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MAYO CLINIC’S CONFLICT OF INTEREST POLICYSPECIAL ARTICLE

From the Division of Gastroenterology and Hepatology (M.C.), Office of Medi-cal-Industry Relations (M.C., M.L.H.), Department of Physical Medicine andRehabilitation (G.L.G.), and Division of Cardiovascular Diseases (S.L.K.),Mayo Clinic College of Medicine, Rochester, Minn; and Department of Ortho-pedic Surgery, Mayo Clinic College of Medicine, Jacksonville, Fla (M.B.W.).

Dr Gamble and Ms Hockema have nothing to disclose. Dr Camilleri hasresearch grants from Merck KGaA, Johnson & Johnson, and ARYx Pharmaceu-ticals and has served as a consultant for Salix Pharmaceuticals, Inc,AstraZeneca, Yamanouchi Pharmaceutical Co, Kosan Biosciences, Inc,Fulfillium, Inc, Theravance, Inc, Microbia, Inc, Propagate Pharma, Ltd,GlaxoSmithKline, Novartis Pharmaceuticals, Wilmington Pharmaceuticals,Takeda Pharmaceuticals America, Inc, Johnson & Johnson Pharma,AbDiagnostics, Inc, Sanofi-Aventis, Domain Associates, LLC, Vela Pharmaceu-ticals Inc, Sucampo Pharmaceuticals, Allergan, Inc, Eli Lilly and Company,Baxter International, Inc, and EnteroMedics Inc. Dr Kopecky has researchgrants from AtheroGenics, Inc, and Endomatrix Inc, and has served as aconsultant for Paringenix, Inc, GlaxoSmithKline, Bristol-Myers Squibb Co, andHawaii Biotech, Inc. Dr Wood is a member of the Board of Directors ofVisionShare, Inc, Steris Corp, Cubist Pharmaceuticals, Inc, and AssistiveTechnology, Inc.

Individual reprints of this article are not available. Address correspondence toMichael Camilleri, MD, Office of Medical-Industry Relations, Mayo ClinicCollege of Medicine, 200 First St SW, Rochester, MN 55905.

© 2005 Mayo Foundation for Medical Education and Research

Principles and Process in the Development of theMayo Clinic’s Individual and Institutional Conflict of Interest Policy

MICHAEL CAMILLERI , MD; GAIL L. GAMBLE, MD; STEPHEN L. KOPECKY, MD; MICHAEL B. WOOD, MD;AND MARIANNE L. HOCKEMA, MA

The Bayh-Dole Act of 1980 added a new dimension tothe goals of scientific research as it sought to stimulate

the translation of American scientific discovery to success-ful commercial activity. This translation has resulted inpatients benefiting from more rapid access to new discov-eries. Essentially, the Bayh-Dole Act enabled institutionsand their investigators to own patents resulting from feder-ally funded research. Moreover, it enhanced opportunitiesfor funding research activities at academic medical centersat a time when reimbursement from the practice of medi-cine was dwindling. For the first time, institutions werepermitted to hold intellectual property rights for inventionsdisclosed by employees, to license technology to commer-cial partners, and to share in a royalty stream with theinventor(s).

The Bayh-Dole Act provided opportunity for the re-search community to commercialize discovery and innova-tion. However, it also created inherent conflicts of interestfor academic centers engaging in research and technologydevelopment with industry. New institutional relationshipswith industry evolved and extended beyond funded re-search into strategic alliances, technology licensing,project partnering, and equipment procurement and testing.

In 1995, federal regulations required all academic medical cen-ters to implement policies to manage individual financial conflictof interest. At the Mayo Clinic, all staff are salaried, and all med-ically related intellectual property from the staff belongs to theclinic. Hence, it was necessary to develop a policy for institutionalconflict of interest to complement the policy for individual con-flicts of interest. This article addresses the principles and processthat led to the development of the Mayo Clinic’s policies thatguide the management of conflict of interest of individuals and ofthe institution. Empowered by the Bayh-Dole Act, the Mayo Clinicparticipates in technology transfer through its entity Mayo Medi-cal Ventures. Individual conflicts of interest arising from suchtechnology transfer are associated with institutional conflictsbecause all individual intellectual property belongs to the institu-tion, per clinic policy. This policy addresses conflicts of interestthat arise in research, leadership, clinical practice, investments,and purchasing. Associated with the statutory annual disclosureon personal consulting and other relationships with industry,which are guided by federal regulations, all research protocols orgrant applications require financial disclosure on initial submis-sion and in annual progress reports. The clinic’s Conflict of Inter-est Review Board was established to review each disclosure andrecommend management of individual and institutional conflictsof interest according to policy.

