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Bioethics Briefings

From Bioethics Briefings

Conflict of Interest in Biomedical Research and Clinical Practice

Highlights
  • The Bayh-Dole Act of 1980, which encourages technology transfer from universities to industry, has facilitated financial relationships between academic biomedical researchers and the biotechnology industry.
  • Financial relationships can create conflicts of interest between researchers’ obligations to abide by scientific and ethical principles and their desire for financial gain.
  • Studies have found correlations with results benefiting sponsors, poor study design, withholding negative data from publication, and other problems.
  • The risk, therefore, is that conflicts could adversely affect the quality of research, possibly harming human subjects and patients along with public trust in the biomedical research enterprise.
  • However, financial relationships with industry also carry benefits, including facilitating the development of new drugs and medical devices and increasing research budgets and opportunities.
  • Policies to manage financial conflicts of interest need to be simplified, standardized, and better enforced.
  • To address the risks to clinical judgment and public trust posed by clinicians’ financial conflicts of interest, Congress passed the Physician Payments Sunshine Acts of 2007 and 2008, which requires manufacturers of drugs, devices, biologicals, and medical supplies to report annually to the Department of Health and Human Services payments and investment interests given to physicians and teaching hospitals.

Framing the Issue

Conflict of interest is a broad term to describe situations where professional judgement risks being compromised by secondary interests. Research and clinical care  both involve judgment about numerous questions, including study design, data interpretation, and treatment plans. That judgment can be compromised when a secondary interest—including a financial interest of individuals or their institution—favors certain decisions or outcomes. Conflicts of interest can damage research quality, harming patients and worsening health outcomes. But even in the absence of evidence that the quality of research or clinical care has suffered, conflicts of interest can create the appearance of impropriety, thereby undermining trust in the results of research, in individual researchers or clinicians and their institutions, and in research and medicine more generally.

Financial conflicts of interest are prevalent among medical school leadership and academic researchers. Medical schools and academic research institutions themselves can hold financial interests in the work of their employees. These financial conflicts of interest can arise a number of different ways, including when doctors receive gifts from or serve as consultants to industry, often pharmaceutical and biotechnology companies, as well as when companies sponsor studies and clinical trials of their own products, and when academic researchers and their institutions seek to commercialize their research through a process called technology transfer. Some of these conflicts should be eliminated to protect research quality, patient health, public trust. Other financial conflicts of interest are best addressed through disclosure and other mitigation or management strategies.

Biomedical Research

The potential conflicts between, on the one hand, the obligation of scientists and their institutions to conduct, oversee, and assess studies according to scientific and ethical principles and, on the other hand, the opportunity for financial gain has been recognized for decades. If research quality suffers as a result of these conflicts of interest, human subjects could be harmed, as could anyone who relies on the research, including patients. There is some disagreement about which financial interests might inappropriately influence whom and under what circumstances, as well as how those risks should be eliminated or managed. One reason for this disagreement is that it is difficult to prove that financial interests cause specific researchers or their institutions to waiver in their commitment to producing quality studies. Instead, analysis shows correlations between financial interests and problems with specific studies or, more often, fields of research. Such correlations are well documented. Several studies have found that industry-sponsored research is both more likely to yield results favoring the sponsor and at a statistically higher risk for bias compared to research receiving funding from other sources. Studies of academic biomedical research have also found correlations between financial relationships with industry and problems with research, including poor study design, a tendency to produce pro-sponsor results, and increased secrecy—scientists refusing to share data with colleagues, withholding negative data from publication, and delaying publication of research results:

  • Among 344 cancer researchers surveyed in a 2018 JAMA article, more than three-quarters had received industry payments and 32% had not fully disclosed these payments in their articles, which were published in major medical journals.
  • Analyzing newspaper articles reporting on the 2009-2010 H1N1 pandemic, a study published in the BMJ in 2014 rated the risk assessments of cited academics with and without financial ties to drug companies selling pandemic-related medications. Those with financial ties rated the health risks of the pandemic as nearly six times higher than academics without such conflicts of interest.
  • A 2016 review published in Research Integrity and Peer Review determined between 43% and 69% of research study reports failed to disclose conflicts of interest.
  • A 2013 systematic review in PLOS Medicine found that studies in which researchers had financial interests in the sugar industry were five times more likely to find no relationship between sugar-sweetened beverages and obesity compared to studies without such reported relationships.

