judge what they feel is — and is not — a relevant conflict of interest. But in this case, subjectivity can breed confusion.
To combat this, other journals like Science Translational Medicine have more concrete guidelines for its authors: All manuscripts must be submitted with “clear disclosures from all authors of any past and present affiliations, funding sources, and financial or management relationships related to the reported research.”
Nature, a leading British scientific journal, gives its authors frank advice: Researchers should disclose “any undeclared competing financial interests that could embarrass you were they to become publicly known after your work was published.”
However, when inaccurate disclosures are published, those interviewed by the News said that the public — especially trained scientists — is not provided with enough information to judge the objectivity of the reported findings.
Yale professor of internal medicine Joseph Ross was among the first researchers to examine the lack of public transparency surrounding industry payments to physicians.
In a 2007 study published in medical journal JAMA, Ross and his co-authors attempted to assess the accessibility and quality of industry payment data in Vermont and Minnesota — the only two states at the time where doctors were required to disclose such information. Their investigation found that information on physicians’ commercial ties were not easily accessible to the public. And the data that was available was of poor quality.
Ross told the News that the 2007 paper helped spark a national conversation about payment transparency. In 2010, Congress went on to pass the Physician Payments Sunshine Act. The act, according to the American Medical Association’s website, increased transparency surrounding the financial ties between the industry, physicians and teaching hospitals. In accordance with the Sunshine Act mandate, the Centers for Medicare and Medicaid Services created the Open Payments Database, which gives the public ready access to data showing any financial relationships that amount to over $10 each year.
The News used the Open Payments Database to assess which Yale School of Medicine faculty received payments of over $10,000 from the industry, and then reviewed the publication history and disclosure statements for qualifying doctors.
In two studies on aspirin use and cancer development published in 2018, Charles Fuchs, the director of the Yale New Haven Hospital’s Smilow Cancer Center, did not disclose his paid consultancy with aspirin manufacturer Bayer Pharmaceuticals. The two studies ultimately showed that aspirin does not lead to the development of a certain type of cancer and can even stave off another.
After inquiries from the News, the journals Gastroenterology and JAMA Oncology looked into whether Fuchs had violated their policies on conflict of interest.
According to Gastroenterology, a conflict of interest refers only to financial arrangements “with a company whose product figures prominently in the submitted manuscript or with a company that makes a competing product.” JAMA Oncology’s policy is broader: A conflict of interest can be either a financial or personal relationship that “could influence (or bias)” the author’s work.
Though Fuchs did not report his relationship to Bayer in the two aspirin studies, he did report the consultancy in 10 other articles that were also published between 2016 and 2018.
“In prior publications that studied new treatments for cancer, I sought to report relevant disclosures of consulting work with the biotechnology and pharmaceutical industry focused on drug development that had existed at that time,” Fuchs wrote in an email. “However, in my other studies assessing the role of risk factors for cancer risk and mortality, I did not consider that my consulting work in drug development represented a potential conflict of interest or a relevant financial activity to studies of cancer risk factors – as guided by journal policies.”
Fuchs wrote to the News, “Although I endeavor to fully disclose my relevant potential conflicts, I overlooked a $3,000 stipend from Bayer Pharmaceuticals in 2016 for a consultation in the area of cancer research unrelated to aspirin.”
Douglas Corley, co-editor-in-chief of Gastroenterology, told the News that Fuchs submitted a new disclosure statement.
“He did not feel there were any direct conflicts related to the research study; he did submit an updated conflict of interest statement to update for any perceived conflicts,” Corley wrote in an email to the News.
Though Corley said that the journal does not “explicitly comment on compliance or non-compliance” with its journal policies, he noted that there were “no substantial deviations from policies that recommended editorial disciplinary actions” with Fuchs. JAMA Oncology Editor-in-Chief Nora Disis said the journal was looking into the incident Jan. 14 but did not respond to a request for an update this week. Fuchs said he submitted an updated disclosure to JAMA Oncology as well.
Another School of Medicine faculty member, Neurology Chair and Yale New Haven Hospital Neurologist-in-Chief David Hafler has researched multiple sclerosis for decades. He argued that without the partnership between researchers and pharmaceutical companies, progress in caring for patients with multiple sclerosis — which was once harder to treat — might not have been possible.
But Hafler is not immune to the confusing nature of disclosure policies. In 2017, he was an author of a PLOS One study funded in part by Bristol-Myers Squibb. In this paper, he did not disclose a consultancy with the pharmaceutical company, though he reported this relationship in a different 2017 article that was supported by the National Institutes of Health and by the Nancy Taylor Foundation for Chronic Diseases Inc.
Hafler told the News that his administrative assistant, who tracks his industry ties, did not record any consultancy fees from interactions with Bristol-Myers Squibb other than the grant funding. He called the consultancy disclosure a mistake, saying that he had “over reported for this instance.”
“Our policy, again, as per the Journals and University, has been that basic scientific investigations that are funded by the NIH are not conflicts of interest needing disclosure when there is unrelated industry funding of activities such as one time advisory board meetings or educational speaking events where original scientific work is presented,” Hafler wrote in an email to the News when asked for comment on his industry-funded studies.