Mayo Clin Proc. 2005;80(10):1340-1346

When these relationships were created, the risk associatedwith the introduction of bias in the conduct of studies waspotentially increased. For individuals, opportunities forcloser relationships with industry also expanded with invi-tations to provide consulting services and to serve on advi-sory boards or even corporate boards of directors. Conflictsof interest and the potential for conflict were inevitable, asdocumented in several scholarly reviews and editorials.1-8

Such conflicts became particularly concerning if they wereperceived to influence the conduct of trials involving hu-man subjects in which patient safety should have been theprincipal concern.

Advances in biomedical research originate from bothacademic institutions and industry. Translation of theseinnovations to clinical practice involves collaborationsthat, of necessity, engender formal relationships betweenindustry and academic centers. Public trust in medical re-search assumes altruistic motives of academic centers andmedical researchers in the conduct of contracts with indus-try. In 1995, formalizing years of intense self-examinationand self-regulation within the research community, theNational Institutes of Health and the Department of Healthand Human Services adopted regulations to address indi-vidual conflicts of interest. Most state laws also require thattax-exempt entities advance new knowledge in the public

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MAYO CLINIC’S CONFLICT OF INTEREST POLICY

interest or risk losing their tax exemption. The key prin-ciples for protecting the research participant in the contextof individual investigator conflicts of interest were identi-fied initially as disclosure and informed consent. However,management of these conflicts has become more complexwith the emergence of institutional conflicts of interest andthe intertwining of conflicts of interest for individual inves-tigators and their institutions.

On one extreme, conflicts of interest could be managedby prohibiting contracts and interaction with industry9; onthe other extreme, institutions could simply avoid the issueentirely or give it minimal attention. Both alternatives ap-pear unfavorable to the public good; thus, measures mustbe devised to facilitate appropriate relationships that posi-tively affect patient care. Existing policies governing con-flict of interest at academic centers throughout the UnitedStates reflect a lack of consistency, according to sur-veys.10,11 Authors have recently recommended measures tobe considered by institutions for managing conflicts ofinterest,12,13 but as yet there are no published policies fromacademic medical centers. Moreover, policies for employ-ment and intellectual property at the Mayo Clinic requiredthe development of customized approaches to individualand institutional conflicts of interest. Specifically, it isworth noting that all Mayo Clinic staff are salaried and thatall medically related intellectual property of the staff be-longs to the Mayo Clinic.

THE NEED FOR AN INSTITUTIONAL POLICY

Conflict of interest, even the appearance of potential con-flict, has always been a concern for scientists committed tothe integrity of their research. In 1921, Dr William J. Mayostated, “Commercialism in medicine never leads to truesatisfaction, and to maintain our self-respect is more pre-cious than gold.” Early in its history, the Mayo Clinicdeveloped policies to help individuals manage conflict ofinterest. The clinic has considered management of conflictof interest as the responsibility of the institution because allphysician/scientist staff work as full-time employees andall intellectual property belongs ultimately to the clinic.

Studies show that patients involved with researchprojects are more aware of potential individual conflict ofinterest than of institutional conflict of interest.14 Compre-hensive studies published in the past 3 years indicate that thepotential for institutional conflicts of interest is germane tomost if not all academic medical centers15 including theNational Institutes of Health.16 Relationships among physi-cians/scientists and their institutions and industry also re-quire careful management to avoid legal liabilities.17,18

Conflicts of interest for the Mayo Clinic as an institutionare linked almost exclusively to individual conflicts of

interest. Therefore, we acknowledge that our recommenda-tions may not apply to conflicts of interest at all medicalcenters. However, we believe our deliberations may serveto stimulate discussion at other medical centers and maylead eventually to a consensus position for the academicmedical community as a whole.