Clinical Practice

As in scientific research, the medical profession’s commitment to objective, patient-centered decision-making can be compromised by secondary financial interests. Financial considerations are, of course, an unavoidable part of medical practice in the U.S., with diverse payment structures determining which services and medications insurance patients can access. The ways physicians are paid are also diverse, with fee-for-service, salaried, managed care, and pay-for-performance mechanisms being common. It is within this already complicated system that financial ties to industry can occur, potentially negatively impacting clinical judgement.

The behavioral science literature suggests that when people make decisions, they have an unconscious bias for choices with the potential for self-gain. A physician deciding which drug to prescribe for a particular patient, for example, is likely to lean toward a drug from a pharmaceutical company to which he is consulting, even if the physician intends to remain objective. Gifts like free samples and dinners can also lead to an increase in prescriptions and other behavior favorable to the drug company. In addition to making decisions for individual patients, physicians are often members of professional organizations that issue standards and guidelines for clinical care. Their employers—including academic medical centers and nonprofit hospitals—must also make decisions about practices and policies that can be influenced by gifts or funding from industry. Therefore, at both the individual and organizational levels, industry interests can impact and interfere with medical professionals’ obligation to make decisions with patients’ best interest in mind.

The following studies suggest the scope of conflicts of interest in clinical practice and some of the effects:

  • A 2017 JAMA study reported that 48% of U.S. physicians received a total of $2.4 billion in payments from drug and medical device companies, with men and those in surgical specialties having the highest probability and value of payments.
  • Among clinical practice guidelines issued by medical organizations for the care of diabetes or hyperlipidemia, a 2011 BMJ study found that almost 50% of authors had disclosed conflicts of interest and 11% had conflicts of interest that they did not disclose.
  • Policies at academic medical centers that limit visits from pharmaceutical company sales representatives to physicians (known as detailing) can affect prescription patterns. Following academic medical centers’  implementation of such policies, a 2017 JAMA study found a modest but significant reduction in prescriptions for the once-detailed drugs, compared to academic medical centers without the policies.
  • In a 2013 national survey, 33% of first year medical students and 57% of fourth year students reported receiving industry-sponsored gifts.

Benefits Along With Risks

In addition to risks, financial relationships with industry offer benefits to individuals and institutions involved in biomedical research and clinical care, as well as to society more generally. They help bring new drugs and medical devices to market and economic growth to the institutions’ regions and the nation as a whole. Indeed, the commercialization of academic research is an explicit goal of government funding, facilitated by the 1980 Bayh-Dole Act, which encourages commercialization activity by federally funded institutions and mandates that institutions share royalties with individual inventors. These collaborations can also boost research budgets, whether directly through research funding or indirectly through gifts, sponsorships, royalty payments, dividends, and proceeds from the sale of start-up companies.

Researchers and medical doctors can also benefit from collaboration with industry and from commercializing their own innovations, including the opportunity to access data, equipment, and materials, and the satisfaction of seeing basic research translated into commercial products. In addition, because average salaries for academic researchers are lower than salaries of nonacademic scientists, health professionals, and engineers, opportunities for additional compensation can assist research institutions with recruitment and retention.

Academic researchers may also have a strong reluctance to give their time, expertise, or resources—including inventions—to industry without being compensated, even when compensation creates a conflict of interest. Some of this reluctance may stem from what commentators have called the “no conflict, no interest” principle, according to which a financial stake increases an individual’s commitment to a project and, therefore, its chances of success. This attitude may also reflect a belief that it is unfair to prevent individuals from profiting from their effort and that restrictions on working with industry are intrusions on privacy and freedom of association.

High-Profile Cases

Conflicts of interest have been alleged or documented in several widely reported incidents involving physicians in organizational leadership, clinical trials, government research, and government oversight of drugs.

