Financial disclosure in oncology leaves ‘room for standardization’
Reporting of financial ties to industry has become an increasingly contentious, ethically murky area in both oncologic research and clinical practice.
In 2018, prominent oncologist José Baselga, MD, PhD, resigned from his position as chief medical officer at Memorial Sloan Kettering Cancer Center after The New York Times and ProPublica uncovered his failure to disclose several million dollars in payments from pharmaceutical and health care companies. Although Baselga acknowledged that his continued presence at Memorial Sloan Kettering would be a “distraction” to the institution, he also maintained that his omissions were unintentional.
The idea that such a major breach could occur inadvertently has generated much conversation about the need to define, clarify and standardize the rules around financial disclosure.
“One of the key issues I’ve seen is not so much that there is malice or complete laziness toward disclosures. I think most everybody out there would say that disclosure is important,” Cole Wayant, DO, PhD, researcher at Oklahoma State University, told HemOnc Today. “The key issue is that we’re essentially expecting self-disclosure from the authors submitting these papers; we’re putting it in the hands of the authors themselves. Often, it’s difficult for people to determine what is a relevant payment. What exactly needs to be disclosed, if not everything?”
Some clinicians feel this expectation for researchers to self-regulate without bias is unrealistic.
Others consider the focus on disclosure reform to be largely an empty gesture that fails to address the true problem.
“The bottom line is that the medical profession, and the oncology profession specifically, does not want to have an honest and serious discussion on conflict of interest. We don’t want to tell these people that they can’t take this money,” Vinay K. Prasad, MD, MPH, assistant professor of medicine at Oregon Health & Science University and a HemOnc Today Next Gen Innovator, said in an interview. “The real solution is divestment. That’s the standard we would have for a politician or a judge in a court of law, but, in oncology, we don’t want to do that. We need to show the public we are willing to do something, but we don’t want to stop taking the money. That’s where disclosure comes in.”
HemOnc Today spoke with oncology researchers about key studies that have yielded insights into and revealed shortcomings of the disclosure process, how inconsistent reporting requirements can be a burden on researchers, and ways in which disclosure can be simplified and standardized.
Research into conflict-of-interest reporting has revealed some concerning data.
These include the findings of Wayant and colleagues, who scrutinized financial relationships between oncologists and industry in clinical trials of cancer drugs that received FDA approval.
For their study, published in JAMA Oncology in 2018, the researchers searched the FDA Hematology/Oncology Approvals & Safety Notifications website for oncology drugs approved between January 2016 and August 2017, matching these approvals to published studies using clinical trial registry numbers. They subsequently collected industry payments data from the Open Payments database for each U.S.-based oncologist study author — restricting the analysis to payments received during the trial — which they then cross-referenced with the disclosure statements of the published trials.
Results showed that of the 344 oncologist authors studied, 263 (76.5%) received at least one industry payment. Additionally, 110 oncologist authors (32%) did not completely disclose payments from the trial sponsor.
Those industry payments may influence oncologists’ prescribing practices, according to results of another study conducted by Aaron P. Mitchell, MD, MPH, medical oncologist in the department of epidemiology and biostatistics at Memorial Sloan Kettering Cancer Center, and colleagues.
The study, published in The Oncologist, showed that oncologists who received annual payments from drug companies appeared more likely to prescribe those companies’ drugs over other agents for certain types of cancer.
Specifically, researchers found that physicians who received payments for a drug each year from 2013 to 2015 appeared more likely to prescribe that drug for renal cell carcinoma (RR = 1.81; 95% CI, 1.58-2.07), chronic myeloid leukemia (RR = 1.22; 95% CI, 1.08-1.39) and lung cancer (RR = 1.69; 95% CI, 1.58-1.82). However, they did not observe this association for prostate cancer.
“Research demonstrates that if clinicians have certain industry relationships, such as receipt of payments, these individuals may be more likely to prescribe those companies’ therapies,” Ryan D. Nipp, MD, MPH, gastrointestinal oncologist and health services researcher at Massachusetts General Hospital Cancer Center and a HemOnc Today Next Gen Innovator, said in an interview with HemOnc Today.
This potential bias in prescribing practices is not ameliorated by disclosure, Mitchell told HemOnc Today.
“We’ve had a bit of an overemphasis on the disclosure end of things lately,” he said. “However, a disclosed payment is still a payment, and it still influences prescribing practices.”
Stricter disclosure policies ultimately may result in less — rather than more — clarity and accessibility.
In a study published in JAMA Oncology, Boothby and colleagues looked at the effects of a disclosure policy change implemented for ASCO Annual Meeting between 2014 and 2015. This change required speakers to report any financial conflicts, whether relevant or not.
The researchers found that the disclosure change led to “information overload” at the 2015 meeting. Notably, 83 of 221 presentations (37.6%) included disclosure slides that were displayed faster than the average human capacity to read and comprehend them.
These rapidly flashed disclosures represent little more than a perfunctory effort that masks a larger problem, according to Prasad, who was an author on the study.