THE PROCESS LEADING TO THE MAYO CLINIC’SPOLICY ON CONFLICT OF INTEREST

Through ongoing communications with staff, the MayoClinic has noted the staff’s sense of responsibility for con-flict of interest, but also their confusion regarding whatactually constitutes conflict of interest and how that con-flict can be managed. Some Mayo Clinic staff perceivedthat a potential conflict of interest was associated with apresumption of wrongdoing. This illustrated a need to edu-cate the staff about the inevitability of conflicts of interestand the importance of establishing standards and effectivemechanisms to manage it.

Most guidelines in prior publications tended to addressconflicts of interest related to clinical trials; however, rela-tionships with industry encompass other everyday func-tions of academic medical or research centers. Dr DavidKorn,2,19 Division of Biomedical and Health Sciences Re-search, Association of American Medical Colleges, stated,“Conflicts of interest are ubiquitous and inevitable in aca-demic life, indeed, in all professional life. The challengefor academic medicine is not to eradicate them, which isfanciful and would be inimical to public policy goals, but torecognize and manage them sensibly and effectively.” Im-proprieties have been reported at academic medical centerswhere institutional and individual conflicts of interest werenot disclosed, reviewed, or managed.

Thus, the Mayo Clinic established a broad-based taskforce and intramural review process to develop recom-mended procedures and policies for handling conflicts ofinterest for individuals and for the institution. The clinicalso sought guidance from national leaders, hosted a na-tional forum to air major issues,20 and reviewed recommen-dations from learned individuals.19,21 Nonfinancial conflictsof interest that may affect individual fame rather than for-tune22 also were recognized but were not addressed in thefirst policy because academic self-interest was considered alegitimate part of the motivation to conduct research, whichis itself a mandate for academics and their institutions.22

GOALS

The goals for the Mayo Clinic Conflict of Interest Policyare as follows: to safeguard patient safety in all clinicalpractice, research, and education efforts; to protect the

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MAYO CLINIC’S CONFLICT OF INTEREST POLICY

TABLE 1. Essential Disclosures

Corporate equity in the form of stock or other ownershipRoyalties or rights to receive future royalties on licensed intellectual

propertyConsulting fees, honoraria, salary, gifts, or in-kind compensation within

the previous 12 monthsResearch or education grants within the previous 12 monthsService on advisory boards or boards of directors within the previous

12 monthsCurrent negotiations relating to any of the above relationshipsAny other relevant external relationships that could influence the

proposed activity

integrity of the institution and the individual; to support andnot impede research efforts; and to acknowledge and de-velop guidance for the management of conflicts of interestfor the institution and for the individual. The Mayo Clinicindividual and institutional conflict of interest policy can beaccessed at www.mayoclinic.org/medicalprofs/conflict.pdf.

DEFINITION OF CONFLICT OF INTEREST ATTHE MAYO CLINIC

Mayo Clinic policy focuses on 4 types of activities thathave the potential for financial conflict of interest: purchas-ing decisions, leadership activities (intramural, includingdecisions made in the clinical practice, and extramural),investments (endowment and pension fund), and research.Because individual and institutional conflicts of interest atthe Mayo Clinic often are intertwined, the potential forboth is considered for all 4 types of activities.

The operational definition of conflict of interest is asfollows (paraphrased from the Mayo Clinic conflict of inter-est policy 2004, www.mayoclinic.org/medicalprofs/conflict.pdf):

A conflict of interest occurs when there is a divergence betweenan individual’s or an institution’s private interests and their pro-fessional obligations either to a patient or to society such that anindependent observer might reasonably question whether actionstaken by the individual or the institution may have been influ-enced by consideration of significant financial conflict of interest.A conflict of interest may pertain to research, investment, leader-ship or purchasing activities; it depends on the situation, and doesnot necessarily reflect on the character or actions of an individual.

From the principles outlined in this definition, guidelineswere developed for managing potential conflicts of interestin purchasing, leadership, investment, and research activi-ties. Disclosures provide sufficient information to assessrelationships with external entities in matters pertinent tothe proposed activity. Elements of essential disclosures arelisted in Table 1. Such disclosures do not imply unmanage-able conflicts of interest.

Significant financial interest must be defined for eachspecific activity. General principles that reflect federalguidelines for significant conflict of interest23 are listed inTable 2.