PLOS One Senior Communications Manager David Knutson said that journal editors review concerns over potential undisclosed competing interests and discuss those issues with authors. Based on their review, the journal “may make an editorial decision to update the competing interests statement with interests that could reasonably be perceived as competing.” He went on to say that Hafler’s PLOS One case, “has not yet been resolved and so we cannot provide further comment for this particular case.”
Hafler said in an Jan. 16 email that he spoke with a PLOS One associate editor after the News’ inquiries.
“It was agreed that we are charged with making these decisions as to what can be viewed as a COI,” Hafler said in the email. “The editor respected that I did not feel that an additional disclosure was required. Having said that, and though these disclosures are readily available from the CMS website, I am a firm believer in full disclosure.”
One health policy expert and an ethics professor interviewed by the News disagreed with the claim that basic science research does not necessarily warrant a conflict of interest disclosure.
Mark Schlesinger, the School of Public Health’s Chair of Health Policy and Management, told the News that disclosing payments that are indirectly linked to the performed research is an opaque process for which there is little oversight. He noted that it is “not unusual” for pharmaceutical companies to pay basic science researchers to present their findings to industry scientists at conferences.
The companies, Schlesinger stated, argue that they want to keep their own scientists aware of relevant advancements to the field. But Schlesinger noted that the extent to which these relationships influence university scientists’ work when they return to their labs is unclear. He said that if university scientists fail to disclose repeated invitations to give presentations at industry-sponsored conferences, it would be a misrepresentation of an industry relationship.
Kayhan Parsi, a Bioethics & Health Policy Professor at Loyola University Chicago’s Neiswanger Institute for Bioethics, said that for transparency’s sake, researchers should disclose their ties regardless of whether the paper is a clinical trial or basic science research.
“I think sometimes people might rationalize it and say to themselves, ‘Well I may have this relationship, but of course it doesn’t bias me so I don’t need to report it,’” he said.
“Throw up the hands”
Yale does not take issue with its faculty pursuing financial relationships with the industry. In fact, the University encourages it.
“Yale University believes that a great university should reach out to the world,” the University’s policy on conflict of interest reads. “Accordingly, the University encourages its faculty to seek and participate in sponsored research, to consult widely, and to engage in other activities that may benefit not only the participants but also the University itself, and the larger public.”
Edward Snyder, chair of the Provost’s Committee on Conflict of Interest, directed the News’ inquiries on University conflict of interest policies to Yale spokeswoman Karen Peart.
Peart said full-time University researchers are required to annually disclose all relevant and significant financial interests — which the University defines as payments, stock, stock options or other ownership interest as well as compensation that amounts to over $5,000 in a year. Significant financial interests could incentivize an individual to act a certain way while conducting University activities or making an administrative decision, according to the policy.
Yale New Haven Hospital — where many School of Medicine physician-scientists provide patient care — is also open to their doctors forming these financial relationships.
Vice President for Yale New Haven Hospital public relations Dana Marnane told the News that Yale New Haven Hospital has a “strong” conflict of interest program. The program includes policies that govern conflict of interest disclosures, a committee that reviews these disclosures and a process to mitigate any potential risk that could impact its personnel’s work.
Mongoven said that disclosures are an acknowledgement that scientists may not be the best judges of distortion when they stand to benefit financially from a published finding. She likened disclosures to a community check on the way financial incentives may cloud concluding judgements.
But to some, full disclosure comes with its own set of potential issues. Yale cardiology professor Alexandra Lansky — who has reported multiple industry relationships — said that disclosing financial ties regardless of their relevance can actually make studies less transparent. She wrote in an email to the News that “of course, the reader is usually ill-equipped” to judge whether a conflict is relevant to the study. She said that researchers have used overdisclosure as a method for “obfuscation, rather than illumination” of relevant conflicts of interest.
“This approach leaves to the reader to decide which, if any of the disclosed positions are in fact conflicts that could present the potential for bias related to the specific manuscript,” she said.
Lansky argues that a lay reader lacks the medical knowledge and scientific savvy to make this judgement. “The tendency is simply to throw up the hands,” she added.
Del Priore, the ophthalmology chair, said that in general there is no such thing as overdisclosing industry ties or being overly transparent. He argued that the information is valuable for the public — physicians, scientists and lay individuals such as patients — to evaluate the research and come to their own conclusion about its quality.
Lansky also pointed to ego as a potential influence in some financial disclosures.
“There is a certain cachet in some quarters to providing the longest possible list of disclosures, as connectedness can be seen as a reflection of the disclosing doctor’s influence in the field,” she wrote.
After the publication of the December report from The New York Times and ProPublica that implicated Dean Alpern, Mehrotra, the editor in chief of the nephrology journal, said that his publication is following suit with other prominent journals such as the New England Journal of Medicine, and will require published authors to submit a standardized disclosure form. The form, which was drafted by the International Committee of Medical Journal Editors, or ICMJE, requires that researchers list all of their financial relationships with the industry in the past three years.
Though the nephrology journal has altered its disclosure policies, many journals still rely solely on authors’ integrity for accurate disclosure statements.
Del Priore, Yale’s ophthalmology chair, advocated for standardization across the field.
“There’s a lot of complexity to this now, and it would be so much better — I don’t see this happening in the very near future — if this was just streamlined and if the regulations were consistent.”
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