Conflicts of interest in translational research

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Journal of Translational Medicine 2004, 2:28http://www.translational-medicine.com/content/2/1/28equity or other ownership interests, royalties, and intellectualproperty rights. A researcher may, for example, receiveconsulting income or equity in exchange for service on ascientific advisory board of a company that then sponsorsclinical research in her lab. Another researcher may bepaid for talks to physician groups about an approvedmedication while simultaneously conducting research onpotential off-label uses of the drug. The investigator or animmediate family member may hold stock in the researchsponsor. These examples are all common cases and mostinstitutions have relatively standardized ways of managingsuch common conflicts.Greater challenges are created when the financial relationshipsbetween commercial interests and investigators areeither ambiguous or complex. Ambiguity can result in anumber of ways, but one of the most frequent occurswhen investigators approach consulting as an extension ofdiscussions among academic colleagues. Thinking thattalking to a corporate representative is the same as talkingto an academic colleague, for example, may lead theinvestigator to make inappropriate disclosures that compromiseintellectual property rights or contractual obligations.Often it is not any one financial interest, but ratherthe combination of multiple financial interests that makesa situation unmanageable. It is extraordinarily difficult,for example, to manage situations in which an investigatoris the founder of a startup company, an inventor on apatent licensed to the company, a consultant to the company,and the recipient of other government and industrygrants for closely related research.How institutions manage potential conflicts offinancial interestSpurred by a combination of bad experiences and newregulations, most research institutions now have policiesin place for the management of some aspects of personalfinancial interests in research. One strategy is simply toprohibit personal financial interests in research. The Associationof American Universities, for example, advocatesoutright prohibition in cases involving research onhuman subjects unless there are "compelling circumstances"that justify an exception [4]. Prohibition forcesfinancially interested researchers to either divest theirinterests or to remove themselves from the research.Although effective, prohibitions are blunt tools and in ouropinion should be used only as a last resort. We say thisnot only because prohibiting financial interests may leaveany number of other equally biasing interests in place [5],but also because, when properly managed, financial interestsmay play a positive role in the development of a translationalresearch program. Access to company resourcesand sharing investigator knowledge are often critical totimely translations of basic science to clinical practice. Thecomplex research enterprise needed to develop clinicalproducts is simply beyond the scope of what many investigatorscan achieve on their own in academic institutions.Fortunately, there are usually less draconian alternativesto outright prohibition. These strategies seek to ensure theintegrity of the research, guarantee public scrutiny andaccess, and, of course, to protect human participants [6].One of most common is to assign key research activitiessuch as recruiting, consenting, and data analysis to teammembers who have no financial stake in the results.Multi-center designs ensure that the biases of any oneinvestigator are less likely to influence the final results.Independent data safety monitoring boards or other oversightcommittees may also check the influence of personalfinancial interests. So, too, will requirements to disclosefinancial interests to publishers, conference organizers,and institutional review boards.Research integrity is further protected by a vigilant stanceregarding publication restrictions. Industry partners havea legitimate interest in protecting proprietary information,but this can usually be honored by providing a shortperiod for review prior to submitting a manuscript forpublication. No contract or agreement, however, shouldgive the sponsor the right to control publication. Workthat requires such control is more appropriately done inindustry rather than in academic laboratories. The closeattention to publication restrictions is particularly importantwhen a researcher may have a student working on anindustry sponsored project. Junior and student scientistsworking in a research program, who may not have anyrelationship with a company, must be able to have freedomin pursuing aspects of projects outside the bounds ofthe research agreement and publishing data in a timelyfashion.Translational research that results in the development of anew company presents particular opportunities and challenges.Because of the importance of small companies toeconomic growth, public research universities often viewthe number of university-related startups as an index oftheir contribution to the state economy. More specificinstitutional interests are created when universities takeequity in startups through licensing agreements. Unlikemore established firms, start-up companies are oftenhighly dependent on obtaining favorable research outcomesfrom a particular project. In many cases, prohibitionmay be the only way to manage the tangle ofinstitutional and individual interests than can result inthis situation. Universities may create "firewalls" betweenthe management of equity and researchers [7]. They mayrequire divestiture or bar researchers from receiving grantsback from companies to which their inventions have beenlicensed. Consulting and other company contacts may bePage 2 of 4(page number not for citation purposes)