GUIDELINES FOR MANAGEMENT OFCONFLICT OF INTEREST

There are multiple mechanisms for managing conflict ofinterest. The first step is always disclosure. Since 2001, theMayo Clinic has mandated annual disclosure by its staff ofall relationships with industry. A statement is signed at thetime of employment, and failure to comply is reported tothe Mayo Clinic Personnel Committee for disciplinary ac-tion. With such an honor system in place, there is noattempt to review individual tax returns. In addition, disclo-sures are updated with each Mayo Clinic Institutional Re-view Board (IRB) or federal grant application. Apart fromdisclosure, current Mayo Clinic policies have discouragedthe development of significant financial conflict of interestby requiring peer review of all external consulting relation-ships, prohibiting stock options as payment for consultingfees, and prohibiting ownership by the professional staff ofmedically related companies. The second step is evaluationor review of the disclosed information by the Conflict ofInterest Review Board to determine whether a significantconflict of interest is present, according to established cri-teria. If a conflict of interest situation is identified, the thirdstep is to institute measures for conflict management. Man-agement of conflict of interest includes disclosure to pa-tients and laboratory personnel, including graduate stu-dents; disclosure in publications and presentations; recusalfrom the principal investigator position and/or access todata management when indicated; escrow of financialholdings; and rarely, divestiture.

PURCHASING DECISIONS

In a large academic medical center, purchasing departmentsoften make quality and price-driven decisions removed fromthe individual user. However, with many technologies ordevices, the user of the technology with the best knowledgeis often the investigator who invented it or may be funded tostudy it. Purchasing decisions include but are not restrictedto the decision to actually purchase a product or technology(ie, the request that a purchase order be generated); theselection of a supplier for a product or technology for evalu-ation, competitive bid, or proposal; and the actual negotia-tion of a purchasing agreement or contract with a supplier ofa product or technology. Individuals who serve on advisoryboards or boards of directors of vendors or competing ven-dors being considered in the purchase are said to have a sig-nificant interest, even if no compensation is involved.

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MAYO CLINIC’S CONFLICT OF INTEREST POLICY

For purchasing decisions, if a significant conflict ofinterest is identified after review by the Conflict of InterestReview Board, management of the conflict of interest mayrequire the following: full disclosure of potential conflictsof interest at the time of purchase discussions; recusal fromchairing or, depending on the level of conflict of interest,participating in a decision-making process; retention of anyequity ownership until research or purchasing decisions arecompleted; and documentation of the recusal in meeting orpurchase decision minutes. The policy also requires thatany purchasing decisions involving sums greater than$30,000 and institutional conflict of interest must be re-viewed by the Conflict of Interest Review Board. Purchasesthat involve technologies discovered and licensed originallyby the Mayo Clinic to a third party require documentationthat the purchase was based on the best interests of thepatient, such as documentation of best performance in theliterature relative to competing technology. According toStark II legislation, the inventors earn no royalty when thetechnology is used at the Mayo Clinic. However, the MayoClinic benefits if a sales-based royalty is received.

LEADERSHIP DECISIONS

For leadership decisions made by any employee on behalfof the Mayo Clinic, management of significant conflict ofinterest may require the following: recusal from chairing orparticipating in the final decision-making process thatcould indirectly affect the relationship of the person withthe company or its competitors and the Mayo Clinic, aswell as documentation of the recusal in the meeting min-utes that record the leadership decision. The process ofrecruiting staff to the Mayo Clinic is not influenced by thepotential to develop intellectual property for income;rather, search committees consist of academic and clinicalleaders and have no representation from the Office ofTechnology Transfer. Incoming staff who own medicallyrelated companies are required to disclose all equity andintellectual property before employment, and their potentialfor conflicts of interest or commitment are monitored by anindependent oversight committee at least twice each year.

For leadership decisions made by non-staff members ofthe Mayo Clinic (eg, members of the clinic’s Board ofTrustees), recusal from final decision-making processesmay be required whenever a personal or potential conflictof interest could directly or indirectly affect the clinic.Recusal is documented in the institutional minutes thatsummarize the decision.

INVESTMENT DECISIONS

Mayo Clinic investment decisions should continue to re-flect the ethical and responsible stewardship of endow-ment, pension, and operational funds. Investment decisions

should be unrelated to any clinical practice, research, oreducation activity.

