RESEARCH ETHICS

Financial Conflicts of Interest 101

How Money Shapes Research and How Policy Can Protect Patients

What are conflicts of interest?

A conflict of interest arises when financial or personal considerations have the potential to compromise or bias professional objectivity. These conflicts are a special concern in biomedical research because they have the potential to influence the outcome of study results or clinical trials. In some cases, such conflicts may result in experimental data that favors a particular commercial product; in others, they may shape unnecessary or dangerous risks for trial participants.

Conflicts of interest, commonly referred to in research literature as COI, may take different forms, including both financial interests and opportunities for professional advancement, which are known as “intangible COI.” However, financial conflicts of interest are simultaneously the most pervasive and easily remedied through policy, since intangible COI are difficult to identify.

A recent case clearly demonstrates the lack of transparency concerning financial conflicts of interest. Dr. Charles Nemeroff of Emory University received $2.8 million from drug company GlaxoSmithKline, but did not report a large portion of this financial COI to the institution. While GlaxoSmithKline paid him from 2000 to 2007, Nemeroff oversaw a project funded by a $3.9 million grant from the National Institutes of Mental Health to study five anti-depressants produced by the pharmaceutical company. But despite rules requiring that universities disclose corporate income in excess of $10,000 per year for researchers working on federal grants, Nemeroff consistently reported receiving far less money than GlaxoSmithKline records showed. The National Institutes of Health rules are designed to ensure that such financial ties do not compromise patient safety and research integrity.

A recent national study on industry sponsorship and research integrity (co-authored by SP Editor-in-Chief Jonathan Moreno) found that “knowledge of compromises in research integrity is widespread” among investigators and is directly correlated to industry support. Respondents to a survey on first-hand knowledge of conflicts indicated that such compromises were present in research participants’ wellbeing, research initiatives, publication of results, interpretation of research data, and scientific advancement. Nine percent of the respondents said they witnessed a situation that compromised research participants’ safety due to industry sponsorship, and participants’ wellbeing were “seriously or significantly compromised” in 40 percent of these instances.

Expert recommendations for how to reduce the number of financial conflicts and their impact on science include standardizing requirements for the dollar thresholds at which researchers must disclose financial conflicts, standardizing the formats for reporting conflicts across institutions, making them more easily discoverable, and requiring COI disclosure in scientific journals and research studies. Many academic journals have disclosure rules, but they are not yet mandatory or uniform, and author compliance is inadequate. Suggestions to prevent undue industry influence include developing rules that preserve the use of industry expertise in research and limiting that industry involvement to an advisory role. Such restrictions could prevent corporations from controlling research design and methods in academic research and clinical trials.

Financial conflicts of interest are a problem since even the appearance of a conflict may undermine the public’s trust in science. For example, it is reasonable to believe that a researcher’s financial relationship with a drug maker would skew his or her judgment on the drugs. Moreover, if investigators in human subjects research have conflicts of interest, influence on their conclusions could endanger subjects and future patients, as the survey participants mentioned above attest. In 2007, New York Times found that psychiatrists who received at least $5,000 from creators of antipsychotic drugs wrote three times as many prescriptions for the drugs, to children and adults, as psychiatrists who received less money or none. These drugs are not approved for most uses in children due to a high risk of side effects.

Why do conflicts of interest exist?

Conflicts of interest originate from research partnerships among industry, academia, and government. Corporate research funding substantially increased over the past 40 years while federal research and development funding remained relatively constant. Although these relationships are essential to the discovery process that can lead to new medical therapies that benefit society, increasing financial relationships between industry and scientists create suspicion that conflicts will cause dangerous partial professional judgments.

Academic researchers and industry grew closer when Congress passed what is known as the Bayh-Dole Act in 1980. The law fostered greater collaboration between researchers and industry by allowing universities to patent discoveries developed using federal funding. Academic researchers subsequently sought ties to industry, believing the connection would accelerate the marketing process.

How do types of conflicts of interest differ?

Conflicts of interest appear in a variety of scenarios that have distinct impacts. However, most COI are complicated because they are comprised of a combination of these characteristics.

Financial COI: Individuals may benefit financially from a certain outcome in a clinical trial or the extent of an invention’s development. Research funding industries may offer scientists different types of financial compensation:

• Equity Interests are a proportion of company ownership in the form of stocks. A scientist with equity interests may be biased towards the company’s products since the financial benefits are dependent upon the success of clinical studies and future marketing ventures. Institutional Review Boards evaluate any research on human subjects conducted at an institution, and members who own equity interests have an incentive to approve studies regardless of IRB rules since a product must be tested before it can enter the marketplace and produce profit for stock owners. IRB conflicts of interest therefore eliminate the independent review that is necessary for patient safety.
• Consulting Fees include income scientists earn by providing expert advice about a product to private companies. This is a less problematic scenario than owning equity interests because consulting fees are typically predetermined. Thus, the scientist’s consulting income is independent of drug testing outcomes. However, a scientist may feel indebted to a company if the consulting fee is substantial, leading to research bias towards the company’s products.