Journal of Translational Medicine 2004, 2:28http://www.translational-medicine.com/content/2/1/28restricted when the investigator or the university has a significantfinancial interest in the startup. Although universitiesare still coming to grips with their own institutionalfinancial interests, there is an emerging consensus thatthey should not conduct clinical research on their owninventions unless a strong case for locating the research atthe university can be made on clinical grounds [8,9]. Fornovel biologic therapies, the investigator who inventedthe approach may be ideally suited to complete the clinicaltranslation. The failure of many novel agents to demonstrateactivity in Phase I may be linked to a disconnectbetween the scientist developing the agent and the physicianrunning the clinical trial. Translational research isdefined as that person being one and the same.Recently, the American Association of Medical Collegespublished suggested guidelines for the management ofconflict of interest based on input from a number of medicalschools [10]. Such documents not only encouragedialogue concerning these issues, but also provide someguidance for individual institutions establishing theirinternal policies.How financial conflicts of interest can affect yourresearch programUnrecognized and unmanaged conflicts of financial interestrepresent major risk factors for programs of translationalresearch. Even when properly disclosed andmanaged, however, outside financial interests may limityour research activities in a variety of ways, ranging frommild to severe. If nothing else, time and staff resourcesmust be allocated to institutional and extra-institutionalreview processes. Because approval is required beforefunding is released or human subjects are enrolled, thepace of research is slowed by outside financial interests.Scientists with personal financial interests in the researchwill usually find themselves barred from participating insensitive research activities, especially those involvingdirect contact with human subjects. This increases thecosts of research as additional staff or consultants arehired to do the work that the financially interested partywould have otherwise performed. But even this strategymay prove difficult if key staff or alternative expert consultantsalso have financial interests. There is a tippingpoint beyond which so many potential team members arefinancially involved that the interests simply can not bemanaged and outright prohibition becomes the onlyoption.In the most extreme circumstances it is possible forresearchers to research themselves out of a job. Their personalfinancial interests in a research sponsor may be sogreat or so complex that their employers are unable toaccept further funding from that sponsor. A line of translationalresearch may simply end for a researcher when heor she is barred from carrying the work into the clinicalarena as a result of individual or institutional financialinterests. This can occur even when the researcher is notactively seeking financial gain. Early basic science work,for example, may lead to an invention that the universitydecides to patent and license. In most universities theresearcher is entitled to a share of whatever revenue is produced.The researcher now has a personal financial interestthat requires management and may disqualify her orhim from participation in later clinical work designed totranslate the basic science into practice. This is an extremecase, of course, but it does happen and it illustrates theoften unseen and unintended implications of how financialinterests are usually managed.Dealing intelligently with financial interests inresearchPublic concern about personal and institutional interestsin research is not going to go away. Nor is the need forindustry collaboration in translational research. Indeedthe need for collaborations between industry andacademia is only going to grow as we move beyond asequential "bench to bedside" model to acknowledge thebenefits of combining clinical and basic biological studies[11]. If financial interests can not be avoided, we can atleast be more thoughtful about how we manage them-asindividual researchers, as industry collaborators, and asacademic research institutions.Individual investigators should recognize that disclosureof personal financial interests, while perhaps uncomfortable,is vital to continued public confidence in science.They must also balance their wish for personal gainagainst the additional oversight and management of theiractivities that will inevitably result. They should recognizethat some financial interests are more easily managedthan others. Consulting income paid as cash, for example,is much more easily managed than consulting incomepaid with equity in the company. The latter creates a longtermfinancial interest and may imply management influence.The understandable desire to "share the wealth"with team members by assisting them in obtaining outsidefinancial interests of their own backfires when it thenbecomes necessary to remove them from the tasks thatthey were hired to do in the first place.The decision to create a company in order to further atranslational research agenda is appealing, often appropriate,but always more complex than researchers typicallyappreciate. It is a risky conceit to believe that one's successin obtaining research grants and managing a researchteam is adequate preparation to launch a business. This isborne out by the fact that technologies licensed to companiesfounded by faculty inventors are generally less suc-Page 3 of 4(page number not for citation purposes)
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