For investment decisions made on behalf of the MayoClinic, the conflict of interest policy specifies that the clinicshould limit its equity holding to 5% or less in any publiclytraded company when the clinic intends to pursue researchor educational activities with that company. The MayoClinic has no limit to investment/equity ownership whenthere is no intention to pursue research or educationalactivities with a company. Similarly, the clinic has no limitto equity ownership in privately held companies (includingthose that become publicly traded through an initial publicoffering) that use the clinic’s intellectual property when noresearch is planned with clinic patients or staff. However, ifresearch activities sponsored by a privately held companyare contemplated, the relationship and research activityshould be reviewed by the IRB to ensure patient safety andby the Conflict of Interest Review Board to manage poten-tial institutional conflict of interest if a Mayo Clinic invest-ment is ongoing or contemplated.

RESEARCH DECISIONS

The literature is replete with examples of societal concernsabout potential conflicts of interest with research results24

and the focus on problems in postmarketing surveillance,25

interpretation of risk-benefit, and the motivation for profit inthe pharmaceutical and device industry. Participation ofMayo Clinic staff in Food and Drug Administration advisoryreview boards is encouraged. Participation in presentationsfor new drug or device applications is permitted, althoughit requires thorough review by the Medical Industry Rela-tions Committee, which also appraises individual andinstitutional conflicts of interest in each request for par-ticipation. Clinical research involving new medicationsand devices that originate usually in the corporate worldis encouraged.

TABLE 2. Significant Conflict of Interest

Equity greater than 5% in a company or equity with a value of more than$10,000 (whichever is less) is considered a significant financial interest.Equity through mutual funds is not considered a significant financialinterest

Rights to receive royalty payments greater than $10,000 per year onlicensed intellectual property are considered a significant financialinterest

Consulting fees, honoraria, salaries, gifts, or in-kind compensation withinthe previous 12 months are considered a significant financial interest ifvalue is greater than $10,000

Research or education grants within the past 12 months that areunrestricted or provide funds in excess of those required for reasonableexpenses incurred in the performance of the sponsored research oreducational activity are considered a significant financial interest

Current negotiations to initiate or modify the above relationships aregenerally regarded as equivalent to a significant financial interest

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MAYO CLINIC’S CONFLICT OF INTEREST POLICY

For research decisions, if the Conflict of Interest ReviewBoard identifies a significant conflict of interest after re-view, oversight or possible recusal from research activitiesmay be required, depending on the level of conflict ofinterest and its potential effect on human studies. Whenthere is institutional conflict of interest pertaining to re-search being conducted at the Mayo Clinic, this likelyinvolves individual conflict of interest because all MayoClinic employees are required to disclose and license anyintellectual property through the clinic’s Office of Tech-nology Transfer. With the current royalty-sharing policy,the share received by inventors and their research programor department actually exceeds the royalty received by thegeneral fund of the Mayo Clinic. Hence, institutional con-flict of interest can be identified and managed pari passuwith the identification of individual conflict of interest.Apart from the share of the inventors, such funds are usedto support the research and education missions of the in-ventors’ research program or department.

Research by or at the Mayo Clinic involving humansubjects or biospecimens and all research requiring IRBapproval require higher levels of management than doesnonhuman research if conflict of interest exists. Whenresearch involves individual or institutional financial con-flict of interest, the Conflict of Interest Review Board shouldbe consulted for advice. Typically, financial conflict of inter-est is determined by virtue of assigned monetary value (thatis, market value) or licensing of a technology and not justdisclosure to the Mayo Clinic’s Office of Technology Trans-fer (Mayo Medical Ventures). Pursuit of a patent is not aformal assignment of monetary value, but it presents thepotential for bias; therefore, the Conflict of Interest ReviewBoard may need to develop management strategies in thissituation.

In general, basic research should be permitted to con-tinue at the laboratory of the investigator who may have aconflict of interest, depending on the nature of the work,the specific expertise available, and the mandate of theBayh-Dole Act. Management of conflict of interest in suchsituations will include disclosure to laboratory personnel,disclosure in presentation and publication of data in scien-tific journals, and disclosure at the point of application forPublic Health Service and/or National Science FoundationNon-Clinical Research Funding (PHS Final Rule 42 CFRPart 50 and 45 CFR Part 94; NSF Rule 59 FR 3308 and 60FR 35820). Management of the conflict of interest will bereevaluated when the discovery leads to studies in hu-mans or their medical records or in biospecimens thatwould require approval by the IRB. Because there is apotential for conflict of interest or a potential for theperception of such a conflict when research results ema-nate from a laboratory with substantial financial interest,

several management guidelines are discussed in the nextsection.