“This is a symptom of the broader disease,” Prasad told HemOnc Today. “The disease is that oncology doesn’t really care about conflict. The powers-that-be — the people who are collecting money hand over fist — do not want to stop taking the money. But they know if we don’t self-regulate, the public will potentially regulate for us. So, we’ve created this token gesture about disclosure.”
A lack of clarity
Differences in protocols for reporting conflicts of interest across journals, scientific meetings and institutions may only complicate matters.
Most journals follow the disclosure guidelines put forth by the International Committee of Medical Journal Editors (ICMJE). According to the ICMJE, a financial conflict of interest occurs when “professional judgment concerning a primary interest (such as patients’ welfare or the validity of research) may be influenced by a secondary interest (such as financial gain).”
The ICMJE outlines the more overt forms of conflict of interest, including employment, consultancies, stock ownership or options, honoraria, patents and paid expert testimony. It also cites less obvious conflicts such as personal relationships or rivalries, academic competition and intellectual beliefs.
Within these guidelines, however, individual journals may have different protocols for disclosure, Wayant said.
“Some journals will require just a disclosure statement, while others will require you to fill out an ICMJE standardized form,” he said. “For example, The New England Journal of Medicine requires every author of their clinical trials to fill out a standardized ICMJE form, which consists of all conflicts, both related and unrelated to the work in question or the present study. On top of that, they have another disclosure paragraph attached to the article that goes into the PDF. They require a little more than other journals do.”
Such variations in disclosure requirements can also be seen at medical conferences and across institutions, Mitchell said.
“There is a lack of clarity in terms of exactly what they do or don’t want disclosed,” he said. “There are differences between conferences, journals and institutions. How far do we look back for conflicts? Is it past 2 years? Past 3 years? Past 5 years?”
He said some institutions, including Memorial Sloan Kettering, are in the process of tracking oncologists’ disclosures institutionally. However, such efforts toward a streamlined approach hinge on uniformity in disclosure requirements.
“If a conference is looking for something different, or wants information from a different time frame, then having done it once still might not be enough,” he said.
For the clinician, this lack of consistency in disclosure requirements often necessitates repeated reporting of conflicts of interest. For researchers and practitioners who are focused on the work of advancing oncology, this may become burdensome.
“There might be a bit of fatigue about the need for everything to be reported everywhere all the time, to the detriment of oncologists’ time,” Mitchell said. “I think there is a bit of justified laziness.”
It becomes an onerous task to have to repeatedly report disclosures, Nipp said.
“However, the instance of a clinician purposely not disclosing their conflicts is likely a rarity,” he added. “Most clinicians likely are not purposefully trying to avoid reporting their conflicts of interest. As issues with failure to disclose conflicts of interest have become highly publicized in recent years, many clinicians have become more careful with reporting disclosures.”
‘Deeply conflicted’ key opinion leaders
Any researcher or clinician is potentially susceptible to bias due to financial ties to industry.
However, there is a small group of oncologists whose misuse of influence can be especially damaging, Prasad said.
“There is a handful of oncologists who have extraordinary influence on the practice of oncology,” he said. “The average doctor can only make decisions for their panel of patients. But an oncologist who is on a guidelines panel or is writing editorials in major journals can affect the practice of many, many oncologists. When you look at this group of oncologists, you will find that they are deeply conflicted.”
For instance, another study by Mitchell and colleagues, published in JAMA Oncology, showed that of the 125 authors of the National Comprehensive Cancer Network guidelines, 85% reported financial conflicts of interest at the end of 2014. Using data from the Open Payments database, researchers found that each of these guideline authors received an average of $10,011 in “general payments,” such as for consulting, meals and lodging.
“The NCCN guidelines mandate Medicare payments for off-label drugs,” Prasad said. “The researchers found a mean conflict of interest of around $10,000, and around 85% with a conflict. I think that's serious conflict.”
Moreover, the general payments that key opinion leaders receive from industry can be substantial.
“Let’s be clear,” Prasad added. “We’re not even talking about money that’s paid to their universities for research. We’re talking about general payments that are paid to the doctor’s bank account.”
Prasad said he has evaluated these payments in many different contexts and has found that such “general payments” often exceed the median annual household income in the United States.
“These key opinion leaders are receiving more than the median household income of a family of four in these payments,” he said. “I believe these payments are poison. I believe they have poisoned the narrative on cancer drugs.”
Prasad said these exorbitant financial contributions have, whether consciously or not, led to influential oncologists becoming “cheerleaders” for marginal cancer agents. He recalled conversations he has had about these drugs with longtime friends who are not oncologists.
“I might tell them about a cancer drug, and they’ll ask, ‘How much does that cost, and what’s the improvement in survival?’ I’ll tell them, ‘It costs $100,000 per year of therapy, and it improves survival by 2.1 months.’ They ask me if I’ve lost my mind.”
The fact that key opinion leaders often have substantially more conflicts of interest than the average oncologist is not an accident, Prasad added. He said these industry payments are often highly strategic.