  • After 19-year-old Jesse Gelsinger died in a gene transfer study at the University of Pennsylvania in 1999, conflicts of interest were among the allegations leveled at the research team and the university. The lead investigator and university held equity stakes in a company with a financial interest in the experiment, and the lead investigator and medical school dean held patents on processes used in the trial. Although no causal relationship was established between these financial interests and the irregularities associated with Gelsinger’s death, the financial interests raised the suspicion that money clouded judgment.
  • More than half of the scientists involved in testing Rezulin, a type-II diabetes drug, had received funding or other compensation from Parke-Davis/Warner-Lambert, its manufacturer. The drug was fast-tracked through Food and Drug Administration approval in 1997 on the basis of their research but was withdrawn from the market three years later when it was shown to have caused liver failure in at least 90 patients. Newspaper reports and academic commentaries in the late 1990s and early 2000s expressed concern that the financially conflicted scientists may have concluded that the drug was safer and more effective than the evidence warranted.
  • In late 2004 and early 2005 the Los Angeles Times published a series of articles detailing financial relationships between the pharmaceutical industry and senior scientists at the National Institutes of Health. The investigation revealed that some staff members collected hundreds of thousands of dollars from companies whose products were the subject of NIH research, and that the NIH failed to disclose these payments to human research subjects. Although no problems were reported with the scientists’ work, the revelations lead some commentators and politicians to question the NIH’s objectivity and commitment to public health.
  • Potential conflicts of interest extend to government advisors. In 2005, an FDA advisory panel voted to allow the painkillers Celebrex, Bextra, and Vioxx to remain on the market, despite data showing that they increased the risk of heart attacks. A week later, the Center for Science in the Public Interest reported that 10 of the 32 panel members had recently provided consultations to the manufacturers of the drugs, leading to speculation that if these conflicted researchers had been left off the panel, the drugs would have been withdrawn from the market.
  • In 2008 and 2009, a Congressional subcommittee investigated conflicts of interest in medicine, leading to front-page news stories about the extensive and sometimes undisclosed financial interests of several prominent academic clinician-researchers, including three Harvard University pediatric psychiatrists who had advocated for the increased use of antipsychotic medicines in children while also receiving significant payments under consulting relationships with the drug makers.
  • In an 2018 investigative report, the New York Times and ProPublica revealed that the chief medical officer of Memorial Sloan Kettering Cancer Center, José Baselga, had failed to disclose millions of dollars of industry funding for published research. Some of the research was published in academic journals, including a journal of which he was as an editor-in-chief. As the president of the American Association for Cancer Research, he also failed to abide by its financial disclosure rules for his advisory and board membership roles in pharmaceutical companies. These financial conflicts of interest were thought to have affected his scientific judgement. For example, Baselga framed the results of Roche-sponsored clinical trials as positive when speaking about them at academic conferences (others viewed the  results as disappointing) without disclosing that Roche had paid him over $3 million in consulting fees.

Safeguarding Research Quality and Trust

To address the risks to clinical judgment and public trust posed by clinicians’ financial conflicts of interest, Congress passed the Physician Payments Sunshine Acts of 2007 and 2008, and in 2013 the Center for Medicare and Medicaid Services (CMS) put forth the final rule, “Transparency Reports and Reporting of Physician Ownership or Investment Interests” also known as the Sunshine Payments rule. To administer the rule, CMS created and manages the Open Payments website, a searchable public website listing all compensation given by pharmaceutical and medical device companies to physicians and teaching hospitals. By making payments public, CMS hopes to cultivate a sense of accountability around physicians’ and teaching hospitals relationships with industry, support patient autonomy, and foster public trust in the medical profession. To help clinicians make the necessary disclosures, the American Association of Medical Colleges (AAMC) launched a global repository known as Convey.

In contrast to the Sunshine laws and rules, the conflict-of-interest policies affecting medical researchers and their institutions are largely self-regulatory systems, some of which are legally mandated. The systems are self-regulatory because they involve institutions, rather than an outside organization or government entity, collecting and monitoring their own researchers’ financial conflicts of interest. Under most of these systems, researchers make an initial disclosure of all their financial interests to their employer, whether that is a university, medical school, or some other research institution. An internal committee or designated official reviews those disclosures to decide whether they create a conflict and, if they do, whether to prohibit the conflict, allow it, or allow it subject to additional measures. These measures can include further disclosure, for example, in all published and oral presentations of the research and to all research subjects, but may also extend to mandating the involvement on unconflicted researchers in a research team. Most systems for reducing conflicts of interest apply only to individual researchers, although some institutions have processes for identifying and managing financial conflicts of interest held by the institution itself. In addition to disclosing financial relationship to their home institutions, individual researchers must also make disclosures to medical journals, conference attendees, and to professional organizations when they are involved in development of guidelines and recommendations.