OPERATIONAL GUIDELINES FOR THECONFLICT OF INTEREST REVIEW BOARD

Practical guidance for the implementation of review anddecision processes was developed for specific situationsthat arise commonly in the context of research at the MayoClinic, as indicated subsequently. This is regarded as workin progress that likely will be refined over time. The Con-flict of Interest Review Board, which includes intramuraland extramural members, has a direct relationship to MayoClinic leadership for matters related to individual conflictof interest. In matters pertaining to institutional conflict ofinterest, this board reports only to the highest governancebody at the clinic, the Board of Trustees, made up primarilyof public members. The Conflict of Interest Review Boardcommunicates to the Personnel Committee leadership atthe Mayo Clinic regarding any situations in which policiesand procedures for conflict of interest have not been fol-lowed by its staff. The Personnel Committee serves as thedisciplinary board.

Mayo Clinic guidelines anticipate that different levels ofconflict of interest may arise that require a tailored orspecific management response by the Conflict of InterestReview Board. Research studies that may involve conflictof interest include single-center or multicenter studies withor without Mayo Clinic equity ownership. Simple disclo-sure of inventions or intellectual property to the Office ofTechnology Transfer does not necessarily constitute a con-flict of interest. The presence of significant financial con-flict of interest may require 1 or more management strate-gies that range from disclosure in the consent form torecusal from participation.

The Mayo Clinic’s policy for ownership of its staff’sintellectual property facilitates oversight because all tech-nology transfer and start-up companies are coordinatedultimately through 1 office, Mayo Medical Ventures,whose officers are well aware of the policy. Similarly, thepolicy that prohibits independent staff ownership of amedically related company (whether clinical facilities26 orbiotechnology-based) reduces the risk of undisclosed con-flicts. Such policies may not apply at other academic medi-cal centers. In practice, most institutional conflicts of inter-est at the Mayo Clinic are identified during the review ofindividual conflict of interest disclosures, and managementstrategies can be recommended at the same review.

For multicenter research studies for which neither theMayo Clinic nor the investigator has a conflict of interest,Mayo Clinic participation and leadership in the study arestrongly encouraged with the usual need for IRB review of

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MAYO CLINIC’S CONFLICT OF INTEREST POLICY

human studies. However, when single-center or multi-center research studies involve the investigator and theMayo Clinic and both have a conflict of interest, participa-tion increases the potential of perceived bias in the conductof the research or a perceived inability to serve the bestinterests of research participants. In these circumstances,apart from IRB approval, Conflict of Interest ReviewBoard assessment is needed to determine whether the re-search may be pursued at the Mayo Clinic and whether theinvestigator may participate. In some situations, addressedin other reports as the “rebuttable presumption,” it may stillbe appropriate to pursue the research at the academic medi-cal center that has a conflict of interest.19 These situationsmay include the uniqueness of the patient population orexpertise or facilities that cannot be replicated at othermedical centers. However, in such situations, safeguardshave been developed in conjunction with the Mayo ClinicIRB to protect the research participant (Table 3). Undercertain circumstances, it may be permissible to enroll morethan 20% of participants in such a study at the Mayo Clinic,as in early clinical studies (phase 1b or 2a studies) or whenthe novel diagnostic or therapeutic procedure is only avail-able at a few medical centers.

CONSIDERATION OF OTHER RECENTLY PUBLISHEDRECOMMENDATIONS

Recently published articles in the New England Journal ofMedicine12 and the Journal of the American Medical Asso-ciation13 have proposed 4 important principles, which havebeen adopted by Mayo Clinic.

First, institutions and institutional decision makersshould fully disclose industry-related financial interestsand relationships and should divest themselves from theseinterests or recuse themselves from responsibility for re-search oversight or conduct of research, consistent with thedraft recommendations from the Department of Health andHuman Services.27

Second, certain facilities should be physically sepa-rated, and sharing of information should be restricted be-tween investment (including endowment and pensionfunds) and research staffs.

Third, oversight should be provided by independentreview panels with expertise in intellectual property, fi-nance, and research, and with no financial or other depen-dence on the institution.13 The Mayo Clinic Conflict ofInterest Review Board includes external members. How-ever, a body entirely comprising external members wasconsidered unlikely to have sufficient understanding of themission and governance of the institution and its relation-ships with industry to serve the needs of the institution or ofsociety in general.