“The industry is smart; there’s a reason why they’re showering money on some people and not others,” he said. “They know that some people are in a position to drive the sale of their products. So, they put their money where it goes to the greatest benefit, where it has the greatest return on investment. That’s why the payments are so high.”
Although financial conflicts of interest carry the risk for influencing physicians’ behavior, there are potentially positive outcomes, Nipp and Beverley Moy, MD, MPH, wrote in an editorial that accompanied the Mitchell and Boothby studies.
“Collaboration between industry and academic researchers may facilitate the development of novel cancer therapies, a shared goal aligning the interests of industry, academia and patients,” they wrote. “In addition, prior work has demonstrated that financial conflicts of interest correlate with greater prominence of research abstracts accepted for presentation at the ASCO Annual Meeting. Whether this reflects bias in the interpretation of the research and/or that industry seeks collaboration with more prominent researchers, or vice versa, is unknown. Nevertheless, this may help explain why such a large proportion of NCCN guideline authors report financial conflicts of interest.”
Although such collaboration creates “challenges and opportunities” and is “necessary to bring advancements to the field,” Nipp and Moy added, they also wrote that more work is needed to assess both the positive and negative consequences of conflicts of interest and to establish better methods for reporting and managing financial conflicts in research and clinical practice.
Although the idea of severing ties with drug companies in oncology remains up for debate, actions can be taken to simplify and standardize the disclosure process.
Wayant said he believes the Open Payments database should be relied upon as a definitive source of disclosure information. He said making a clinician’s database link available as their disclosure statement would take some of the burden off oncologists to self-disclose.
“I have always advocated for a move away from self-disclosure toward a more open system of transparency,” Wayant said. “If I’m a U.S. physician and my disclosure statement is a link to my Open Payments database profile, then the public can decide whether my conflicts are relevant, or whether they have undercut the legitimacy of my arguments in this paper. This way, it’s not up to the physician to identify their own blind spots.”
“Systems for uniformly reporting financial conflicts of interest seem like a plausible solution for improving consistent disclosure of potential conflicts of interest,” Nipp said. “This could help to keep both sides accountable — industry and the clinicians who may be getting funding.”
Mitchell agreed that some sort of user-friendly, uniform source of disclosure information would improve transparency and, ideally, prevent redundancies in conflict-of-interest reporting for clinicians.
“There’s definitely room for standardization of what is considered a ‘relevant’ disclosure and what is considered any reportable disclosure, and ways to do this in a simplified, centralized fashion,” he said. “We have Open Payments, which puts the burden on the companies. As physicians, we don’t have to make additional efforts or take any action to report disclosures to Open Payments. All of the necessary information will be there, and it will decrease some of the fatigue for oncologists.”
However, experts acknowledged that the database is not always accurate, with some researchers being listed as receiving funding for projects in which they were invited to participate but had declined.
When trying to correct the problems of financial ties in oncology, it is important to focus on the big picture, Prasad said.
“We get too bogged down in whether the average oncologist goes to a dinner,” he said. “That’s not the root of the problem. That’s not where the big money is being given.”
Nipp said he would like to see some focus on educating clinicians about financial conflicts of interest.
“Most clinicians never received formal training about potential conflicts of interest, and thus we don’t fully understand all the positive and negative consequences,” he said.
“Further, as this discussion continues, it will be important to define whether all financial conflicts of interest need to be avoided, and where does the line get blurred?” he added. “It’s interesting and it’s worth discussing.” – by Jennifer Byrne
Boothby A, et al. JAMA Oncol. 2016;doi:10.1001/jamaoncol.2016.2706.
ICMJE. Conflicts of interest. Available at: www.icmje.org/recommendations/browse/roles-and-responsibilities/author-responsibilities--conflicts-of-interest.html. Accessed on Oct. 28, 2019.
Mitchell AP, et al. JAMA Oncol. 2016;doi:10.1001/jamaoncol.2016.2710.
Mitchell AP, et al. Oncologist. 2019;doi:10.1634/theoncologist.2018-0423.
Nipp RD and Moy B. JAMA Oncol. 2016;doi:10.1001/jamaoncol.2016.2726.
Wayant C, et al. JAMA Oncol. 2018;doi:10.1001/jamaoncol.2018.3738.
For more information:
Aaron P. Mitchell, MD, MPH, can be reached at 485 Lexington Ave., Second Floor, Office 2693, New York, NY 10017; email: firstname.lastname@example.org.
Ryan D. Nipp, MD, MPH, can be reached at 55 Fruit St., Boston, MA 02114; email: email@example.com.
Vinay K. Prasad, MD, MPH, can be reached at 3303 SW Bond Ave., Portland, OR 97239; email: firstname.lastname@example.org.
Cole Wayant, DO, PhD, can be reached at 1111 W. 17th St., Tulsa, OK 74107; email: email@example.com.
Disclosures: Mitchell reports receiving a research award from the Conquer Cancer Foundation in 2018, for which the foundation received funding from Merck. Prasad reports giving lectures for Pfizer. Nipp and Wayant report no relevant financial disclosures.