Conflicts of Interest in Clinical Trials: This type of conflict is especially concerning because preferential treatment to a particular experimental group in a clinical drug study could harm research participants and future patients. For example, biased research may signal to the Food and Drug Administration that it should approve a drug that does not actually meet safety standards. If the drug is allowed to enter the market, doctors prescribing it may endanger their patients since they are unaware of its actual risk.
Further, doctors who recruit their own patients into clinical trials for which they are investigators may be so hopeful for their patients’ improvement that they believe a treatment is more successful than it is in reality. Moreover, a doctor may have patients with similar health characteristics, and placing them in the same trial keeps it from remaining a randomized trial-a standard requirement for producing objective results.

Industry COI: Industry-funded studies are more likely to draw conclusions favorable to their company’s product. However, industry sponsorship does not immediately indicate a conflict of interest because a company would not fund a clinical trial if it did not believe it may be a success. Nevertheless, a company can exercise undue influence over a study’s design that may impact its conclusion.

Industry may also interfere with research by delaying the publication of negative results after the trial’s conclusion to avoid negative attention. In one case, a pharmaceutical company postponed for seven years publication of a study that concluded the widely prescribed levothyroxine was no more effective than a less-expensive generic.

As well, presenting physicians with gifts like expenses-paid meetings in exotic locations, complementary meals, and other small items branded with a company’s name may create an unconscious bias towards the industry sponsor’s products. Leading medical schools and hospitals, such as Johns Hopkins, acknowledge this form of COI and largely ban such items.

Institutional COI: A conflict of interest is institutional rather than individual if research at the institution could affect its investment holdings, patents, or funding sources. Researchers and physicians at the institution may collectively feel allegiance to the institution’s investments or funders. When funders include nonprofits like patient advocacy organizations, COI becomes more complex since corporations may form and run these nonprofits, using them to funnel payments to researchers. The American Medical School Association grades the level of COI at top academic medical centers based on the presence or absence of policies regulating interactions between students and faculty with pharmaceutical and device industries.

What is the current state of conflict of interest policies?

Conflict of interest policies aim to separate private industry and researchers just enough to avoid harm to scientific integrity and patients, but preserve the collaboration benefits. The Public Health Service, a division of the U.S. Department of Health and Human Services that includes NIH, requires that all institutions that receive PHS grants adopt policies on individual COI to promote objectivity. All PHS grant recipients are required to report significant financial interests, defined as financial gains over a $10,000 value, or equity stakes in companies in excess of 5 percent. This sum does not include salary from an investigator’s institution or income from participation in events sponsored by public or nonprofit entities, which is a problem since many for-profit companies create nonprofit counterparts to filter funds without technically breaking rules. There currently is no universal institutional policy, as rules vary in stringency and effectiveness across schools and research organizations.

Most peer-reviewed journals, such as the New England Journal of Medicine and Journal of the American Medical Association, require authors to disclose all potential conflicts of interest, but many do not have financial COI policies for peer reviewers or editors.

What policies could mitigate conflicts of interest?

The Institute of Medicine, part of the National Academies of Science, convened a committee to examine conflicts of interest in medical research and make recommendations, which were released in a report in April 2009. Although the IOM does not possess policy-making authority, it has influence over the FDA and Congress. The report cites disclosure as “a critical but limited first step in the process of identifying and responding to conflicts of interest.”

Financial COI disclosure should be standardized so all institutions have the specific information required to accurately assess relationships between industry and scientists, the report suggests. In addition to disclosure, researchers with significant financial conflicts should be banned from conducting human subjects research. Medical institutions should create standing COI committees and NIH should require its research grantees to follow the committees’ rules, the IOM recommends.

The IOM advises that Congress create a national program that requires pharmaceutical, medicine device, and biotechnology companies and their foundations to publicly report payments to researchers, physicians, institutions, professional societies, patient advocacy groups, and continuing medical education providers. Payment information should be readily available on a public website so individuals, journals, and universities could verify disclosures.

What recent activity could lead to conflict of interest policy reform?

The Public Health Service sought public comments “on whether the HHS should amend its regulations on the responsibility of applicants for promoting objectivity in research for which PHS funding is sought and on responsible prospective” until July 7, 2009. Final rule changes, if any, are forthcoming.

In addition, U.S. Senators Chuck Grassley (R-IA) and Herb Kohl (D-WI) introduced S. 301, the Physician Payment Sunshine Act-legislation aimed at reducing COI and increasing transparency-on January 22, 2009. If passed, manufacturers and group-purchasing organizations would be required to report their payments to physicians and physician-owned entities if valued over $500. The bill is currently in the Committee on Finance, but Grassley’s aggressive investigations on apparent COI convinced at least two companies, Eli Lilly & Co. and Merck & Co., to abide by the bill’s rules beginning in 2009 nonetheless.

Vivian Cheng is an intern with Science Progress.

Tags: bioethics, Research ethics

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