Fourth, there should be greater oversight of researchinvolving human participants and the operation of IRBreview and systematic assessment of the outcomes of thatoversight.28 The chair of the Mayo Clinic’s IRB serves as amember of the Conflict of Interest Review Board, and thesecretaries of the 2 boards coordinate a group of adminis-trators from the Mayo Clinic’s Research Services Depart-ment and the Office of Compliance. Mayo Clinic policyrequires an annual progress report of each protocol forextension of initial IRB approval, which is for 1 year. Theprogress report requires disclosure of any change in finan-cial interest of each investigator listed on the protocol. Theclinic’s internal audit office performs audits of randomlyselected active research protocols.

CONCLUSIONS

Blumenthal29 has written, “Relationships between aca-demic institutions and industry in the life sciences continueto fascinate, perplex, trouble, and embarrass academicinvestigators, university administrators, industrial compa-nies, and government policymakers.” However, the com-mon good of patients requires that the Mayo Clinic and itsstaff participate fully in the biomedical research arena andin the translation of new discoveries to clinical applica-tion. The Mayo Clinic’s conflict of interest policies re-garding purchasing, leadership, investment, and researchhave been established to allow the relationships to go

TABLE 3. Precautions for Participation in Research WhenInvestigator and/or Institution Has Significant Financial

Conflict of Interest

Study development is made by a steering committee consisting of MayoClinic (investigator) and non-Mayo Clinic members (including plans fordesign, conduct, and analysis)

Mayo Clinic enrolls less than 20% of total participantsConflicted investigator may not participate in operational aspects of

study, may not enroll patients or gain informed consent, and cannot besite (Mayo Clinic) principal investigator

Informed consent must be obtained by a nonconflicted investigator whohas no access to the data

Study must be a triple-blind design: patients, investigators, assistants/technicians must be unaware of randomization groups (if appropriate)and results

Data management activities may not occur at investigator institution(Mayo Clinic)

There must be an independent Data Safety Monitoring Board and ClinicalEvent Committee with a priori stopping rules for both safety andefficacy

Central core laboratory must be used when using surrogate end points forefficacy

Dataset must be given to an independent statistician for comparison at theend of the study

Data analysis and interpretation monitoring committee must review anyjournal or regulatory reports

Individual or institutional conflict of interest must be disclosed to all studyparticipants in informed consent, and to all study coinvestigators,fellows, and students working on the project

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forward yet still protect the patient, the individual, and theinstitution. The Mayo Clinic has used monetary valuesconsistent with 1995 Public Health Service regulations todefine significant financial conflicts. Clinic representa-tives meet with leaders of other academic medical centersto compare approaches and develop further consensusregarding identification and management of conflicts ofinterest. Currently, we perceive that it is useful to sharewith readers at the Mayo Clinic and at other medicalcenters the principles and process that were key to thedevelopment of the Mayo Clinic’s policy, which willcontinue to evolve and require periodic review to ensureconsistency with federal and state regulations, nationaltrends, and Mayo Clinic values in order to maintainthe public trust.13 These policies will need to be adaptedto the clinic’s employment policy (of all-salaried staff)and the policy that all medically related intellectual prop-erty developed by all–Mayo Clinic staff belongs to theclinic.

We are grateful to the Mayo Clinic Conflict of Interest task forcemembers for their contributions to the submitted manuscript: GailL. Gamble, MD (Chair), Charles H. Adler, MD, PhD, Nelson S.Brewer, MD, Michael Camilleri, MD, William P. Cooney III, MD,Ann E. Decker, JD, Eugene P. DiMagno, MD, James R. Francis,David L. Hayes, MD, Marianne L. Hockema (secretary), RobertM. Kisabeth, MD, Stephen L. Kopecky, MD, David E. Larson,MD, Barbara L. Porter, James A. Rogers, JD, Craig A. Smoldt,and Richard M. Weinshilboum, MD.

REFERENCES1. DeAngelis CD. Conflict of interest and the public trust [editorial]. JAMA.