This self-regulatory system has been in place for decades in the U.S., under federal regulations that require research institutions to monitor, report, and manage the financial conflicts of interest of their biomedical researchers conducting federally funded research. In 2011, the Department of Health and Human Services strengthened existing requirements for disclosure and management, including by lowering the reporting threshold from $10,000 to $5,000 and broadening disclosure requirements to include a wide range of industry-funded activities, as well as financial relationships with nonprofit organizations. Under these revised rules, institutions collecting disclosures from individual scientists are charged with judging the potential impact of disclosed relationships on research quality and reporting management plans for identified financial conflicts of interest to N.I.H.

Groups representing researchers and their institutions, including AAMC, have criticized HHS’s regulations, arguing that they create undue financial and logistical hurdles without improving the objectivity of research. In its COI Metrics Project designed to assess the impact and effectiveness of the final rule, AAMC has reported that while the number of disclosed conflicts of interest  has increased substantially since 2011—along with the cost to institutions of collecting and acting on these disclosures—the number of interests deemed significant enough to report to the NIH has not increased. Critics have also argued that the HHS regulations do not go far enough because they fail to recognize that financial ties to industry at the institutional level may also compromise research integrity.

Despite federal policies addressing financial conflicts of interest in research, as well as professional body reports on the issue and several prominent public cases, institutional policies and practices in this area remain variable. Some policies strongly recommend that a financially conflicted individual not be involved in human subject research, while others are silent on that issue. Some policies urge public disclosure in all publications and presentations, but others do not specify if or when public disclosure is necessary. In addition, studies have shown that conflict of interest policies are not well understood by those who must comply with them. There is a need for ongoing efforts to streamline, simplify, harmonize, and better enforce the policies. Furthermore, to achieve the kind of buy-in that these policies need, education for and outreach to those who must comply with and enforce them is required, including as part of graduate and medical training. Otherwise, conflict-of-interest policies will be seen as pesky rules rather than important safeguards to research quality and trust.

Progress has been made towards standardizing the reporting of conflict of interests to academic journals. Following recommendations from the Institute of Medicine’s 2008 report Conflict of Interest in Medical Research, Education, and Practice, the AAMC created  its Convey tool to organize and disclose researchers’ industry relationships. Despite AAMC’s history of resistance to federal regulatory schemes, this initiative shows both that professional organizations recognize problems within the current system and that they have the will to address them within their own spheres of influence.

Setting Effective and Ethical Policies

An important barrier to improving conflict of interest policies in the biomedical research context is surely the mixed message to the biomedical research community on the propriety of financial interests. On the one hand, an outcry often accompanies revelations of financial interest because of a strong suspicion that money can cause bias. On the other hand, technology transfer and receipt of industry research funds are encouraged and expected, carrying significant benefits for researchers and their institutions. There is no simple solution to this conundrum. Institutions, policymakers, and professional organizations need to acknowledge the benefits and risks of the financial relationships and the care required to navigate them. A sympathetic response to the bind some institutions and individuals feel themselves to be in—and tools for avoiding or managing financial conflicts of interests—have proved more useful than condemnation or cavalier disregard.

Finally, continued discussion about the relationships among incentives in research, funding, and financial conflicts of interest in clinical care is important. As much as possible, this discussion should reach outside the biomedical community to include policymakers, advocacy and professional organizations, and the media. Otherwise, the management of financial conflicts of interest runs the risk of being seen simply as window dressing—a way to make research-industry financial relationships appear innocuous without assuring that they really are.

Josephine Johnston, LLB, MBHL, is director of research and a research scholar at The Hastings Center. Bethany Brumbaugh is a student at Harvard Medical School and a former research assistant/project manager at The Hastings Center.

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