2000;284:2237-2238.2. Korn D. Conflicts of interest in biomedical research. JAMA. 2000;284:

2234-2237.3. Martin JB, Kasper DL. In whose best interest? breaching the academic-

industrial wall [published correction appears in N Engl J Med. 2001;344:536].N Engl J Med. 2000;343:1646-1649.

4. Campbell EG, Louis KS, Blumenthal D. Looking a gift horse in themouth: corporate gifts supporting life sciences research. JAMA. 1998;279:995-999.

5. Lo B, Wolf LE, Berkeley A. Conflict-of-interest policies for investiga-tors in clinical trials. N Engl J Med. 2000;343:1616-1620.

6. Shalala D. Protecting research subjects—what must be done. N Engl JMed. 2000;343:808-810.

7. Morin K, Rakatansky H, Riddick FA Jr, et al. Managing conflicts ofinterest in the conduct of clinical trials. JAMA. 2002;287:78-84.

8. Drazen JM, Koski G. To protect those who serve [editorial]. N Engl JMed. 2000;343:1643-1645.

9. Rothman KJ. Conflict of interest: the new McCarthyism in science.JAMA. 1993;269:2782-2784.

10. McCrary SV, Anderson CB, Jakovljevic J, et al. A national survey ofpolicies on disclosure of conflicts of interest in biomedical research. N Engl JMed. 2000;343:1621-1626.

11. Cho MK, Shohara R, Schissel A, Rennie D. Policies on faculty conflictsof interest at US universities. JAMA. 2000;284:2203-2208.

12. Moses H III, Braunwald E, Martin JB, Thier SO. Collaborating withindustry—choices for the academic medical center. N Engl J Med. 2002;347:1371-1375.

13. Johns MM, Barnes M, Florencio PS. Restoring balance to industry-academia relationships in an era of institutional financial conflicts of interest:promoting research while maintaining trust. JAMA. 2003;289:741-746.

14. Kim SY, Millard RW, Nisbet P, Cox C, Caine ED. Potential researchparticipants’ views regarding researcher and institutional financial conflicts ofinterest. J Med Ethics. 2004;30:73-79.

15. Bekelman JE, Li Y, Gross CP. Scope and impact of financial conflicts ofinterest in biomedical research: a systematic review. JAMA. 2003;289:454-465.

16. Steinbrook R. Conflicts of interest at the NIH—resolving the problem. NEngl J Med. 2004;351:955-957.

17. Blumenthal D. Doctors and drug companies. N Engl J Med. 2004;351:1885-1890.

18. Studdert DM, Mello MM, Brennan TA. Financial conflicts of interest inphysicians’ relationships with the pharmaceutical industry—self-regulation inthe shadow of federal prosecution. N Engl J Med. 2004;351:1891-1900.

19. AAMC. Financial conflicts of interest in clinical research. Available at:www.aamc.org/members/coitf/start.htm. Accessibility verified August 24,2005.

20. Holmes DR Jr, Firth BG, James A, et al. Conflict of interest. Am Heart J.2004;147:228-237.

21. AAU Task Force on Research Accountability. Report on UniversityProtections of Human Beings Who Are the Subjects of Research. Washington,DC: Association of American Universities; 2000.

22. Levinsky NG. Nonfinancial conflicts of interest in research. N Engl JMed. 2002;347:759-761.

23. Department of Health and Human Services. Draft: Financial relation-ships and interests in research involving human subjects: guidance for humansubject protection. Fed Register. 2003;68:15456-15460.

24. Friedman LS, Richter ED. Relationship between conflicts of interest andresearch results. J Gen Intern Med. 2004;19:51-56.

25. Fontanarosa PB, Rennie D, DeAngelis CD. Postmarketing surveil-lance—lack of vigilance, lack of trust. JAMA. 2004;292:2647-2650.

26. Iglehart JK. The emergence of physician-owned specialty hospitals [pub-lished correction appears in N Engl J Med. 2005;352:638]. N Engl J Med.2005;352:78-84.

27. Lipton S, Boyd EA, Bero LA. Conflicts of interest in academic research:policies, processes, and attitudes. Account Res. 2004;11:83-102.

28. Emanuel EJ, Wood A, Fleischman A, et al. Oversight of human partici-pants research: identifying problems to evaluate reform proposals. Ann InternMed. 2004;141:282-291.

29. Blumenthal D. Academic-industrial relationships in the life sciences. NEngl J Med. 2003;349:2452-2459.

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